Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Aim To investigate whether and how Huy- izhenbao tablets regulated osteoarthritis pain.Methods We transected the meniscotibial ligament of mice, which caused osteoarthritis by destabilizing the medial meniscus ( DMM).Different doses of Huyizhenbao tablets (12.5,25,50 mg • kg-1) were administered intragastrically.Dynamic and static mechanical allo- dynia were measured.The spinal cord slices were pre¬pared to record miniature excitatory postsynaptic cur-rents (niEPSCs) and miniature inhibitory postsynaptic currents (mlPSCs) by using patch clamp electrophysi¬ological recordings.The phosphorylation of NMDA re¬ceptor ( N-methyl-D-aspartate receptors) (rluNl sub- unit at S897 residue ( pS897-GluNl ) was observed by immunohistochemistry.Results Huyizhenbao tablets dose-dependently attenuated the dynamic and static mechanical allodynia induced by DMM, reduced the frequency of niEPSCs and inhibited the pS897-GluNI level.Huyizhenbao tablets had no effects on mlPSCs.Conclusions Huyizhenbao tablets effectively alleviate osteoarthritis pain by blocking the presynaptic release of excitatory transmitter glutamate and inhibiting the phosphorylation of NMDA receptor in spinal cord dorsal horn.

The epidural venous plexus is considered as a cause of low back and leg pain but has been neglected for a long time. As an auxiliary drainage system of the vena cava, the epidural venous plexus plays an important role in the circulation of body fluids, and its tortuous expansion may lead to clinical symptoms similar to a herniated disc or spinal stenosis, by compressing nerve roots or dura. Due to the lack of specificity of imaging findings, it is difficult to distinguish accurately from disc herniation or spinal stenosis. The epidural venous plexus is tortuous and thin-walled, which is easy to be broken during the operation that resulted in obscuring the surgical field and leading to other complications such as postoperative hematoma. Despite researches of epidural venous plexus have been carried out for years, details are still left unknow. We hereby reviewed the latest research progress of the epidural venous plexus including anatomical structure, morphological characteristics, clinical significance and imaging examination.

Objective To evaluate the effect of different gargling liquid on colony number in air during oral ultrasound scaling for patients with periodontitis.Methods Patients with mild (n=54), moderate (n=54), and severe chronic periodontitis (n=54) were selected, then patients with same degree of periodontitis were randomly divided into three groups, with 18 in each group. Before scaling, patients in each group of mild, moderate, and severe periodontitis were given honeysuckle liquid (gargle A), 3％ hydrogen peroxide (gargle B), and normal saline (gargle C) respectively. Bacterial culture and identification of air specimens were conducted at 0 and 30 minutes after the beginning of ultrasonic scaling as well as 10, 20 minutes after the end of ultrasonic scaling.Results Variance analysis of three-factor factorial design data showed that degree of periodontitis, types of gargling liquid, and sampling time had interaction (F=2.666, P=0.002). Comparisons of air colonies: At the beginning of scaling, there was no significant difference in colony number of air around patients using different gargling liquid in mild, moderate and severe groups (all P＞0.05). Among patients using the same gargling liquid at 30 minutes after the beginning of scaling, colony number of air was the lowest around patients with mild periodontitis and the highest around patients with severe periodontitis, colony numbers of air around patients with gargle A and B were lower than that of patients with gargle C. Comparison of each sampling points showed that colony number of air around the right side of patients' head was highest, differences were all statistically significant (all P＜0.05). 20 minutes after the end of scaling, there was no significant difference in colony number among groups compared before scaling (all P＞0.05). The main isolated strains in the air were Streptococcus viridans (32.53％), coagulase negative staphylococcus (24.56％), and filamentous fungi (18.48％).Conclusion There are variety of opportunistic pathogens in the air during oral ultrasound scaling, and the number of colonies is positively correlated with the degree of periodontitis. honeysuckle liquid has a good effect on reducing the number of air colonies during and after scaling.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. Trial Registration Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.
Adult ; China ; Cross-Over Studies ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Peritoneal Dialysis ; adverse effects ; instrumentation ; methods ; Quality of Life ; Temperature

Objective To establish an automatic warning program which accommodates to the test procedures in medical laboratory centerand and to put into operation.Methods Based on laboratory information management system (LIS),automatic warning program was established,which composed of maintenance of warning rules,feedback of vulnerabilities in rules,solutions of feedback targets and evaluation of ride-effectiveness.The results of performance were assessed after operation for six months in Guangzhou Kingmed Medical Laboratory Center.Results An automatic warning program containing 13 kinds of rule templates was successfully established.The multi-point warning program via asynchronous structure for six specialized testing procedures was realized.A total of 1 523 warning rules were included in the rule bank and 24 000 reports were verified on average each day.The average passing rate of reports was 70.2％ and the passing rate of single test was 83.9％.The approval time for reports was reduced by 10 to 40 minutes compared with that without using the automatic warning program.The efficiency for report approval was improved by 25 percent.Conclusion Automatic warning program may ensure the high quality of test reports,ease pressure on staff and improve work efficiency.

Objective To assess the relationship between the comprehensive geriatric assessment (CGA)score and the mortality rate of elder inpatients with decompensated chronic heart failure (CHF). Methods One hundred and thirty-four elder inpatients who were more than 75 years and diagnosed with decompensated CHF in Department of Geriatrics from July 201 3 to July 201 5 were included and assessed by CGA.Logistic regression analysis was used to evaluate the effects of CGA scores on the mortality rate of elderly inpatients with decompensated CHF.Results Significant differences between death patients and survival patients were found in age,serum lipid,atrial flutter/atrial fibrillation,mean blood pressure and cardiac function classification (P <0.05).In the CGA scoring system,significant differences between death patients and survival patients were found in health assessment,ability of daily life and mental state (P <0.05).The significant difference of the CGA scores between death patients and survival patients appeared in the score constitution(P <0.001 ).In Logistic regression analysis,age,lipid level,cardiac function classification,CGA score were screened as the risk factors of the death in the decompensated CHF inpatients,which together influenced the prognosis of inpatients,so the value of P(bilateral)<0.05.Conclusions In the study of elder inpatients with decompensated CHF,age,serum lipid,cardiac function classification and the CGA score are the risk factors of the mortality rate of inpatients with decompensated CHF.

Recombinant adeno-associated virus (rAAV) serotype 2, 3 and 8 vectors are the most promising liver-tropic AAV serotype vectors. Liver diseases are significant problems in China. However, to date, few studies on AAV neutralizing antibodies (Nabs) were working with the Chinese population or with the rAAV3 vectors. The present study aimed to determine the prevalence of Nabs in Chinese population against wild-type AAV2, AAV3 and AAV8 capsids as well as additional two AAV3 variants. In addition, we performed a preliminary analysis to investigate the potential influence of traditional Chinese medicine body constitutions on AAV Nabs. Our work demonstrated that the majority of healthy Chinese subjects were positive for AAV Nabs, with the order of AAV2>AAV3=AAVLK03>AAV8. There was no difference between: 1) AAV3 and its variants; 2) male and female subjects; and 3) different age cohorts (≤35, 36-50, and ≥51 years old). People in the Qi-deficiency constitution had significantly increased AAV8 Nabs than people in the Gentleness constitution. Our studies may have impact on the future clinical design of AAV-based gene therapy in the Chinese population.
Adult ; Aged ; Antibodies, Neutralizing ; blood ; Antibodies, Viral ; blood ; Body Constitution ; Dependovirus ; classification ; immunology ; Female ; Genetic Vectors ; Humans ; Liver ; virology ; Male ; Middle Aged ; Serogroup