Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

The human use experience of traditional Chinese medicine(TCM) is of great significance for the development of new traditional Chinese medicine. In 2023, the National Medical Products Administration(NMPA) issued the Special Regulations on Registration Management of Traditional Chinese Medicine, which explicitly encouraged the conduct of high-quality human use experience research on TCM clinical practice to obtain sufficient evidence for registration support. It also required that human use experience research should comply with relevant requirements and undergo registration verification. The quality of human use experience research on TCM directly determines the reliability of the evidence. This article discussed the quality requirements for human use experience research on TCM from the perspectives of basic requirements, organizational management, key pharmaceutical information, scientific research, risk management, ethical compliance, and study implementation and proposed differential treatment in quality requirements and registration verification focus based on different research purposes, stages, and types of studies. While ensuring the authenticity of data, retrospective studies should pay particular attention to the integrity of the data, and prospective studies should focus on the normativity of the data, which may affect the research conclusions. Human use experience research, as part of drug registration materials, falls within the scope of relevant regulatory oversight. Researchers should have a strong awareness of regulations to avoid serious quality issues. The standardized conduct of human use experience research on TCM requires joint efforts from regulatory authorities, applicants, research institutions, and researchers to establish a research quality management system based on the clinical characteristics of TCM.
Humans ; Medicine, Chinese Traditional ; Prospective Studies ; Reproducibility of Results ; Retrospective Studies ; Pharmaceutical Preparations ; Drugs, Chinese Herbal/therapeutic use*

Evidence-based medicine plays an important role in promoting the scientific nature of clinical decision-making. Howe-ver, there is a problem where evidence derived from clinical research may not necessarily be applicable to individual patients. Evidence-based medicine has been introduced into the field of traditional Chinese medicine(TCM) for over 20 years, and although certain achievements have been made, the overall level of clinical research evidence based on the principles of evidence-based medicine in TCM is not high. The acceptance of TCM diagnosis and treatment guidelines developed based on evidence-based medicine methods is generally low. As revealed by the analysis of the problems in the application of evidence-based medicine in the field of TCM, it is found that there is a structural contradiction between clinical randomized controlled trial(RCT) of TCM and the characteristics of TCM clinical practice. They cannot comprehensively, objectively, and truthfully reflect the clinical efficacy and safety of TCM. Conducting clinical RCTs of TCM in pursuit of "evidence" actually means giving up the advantages of TCM in clinical treatment based on syndrome differentiation, prescription changes along with syndromes, and treatment in accordance with three categories of disease cause, which leads to sacrificing some clinical effectiveness of TCM. Based on the concept of evidence-based medicine, this article proposed the construction of "clinical syndrome-based medicine" based on the optimal clinical experience, which was suitable for the characteristics of TCM clinical practice. The key to clinical syndrome-based medicine is the optimal clinical experience, and the core elements of the optimal clinical experience are regularity and reproducibility. Real-world research methods are recommended as a reference for obtaining the optimal clinical experience. Clinical syndrome-based medicine, combining the characteristics of TCM clinical practice and incorporating the concept of evidence-based medicine, is the product of integrating TCM into evidence-based medicine. It is dedicated to improving the clinical efficacy of TCM along with evidence-based medicine.
Humans ; Reproducibility of Results ; Medicine, Chinese Traditional ; Treatment Outcome ; Evidence-Based Medicine ; Syndrome ; Drugs, Chinese Herbal/therapeutic use*

Objective:To analyze the trend of late-diagnosis of HIV-infected men who have sex with men (MSM) before and after the AIDS Conquering Project in Guangxi Zhuang Autonomous Region (Guangxi) and its influencing factors, in order to find out the population groups that need priority intervention at the present stage.Methods:The HIV-infected MSM in Guangxi from 2005-2021 were selected from the National Integrated HIV/AIDS Control and Prevention Data System. The Joinpoint 4.9.1.0 software was used to test the time trend of late-diagnosis and non-late-diagnosis cases, and logistic regression was applied to analyze the factors influencing the proportion of late-diagnosis at each stage.Results:From 2005 to 2021, 5 764 HIV-infected MSM were reported in Guangxi from 2005 to 2021, with an overall late-diagnosis of 28.45% (1 640 cases). Under the 2015 baseline data as the boundary, the proportion of late-diagnosis cases showed a trend of sharp decline followed by stabilization from 2005 to 2015, average annual percent change= -6.90% ( P<0.001). The effect of factors such as resident population, occupation as a farmer or worker, and sample originating from medical consultation on late-diagnosis changed considerably before and after the implementation of the project, and the factors influencing late-diagnosis at this stage were age, resident population, occupation as a farmer, worker or student. The factors influencing late-diagnosis at this stage are age, resident population, and occupation as a farmer, worker and a student. Conclusions:The proportion of late diagnosis cases of HIV-infected MSM in Guangxi decreased significantly before and after the project. However, late-diagnosis should not be neglected and precise prevention and control should be carried out for the resident population, farmers, workers or students.

