A 49-year-old male patient with type 2 diabetes mellitus and diabetic nephropathy received long term use of retaglinide thrice daily orally, 1-mg in the morning, 2-mg in the afternoon and 1-mg in the evening. Because of the sudden acute cerebral infarction, clopidogrel was added, on the 4th day of the medication, the fasting blood glucose in the patient decreased to 2.6-mmol/L. It was considered that the interaction of clopidogrel and repaglinide caused the increase of repaglinide plasma concentration, which resulted in severe hypoglycemia in the patient. Clinical pharmacist suggested stopping repaglinide and using insulin. The physician reduced the dosage of repaglinide to twice daily, 1-mg in the morning and 0.5-mg in the afternoon, and after 3 days the patient′s fasting blood glucose fluctuated between 4.0 and 4.5-mmol/L. Since the patient had diabetes nephropathy and renal insufficiency, which might increase the risk of hypoglycemia, repaglinide was stopped, and insulin glutamine 3 U was injected subcutaneously before meals, at the same time blood glucose was closely monitored. Fasting blood glucose fluctuated between 4.9 and 5.4-mmol/L after insulin treatment.

A perfect pharmacovigilance database is the core pillar of pharmacovigilance activities. At present, the United States, Japan, Europe, and the World Health Organization have all established comparatively mature pharmacovigilance databases, which have played an important role in adverse drug reaction (ADR) monitoring, ADR signal mining, and post marketing re-evaluation of drugs. This paper summarizes the data sources, data accessibility, available elements, data quality control, and data utilization status of the 4 major databases mentioned above, so as to provide references for clinical pharmacovigilance activities and improvement of the construction of pharmacovigilance database in China.

A 38-year-old female patient with thyroid nodule received Xingqi Sanjie cream 30 g orally twice daily for 4 treatment courses in total. Each treatment course was 1 month and the interval between the 2 courses was 14 days. On the 29th day of the 4th treatment course, the patient developed poor appetite, yellowish skin and sclera, and dark urine. Laboratory tests showed alanine aminotransferase (ALT) 3-201-U/L, aspartate aminotransferase (AST) 2-262-U/L, total bilirubin (TBil) 257.2-μmol/L, direct bilirubin (DBil) 186.9-μmol/L, and alkaline phosphatase (ALP) 159-U/L. Drug-induced liver injury (severe) was diagnosed, which was considered to be related to Xingqi Sanjie cream. The drug was stopped, and symptomatic and supportive treatments including hepatoprotection and rehydration were given. Twenty-two days later, the above symptoms in the patient were improved. Laboratory tests showed ALT 209-U/L, AST 117-U/L, TBil 92.7-μmol/L, DBil 63.2-μmol/L, and ALP 82-U/L. Fifty-one days later, the yellowish skin and sclera in the patient subsided, and the urine color returned to normal. Laboratory tests showed ALT 37-U/L, AST 22-U/L, TBil 30.3-μmol/L， DBil 14.7 μ mol/L, and ALP 58-U/L.

Objective To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).　Methods Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300-mg and ritonavir 100-mg every 12-hours for 5 consecutive days.　Results Three hundred and sixty-four patients were entered in the analy- sis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05).　Conclusions Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.

A 75-year-old male patient with lung cancer received intravenous infusion of sintilimab 200-mg on day 1, 21 days as one cycle. Three days after the 5th cycles of treatment, the patient developed edema of lower limbs and yellowish skin on whole body. Laboratory tests showed alanine aminotransferase (ALT) 914-U/L, aspartate aminotransferase (AST) 622-U/L, alkaline phosphatase (ALP) 385-U/L, total bilirubin (TBil) 152.6-μmo1/L, direct bilirubin (DBil) 87.9-μmol/L, indirect bilirubin (IBil) 64.7-μmol/L and total bile acid (TBA) 25.8-μmol/L. The liver injury caused by other reasons was excluded by laboratory and auxiliary examination, and it was diagnosed as drug-induced liver injury, which was considered to be related to sintilimab. Drugs such as reduced glutathione, compound glycyrrhizin, ademetio- nine, polyene phosphatidylcholine, magnesium isoglycyrrhizinate, and ursodeoxycholic acid successively were given. The patient′s edema of lower limbs and yellowish skin gradually subsided. After 25 days of treatments, laboratory tests showed ALT 33-U/L, AST 33-U/L, ALP 92-U/L, TBil 18.2-μmol/L, DBil 5.2-μmol/L, IBil 13.0-μmol/L, and TBA 7.4-μmol/L.

Objective To understand the occurrence and the clinical characteristics of meropenem- related central nervous system (CNS) adverse reactions.　Methods Using the hospital information system, the electronic medical records of patients who were hospitalized in the Department of Respiratory， the 305 Hospital of the People′s Liberation Army from January 2016 to December 2021 and received meropenem were collected. Medical records of patients who developed CNS symptoms after meropenem administration were screened and analyzed retrospectively. The data extracted from the medical records mainly included gender, age, infectious diseases, underlying diseases, renal function at admission ［serum creatinine, endogenous creatinine clearance (Ccr)］ in the patient, the application of meropenem (dose, whether dose was adjusted according to Ccr), and the occurrence (occurrence time, main clinical manifestations, etc.), treatment, and outcome of meropenem-related CNS adverse reaction. The incidence of meropenem-related CNS adverse reactions was calculated, and their clinical characteristics was descriptively analyzed.　Results A total of 636 patients used meropenem during the set period and 17 of them developed meropenem-related CNS adverse reactions, with an incidence of 2.7%. Among 17 patients, 10 were male and 7 were female, aged from 74 to 94 years with a median age of 86 years. Thirteen patients had pulmonary infection (one with urinary system infection) and 4 had acute exacerbation of chronic obstructive pulmonary disease (2 with type Ⅱ respiratory failure); 14 patients had combined renal insufficiency (10 of them had a Ccr <50-ml/min) and 5 had sequelae of cerebral infarction. Ten patients were with Ccr <50-ml/min and 3 of them did not adjust the dose of meropenem according to Ccr, resulting in excessive dosage. The time to onset of CNS symptoms in 17 patients ranged from 1 to 7 days after starting meropenem, with a median time of 3 days. Twelve patients presented mainly with psychiatric disorders (including delirium, agitation, hyperarousal, hallucinations, confusion and sleep reversal, etc.), and 5 with limb or orolingual convulsions. Meropenem was discontinued in all 17 patients after the onset of CNS symptoms and 5 of them were given symptomatic treatments. Symptoms were relieved after 1-7 days in all the patients, with a median time of 3 days.　Conclusions Meropenem- related CNS adverse reactions are more common in elderly patients and patients with renal insufficiency, respiratory failure, and a history of CNS diseases. The main manifestations are mental disorders and convulsions, which mostly occur within one week of drug use. Stopping meropenem in time and receiving appropriate symptomatic treatments contribute a good prognosis in patients.

