Nucleotide analogues (NAs) and interferon are still the first-line drugs for the treatment of chronic hepatitis B (CHB), but they still cannot completely eliminate covalently closed circular DNA (cccDNA) within hepatocytes. The clinical cure, or the disappearance of HBsAg, is the ideal goal of antiviral therapy. Although interferon therapy has a significantly greater HBsAg clearance rate and seroconversion rate than NAs, combination or sequential treatment can improve the HBsAg clearance rate and seroconversion rate to a certain extent, and only a small proportion of CHB patients can achieve clinical cure. Therefore, finding indications that predict clinical cure before and during antiviral treatment is crucial for identifying patients who are more likely to achieve HBsAg clearance at an early stage, improving clinical cure rates, and reducing treatment costs. This article reviews the research progress on predictive indicators of clinical cure of chronic hepatitis B in the past five years, explores the value of each indicator in predicting clinical cure, and provides a reference for optimizing CHB treatment strategies.

Nucleotide analogues (NAs) and interferon are still the first-line drugs for the treatment of chronic hepatitis B (CHB), but they still cannot completely eliminate covalently closed circular DNA (cccDNA) within hepatocytes. The clinical cure, or the disappearance of HBsAg, is the ideal goal of antiviral therapy. Although interferon therapy has a significantly greater HBsAg clearance rate and seroconversion rate than NAs, combination or sequential treatment can improve the HBsAg clearance rate and seroconversion rate to a certain extent, and only a small proportion of CHB patients can achieve clinical cure. Therefore, finding indications that predict clinical cure before and during antiviral treatment is crucial for identifying patients who are more likely to achieve HBsAg clearance at an early stage, improving clinical cure rates, and reducing treatment costs. This article reviews the research progress on predictive indicators of clinical cure of chronic hepatitis B in the past five years, explores the value of each indicator in predicting clinical cure, and provides a reference for optimizing CHB treatment strategies.

0bjective:To observe The effects of 12-week Tai Chi Cardiac Rehabilitation Programme(TCCRP)and conven-tional exercise rehabilitation program(CERP)on inflammatory factors and adhesion molecules in patients with coronary heart disease(CHD).Method:Forty-six patients with CHD were jointly recruited from Anzhen Community Service Center at Bei-jing Chaoyang District and Wanjie Rehabilitation Hospital at Shandong Zibo from Oct.2020 to Nov.2021,and were randomly divided into the TCCRP group(n=23)and the CERP group as the control group(n=23)ac-cording to a 1∶1 ratio.Thirty-four patients completed the whole program,14 patients in the TCCRP group and 20 patients in the CERP group.All program were 60 min per time,3 times a week for a total of 12 weeks,including 4 weeks of in-hospital rehabilitation and 8 weeks of remote on-line home-based rehabilita-tion.Inflammatory factors and adhesion molecules were detected before and after the intervention.Result:After 12 weeks of intervention,C-reactive protein(CRP),interleukin 6(IL-6),vascular cell adhe-sion molecule(VCAM-1),and intercell adhesion molecule(ICAM-1)all decreased significantly(P＜0.01).The anti-inflammatory factor interleukin 10(IL-10)increased significantly in the TCCRP group(P＜0.0l).There was no significant difference between the two groups before the intervention(P＞0.05),and the VCAM-1 in the TCCRP group was significantly lower than the CERP group after the intervention(P＜0.05).Conclusion:In patients with coronary heart disease,the 12-week TCCRP and CERP intervention can effectively reduce the levels of pro-inflammatory factors CRP,IL-6 and adhesion molecules ICAM-1 and VCAM-1.The TC-CRP can effectively improve the level of anti-inflammatory factor IL-10 and reduce the expression of adhesion molecule VCAM-1 compared with CERP,which indicate a more positive effect on regulating the balance between pro-inflammatory and anti-inflammatory factors and improving the anti-inflammatory and anti-adhesion ability.

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

0bjective:To observe The effects of 12-week Tai Chi Cardiac Rehabilitation Programme(TCCRP)and conven-tional exercise rehabilitation program(CERP)on inflammatory factors and adhesion molecules in patients with coronary heart disease(CHD).Method:Forty-six patients with CHD were jointly recruited from Anzhen Community Service Center at Bei-jing Chaoyang District and Wanjie Rehabilitation Hospital at Shandong Zibo from Oct.2020 to Nov.2021,and were randomly divided into the TCCRP group(n=23)and the CERP group as the control group(n=23)ac-cording to a 1∶1 ratio.Thirty-four patients completed the whole program,14 patients in the TCCRP group and 20 patients in the CERP group.All program were 60 min per time,3 times a week for a total of 12 weeks,including 4 weeks of in-hospital rehabilitation and 8 weeks of remote on-line home-based rehabilita-tion.Inflammatory factors and adhesion molecules were detected before and after the intervention.Result:After 12 weeks of intervention,C-reactive protein(CRP),interleukin 6(IL-6),vascular cell adhe-sion molecule(VCAM-1),and intercell adhesion molecule(ICAM-1)all decreased significantly(P＜0.01).The anti-inflammatory factor interleukin 10(IL-10)increased significantly in the TCCRP group(P＜0.0l).There was no significant difference between the two groups before the intervention(P＞0.05),and the VCAM-1 in the TCCRP group was significantly lower than the CERP group after the intervention(P＜0.05).Conclusion:In patients with coronary heart disease,the 12-week TCCRP and CERP intervention can effectively reduce the levels of pro-inflammatory factors CRP,IL-6 and adhesion molecules ICAM-1 and VCAM-1.The TC-CRP can effectively improve the level of anti-inflammatory factor IL-10 and reduce the expression of adhesion molecule VCAM-1 compared with CERP,which indicate a more positive effect on regulating the balance between pro-inflammatory and anti-inflammatory factors and improving the anti-inflammatory and anti-adhesion ability.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).
Recombinational DNA Repair ; DNA-Binding Proteins/metabolism* ; DNA Repair ; DNA Damage ; DNA

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Maili moxibustion can alleviate cancer pain, reduce bone marrow suppression, alleviate gastrointestinal reaction of chemotherapeutic drugs, alleviate cancer-related fatigue, inhibit neurotoxic reaction, improve quality of life and prolong patients' survival. It plays therapeutic effects by regulating immunity, inhibiting tumor cell proliferation and regulating tumor microenvironment. The researches of Maili moxibustion for tumor focus on reducing the toxic or side effects of radiotherapy or chemotherapy. In the future, we should continue to study the combination of Maili moxibustion and other therapies on the treatment of tumor.