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).

Objective To investigate the effect of Compound Lingdan Capsule on serum biochemical parameters and liver fibrosis degree in a mouse model of liver fibrosis. Methods A total of 125 specific pathogen-free male C57BL/6 mice were randomly divided into normal control group with 5 mice, CCl 4 model group with 15 mice, low-, middle-, and high-dose CCl 4 groups (0.8, 1.6, and 3.2 mg·g -1 ·d -1 ) with 15 mice in each group, DDC model group with 15 mice, and low-, middle-, and high-dose DDC groups (0.8, 1.6, and 3.2 mg·g -1 ·d -1 ) with 15 mice in each group. After successful modeling, the mice in the administration groups were given Compound Lingdan Capsule suspension at the respective doses by gavage, and those in the normal control group and the model group were given an equal volume of normal saline by gavage, for 4 consecutive weeks. Blood samples were collected from the eyeballs, and serum was used to measure aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and bilirubin. Liver tissue samples were collected at the same site of the right lobe of the liver for pathological observation, Sirius Red staining, α-SMA antibody staining, and COL1A1 antibody staining. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. Results Compared with the model group, each dose group had significant reductions in the serum level of ALT and a significant increase in the serum level of albumin after the administration of Compound Lingdan Capsule (all P < 0.05), the levels of AST and bilirubin in the middle and high dose groups were lower (all P < 0.05), and the difference of each index in the high dose group was more significant than that in the low dose group (all P < 0.05). Each dose group had varying degrees of improvement in the pathological changes of the liver and a significant reduction in the number of Sirius Red staining-positive cells, as well as varying degrees of reduction in the protein expression of α-SMA and COL1A1. Conclusion Compound Lingdan Capsule can improve liver function and reduce liver fibrosis degree in mice with liver fibrosis.

Hepatic hydrothorax (HH) is a challenging complication of liver cirrhosis associated with portal hypertension, and its pathogenesis and therapeutic measures remain unknown. This article summarizes and reviews the advances and challenges in the research on the pathogenesis, clinical manifestations, diagnosis, and treatment of HH and proposes a multidisciplinary treatment strategy, including reducing the production of ascites, preventing effusion from entering the thoracic cavity, removing pleural effusion, occluding the pleural cavity, and performing liver transplantation, so as to provide a reference for more clinicians.

Dyslipidemia is one of the most common complications of primary biliary cholangitis (PBC). This article reviews the latest research on lipid profile, the risk of cardiovascular diseases, and treatment of PBC with hyperlipidemia. Different from other liver diseases, PBC with hyperlipidemia has a unique lipid profile, which changes dynamically with disease progression. It is generally not considered that there are increased risks of atherosclerosis and cardiovascular disease. For those who have indications for treatment, statins are recommended as the first choice. In the future, more in-depth systematic studies are needed to clarify its diagnosis, treatment, and management processes.

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.

Aim To study the effect of estrogen on the migration of breast cancer cells and the possible underlying mechanisms.Methods Human breast cancer cell lines MCF-7(estrogen receptor, ER+) and MDA-MB-468(ER-) were employed as a model system.Cells were treated with E2 and pretreated with CANP inhibitor(calpeptin)where needed.Wound-healing assay was applied to evaluate cell migration, Western blot assay was performed to observe protein level, and fibronectin expression was silenced by specific siRNA transfection.Results ① Treatmentof MCF-7 and MDA-MB-468 cellswith E2(50 nmol·L-1) increased cell migration by(51.55±5.50) ％(P<0.01)and (40.78±4.78)％(P<0.05), respectively;② E2 significantly up-regulated the expression of FN protein in MCF-7 and MDA-MB-468 breast cancer cells, which was 2.11 times(P<0.05)and 1.86 times(P<0.01), respectively;③ Pretreatment with calpeptin(10 μmol·L-1) decreased E2-induced cell migration by (49.55±6.44)％(P<0.05) in MCF-7 and(36.85±4.40)％ (P<0.01)in MDA-MB-468 cells;④ Calpeptin pretreatment inhibited E2-induced fibronectin up-regulation by(80.12±4.55)％ and(78.84±5.70) ％(P<0.01), respectively;⑤ Knockdown of FN with siRNA suppressed cell E2-induced migration by(40.65±5.80)％(P<0.01)in MCF-7 and(40.88±6.02)％(P<0.05)in MDA-MB-468 cells.Conclusion E2 stimulates the migration of breast cancer cells with or without ER expression and a calpain-FN signaling pathway may be involved in the E2 action.

Objective To know the mastery degree of percutaneous coronary intervention (PCI) preoperative nursing knowledge in nurses who are working in emergency department and cardiac ward. Methods 158 cases of nurses who came from three different class Ⅲ grade hospitals with qualification for emergency PCI surgery of the Guizhou province were surveyed with self-made questionnaire. The survey was conducted in nurses who were working in different departments, and the educational background, age, title, category, the cognitive situation of the PCI preoperative nursing knowledge and necessity of preoperative preparations were investigated in nurses. Results The whole pass rate was 48.10%; high qualification, high education, higher title of nurses for the nursing knowledge of the emergency PCI were better; the emergency PCI preoperative preparations for the necessity of cognitive about nurses were on the low side. Conclusion The cognition of the nursing knowledge and the necessity of emergency PCI in preoperative preparations as whole are on the low level, so specialized training should be strengthened to enhance the ability of specialized nursing.