Two patients (patient 1, a 49-year-old female; patient 2, a 51-year-old female) took Anshen Bunao liquid 10-ml twice daily orally by themselves because of poor sleep. None of the 2 patients had concomitant medications. Patient 1 and patient 2 developed fatigue and poor appetite after 7 and 10 days of Anshen Bunao liquid treatment, respectively. Laboratory tests showed that alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were 1-147-U/L, 1-271-U/L, 215-U/L and 805-U/L, 333-U/L, 227-U/L, respectively. Then Anshen Bunao liquid was stopped and hepatoprotective therapy was given. Seven days later, symptoms of fatigue and poor appetite in the 2 patients were improved, amd laboratory tests showed that the levels of ALT, AST, ALP decreased to 222-U/L, 396-U/L, 122-U/L and 85-U/L, 23-U/L, 129-U/L, respectively. Patient 1 took Anshen Bunao liquid again. Two days later, she developed abdominal discomfort with vomiting, ALT was 409-U/L, and AST was 339-U/L. After stopping the drug and giving liver-protective treatments for nearly 4 months, ALT was 32-U/L, AST was 22-U/L, and ALP was 89-U/L. Patient 2 did not take the drug again. Re-examination after 138 days after discharge, ALT was 39-U/L, AST was 28-U/L, and ALP was 130-U/L.

A 67-year-old male patient with small cell lung cancer was given chemotherapy combined with immunotherapy (irinotecan+nedaplatin+tislelizumab), 21 days as a cycle. The patient′s cough was significantly improved without blood in sputum. After 2 cycles of treatment, chemotherapy and immunotherapy were suspended because of grade Ⅳ bone marrow suppression, and radiation therapy was changed. After the 29th radiotherapy, the patient developed paroxysmal cough and sputum with bloody, accompanied by shortness of breath and no fever. Blood gas analysis showed type Ⅰ respiratory failure. Chest computed tomography (CT) showed new pleural reticular vague shadows in both lungs, especially in the right lung. Radiotherapy was stopped and chemotherapy was restarted. The patient's cough and expectoration were improved, but the shortness of breath gradually aggravated. The interstitial pneumonia lesions involved both lungs rather than being localized, by which radiation pneumonitis were ruled out. Virus and atypical pathogen infection were excluded by etiology and imaging examination. Immune-related pneumoniatis complicated with infection caused by tislelizumab was considered. High-dose methylpre- dnisolone combined with gamma globulin and infliximab were given to inhibit immune response, mero- penem, moxifloxacin, voriconazole were given successively to prevent infection, and oxygen inhalation was given. The patient′s cough, expectoration, and shortness of breath disappeared, oxygenation index was improved, and chest CT showed that the range of interstitial changes in both lungs gradually reduced.

A 73-year-old male patient with metastatic sarcomatoid carcinoma of lymph node received an IV infusion of tirelizumab 200-mg on day 1, and 3 weeks was 1 cycle. After 10 cycles of treatment, the patient developed dizziness, chest tightness, nausea, and vomiting. Laboratory tasts showed random blood glucose 99.1-mmol/L, serum creatinine (Scr) 260 μ mo/L, blood potassium 5.8-mmo/L, blood sodium 129-mmol/L, and blood osmotic pressure 368 mOsm/(kg·H2O). Blood gas analysis showed pH 7.1 and lactic acid 2.8-mmol/L. Ketoacidosis was considered and treatments such as rehydration, hypoglycemic with insulin, and electrolyte supplement were given. After 5 days of treatments, the patient′s symptoms were improved, and laboratory tests showed blood potassium 4.4-mmol/L, blood sodium 134-mmol/L, carbon dioxide binding capacity 17.0-mmol/L, and fasting C-peptide 0.02-nmol/L. Seven days later, laboratory tests showed fasting C-peptide 0 and 2 h post-prandial C-peptide 0. The patient was diagnosed with fulminant type 1 diabetes mellitus, which was considered to be related to tirelizumab. After 19 days of treatments, laboratory tests showed fasting blood glucose 5.8-mmol/L, blood glucose at 2 hours after meal 19-mmol/L, Scr 102-μmol/L, blood sodium 139-mmol/L, blood chlorine 108-mmol/L, and blood potassium 3.9-mmol/L.

A 49-year-old female patient took febuxostat 20-mg once daily orally due to chronic kidney disease and hyperuricemia. On day 9 of medication, the patient developed facial hot flashes, and then purplish red maculopapules gradually appeared on the head, face, trunk, and both lower limbs. The rash were aggravated and spread gradually all over the body, involving the eyes, mouth, and vaginal mucosa. Lysis blisters appeared at the waist, and the area of epidermalysis was less than 10%. Laboratory tests showed white blood cell count 2.1×109/L, neutrophil count 1.7×109/L, hemoglobin 59-g/L, platelet count 97×109/L, C-reactive protein 105.6-mg/L; serum creatinine 1-062-μmol/L, and uric acid 647-μmol/L; human leukocyte antigen B*5801 allele was positive. Severe erythema multiforme induced by febuxostat was considered. Febuxostat was stopped immediately and treatments including protective isolation care, methylprednisolone, immunoglobulin, hemodialysis combined with hemoperfusion were given. On day 16 of treatments, black scab was found on the lip mucosa, and 30% skin scab peeled off. After 19 days of treatments, most of the scabs of whole body fell off, and new skin was visible. Laboratory tests showed that white blood cell count and platelet count returned to normal, C-reactive protein was 2.41-mg/L, serum creatinine was 582-μmol/L, and uric acid was 424-μmol/L.

Objective To explore the adverse reaction risk signals of perampanel-related psychia- tric disorders, and provide reference for the clinical safe application of perampanel.　Methods The US FDA Adverse Event Reporting System database was searched, and the adverse event (AE) reports on psy- chiatric disorders from the third quarter of 2012 to the third quarter of 2021, which judged perampanel as the primary suspect drug were collected. The expression of AE was standardized using the preferred term (PT) in the Medical Dictionary for Regulatory Activities. Data such as patient general condition and psychiatric AE outcomes was extracted from AE reports and was analyzed descriptively. Risk signal mining for psychiatric adverse reactions to perampanel was performed using the reporting odds ratio (ROR) method. The positive signal PT was set as that the number of AE reports was 3 and more and the lower limit of the 95% confidence interval (CI) of the ROR was greater than 1.　Results A total of 922 reports on psychiatric AE with perampanel as the primary suspect drug were collected. Of the 922 patients involved, 439 were male, 441 were female, and 42 were unknown in gender. Age were recorded in 676 patients, and the age was (38±19) years. AE outcomes were recorded in 807 patients, of which hospitalization/prolonged hospitalization, urgent treatment needs, life threatening, and death due to AE occurred respectively in 409 (44.4%), 316 (34.3%), 60 (6.5%) and 22 patients (2.4%). The 922 AEs involved 1-580 PTs, and 46 PTs were detected with positive signals by ROR method. The top 5 PTs mostly reported were aggression (286 AEs), irritability (128 AEs), suicidal ideation (110 AEs), suicide attempt (100 AEs), and anger (77 AEs). The top 5 PTs with strongest signal intensity (ROR value) were postictal psychosis (383.13), schizophreniform disorder (355.27), homicidal ideation (203.56), dissociative disorder (119.64) and delusional perception (108.34), among which dissociative disorder and postictal psychosis were AEs not recorded in the drug labels. In the 46 PTs with positive signal, 14 (30.4%) were not recorded in the drug labels, and the other 12 PTs were listed as sexually inappropriate behaviour (81.43), suspiciousness (65.20), disinhibition (32.72), impulsive behaviour (31.18), perso- nality change (22.56), abnormal behaviour (16.31), social avoidant behaviour (12.95), restlessness (6.15), bipolar disorder (5.23), affect lability (5.09), nightmare es (2.86), and fear (2.79).　Conclusion psychiatric adverse reaction is a common and serious adverse reaction of perampanel, which should be paid attention to clinically.

