The research and development of innovative drugs targeting the clinical cure of chronic hepatitis B has become active in recent years. In the clinical trials of new drugs for hepatitis B, the use of new design concepts, new methods, and new technologies to evaluate the efficacy of innovative drugs is expected to shorten the clinical research process of candidate new drugs and reduce the cost of new drug development. However, the new designs such as seamless adaptive design and master plan design have few practical applications in clinical trials of innovative hepatitis B drugs. This article will focus on the methodological factors in the design of phase II/III clinical trials of innovative hepatitis B drugs, and introduce the key points of the new clinical trial design in order to provide methodological references for the development of innovative hepatitis B drugs.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER, Cx30-CreER, and Fgfr3-iCreER) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER transgenic lines used in functional studies should be carefully selected.

Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.
Animals ; B-Lymphocytes ; immunology ; Disease Models, Animal ; Female ; Immunity, Humoral ; Lymph Nodes ; immunology ; Myasthenia Gravis, Autoimmune, Experimental ; immunology ; Protein Subunits ; immunology ; Proto-Oncogene Proteins c-bcl-6 ; immunology ; Rats, Inbred Lew ; Receptor Cross-Talk ; Receptors, Cholinergic ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.
Critical Pathways ; Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic

Objective To study the association between chronic kidney disease (CKD) and dilated Virchow-Robin space (dVRS) in acute lacunar ischemic stroke patients.Methods A total of 1078 acute lacunar ischemic stroke patients admitted to our hospital were divided into mild dVRS group 1 (n=737) and moderate-severe dVRS group 1 (n=341) according to the severity of their dVRS in basal ganglia (BG),and into mild dVRS group 2 (n=789) and moderate-severe dVRS group 2 (n =289) according to the severity of their dVRS in centrum semiovale (CSO).Their kidney function was assessed according to the estimated glomerular filtration rate (eGFR).CKD was classified into stage 1,stage 2,stage 3a and stage 3b.The association between renal function and dVRS was analyzed by multivariate logistic regression analysis.Results The age was older,the number of females was greater,the incidence of hypertension and CKD was higher,the proportion of smoking was lower in moderate-severe dVRS group 1 than in mild dVRS group 1 (P＜0.05).The incidence of hypertension was higher in moderate-severe dVRS group 2 than mild dVRS group 2 (P＜0.05).Multivariate logistic regression analysis showed that age,hypertension,stage 2 CKD,stage 3a CKD and stage 3b CKD were the independent risk factors for severe dVRS in BG (P＜0.05,P＜0.01).Hypertension was an independent risk factor for severe dVRS in CSO (P=0.04).Conclusion CKD is an important risk factor for dVRS in BG.However,it is not associated with dVRS in CSO.This result highlights the different pathological mechanisms and risk factors for dVRS in BG and CSO.

Objective To evaluate the effect of tranexamic acid on the blood loss and coagulation function after liver resection in patients with hepatocellular carcinoma (HCC).Methods Seventy patients with hepatectomy who underwent liver resection were randomly divided into control group and treatment group,each group 35 cases.Control group was given 0.9％ NaCl injection 10 mg · kg-1.Treatment group was given tranexamic acid 10 mg · kg-1.Two groups were used at half an hour before operation.The surgical bleeding volume and postoperative coagulation function between two groups were compared.Results The operation time,time of hilar occlusion in treatment group were (157.98 ±22.36),(30.14 ±5.64) min,had no significant difference with those in control group,which were (154.98 ± 23.65),(28.79 ± 5.79) min (P ＞ 0.05).The surgical blood transfusion,bleeding volume,infusion of erythrocyte suspension in treatment group were (879.65 ± 59.36) mL,(768.97 ± 45.65) mL,(1.36 ± 0.59) U,had significant differences with those in control group,which were (1054.91 ±61.32) mL,(869.64 ±46.69) mL,(2.01 ±0.65) U (all P ＜0.05).The percentage of activated thromboplastin (APTT),prothrombin time (PT),platelet (PLT) in treatment group at 24 h after operation were (41.56 ±5.46)s,(13.48 ±3.16)s,(167.89 ±35.87) × 109/L,had no significant difference with those in control group,which were (43.19 ± 5.69) s,(14.59 ± 2.49) s,(162.35 ± 41.59) × 109/L (all P ＞0.05).The fibrinogen (FIB) in treatment group and control group were (3.27 ±0.56),(3.01 ±0.59)g · L-1,with significant difference (P ＜ 0.05).There was no adverse drug reactions in two groups during the treatment.Conclusion Giving methotrexate injection to hepatocarcinoma patients before liver resection can reduce the amount of surgical bleeding,and improve the patients' postoperative coagulation function.