Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

ObjectiveTo investigate the effects of using the polysaccharides from two Chinese medicine compound prescriptions as the carbon source on the growth of Bacteroides fragilis and to decipher the mechanism from the perspective of differential expression of polysaccharide utilization loci （PULs） based on transcriptomics. MethodThe media with different carbon sources ［20% polysaccharides of Lizhongtang， polysaccharides of Shenling Baizhusan， glucose， and brain heart infusion （BHI） Broth］ were used for the anaerobic culture of B. fragile ATCC25285. The effects of different carbon sources on the growth of B. fragilis ATCC25285 were determined by continuous sampling and spectrophotometry. Then， transcriptome sequencing was performed for the cultures obtained with different carbon sources to study the mechanism of different carbon sources in regulating bacterial growth. ResultThe concentration of bacteria with the polysaccharide of Lizhongtang， polysaccharide of Shenling Baizhusan， BHI Broth， and glucose as the carbon sources peaked at 26， 32， 26， 38 h， respectively， and the bacteria in all the four groups achieved robust growth. Gene ontology （GO） enrichment indicated that the differentially expressed genes in the Lizhongtang polysaccharide group and Shenling Baizhusan polysaccharide group were concentrated in the transport and transmembrane transport of dicarboxylic acid. The Shenling Baizhusan polysaccharide and BHI Broth groups showed high expression of PUL 4 and 27， glycoside hydrolase 13 （GH13）， and glycosyl transferases 5 （GT5）. PUL9 was highly expressed in Shenling Baizhusan polysaccharide group， and PUL 17， 19， and 20， GH3， and GH144 in the BHI Broth group. PUL27 and GT5 were highly expressed in Shenling Baizhusan polysaccharide and glucose groups. PUL 4 and 9 and GH13 were only highly expressed in Shenling Baizhusan polysaccharide group， and PUL 2， 17， and 19 and GH2 in the glucose group. Both Lizhongtang polysaccharide group and BHI group highly expressed PUL 4， 17， 19， 20， and 27， GH3， and GH144. PUL 2， 8， 23， and 27， GH2， and GH57 were highly expressed in Lizhongtang polysaccharide group， while GH13 showed high expression in the BHI group. Both the glucose and Lizhongtang polysacharride groups showed high expression of PUL 4 and 27 and GH2. PUL 4， 8， 20， and 23， GH3， and GH144 were highly expressed in Lizhongtang polysaccharide group， while PUL30 was highly expressed in the glucose group. ConclusionThe in vitro experiments and transcriptome sequencing results confirmed that the expression of PULs and GH may provide benefits or costs to the adaptive growth of Bacteroides fragilis ATCC25285 cultured with different carbon sources， which may be one of the mechanisms by which polysaccharides from Chinese medicine compound prescriptions regulate the growth of B. fragilis ATCC25285. The findings can provide a reference for further research on the relationship between B. fragilis metabolic pathway and polysaccharides of Chinese medicine compound prescriptions.

Objective To evaluate the feasibility and safety of tracheal extubation in operating room for patients with end-stage chronic obstructive pulmonary disease (COPD) after single-lung transplantation. Methods Clinical data of 57 recipients who underwent single-lung transplantation due to end-stage COPD were retrospectively analyzed. According to the evaluation indexes of tracheal extubation in operating room established by our hospital, 17 recipients eligible for tracheal extubation in operating room were assigned into the operating room extubation group (OR extubation group) and 40 recipients receiving tracheal extubation in intensive care unit (ICU) were allocated in the ICU extubation group. The evaluation results of intraoperative tracheal extubation and postoperative recovery were compared between two groups. Results Compared with the ICU extubation group, recipients in the OR extubation group had higher oxygenation index, lower arterial partial pressure of carbon dioxide (PaCO₂), lower blood lactic acid level, less fluctuation range of blood pressure and fewer cases receiving extracorporeal membrane oxygenation (ECMO) during operation (all P < 0.05). Two recipients in the OR extubation group received repeated tracheal intubation at 6 and 8 h after returning to ICU, and tracheal extubation at postoperative 6 and 9 d. In the OR extubation group, time of postoperative mechanical ventilation, length of postoperative ICU and hospital stay of the recipients were shorter than those in the ICU extubation group (all P < 0.05). The incidence of grade 3 primary graft dysfunction (PGD), atrial tachyarrhythmia, continuous renal replacement therapy and 1-year survival rate did not significantly differ between two groups (all P > 0.05). Conclusions The tracheal extubation regimen in the operating room for COPD patients after single-lung transplantation established by our hospital is safe and feasible, which shortens the time of postoperative mechanical ventilation, the length of postoperative ICU and hospital stay, whereas does not increase the incidence of postoperative complications.

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Objective To explore the activition and polarization of microglia in the epileptic rats induced by lithium chloride-pilocarpine. Methods One hundred male SD rats were randomly divided into five groups: control group and different time points model groups including 1d,3d,7d and 14d. Epilepsy models were established by lithium chloride-pilocarpine intraperitoneal injection. The control group was given the same dosage of normal saline. The morphology change was detected by immunofluorescence,and the expressions of iNOS and Arg-1 were determined by IHC at respective time points. Results Compared the model groups with control group,microglia was activated,synapsis was shorten,volume got bigger,most of them seemed as amoebocyte,the expression of iNOS increased and Arg-1 decreased,especially at 3d.ConclusionThe results from this study indicated that microglia was activated and polarized in epileptic rats induced by pilocarpine.