Objective To understand the clinical characteristics of rivaroxban- related adverse events (AE) in perioperative patients.　Methods The relevant databases at home and abroad (as of April 20, 2020) were searched and the case reports of AE associated with rivaroxban used during perioperative period were collected. Relevant information in patients (nationality, gender, age, medical history, application of rivaroxaban, combined drugs, and the occurrence, treatment, and outcome of AE, etc.) was extracted and analyzed descriptively.　Results A total of 42 case reports of AE caused by rivaroxban during perioperative period were collected, involving 46 patients from 11 countries. Of the 46 patients，25 (54.3%) were male and 21 (45.7%) were female with an age of 16-96 years. In terms of the reasons for medication, 34 patients used rivaroxban before operation for prevention of postoperative venous thrombosis, 7 used rivaroxban after operation for prevention atrial fibrillation, stroke, or systemic thrombosis after operation, 4 discontinued rivaroxban during perioperative period, and 1 did not explain the reason for using rivaroxban. Past medical history were described in 21 patients, including hypertension, hyperlipidemia, and diabetes, etc. Combined medication was described in 22 patients, including antibiotics, non-steroidal anti-inflammatory drugs, analgesics, cardiovascular and cerebrovascular drugs, etc. The onset time of AE was recorded in 31 patients, which was 2 hours to 2 months after medication and most within 1 month. AE associated with rivaroxban were bleeding in 29 patients, liver injury in 7 patients, anaphylaxis in 6 patients, kidney injury in 3 patients, thrombosis in 3 patients, thrombocythemia in 2 patients, thrombocytopenia, pulmonary embolism, acute attack of coronary atherosclerotic heart disease, and visual loss in 1 patient each. After the occurrence of AE, 31 patients were improved after rivaroxban withdrawn, switching to other anticoagulants, and receiving symptomatic treatment; 1 patient improved after changing concomitant medications as well as reducing the dose of rivaroxban; 2 patients did not stop the drug in time and developed new allergic reaction; 2 patients were improved after using rivaroxban again; 1 patient died of hemorrhagic shock due to gastrointestinal bleeding; 9 patients′ outcome were unknown. Among the 46 patients, 18-had medication errors, of which 16-had dose error and 2 had compatibility errors.　Conclusions Hemorrhage is the most common AE related to rivaroxban in the perioperative use of rivaroxban, which mainly occurs within 1 month after medication. The overall prognosis is good after rivaroxban withdrawal, switching to other anticoagulants, and symptomatic treatment. Medication error is one of the causes of AE related to rivaroxban in perioperative period.

Objective To explore the safety of azivudine tablets in the treatment of moderate coronavirus disease 2019 (COVID-19).　Methods Clinical data of adult COVID-19 patients who were hospitalized and treated with azivudine tablets at Xinglin Branch, the First Affiliated Hospital of Xiamen University from August 18 to September 18, 2022 were collected. The incidence, clinical manifestations, severity， and outcome of adverse reactions during treatment were analyzed descriptively and statistically.　Results A total of 117 patients were entered in the analysis, including 68 males (58.1%) and 49 females (41.9%); the age ranged from 18 to 76 years, with a median age of 44 years. The course of COVID-19 before taking azivudine tablets ranged from 2 to 25 days, with an average time of 13 days. Azivudine tablets were applicated for 2-14 days with an average time of 8 days. Among 117 patients, 10 patients (8.5%) had adverse reactions during taking azivudine tablets, including 5 patients with gastrointestinal reactions (2 had nausea, 2 had diarrhea, and 1 had abdominal distension), 2 patients with liver dysfunction and 2 patients with dizziness, 1 patient with elevated serum triglyceride level, and 1 with fatigue. Of them, one patient had 2 times of adverse reactions, which manifested as dizziness and abdominal distension. All patients recovered after discontinuation of azivudine tablets and/or symptomatic treatments. The severity of adverse reactions was grade 1 in 7 patients and grade 2 in 3 patients, and no grade 3 and above serious adverse reactions occurred. All adverse reactions observed in the study had been recorded in the drug label, and no new adverse reactions were found.　Conclusions Azivudine tablets is safe and well tolerated in the treatment of moderate COVID-19. The common adverse reactions were gastrointestinal reactions, abnormal liver function, and dizziness.

Signal detection of adverse drug reaction (ADR) is an important research method in post marketing pharmacovigilance. In recent years, the number of literature on ADR signal detection in China has increased significantly. However, there are still many problems in this kind of research, such as unclear understanding of the concept of ADR signal, unclear purpose of signal detection research, limited signal source, inadequate processing of data in detection, unduly single data mining algorithm, unduly short time period in data selection, and no processing and analysis on bias in signal detection. This paper provides some views on these common problems in order to improve the quality of ADR signal detection research in China.

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline develo- pment and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.

A 35-year-old female patient with diabetes ketoacidosis received insulin, meropenem, ganciclovir, correction of acidosis, and fluid infusion due to pulmonary infection. Because sputum culture results suggested aspergillus infection, ganciclovir was stopped and replaced by caspofungin; because the patient′s peak temperature dropped, meropenem was stopped and replaced by piperacillin sodium and tazobactam sodium. Before antibacterial treatments, the blood potassium and calcium were 3.7-mmol/L and 2.07-mmol/L, respectively, and the blood potassium and calcium were 3.5 and 2.18-mmol/L, 3.0 and 1.89-mmol/L, 2.6 and 1.96-mmol/L, and 3.0 and 1.97-mmol/L, respectively on the 3rd, 6th, 8th, and 10th days after using caspofungin and on the 2nd, 3rd, 7th, and 9th days of treatment with piperacillin sodium tazobactam sodium. Piperacillin sodium tazobactam sodium was stopped, caspofungin, potassium and calcium supplements, and other symptomatic treatments were continued. Two days later, blood potassium was 3.0-mmol/L and blood calcium was 1.96-mmol/L. Then caspofungin was stopped and replaced by voriconazole. Three days later, the blood potassium was 3.8-mmol/L and the blood calcium was 2.12-mmol/L. It was considered that the hypokalemia and hypocalcemia were possibly induced by caspofungin.

A 69-year-old male patient with depression was treated with amfebutamone and mirtazapine for a long time. Because of poor control of symptoms, the treatment plan was adjusted to oral duloxetine (60-mg in the morning) and mirtazapine (15-mg at night). After 13 days of treatments, the patient developed high fever (41.0-℃) with disturbance of consciousness, followed by muscle rigidity and dyspnea. His heart rate was 180 beats/min and blood oxygen saturation was 0.84. Laboratory tests showed serum creatinine (Scr) 609-μmol/L, creatine kinase (CK) 7-102-U/L, myoglobin (MYO)>3-000-μg/L, aspartate aminotransferase (AST) 88-U/L， and total bilirubin (TBil) 33.7-μmol/L. ECG monitoring showed rapid atrial fibrillation. The patient was diagnosed with malignant syndrome caused by duloxetine after excluding infection and other conditions. Duloxetine and mirtazapine were stopped immediately, and symptomatic and supportive treatments including endotracheal intubation, hemofiltration, improvement of water-electrolyte balance, and hepatoprotection were given. On the 6th day of drug withdrawal, the patient′s temperature was 38.2-℃, the blood oxygen saturation was 0.96, muscle tone was improved, and muscle tremor disappeared. On the 16th day of drug withdrawal, the patient′s condition was obviously improved, the consciousness was clear, the temperature was normal, the call could be answered, and no limb convulsion and muscle tremor occurred. Laboratory tests showed Scr 116-μmol/L, CK 250-U/L, MYO 148-μg/L, AST 38-U/L, and TBil 21.4-μmol/L.