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.
Consensus ; Drug Prescriptions ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Reproducibility of Results

Background::Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods::Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results::With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions::Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

Aim To explore the regulatory mechanism of berberine in the high glucose (HG) -induced podocyte ferroptosis. Methods Western blot and R T - qPCR were used to detect the changes of G P X 4, PTGS2, ACSL4, podocin, and desmin at different time (0 h, 6 h, 12 h, 24 h, 36 h) of HG stimulation, and the relative expression of Nrf2, HO-1, GPX4 and podocin under HG after treated with berberine. The proliferation of podocytes stimulated by HG at different time points was observed by EdU staining. The therapeutic effect of berberine on podocyte damage was screened by CCK-8, and the effect of berberine on the level of oxidative stress in HG-induced podocytes were measured by fluorescence inverted microscope, GSH and GSSG kits. In addition, transmission electron microscopy was employed to observe the ultrastructural characteristics of podocytes in each group. Results The expression of podocin and GPX4 was significantly reduced at 24 h, and the mRNA levels of ACSL4 and PTGS2 were significantly up-regulated. Berberine could notably increase the expression of Nrf2, HO-1, GPX4 and podocin, and reduce the levels of PTGS2 and ACSL4. Moreover, berberine significantly improved the levels of ROS and GSH in podocytes under HG conditions, thereby alleviating membrane blistering, mitochondrial shrinkage and other morphological changes of HG-induced podocytes. Conclusions In this study, the number of podocytes decreases, which is a death mode different from autophagy and apoptosis, that is, ferroptosis. Berberine can alleviate the occurrence of this phenomenon by mediating the Nrf2/ H0-1/GPX4.

【Objective】To explore the role of lncRNA Xist in proliferation and migration of rat bone marrow mesenchymal stem cells（BMSC）and its possible mechanism.【Methods】BMSC were isolated，cultured and identified from the femur and tibia of 3 weeks old SD female rats in vitro. SiRNAs was designed and screened to acquire a high silencing efficiency siRNA. Lipo2000 was used to transfected si- Xist and si- NC into BMSC of the experimental group（si- Xist group）and the control group（si-NC group）. BMSC proliferation capacity was determined by CCK-8 assay. The transverse and longitudinal mobility of BMSC were measured by wound healing assay and transwell migration assays. QPCR was performed to verify the silencing efficiency of lncRNA Xist and detect the expression levels of SDF- 1 and CXCR4 mRNA. Western blot was used to quantify the expression of CXCR4 protein.【Results】The P3 generation BMSC shows shuttle- like or whirlpool-like，and flow cytometry showed CD11b（-），CD34（-），CD45（-），CD44（+），CD90（+），CD105（+）. When siRNAs were used to interfere with the expression of lncRNA Xist in BMSC ，the silencing efficiency of three siRNAs was 67.92% ，68.72% and 98.32% ，respectively. CCK- 8 assay showed that the OD450 value of si- Xist group decreased compared with si-NC group at 24 h and 48 h（P < 0.001，P < 0.01，respectively）and had no statistical difference at 12 h（P > 0.05）. Wound healing assay showed that the wound healing percentage of si-Xist group was lower than that of si-NC group（P < 0.05）；and the transwell migration assay showed that，compared with si- NC group，the cells that migrated through the polycarbonate membrane were obviously decreased at 6 h（P < 0.001）. QPCR experiment showed that CXCR4 expression in si-Xist group was lower than that in si-NC group at mRNA level（P < 0.05），while SDF-1 expression showed no significant statistical difference（P > 0.05）. Western blotting confirmed that CXCR4 expression in si- Xist group was lower than that in si-NC group（P < 0.05）.【Conclusions】LncRNA Xist promotes proliferation and migration of rat BMSC by regulating CXCR4 expression.