Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.

The manufacturing process is crucial for ensuring the safety and efficacy of traditional Chinese medicine(TCM) preparations. Using advanced technologies, innovative methods, and new equipment tailored for TCM to enhance the quality control of TCM preparations in the manufacturing process helps to ensure the product quality and foster high-quality development of the TCM industry. Upon current technical requirements, such as Guideline for Studies on Pharmaceutical Changes in Marketed Traditional Chinese Medicine Preparations(Trial) and Guideline for Study on Quality Control in Manufacturing Process of Oral Traditional Chinese Medicine Preparations(Trial), this paper analyzes the characteristics and current development of quality control in the manufacturing process of TCM preparations. It also discusses the significant roles that quality control in manufacturing process plays in ensuring the quality consistency and in the evaluation and decision-making of changes in marketed TCM preparations. Furthermore, to benefit the high-quality development of the TCM industry, this paper offers recommendations for improving quality control of TCM preparations in the manufacturing process and implementing new technologies and methods.
Quality Control ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/standards* ; Decision Making ; Humans

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To identify clinical risk factors for early major adverse cardiovascular events (MACEs) following surgical correction of supravalvar aortic stenosis (SVAS). Methods Patients who underwent SVAS surgical correction between 2002 and 2019 in Beijing and Yunnan Fuwai Cardiovascular Hospitals were included. The patients were divided into a MACEs group and a non-MACEs group based on whether MACEs concurring during postoperative hospitalization or within 30 days following surgical correction for SVAS. Their preoperative, intraoperative, and postoperative clinical data were collected for multivariate logistic regression. Results This study included 302 patients. There were 199 males and 103 females, with a median age of 63.0 (29.2, 131.2) months. The incidence of early postoperative MACEs was 7.0% (21/302). The multivariate logistic regression model identified independent risk factors for early postoperative MACEs, including ICU duration (OR=1.01, 95%CI 1.00-1.01, P=0.032), intraoperative cardiopulmonary bypass (CPB) time (OR=1.02, 95%CI 1.01-1.04, P=0.014), aortic annulus diameter (OR=0.65, 95%CI 0.43-0.97, P=0.035), aortic sinus inner diameter (OR=0.75, 95%CI 0.57-0.98, P=0.037), and diameter of the stenosis (OR=0.56, 95%CI 0.35-0.90, P=0.016). Conclusion The independent risk factors for early postoperative MACEs include ICU duration, intraoperative CPB time, aortic annulus diameter, aortic sinus inner diameter, and diameter of the stenosis. Early identification of high-risk populations for MACEs is beneficial for the development of clinical treatment strategies.

Objective:To evaluate the predictive value of postnatal esophageal deviation index for clinical outcomes of fetuses with left-sided congenital diaphragmatic hernia (L-CDH).Methods:This retrospective study analyzed the clinical data of 103 neonates with prenatally diagnosed L-CDH who were admitted to Guangzhou Women and Children's Medical Center from January 2016 to February 2023. These patients were divided into the survival group ( n=82) and the death group ( n=21) according to the outcomes, and the extracorporeal membrane oxygenation (ECMO) group ( n=25) and the non-ECMO group ( n=78) according to whether ECMO support was required. Thoracoabdominal X-ray screening was performed on all neonates within 24 h after admission and the esophageal deviation index and cardiac deviation index were calculated. Independent sample t-test or Fisher's exact probability test were used to analyze the differences in general condition and postnatal imaging features between different groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of postnatal imaging features in predicting the prognosis of L-CDH. Results:The esophageal deviation index and the cardiac deviation index of neonates in the survival group were lower than those in the death group [(10.5±5.3)% vs. (18.0±4.5)%, t=－5.47; (37.7±7.1)% vs. (42.8±8.2)%, t=－2.62; both P<0.05], while that were both higher in the ECMO group compared with the non-ECMO group [(18.0±4.3)% vs. (10.1±5.2)%, t=6.34; (42.4±7.9)% vs. (37.6±7.1)%, t=2.63; both P<0.05]. ROC curve showed that the area under the curve (AUC) for predicting the need for ECMO support was 0.879 (95% CI: 0.805-0.953) for esophageal deviation index and 0.712 (95% CI: 0.570-0.854) for cardiac deviation index, with the optimal cut-off values of 11.7% and 41.7%, respectively. The AUC for predicting the survival rate in patients with L-CDH by esophageal deviation index and cardiac deviation index were 0.854 (95% CI: 0.761-0.947) and 0.735 (95% CI: 0.582-0.887), respectively, with the corresponding optimal cut-off values of 15.8% and 41.7%. Conclusion:Postnatal esophageal deviation index is of value in predicting the need for ECMO support and survival rate in patients with L-CDH.

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Objective To explore the ideas,methods and pathways for the registration of Chinese medicine prescriptions in overseas countries,to form a strategy for overseas registration of Chinese medicine,and to provide technical support and reference for China's Chinese medicine prescriptions to go abroad.Methods Five representative countries were selected to form corresponding expert teams and exchange platforms for international cooperation.The laws,regulations,rules,standards,specifications and technical guidance documents related to Chinese medicine prescription preparations of the target countries were used as pathway research materials,and the documents were translated directly,naturalized,proofread and diagrammed,and a problem-oriented mechanism for consultation with domestic and international experts was established to form a pathway for overseas registration of Chinese medicine prescription preparations.Results The path for standardization of overseas registration of Chinese medicines was clarified,and the detailed registration paths and corresponding work strategies of Chinese medicines in five countries were formulated with flow charts,tables and explanatory texts.Conclusion By developing standardized registration pathways for traditional Chinese medicine in target countries,reference can be provided for the internationalization of Chinese herbal formula preparations.