A 68-year-old female patient with breast cancer and lung metastasis received fulvestrant injection (fulvestrant) 0.5 g intramuscularly on day 1, and palbociclib capsules (palbociclib) 75-mg once daily orally for 21 days with a 7-day interval; 28 days was a cycle. Before treatments, laboratory test showed brain natriuretic peptide 811.3-ng/L and the electrocardiogram showed no obvious abnormality. During the 7th treatment cycle, the patient developed dyspnea after climbing stairs, accompanied by chest pain, chest tightness, and palpitations. N-terminal pro-brain natriuretic peptido (NT-proBNP) was 4-001-ng/L. Echocardiography showed that the left ventricular ejection fraction (LVEF) was 25%, the left ventricular wall motion was generally weakened, the left ventricle was enlarged, and the left ventricular systolic and diastolic functions were reduced. Electrocardiogram showed sinus tachycardia and ST-T changes. Heart failure with reduced ejection fraction caused by fluvestrant and palbociclib was considered. The 2 drugs were discontinued and anti-heart failure therapy including sacubitril valsartan, torasemide, and metoprolol succinate was given for 40 days. The patient′s dyspnea and chest tightness were improved. Laboratory test showed NT-proBNP 4-345-ng/L, echocardiography showed LVEF 26%, and coronary angiography showed no stenosis. Coronary artery disease was excluded, and chronic heart failure was diagnosed, with cardiac function of grade Ⅲ. After implanting the implantable cardioverter defibrillator and continuing the anti-heart failure drug treatment for 24 days, NT-proBNP decreased to 2-321-ng/L, LVEF was 25%, and cardiac function was grade Ⅰ-Ⅱ.

Objective To systematically evaluate the occurrence of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).　Methods PubMed, Embase, The Cochrane Library, CNKI, WanFang, and VIP databases were searched up to April 30, 2022. Randomized controlled trials (RCT) about NSCLC treated with EGFR-TKI (8 kinds listed in China, including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, almonertinib, and furmonertinib) compared with chemotherapy were collected. Patients was treated with EGFR-TKI monotherapy in the trial group and chemotherapy in the control group. The outcomes included the occurrence of ILD. RevMan 5.4-software was used for meta-analysis, and the effect sizes were odds ratio (OR) and the 95% confidence interval (CI).　Results A total of 15 RCT were entered in the analysis, including 6 about gefitinib, 5 about erlotinib, 2 about icotinib, and 2 about afatinib， involving 2-318 patients in the trial group and 1-975 in the control group. Meta-analysis showed that the overall incidence of ILD in the trial group were higher than that in the control group ［1.47% (34/2-318) vs. 0.51% (10/1-975), OR=2.44, P=0.004］; difference in incidences of ILD-related death between the 2 groups was not significant ［0.35% (8/2-318) vs. 0.05% (1/1-975), OR=3.29, P=0.07］. The severity of ILD was graded in 14 RCT, and the meta-analysis showed that the incidence of more than grade 3 ILD in the trial group was higher than that in the control group ［0.62%(13/2-089) vs. 0.11% (2/1-864), OR=2.60, P=0.04］. The overall incidences of ILD and the incidences of more than grade 3 ILD in the gefitinib group were higher than those in the corresponding control groups ［2.31%(27/1-167) vs. 0.71% (8/1-123), OR=2.88, P=0.004; 0.86% (7/1-167) vs. 0.09% (1/1-123), OR=3.98, P=0.03］. There was no significant difference in ILD occurrence between the trial group and the control group for afatinib and erlotinib (all P>0.05). No ILD occurred in the trail group or in the control group in RCT about icotinib.　Conclusions Compared with chemotherapy, NSCLC patients receiving EGFR-TKI, especially gefitinib, have higher risks of ILD and serious ILD. Therefore, clinical vigilance and monitoring should be strengthened.

A 56-year-old male patient with nasopharyngeal carcinoma had progressed disease after receiving radiotherapy, chemotherapy, and targeted therapy, etc. Then he received chemotherapy combined with immunotherapy (capecitabine and sintilimab). Before receiving the 3rd immunotherapy, no abnormality was found in the relevant examination in the patient. On the 3rd day of treatment, he developed cough, shortness of breath, and other symptoms, and chest CT imaging indicated inflammatory lesion of both lungs. The results of sputum culture, sputum smear examination, G test, GM test, and autoantibody examination were all negative. Infectious pneumonia and interstitial pneumonia with autoimmune features were excluded. The common respiratory adverse reaction to capecitabine was pharyngeal discomfort, and no large-scale pneumonia caused by capecitabine was reported. Therefore, it was considered to be immune- associated pneumonitis cause by sintilimab. Treatments such as intravenous injection of methylprednisolone, IV infusion of cefoperazone sodium and sulbactam sodium and moxifloxacin were given and the patient′s condition was improved. After that, methylprednisolone dose was gradually reduced, and then changed to oral prednisone. On the 10th day of oral prednisone, the symptom of shortness of breath worsened. Chest CT imaging indicated that the pneumonitis was more severe than before. Intravenous methylprednisolone was re-given but the condition was not improved.

Objective To explore the clinical characteristics of syndrome of inappropriate antidiu- retic hormone secretion (SIADH) induced by duloxetine.　Methods The diagnosis and treatment of a patient with duloxetine-related SIADH who was admitted to Nanjing Drum Tower Hospital Affiliated to Medical College of Nanjing University was reported, and the main clinical data (gender, age, prevalent diseases, use of duloxetine, combined medication, occurrence of SIADH, and intervention and outcome) of the case and related cases collected from the PubMed and Embase databases (up to December 31, 2021) were analyzed by descriptive statistics.　Results A total of 27 patients were included in the analysis, including 6 males and 21 females, aged from 38 to 92 years with a median age of 74 years. duloxetine with daily dose of 20, 30, 40, 60-mg and unknown dose were in 5, 9, 1, 10 and 2 patients, respectively, and one patient with daily dose of 30-mg developed SIADH after a single overdose of 450-mg. Sixteen patients were treated with drugs that may cause hyponatremia or interact with duloxetine. Among them, 6, 2, 6, and 2 patients were treated with 1, 2, 3, and 4 drugs, respectively. The time from the beginning of duloxetine administration to the occurrence of SIADH, was 2 days to 36 months in 26 patients, with a median time of 3 days, except that one patient of overdose was 1 hour after administration, among which 21 patients occurred within 7 days. The main clinical manifestations of SIADH included nervous system symptoms (headache, dizziness, drowsiness, etc. in 20 patients), digestive system symptoms (nausea, vomiting, anorexia, etc. in 15 patients), and systemic symptoms (fatigue, limb weakness, etc. in 6 patients). When SIADH was diagnosed, the serum sodium level of the 27 patients was 98 to 132-mmol/L, with a median level of 117-mmol/L. The severity of SIADH with grade 1, 3, and 4 was in 1 (3.7%), 7 (25.9%), and 19 (70.4%) patients, respectively. After the diagnosis or suspicion of duloxetine-related SIADH, duloxetine was discontinued in all patients, fluid intake was restricted and sodium supplement was administered. Furosemide was given in 5 patients, and the serum sodium levels returned to normal within 2 to 15 days, with a median recovery time of 5 days.　Conclusions Duloxetine- related SIADH mostly occurs within 7 days after the start of medication, and the degree is more serious. After stopping duloxetine, restricting the fluid intake, giving sodium supplement, and giving diuretics depending on the condition, the patient has a good prognosis.

