Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To mine and conduct comparative analysis for hepatic dysfunction adverse events of voriconazole and other antifungal drugs,based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide reference for clinical practice.Methods Data from January 2004 to March 2022 in FAERS were retrieved.We estimate the association between the hepatic dysfunction events and voriconazole using reporting odds ratio(ROR)for mining the adverse drug event report signals and compare voriconazole with the full database and other antifungal drugs.Results A total of 646 reports of hepatic dysfunction related to voriconazole as the primary suspect drug were collected totally.The median time to event of the hepatic dysfunction events was 8 d.The overall ROR 95％confidence interval(CI)for hepatic-related adverse drug events was 6.82(95％CI=6.26-7.42).Comparing to other antifungal drugs,voriconazole significantly increased the risk of hepatic dysfunction compared with fluconazole,isavuconazole and amphotericin B,with RORs of 2.19(95％CI=1.94-2.47),2.31(95％CI=1.66-3.22)and 1.26(95％CI=1.08-1.48).The top 10 adverse event signals are cholestasis,hepatic cytolysis,mixed liver injury,hepatitis cholestatic,blood alkaline phosphatase increased,γ-glutamyltransferase increased,hepatic function abnormal,hepatocellular injury,liver function test abnormal and hepatosplenomegaly,and all of them have great correlation with voriconazole(ROR＞5).Conclusion Voriconazole is closely related to hepatic dysfunction,indicating that clinical attention should be paid to patients'hepatic function indicators during medication.Since the risk of hepatic dysfunction caused by voriconazole depends on several factors including the underlying disease of the patient and the exposure level of the drugs,close clinical and laboratory monitoring,including therapeutic drug monitoring,are essential to prevent or promptly recognize further deterioration of the hepatic function.

Separation and determination of chiral and achiral impurities in glimepiride tablets by supercritical fluid chromatography. Chiral and achiral impurities were separated on a ACQUITY UPC² Trefoil^TM CEL1 column (150 mm × 3.0 mm, 2.5 μm) maintained at 30 ℃ with the mobile phase containing a mixture of CO₂ and methanol-isopropanol (1∶1) at 1 mL·min^-1, and the detection wavelength was set at 228 nm. The back pressure was set at 13.8 MPa. The injection volume was 5 μL. In the chromatogram of the system suitability solution, the peaks elute in the following order: impurity Ⅳ, impurity Ⅴ, glimepiride, impurity Ⅲ, impurity Ⅰ and impurity Ⅱ. The six substances were separated successfully in 6 min using the proposed method with a resolution factor of 2.9, 1.6, 3.0, 2.0, 6.4. The impurity Ⅰ-Ⅴ detection limit (S/N = 3) was 0.17, 0.10, 0.06, 0.15, 0.10 μg·mL^-1, respectively. Good linear relationship was established between the peak response and the concentration in the range of 0.48-51.30 μg·mL^-1 for all impurities. The spiked recovery of impurity Ⅰ-Ⅴ was found to be acceptable for 99.9%, 98.9%, 102.1%, 100.1%, 96.3% (n = 9), respectively. The related substance and assay results of 11 sample batches are consistent with the results obtained using the HPLC method in the Chinese Pharmacopoeia. Compared to the two HPLC methods in the Chinese Pharmacopoeia, the established supercritical fluid chromatography method can simultaneously separate glimepiride and its 5 impurities in a single run, and it has the following advantages: simplified sample preparation, greatly reducing the volumes of organic solvents, environmentally friendly, high accuracy and good reproducibility. It can be employed for the quality control of the chiral and achiral impurities in glimepiride tablets.

ObjectiveTo explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in M1 region combined with dorsolateral prefrontal cortex (DLPFC) on electroencephalogram (EEG) θ frequency band amplitude of patients with neuropathic pain (NP) after spinal cord injury. MethodsFrom June, 2022 to June, 2023, 50 NP patients after SCI in Qingdao University Affiliated Hospital were included and divided into M1 region stimulation group (n = 25) and M1 region combined with DLPFC stimulation group (the combined stimulation group, n = 25). M1 region stimulation group received 10 Hz rTMS in the left M1 region, while the combined stimulation group received same stimulation in left M1 region combined with DLPFC, for three weeks. Before and after intervention, the pain was assessed with Short Form of McGill Pain Questionnaire (SF-MPQ), the depression and anxiety status were evaluated using Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), and the EEG θ frequency band amplitude was recorded to detect the changes of brain electrophysiological activity. ResultsFour cases in M1 region stimulation group, and two cases in the combined stimulation group were dropped. After intervention, the total score of SF-MPQ and the scores of the subscales, the scores of HMMD and HAMA decreased in both groups (|t| > 2.523, P < 0.05). The EEG θ frequency band amplitude significantly reduced in the prefrontal and frontal regions in M1 region stimulation group (|t| > 5.243, P < 0.001), and it also significantly reduced in the prefrontal, frontal regions, central and parietal regions in the combined stimulation group (|t| > 4.630, P < 0.001). All the scores were lower (|t| > 2.270, Z = -1.973, P < 0.05), and the EEG θ frequency band amplitude in the prefrontal, frontal regions, central and parietal regions were lower (P < 0.05) in the combined stimulation group than in M1 region stimulation group. ConclusionHigh frequency rTMS is an effective analgesic method on NP after SCI, which can improve their depression and anxiety symptoms and reduce the EEG θ frequency band amplitude. Compared with M1 region rTMS stimulation, the combination of M1 region and DLPFC rTMS is more effective.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.