Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Objective:To explore the application value of posture adaptation training combined with continuous pas-sive exercise rehabilitation for patients after coronary artery bypass grafting(CABG).Methods:A total of 100 pa-tients with coronary heart disease(CHD)undergoing CABG in our hospital were enrolled,divided into single group(n=50,received single continuous passive exercise rehabilitation intervention)and combined group(n=50,re-ceived posture adaptation training based on single group)according to color grouping method.Both groups were in-tervened for two months.Clinical indexes,cardiac function indexes,cognitive function,exercise endurance,serum levels of neuron specific enolase(NSE),S-100β protein and satisfaction were analyzed and compared between two groups.Results:Compared with single group after intervention,there were significant reductions in first out of bed time,first anal exhaust time and length of hospital stay,and significant rise in left ventricular ejection fraction(LVEF),cardiac index(CI),left ventricular fractional shortening(LVFS),score of Montreal cognitive assessment(MoCA)scale,6min walking distance,and significant reductions in serum levels of NSE[(19.93±1.90)μg/L vs.(16.59±2.25)μg/L]and S-100β protein[(6.72±0.34)μg/L vs.(3.96±0.19)μg/L]in combined group,P=0.001 all.Satisfaction in combined group was significantly higher than that of single group(94.00％vs.80.00％,P=0.037).Conclusion:Posture adaptation training combined with continuous passive exercise rehabilitation can sig-nificantly improve the clinical indexes,promote cardiopulmonary function and cognitive function recovery in pa-tients undergoing coronary artery bypass grafting after operation.

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans). Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test. Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20 μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that af-fect the central nervous system by affecting the level of monoamine neurotransmitters.Abuse of pipera-zines will produce stimulating and hallucinogenic effects,accompanied by headache,dizziness,anxiety,insomnia,vomiting,chest pain,tachycardia,hypertension and other adverse reactions,and may even cause cardiovascular diseases and multiple organ failure and lead to death,seriously affecting human physical and mental health and public safety.The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community.The study of its pharmacological toxi-cology and analytical methods has become a research hotspot in the field of forensic medicine.This paper reviews the in vivo processes,sample treatment and analytical methods of existing piperazines,in order to provide reference for forensic identification.

Objective:To explore a better measurement mode of shear wave elastography (SWE) in the skin of lymphedema limbs, and to test its diagnostic efficacy in lymphedema.Methods:Between 1st and 10th August, 2023, 22 healthy volunteers were recruited in the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ulrasound, the First Afiliaed Hospital of Sun Yat-Sen University to measure the Young's modulus (E-value) of limb skin by SWE using a gel pad (GP group) and the thick-layer coupling gel (CG group) respectively. Then between 15th August and 28th September, 2023, 11 patients with 13 lower limb lymphedema, who were treated in the Department of Microsurgery, Orhopaedic Trauma and Hand Surgery, the First Affiliaed Hospital of Sun Yat-Sen University, were consecutively enrolled to find out the E-value of skin in oedematous limbs. The receiver operating characteristic curve (ROC) was constructed and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated to evaluate the diagnostic efficiency. SPSS 26.0, R studio and GraphPad Prism 8 software were used for statistical analysis. Paired sample non-parametric test (Wilcoxon signed rank test) was used to compare the difference in E-value between the 2 groups. P<0.01 was considered statistically significant. Spearman correlation test was used to analyse the correlation of E-value values between the GP group and CG group. Results:Overall, it was found from the healthy volunteers that E-value of skin in distal limbs were higher than that in proximal limbs, especially in lower extremities. E-value of all scanned location in GP group were found higher than those of CG group with statistically significant difference ( P<0.01), and the values of interclass correlation coefficient (ICC) showed a good repeatability. The 11 patients with lymphedema in 13 lower extremities were examined with the thick-layer coupling gel. The skin E-value in calf of patients with lymphedema were significantly higher than that of the healthy volunteers ( P<0.01), except the skin of thighs ( P>0.01). A lymphedema was diagnosed while either a skin E-value was 27.6 kPa calculated by Youden index or with the thickness of skin was 2.3 mm. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy in the diagnosis of a lymphedema were found at 92.3%, 100%, 100%, 95.7% and 97.1%, respectively. The area under curve (AUC) of ROC was 0.962. The correlation coefficients (R) of E-value in arm, forearm, thigh and lower leg in the GP group and CP group were 0.665, 0.882, 0.850 and 0.815, respectively, which were all significantly correlated. Conclusion:Application of thick layer coupler in ultrasound skin SWE is highly feasible, and the combination of ultrasound skin SWE and skin thickness has higher diagnostic efficiency in the diagnosis of lower extremities lymphedema. It allows more accurate ultrasonic image technical support for early monitoring and diagnosis of lymphedema, microsurgical treatment and a quantitatively perioperative evaluation.