Most patients with drug-induced liver injury (DILI) have a good prognosis. However, 11%-17% of the patients will suffer from chronic DILI, and 6%-10% will suffer from acute liver failure, even death or need for liver transplantation. In 2019, the incidence of DILI in China was 23.8/100-000 person year, which was far higher than that in western countries, so the study on DILI should not be ignored. This paper summarizes the hot issues in the field of DILI in recent years, mainly including the new diagnostic markers, the genetic susceptibility, the in vivo and in vitro models of idiosyncratic DILI, the diagnosis of chronic DILI, the treatment scheme, the prognosis model, the liver injury caused by immune checkpoint inhibitors, etc., in order to provide a reference for clinical workers in future research.

In 2022, a total of 22-868 cases of medication error (ME) from 315-hospitals in 26 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 14.55% compared with that in 2021 (275-hospitals), and the number of reported ME cases increased by 16.76% compared with that in 2021 (19-585 cases). In 22-868 cases of ME reports, 155 (0.68%) were classified as grade A, 18-981 (83.00%) as grade B, 3-076 (13.45%) as grade C, 422 (1.85%) as grade D, 75 (0.33%) as grade E, 156 (0.68%) as grade F, 1 (<0.01%) as grade G, and 2 (0.01%) as grade H; no MEs of grade I occurred. Among the 22-713 patients involved in MEs of grade B to I, 12-668 (55.77%) were male and 10-045 (44.23%) were female; their ages were from 1 day to 102 years; 2-453 (10.80%) were children (<18 years old), 11-374 (50.08%) were young and middle-aged adults (≥18 to <60 years old), and 8-886 (39.12%) were elderly (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 134 (57.27%) males and 100 (42.73%) females, aged from 4 days to 94 years, of which 37 (15.81%) were children, 83 (35.47%) were young and middle-aged adults, 114(48.72%) were elderly. The serious MEs (grade E-I) mainly occurred in the administration link ［74.36% (174/234)］. The 155 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 22-713 grade B-I MEs, 17-102 (75.30%) were triggered by physicians, 4-072 (17.93%) by pharmacists, 764 (3.36%) by nurses, 461 (2.03%) by patients and their family members, and 314 (1.38%) by other persons; the proportion of MEs triggered by physicians increased year by year for 4 consecutive years; the triggers of serious MEs were mainly patients and their family members ［61.97% (145/234)］. Among these MEs, 9-238 (40.67%) occurred in clinics, 7-183 (31.63%) in hospital wards, 4-620 (20.34%) in pharmacies, 1-063 (4.68%) in pharmacy intravenous admixture services, 213 (0.94%) in the nurse stations, 321 (1.41%) in patients′ home, 6 (0.03%) in the community health service stations, and 69 (0.30%) in other places. Among the 234-severe MEs, 129 (55.13%) occurred in the patient′s home, and the proportions of MEs and serious MEs occurred in the home increased year by year for 4 consecutive years. The top 3 contents of ME were wrong drug class (4-285, 18.40%), wrong dosage (4-115, 17.67%), and wrong administration frequency (2-808, 12.06%). The top 3 persons who discovered the ME were pharmacists (17-575, 74.74%), patients and their family members (2-654, 11.29%), and physicians (1-752, 7.45%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8-665, 31.94%), tiredness (4-249, 15.66%), and insufficient training of medical workers (3-502, 12.91%).

Objective To compare the clinical efficacy and safety of cefdinir dispersible tablets selected in the national centralized volume-based procurement (VBP) and the original drug cefdinir capsules.　Methods Clinical data of single-use cefdinir in outpatient of Xuanwu Hospital, Capital Medical University between January 1, 2020 and December 31, 2021 were collected through the hospital information system. The clinical data included gender, age, type of medical insurance, type of infection, application of cefdinir, whether to combine other antibacterial drugs, laboratory test results such as blood routine, C-reactive protein, liver and kidney function before and after cefdinir treatment, and adverse reaction report of cefdinir. After propensity score matching (PSM) of the age, sex, type of medical insurance, type of infection and whether to combine with other antibacterial drugs in the cefdinir dispersible tablets group selected in the VBP (VBP group) and the original cefdinir group (original group), the clinical application in patients in the 2 groups was compared to indirectly evaluate the efficacy of the 2 drugs. The white blood cell count, neutrophils percentage, and C-reactive protein levels before and after the use of cefdinir was compared to evaluate the efficacy. Adverse drug reaction report of cefdinir and liver and kidney function before and after the use of cefdinir were compared to evaluate the safety.　Results A total of 9-514 patients treated with cefdinir were entered, including 7-037 patients in the VBP group and 2-477 patients in the original group. After PSM, each group comprised 1-268 patients, the differences in gender, age, type of infection, and combination with other antibacterial drugs were not statistically significant (all P>0.05). The daily dose, course, and use density of cefdinir in the VBP group were lower than those in the original group［(0.30±0.04) g vs. (0.35±0.12) g, P<0.001; 8(4, 8) d vs. 10(8, 10) d, P<0.001; (3.96±1.70) g vs. (5.22±2.03) g, P<0.001］. The white blood cell count, neutrophils percentage, and C-reactive protein levels after the cefdinir application in patients in the VBP group were lower than those before the use of the cefdinir ［11.2(8.7, 13.8)×109 vs. 7.2(5.5, 9.9)×109, P<0.001; 80(74, 87)% vs. 66(56, 73)%, P<0.001; 23(10, 64) mg/L vs. 13(6, 44) mg/L, P=0.032］. No adverse drug reactions related to cefdinir were reported in the 2 groups. The differences in alanine aminotransferase, aspartate aminotransferase, blood creatinine, and urea nitrogen levels in patients between the 2 groups before and after use of cefdinir were not statistically significant (all P>0.05). The difference in aspartate aminotransferase before and after use of the cefdinir in the original group was statistically significant ［21(18, 23) U/L vs. 23(20, 29) U/L, P=0.040］, and the differences in alanine aminotransferase, blood creatinine, and urea nitrogen levels were not statistically significant (all P>0.05). The detection values of liver and kidney function in the 2 groups before and after use of the cefdinir were within the reference range.　Conclusion No significant differences were found in the clinical efficacy and safety between the VBP cefdinir dispersible tablets and the original cefdinir capsules.