Objective To explo the antioxidant effect and molecular mechanism of gastrodin (Gas) in epilepsy (EP) rats induced by LiCl-pilocarpine (PILO) . Methods Eighty male SD rats were randomly divided into 5 groups: sham group, EP group, therapy groups (pretreated with 60 mg/kg, 90 mg/kg, 120 mg/kg of gastrodin respectively) . The EP model was esteblished by peritoneal injection of LiCl-PILO. Therapy groups were pretreated with various concerntration of Gas. The control group was given the same dosage of normal saline. The alteration of behavior was observed, the concentration of catalase (CAT), glutathion (GSH), superoxide dismutase (SOD), glutathion reductase (GR), total antioxidtion (T-AOC) and malondialdehyde (MDA) in rats brain cortex were detected by chemical colorimetric method, phosphorylation of p38 was determined by western blot. Results There was no EP seizure in sham group,and the EP seizure degree in therapy groups (gas pretreated groups) was significantly decreased,and had statistically significant difference with EP group (P<0.05) . The EP model rats exhibited a significant decrease in the concentration of endogenous antioxidants (CAT, GSH, SOD, GR and T-AOC), while an increase of the concentration of MDA and phosphorylation p38 protein as compared to sham group (P<0.05) . After treatment of the Gas,treatment group rats attenuated the seizure degree,exhibited a significant increase of the concentration of endogenous antioxidants (P<0.05),while a decrease in concentration of MDA and phosphorylation of p38 as compared to model group (P<0.05) . Conclusion Gas may have a neuroprotective role in central nervous system of epileptic rats modle by down-regulateing the seizure degree and the activity of p38 kinase and up-regulateing the content of endogenous antioxidants.

Hedgehog pathway regulates the physiological process of tumor cells, including proliferation, cycle, invasion and metastasis, and maintains tumorigenesis and development. With abnomal activation of Hedgehog pathway, most tumors response poorly to chemotherapy, which is mediated by Hedgehog pathway through activation of target gene and crosstalk with other pathways. Herein, Hedgehog pathway has been an important target for reversing resistance. In this study, the Hedgehog pathway and role of Hedgehog-mediated resistance in recent years are reviewed.

Objective To study the incidence of low triiodothyronine (T3) syndrome in critical patients,and compare the prognosis evaluation value between low T3 syndrome and acute physiology and chronic health evaluation (APACHE) Ⅱ score.Methods A total of 160 critical patients were enrolled.APACHE Ⅱ score of patients were recorded at admission,and thyroid hormone levels were measured on the first and the third day after admission.The patients who were low T3 level were enrolled into observation group,and the patients who were normal T3 level were as control group.The patients were followed up for 28 d,then were divided into death group and survival group according to the prognosis.The prognosis evaluation value was compared between T3 and APACHE Ⅱ score by receiver operating characteristic (ROC) curve.Results The incidence rate of low T3 syndrome was 25.6％ (41/160).During the follow-up phase,the fatality rate in observation group was 41.5％(17/41),and in control group was 29.4％ (35/119),there was statistical difference (P ＜ 0.05).The ROC area under curve of T3 was 0.657 (95％ CI:0.712-0.846),APACHE Ⅱ score was 0.672 (95％ CI:0.721-0.857),and there was no statistical difference (P ＞ 0.05).Best cut-off value of T3 was 0.41 μ g/L resulting in 76.9％(40/52) sensitivity and 78.7％(85/108) specificity.Conclusion Critical patients complicated with low T3 syndrome has poor prognosis,and T3 may be a predictive marker in evaluating the prognosis of critical patients.

This study was aimed to develop the method for determination of mannitol and meglumine in diterpene lactones of Ginkgo Injection. The HPLC-ELSD was used to determine mannitol and meglumine in diterpene lactones of Ginkgo Injection. The analysis was carried out on Waters XBridge Amide (4.6 mm í 150 mm, 3.5 μm) column. The mobile phase was the mixture of acetonitrile, and 50 mmol·mL-1 ammonium acetate with a linear gradient elu-tion at a flow rate of 1.0 mL·min-1. The column temperature wad maintained at 30℃. The operating conditions of the ELSD were a nebulizer nitrogen with the flow rate of 2.0 L·min-1 and an evaporator tube at the temperature of 90℃. The results showed that mannitol had a good linear relationship in a range of 1.9665 μg - 19.665 μg. The average recovery rate was 100.57% (RSD = 0.92%, n = 9). The meglumine showed a good linear relationship in a range of 0.4838 μg - 4.638 μg. The average recovery rate was 100.67% (RSD = 0.72%, n = 9). It was concluded that this method was simple and accurate with good reproducibility. It met with the requirement of the determination of the contents of mannitol and meglumine in diterpene lactones of Ginkgo Injection.