Objective:To analyze the current status of salary system reform in public hospitals in Mianyang City, Sichuan Province, and provide reference for the deepening of salary system reform in public hospitals.Methods:From April to May 2023, a self-designed survey questionnaire was used to conduct a survey of medical staff in five municipal tertiary public hospitals through the Wenjuanxing platform. The survey questionnaire mainly included the basic information of the survey subjects, the implementation status of the salary system, and employee satisfaction with salary. In May 2023, semi-structured interviews were conducted with relevant personnel from government departments and public hospitals involved in the reform. The interview content included the reform measures taken and their impact, changes in medical staff salaries after the reform, and the current difficulties faced by the reform. Descriptive analysis was conducted on the data, and Chi-square test was used to compare the count data. Kendall′s tau-b test was used to analyze the correlation between salary level and basic information of the survey subjects.Results:In the reform of the salary system in public hospitals in Mianyang City, measures such as system construction, total salary quota determination and dynamic control, and salary management for non-establishment employees have been mainly adopted. 826 valid questionnaires were collected, with an effective response rate of 94.5%. The annual income level was positively correlated with age, education level, years of work experience, and professional title level ( r=0.420, P<0.001; r=0.245, P<0.001; r=0.364, P<0.001; r=0.504, P<0.001). Compared with the personnel in the same positions at the same level of hospitals in other cities and states in Sichuan Province, 274 people (33.2%) were quite satisfied or very satisfied with the current salary level; 350 people (42.3%) were quite satisfied or very satisfied with the salary distribution mechanism, and 441 people (53.4%) were quite satisfied or very satisfied with non-economic salaries. The proportion of survey respondents who believe that the existing salary structure and performance evaluation methods could reflect their actual work value was 464 people (56.2%) and 423 people (51.2%), respectively. A total of 10 people were interviewed, with 4 individuals believing that the salary level has increased after the reform, but the change was not significant compared to before the reform; 8 individuals believed that the current reform does not involve the reform of the salary structure; 6 individuals believed that the internal performance based salary distribution mechanism in hospitals was not sound; 3 individuals believed that there was insufficient attention to the reform of non-economic compensation; 7 individuals believe that the difficulties in the salary system reform were mainly concentrated on the unified understanding of policies, how to determine the increase in the total salary quota, and how to reasonably distribute it internally. Conclusions:Mianyang City has scientifically determined the total salary and implemented dynamic control, enhancing the public welfare nature of public hospitals, while also taking into account the salary management of employees both inside and outside the establishment, promoting equal pay for equal work. However, there were also issues such as disagreements on the dynamic adjustment of the total salary, an imperfect internal distribution mechanism within hospitals, and an incomplete salary system reform. It is necessary to further strengthen top-level design, reasonably increase salary levels, improve the internal distribution mechanism, and optimize the salary structure to continue deepening the reform of the salary system in public hospital.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

The objective of present study was to develop a simple and reliable voiding spot assay (VSA) system to evaluate the lower urinary tract function of mice, and to establish it as a standardized protocol. Ultraviolet (UV) light was used to screen out the filter paper without autofluorescence and with optimal urine diffusion properties. Next, the appropriate wavelength of UV was determined based on the quality of the photographic image of urine spots on the filter paper. To confirm that the urine stain area on the filter paper was correlated with the amount of urine, a volume-area standard curve was constructed. The utility of this VSA system was validated using female wild-type C57BL/6J mice aged 12-13 weeks, and the data generated under identical procedural settings were compared among laboratories. Furthermore, this VSA system was employed to analyze the changes in voiding patterns in mice with urinary tract infections or transportation stress. No. 4 filter paper with a thickness of 0.7 mm was identified as the most suitable material for VSA, exhibiting no autofluorescence and facilitating optimal urine diffusion. The filter paper retained its integrity during the assay, and there was a linear correlation between urine volume and stained area under 365 nm UV light. Utilizing this VSA system, we determined that female wild-type C57BL/6J mice produced approximately 695.8 μL total urine and 5.5 primary voiding spots (PVS) with an average size of 126.4 μL/spot within 4-h period. Over 84% of PVS volumes ranged from 20 to 200 μL. Notably, PVS volumes of mice were similar across different laboratories. Mice with urinary tract infections or transportation stress exhibited significant changes in VSA parameters, including increased voiding frequency, PVS number, and decreased PVS volume. Therefore, this VSA system can be used to evaluate the urinary function of normal mice, as well as those with urinary tract infection or transportation stress.
Mice ; Female ; Animals ; Urodynamics ; Mice, Inbred C57BL ; Urination ; Urinary Bladder ; Urinary Tract Infections