Objective To investigate the clinical characteristics of pemphigoid caused by immune checkpoint inhibitors (ICIs).　Methods The relevant databases at home and abroad (up to October 15, 2021) were searched and the case reports on pemphigoid caused by ICIs were collected. The relevant information of patients (gender, age, tumor type, drug varieties of ICIs, incubation period of pemphigoid, main symptoms, distribution site of lesions, biopsy and immunological examination, treatment and outcome, etc.) were collected and analyzed descriptively.　Results A total of 82 relevant literature were included, involving 103 patients, 72 males and 31 females, aged 30-90 years, of which 82 (79.6%) were ≥60 years old. The primary diseases were melanoma in 45 cases (43.7%) and lung cancer in 29 cases (28.2%). The 103 patients involved 6 varieties of ICI, including programmed cell death 1 receptors ［pablizumab (47 cases, 45.6%), navulizumab (44 cases, 42.7%), and terepril (4 cases, 3.9%)］， and programmed cell death ligand 1 inhibitors ［atezumab (3 cases, 2.9%), duvalizumab (2 cases, 1.9%)], and CTLA-4 inhibitor ipimamab (3 cases, 2.9%). Eighty-four patients had a record of the time from the beginning of ICI to the occurrence (incubation period) of pemphigoid. The incubation period of pabolizumab was 3-850 days, of navulizumab was 21-790 days, and of terepril was 70-728 days. Among 103 patients, 88 (85.4%) were bullous pemphigoid, 8 (7.8%) were mucous pemphigoid, 4 (3.9%) were non bullous pemphigoid, and 1 (1.0%) was dyshidrosiform pemphigoid; the clinical manifestations were bullous and vesicular lesions in 98 cases (95.1%), rash in 51 cases (49.5%), and pruritus in 48 cases (45.6%). Nine four patients had skin biopsy results, 78 patients (83.0%) had eosinophil infiltration in the lesion site; immunological examination was performed in 92 cases (97.8%), of which 63 cases (68.5%) were IgG and C3 deposits. Thirty-five patients had pemphigoid associated antigen test records, BP180 was detected in 25 patients, and 24 patients (96%) were positive; BP180 and BP 230 were detected simultaneously in 8 cases, both were positive in 6 cases, and BP180 was positive and BP 230 was negative in the other 2 cases; BP-Ag2 was detected in 2 cases, all of them were positive. After treatment with glucocorticoid or immunosuppressant and/or withdrawal of ICIs, 86 (83.5%) of 103 patients were improved, and 6 were not; 8 cases died, of which 7 cases of pemphigoid were improved but died of other causes, and 1 case died of unreported causes; 9 cases did not report the outcome.　Conclusions ICIs can cause pemphigoid, and the incidence in the elderly is higher. The incubation period of pemphigoid varies from 3 days to more than 2 years. After glucocorticoid or immunosuppressant treatment and/or withdrawal of ICIs, most patients had good prognosis.

A 51-year-old patient with yolk sac tumor received BEP regimen ［intramuscular injection of bleomycin 30-mg, on day 2, 9, and 16), IV infusions of etoposide 100-mg/(m2· d) and cisplatin 20-mg/m2 on day 1 to 5］ after comprehensive staging surgery for ovarian cancer, 21 days was a cycle. No interstitial changes in her lungs were found on chest CT before operation and before each chemotherapy cycle. On the 12th day of the 4th treatment cycle, the patient developed cough, expectoration. Laboratory tests showed white blood cell count 0.63×109/L, neutrophil count 0.16×109/L, hemoglobin 82-g/L, platelet count 42×109/L. Chest CT showed a little grid shadow in both lungs. The patient was diagnosed with myelosuppression (grade Ⅳ) and pulmonary infection. Bleomycin treatment in the 3rd week of the 4th cycle was stopped. Granulocyte colony stimulating factor, thrombopoietin, meropenem, bromhexine, blood transfusion, fluid infusion, and other symptomatic and supportive treatment were given. Bone marrow suppression was relieved, but cough and expectoration were aggravated. Chest CT showed a little grid shadow in both lungs. Glucocorticoid and amphotericin B were added, and non-invasive ventilator assisted ventilation and other symptomatic support treatments were given, but the patient′s condition worsened, and respiratory failure and death occurred 45 days after the 4th cycle of chemotherapy.

It was a very common phenomenon that an original drug was replaced by a generic drug after its patent expires. In order to further verify the efficacy and safety of domestic generic drugs selected in the national centralized volume-based procurement, the National Healthcare Security Admini stration guided a number of medical institutions to carry out large-scale real-world studies on clinical efficacy and safety of generic drugs, involving drugs for treating cardiovascular and cerebrovascular diseases, neuropsychiatric diseases, chronic hepatitis B, and tumor, and anesthetics. More than 110 thousands patients were included in the study. Evidence from real world studies and randomized controlled trials can complement each other. Because of the diversity of data, the complexity of design, the high requirements of analytical methods, and the uncertainty of the interpretation of results in the real world studies, higher requirements for the safety and efficacy evaluation and regulatory decision-making of generic drugs are put forward. Possible recommendations to constantly promote the scientificalness and standardization of the production and use of real world evidence are as follows: further strengthen the informatization construction in medical institutions and promote the standardization and convenience in real world data use, improve the scientificalness of research design and data processing, explore and improve the real world evidence quality evaluation criteria, strengthen the awareness of data security and pay attention to the participants′ privacy protection, etc.

A 77-year-old male patient received amiodarone 0.2 g twice daily orally for arrhy- thmia. After 15 months of amiodarone treatment, he developed some symptoms such as poor appetite, reduced diet, nausea and vomiting, and dysphagia. After 22 months of amiodarone treatment, laboratory tests showed white blood cell count 13.5×109/L, neutrophil 0.78, C-reactive protein 117.4-mg/L, erythrocyte sedimentation rate 32-mm/1 h, alanine aminotransferase (ALT) 286-U/L, aspartate aminotransferase (AST) 215-U/L, alkaline phosphatase (ALP) 107-U/L, γ-glutamyl transferase (γ-GT) 45-U/L, total bilirubin (TBil) 14.8-μmol/L, direct bilirubin 9.3-μmol/L, and albumin 30-g/L. After treatments with anti-infection, hepatoprotection, and albumin supplementation, the above symptoms were improved and amiodarone was continued. After 40 months of amiodarone treatment, laboratory tests showed ALT 87-U/L, AST 106 U/L, ALP 308-U/L, γ-GT 1-242 U/L, and TBil 11.2-μmol/L. According to the results of liver biopsy, it is suspected that the patient was alcoholic liver fibrosis. After excluding alcoholic liver disease, viral hepatitis, autoimmune liver disease, and tumors by imaging and liver biopsy, it was considered to be associated with long-term use of amiodarone. Amiodarone was withdrawn, but the patient died 3 months later because of ascites and jaundice.

Objective To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.　Methods The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.　Results A total of 4-511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3-039 in the generic drug group and 1-472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group ［0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674］. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions (P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant ［1.6‰ (5/3-039) vs. 2.7‰ (4/1-472), P=0.721; 0.7 ‰ (2/3-039) vs. 0.7 ‰ (1/1-472), P=1.000］.　Conclusion The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective To explore the efficacy and safety of fenofibrate combined with ursodeoxycholic acid (UDCA) in the treatment of primary biliary cholangitis (PBC) with poor biochemical response.　Methods The medical records of early PBC patients who were diagnosed with poor biochemical response to UDCA and treated with fenofibrate in Outpatient Department of the Liver Research Center of Beijing Friendship Hospital, Capital Medical University from January 2010 to January 2018 were collected and analyzed retrospectively, so as to evaluate the efficacy and safety of combination treatment. The combination treatment regimen consisted of fenofibrate and UDCA. The efficacy indicators were the efficacy rate and biochemical response rate. When the serum alkaline phosphatase (ALP) decreased to below the baseline value before treatment after 12 months of combination therapy, it was  defined as effectiveness, and when it decreased to <1.5 times of upper limit of normal (ULN), the biochemical response was achieved. The safety indicator was the incidence of adverse reactions (liver injury, kidney injury, etc.) related to fenofibrate.　Results A total of 42 patients were enrolled in the analysis, including 12 males and 30 females. The age was (53±10) years when fenofibrate was added and the duration of combination therapy was from 5 days to 34 months. The efficacy analysis of 34 patients with combined treatment showed that the average level of ALP decreased from the baseline value after 12 months of treatment, of which 10 patients (29.4%) fell to the reference value range, and the effective rate was 100%. The ALP was 235 (210, 326) U/L before treatment and decreased to 134 (104, 190) U/L after 12 months of treatment, with a statistically significant difference (P=0.001). Of the 34 patients, 25 (73.5%) achieved biochemical response. The ALP before treatment was 221 (198, 256) U/L and decreased to 125 (99, 143) U/L after 12 months of treatment, with a statistically significant difference (P=0.010). Of the 42 patients, 16 (38.1%) developed adverse reactions related to fenofibrate, including liver injury in 8 patients (19.0%, one case was complicated with hearthurn), kidney injury in 4 patients (9.5%), myalgia, facial edema, heartburn, headache, and skin itch with rash in 1 patient each (each 2.3%). Of the 8 patients with liver injury, 4 were mild, 1 was moderate, and 3 were severe; the mild cases were not intervened, and the alanine aminotransferase (ALT) returned to the baseline level after 2 months; in moderate and severe cases, ALT and total bilirubin returned to the baseline level after stopping fenofibrate and receiving liver protection treatment. Of the 4 patients with renal injury, the serum creatinine (Scr) in 2 patients returned to the baseline level after withdrawal of fenofibrate, in the other 2 patients it recovered to the reference value range spontaneously without drug withdrawal.　Conclusions Fenofibrate combination with UDCA is effective in the treatment of early PBC patients with poor biochemical response, the rate of biochemical response is 73.5%. The common adverse reactions of fenofibrate are liver injury and kidney injury. During the medication, the patients′ liver and kidney function should be closely monitored.

Objective To know the clinical characteristics of liver injury related to thalidomide and its analogs.　Methods The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.　Results A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).　Conclusions Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

Objective To explore the risk signals of brigatinib-related adverse events (AEs) and provide reference for the safe use in clinical practice.　Methods The US FDA Adverse Event Reporting System database was searched and AE reports on brigatinib as the primary suspect drug from April 1, 2017 to March 31, 2022 were collected. AEs were standardized and classified according to the preferred terms (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities 24.0. Reported odds ratio (ROR) and proportional reporting odds ratio (PRR) methods were used to mine the AE risk signals of brigatinib. An AE with reports ≥3, ROR≥2, 95% confidence interval (CI) lower limit of ROR>1, or reports ≥3, PRR≥2, and χ2>4 was defined as a positive signal. Positive PT signals were analyzed using descriptive method.　Results A total of 1-564 AE reports were included in the analysis, involving 672 PTs. After analysis using ROR and PRR methods, 52 PTs with positive risk signals were obtained, involving 16 SOCs. The top 10 PTs in report amount were fatigue, diarrhea, nausea, cough, abnormal serum creatine phosphokinase, dyspnea, headache, rash, vomiting, and hypertension, all of which were common AEs in the instructions. The top 10 PTs in signal intensity were pituitary infarction, radiation necrosis, elevated amylase, esophageal varices, early saturation, elevated lipase, abnormal serum creatine phosphokinase, pulmonary toxicity, prolonged activated partial thromboplastin time, and photosensitivity. Among them, the PTs ranked 1st, 2nd, 4th, 5th, 8th, and 10th were not recorded in the label. Pneumonia and interstitial lung disease (ILD) were serious AEs, with 31 and 8 reports, respectively. In the 52 PTs, 28 were not included in the drug label, involving 12 SOCs.　Conclusions The main adverse reactions of brigatinib were diarrhea, nausea, cough, and abnormal serum creatine phosphokinase and serious adverse reactions such as pneumonia and ILD were both reported, which were consistent with the common AE recorded in the drug label. In addition, brigatinib might cause pituitary infarction, radiation necrosis, pulmonary toxicity, photosensitivity, etc., which should be vigilant in clinical practice.

An 85-year-old male patient received left thyroxine sodium (LT4) 50 μg orally once daily for replacement therapy because of ischemic stroke and hypothyroidism. Next day, laboratory test showed that blood potassium was 3.0 mmol/L. He was given potassium chloride sustained-release tablets 1 g orally thrice daily. Six days later, the patient complained of a rapid heartbeat after slight activity. Laboratory tests showed that blood potassium was 3.3 mmol/L and a potassium magnesium aspartate tablet was administered orally thrice daily. After 8 days of potassium supplementation treatments, the patient's blood potassium level was 3.5 mmol/L, while the blood pressure increased to 163/90 mmHg. Losartan potassium 50 mg once daily was given orally.  Clinical pharmacist consulted and learned that the patient continued to take his own LT4 75 μg once daily while following the doctor's instructions to take LT4 50 μg once daily. The patient was instructed to immediately stop taking his own medication and the LT4 dose was adjusted to 75 μg once daily. Thirteen days later, the patient's serum potassium returned to 4.0 mmol/L and no further discomfort occurred.

Objective To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.　Methods The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.　Results A total of 1-486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant(all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM ［before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752)； after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05］. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy.　Conclusion The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Chemotherapy-induced peripheral neuropathy (CIPN) usually manifests as persistent pain and sensory abnormalities, and in severe cases, loss of vibration and joint position sensation, autonomic and motor dysfunction may occur, severely affecting patients′ quality of life. Mitochondrial dysfunction may be one of the mechanisms by which chemotherapeutic drugs induce peripheral neuropathy. Different mitochondrial dysfunction caused by different chemotherapy agents are reviewed from 5 aspects in this paper, including abnormal neuronal mitochondrial morphology, activation of mitochondrial permeability transition pore and its associated calcium imbalance, dysfunction of mitochondrial bioenergetics, oxidative stress, and abnormal axonal mitochondrial transport. Avoiding or improving mitochondrial dysfunction is the main strategy to prevent or mitigate CIPN.

Objective To investigate the difference in clinical characteristics of drug-induced liver injury (DILI) between patients of different gender.　Methods Through the hospital electronic medical record system, clinical data of patients hospitalized because of DILI at Liver Research Center, Beijing Friendship Hospital, Capital Medical University from January 2005 to January 2021 were collected and retrospectively analyzed. The collected information included gender, age, body mass index, underlying diseases, medication, results of the first laboratory tests after admission, clinical manifestation and types of DILI, etc. The patients were divided into 2 groups according to gender and the clinical characteristics of DILI were compared. The factors affecting death/liver transplantation in DILI patients were analyzed by Cox regression method.　Results A total of 616 patients with DILI were entered, including 139 males (22.6%) and 477 females (77.4%). The median age was 56 (47, 64) years, ranging from 18 to 80 years. Drugs that caused DILI were traditional Chinese medicine and/or health care products (TCMHCP) in 345 patients (56.0%), western drugs in 148 patients (24.0%), and TCMHCP and western drugs in 123 patients (20.0%). Death/liver transplantation occurred in 42 patients (6.8%), including 3 liver transplantation, 19 death directly caused by the liver disease, and 20 death with causes other than liver disease. The incidences of dark urine and abdominal distension, severe liver injury, and death/liver transplantation in male patients were all higher than those in female patients, respectively ［71.9% (100/139) vs. 60.0% (286/477), P=0.010; 28.8% (40/139) vs. 18.7% (89/477), P=0.010; 46.8% (65/139) vs. 40.5% (193/477), P<0.001; 15.1% (21/477) vs. 4.4% (21/139), P<0.001］. Laboratory test results such as the white blood cell count, hemoglobin, total bilirubin, direct bilirubin, total bile acid, triglyceride, and low density lipoprotein cholesterol in male patients were all higher than those in female patients, while the levels of pre-albumin, immunoglobulin G, immunoglobulin M, and serum creatinine were lower (all P<0.05). Cox regression analysis showed that male, older age, low albumin, high total bile acid, high serum creatinine, and prolonged international normalized ratio (INR) were the independent influencing factors of death/liver transplantation in patients with DILI.　Conclusions Clinical manifestation are different in DILI patients of different gender hospitalized in the Liver Research Center, Beijing Friendshop Hospital, Capital Medical University. In male patients, cholestasis is more obvious, the disease condition is more serious, and death/liver transplantation is more common. Male patients and patients with older age, lower albumin, higher total bile acid, higher serum creatinine, and higher INR are more prone to death/liver transplantation, which should be paid attention to in clinic.

A 98-year-old male patient received cefoperazone sodium and sulbactam sodium and ambroxol etc. due to pulmonary infection. Before treatments, the patient′s coagulation function was basically normal, and the platelet count was within the reference range. Due to poor anti-infection effect, cefoperazone sodium and sulbactam sodium was changed to voriconazole combined with piperacillin sodium and tazobactam sodium 13 days later, which was adjusted to voriconazole, meropenem and linezolid glucose injection 7 days later. Three days after linezolid administration, the patient′s temperature was 39.3-℃, and scattered dark red petechiae appeared on his both hands, upper limbs, shoulders and back, with some appearing as patchy ecchymosis, without tenderness pain and fading when pressing. Laboratory tests showed that prothrombin time was 18.4-s, international normalized ratio was 1.50, activated partial thromboplastin time was 53.6-s, fibrinogen was 5.11-g/L, and plasma D-dimer was 4.27-mg/L. It was considered to be allergic purpura, which might be related to linezolid glucose injection. The drug was stopped and replaced by tigecycline, and the treatment such as anti-allergy, fluid replacement, and plasma infusion were given. Eleven days later, the patient′s skin petechiae and ecchymosis disappeared. Laboratory tests showed prothrombin time 16.2-s, international normalized ratio 1.28, activated partial thromboplastin time 35.6-s, fibrinogen 2.62-g/L, and plasma D-dimer 2.48-mg/L.

A 32-year-old male patient with community-acquired pneumonia received levofloxacin hydrochloride injection 0.6 g by intravenous infusion once daily. About 30-minutes after the first medication, the patient developed blister-like red rash on the palms of both hands and pelma of both feet. Considering that it was related to levofloxacin hydrochloride injection, the drug was discontinued and an IV infusion of dexamethasone sodium phosphate injection 5-mg was given. On the second day, the patient′s body temperature was 39.8-℃, the rash and itching symptoms were aggravated, scattered erythematous rash appeared on his face, chest and back, both upper and lower limbs, and erosion and ulcer appeared on the mucous membranes of the mouth, eyes and vulva. The patient was diagnosed as having Stevens-Johnson syndrome. Anti-inflammatory and anti-allergic treatments such as methylprednisolone, calcium gluconate, ganciclovir, imipenem and cilastatin sodium, pantoprazole, as well as symptomatic and supportive treatments such as mucosal repair, nutritional support, skin care, etc. were given. Seven days later, the patient′s temperature returned to normal; 7 days later, many blister-like red skin rashes on the trunk became pale and collapsed; 24 days later, new skin could be seen on the hands and feet of the patient, the erythematous rash on the chest and back was subsided, and the mucosa of the mouth and vulva was well healed.

Objective To compare the efficacy and safety between the generic sertraline tablets, which was selected in the national centralized volume-based procurement of drugs (trade name: Weitating), and the original sertraline tablets (trade name: Levofloxacin) in the treatment for depressive disorder, and to provide a basis for promoting the rational use of the generic drugs.　Methods Real world study using retrospective mirror-image comparison was adopted. The outpatient data of patients who were prescribed sertraline tablets one year after the implementation of the national centralized volume-based  procurement policy in Beijing Anding Hospital, Capital Medical University were collected. The patients were divided into the generic drug group and the original drug group. After the propensity score matching, the daily dose of prescription, blood concentration of sertraline, and incidence of abnormal laboratory test items (prolactin, liver and kidney function, blood lipids, etc.) of patients in the 2 groups were analyzed.　Results A total of 13-659 patients with depression, generalized anxiety disorder, and obsessive-compulsive disorder were enrolled in the study, including 5-973 (43.73%) patients in the generic drug group and 7-686 (56.27%) patients in the original drug group. Among the 5-973 patients in the generic drug group, 2-167 (36.28%) were male and 3-806 (63.72%) were female, aged (34±18) years, ranging from 6 to 94 years. Among the 7-686 (56.27%) patients in the original drug group, 2-709 (35.24%) were male and 4-977 (64.75%) were female, aged (35±19) years, ranging from 6 to 95 years. The difference between the daily dose of sertraline in prescription in the generic drug group and the original drug group was statistically significant ［(161.00±46.58) mg vs. (166.34±43.67) mg, t=6.614, P<0.001］. The difference of blood concentration of sertraline in patients between the generic drug group and the original drug group was statistically significant ［(50.41±39.49) μg/L vs. (53.80±39.62) μg/L, t=2.616, P=0.009］. The differences in incidence of prolactin elevation and liver and kidney dysfunction between the 2 groups were not statistically significant (all P>0.05). The difference in the proportion of patients with high-density lipoprotein cholesterol lower than limit of the reference value between the generic drug group and the original drug group was statistically significant ［41.75% (734/1-758) vs. 38.28% (673/1-758), χ2=4.409, P=0.039］. The difference in the proportion of patients with low-density lipoprotein cholesterol higher than the upper limit of the reference value between the 2 groups was statistically significant ［41.75% (734/1-758) vs. 45.39% (798/1-758), χ2=4.738, P=0.032］.　Conclusion In this study, no clinically significant differences in efficacy and safety of the generic and original sertraline tablets were found.

Objective To explore the adverse reaction risk signals of Xuesaitong injection, and provide reference for the safe and reasonable application of the drug.-Methods The risk signals of adverse reactions/events (AR/AE) associated with Xuesaitong injection were mined using 3 methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), and the Comprehensive Standard-Method of Medicines and Healthcare Products Regulatory Agency (MHRA) based on data in Shandong Province Adverse Drug Reaction Monitoring Center Database from 2018 to 2020.　Results A total of 2-606 AR/AE reports with Xuesaitong injection as the primary suspect drug were collected, involving 1-209 males (46.39%) and 1-397 females (53.61%). The median age of these patients was 63 years, ranging from 10 to 100 years, and 55.72% (1-452/2-606) of them were over 60 years. Severe AR/AE accounted for 13.24% (345/2-606). AR/AE involved a total of 15 organs/systems, and relevant preferred names (PN) appeared 4-218 times. Among them, the organs/systems involved ranking top 3 in frequency were skin and accessories ［37.15% (1-567/4-218)］, systemic disorders ［18.21% (768/4-218)］, and central and peripheral nervous system ［14.13% (596/4-218)］. There were a total of 19 risk signals that were positive by the ROR, PRR, and MHRA method, including sneezing, worsening palmus, discomfort in the cardiac area, dry throat, worsening headache, distention in the head, shortness of breath, convulsions, chills, high fever, chest tightness, tachycardia, worsening dizziness, papules, skin warm, palpitation, palmus, feeling cold, and erythema. The top 5 PN with severe cases were shortness of breath, high fever, convulsions, tachycardia, and chest tightness.　Conclusions Xuesaitong injection can lead to severe anaphylaxis and the most common organs/systems involved are skin and accessories, systemic disorders, and central and peripheral nervous system. Severe cases often present with shortness of breath, high fever, convulsions, tachycardia, and chest tightness, which require intensive monitoring during use of the drug.