Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Objective To retrieve,analyze and synthesize evidence on post-transplant diabetes mellitus(PTDM)in lung transplant patients,providing reference for clinical healthcare professionals in preventing and managing PTDM in lung transplant patients.Methods Based on the"6S"evidence model,systematic searches were conducted across guideline websites,professional associations,and Chinese/English databases regarding post-transplant diabetes mellitus(PTDM)in lung transplant patients.The search period spanned from data-base inception to January 2025.Two researchers independently completed literature screening,quality assess-ment,and evidence extraction.Results A total of 14 articles were included,comprising 1 clinical decision,2 guidelines,5 expert consensuses,2 specifications,1 evidence summary,and 3 systematic reviews.Twenty-four pieces of best evidence were synthesized from seven aspects:risk factors,diagnosis,screening,prevention,treatment,glycemic control targets,and health education.Conclusion The best evidence for preventing and managing post-transplant diabetes mellitus in lung transplant patients provides an evidence-based foundation for clinical practice among healthcare professionals.Evidence should be selected and applied according to spe-cific clinical situations and patient needs.

Evidence mapping is a novel method of evidence synthesis that has been increasingly applied in the field of TCM in recent years. This article provided a comprehensive and detailed introduction to the origin, definition, and characteristics of evidence mapping. It systemically reviewed and summarized published studies on evidence mapping in TCM, exploring common issues encountered during the production and reporting of TCM evidence mapping research. Such issues included the failure to highlight the advantages of TCM in the research topic, lack of prior registration of the study, limited scope of searches, unclear inclusion and exclusion criteria, insufficient standardization in literature screening and data extraction, inadequate overall quality assessment, obscure process of evidence synthesis, lack of targeted evidence analysis, and insufficiently standardized reporting of results. Corresponding improvement strategies were proposed to enhance the quality of TCM evidence mapping literature, increase the reliability and applicability of research outcomes, and thereby promote the modernization and internationalizati.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:This work aims to evaluate the clinical values of comprehensive genomic profiling examination based on circulating tumor DNA (ctDNA) in advanced lung cancer patients.Methods:This is a single-center, retrospective study that collected peripheral blood samples from patients with advanced lung cancer and performed gene mutation analysis using the TruSight Oncology 500 ctDNA assay kits. Between February 2022 and March 2023, a total of 82 patients were enrolled in Zhongshan Hospital, Fudan University, and 76 patients were included in the final analysis.According to the AMP/ASCO/CAP guidelines, mutations of targeted genes were divided into four levels (Tier I-IV), and the effectiveness of targeted therapy guided by ctDNA was evaluated. Descriptive statistics were used for basic characteristics, and the analysis of factors related to tumor mutational burden (TMB) was performed using the rank-sum test.Results:The ctDNA detection success rate was 92.7%(76/82).The median turnaround time for ctDNA testing was 10.5 days (9,13 days). At least one actionable mutation (Tier I or Ⅱ) was detected in 82.9%(63/76) of patients, and 28.6% (18/63) of patients received matched therapy, achieving a disease control rate of 18/18 and an objective response rate of 12/18.Conclusion:Comprehensive genomic profiling based on ctDNA can effectively identify actionable alterations in patients with advanced lung cancer and provide valuable information for matched therapy.

Objective　To explore the relationship between white matter hyperintensity (WMH) and clinical symptoms in patients with multiple system atrophy (MSA),and the risk factors of WMH in patients with MSA.Methods　A total of 88 patients with MSA were included.The periventricular white matter hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were assessed according to MRI and the Fazekas scale.The patients were divided into three groups according to the severity of PVH or DWMH.The baseline data,motor symptoms,cognitive function,urinary symptoms and constipation were compared among different groups.Logistic regression was used to analyze the risk factors of WMH in patients with MSA.Results　A significant difference was detected in age at admission,age at onset,hypertension,coronary heart disease,UMSARS total score,UMSARS Ⅱ score and UMSARS Ⅳ score between different PVH grades.A significant difference was detected in age at admission,age at onset,hypertension,coronary heart disease,UMSARS total score,UMSARS Ⅰ score,UMSARS Ⅱ score and UMSARSⅣ score between different DWMH grades.Logistic regression analysis showed that age at admission and hypertension were independent risk factors for WMH in patients with MSA.Conclusion　WMH is present in some MSA patients and related to motor symptoms and severity of the disease.Age and hypertension influence the occurrence of WMH.

Objective:To investigate the effects of decorin (DCN) on the proliferation, migration and invasion of bladder cancer cells.Methods:Bladder cancer T24 cell line was used as the research object. MTT assay was used to detect the inhibitory effect of DCN at different concentrations (0, 5, 10, 20, 30, 40, 50 mg/L) on T24 cell proliferation at 24, 48, 72 and 96 h. The effects of DCN on T24 cell cycle and apoptosis were analyzed by flow cytometry. MTT assay, Transwell migration and invasion experiments were used to detect the effects of DCN on the adhesion, migration and invasion ability of T24 cells. The effects of DCN on TGF-β1 and P21 protein expression were detected by ELISA and Western blotting.Results:T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN at 24, 48, 72 and 96 h, and there were statistically significant diffe-rences in cell proliferation activity ( F=168.64, P<0.001; F=165.81, P<0.001; F=291.02, P<0.001; F=148.93, P<0.001). T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the cell proliferation activities were (60.71±3.03)%, (40.82±2.09)%, (37.24±1.63)%, (25.65±2.55)%, (23.00±2.67)%, (10.78±1.17)%, (11.04±0.96)%, respectively, and there was a statistically significant difference. At the concentration of 40 mg/L, the proliferation activity reached the lowest level, and the inhibitory effect on cell proliferation was the strongest. At concentrations of 40 and 50 mg/L, the cells in G 1 phase reached the peak value, while the cells in S phase reached the lowest value, and the cells in G 2 phase remained unchanged throughout the treatment process. T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the apoptosis rates of cells were (12.18±1.17)%, (21.24±1.05)%, (19.80±1.20)%, (26.52±1.40)%, (30.86±1.40)%, (52.99±1.22)%, (43.04±2.16)%, respectively, and there was a statistically significant difference ( F=178.54, P<0.001). The differences between 5, 10, 20, 30, 40, 50 mg/L DCN and 0 mg/L DCN were all statistically significant (all P<0.001). When T24 cells were treated with 0, 40 mg/L DCN for 72 h, the cell adhesion rates were (37.14±1.35)% and (59.86±1.95)%, the numbers of migrated cells were 53.86±3.18 and 12.86±1.35, and there were statistically significant differences ( t=25.25, P<0.001; t=31.36, P<0.001). When DCN was applied to T24 cells for 48 h, the numbers of invasion at 0, 40 mg/L were 235.14±3.44 and 160.86±3.13, and there was a statistically significant difference ( t=2.27, P<0.001). When T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, the relative expression levels of TGF-β1 were 85.67±3.35, 45.51±1.19, 49.93±4.15, 47.64±3.53, 46.05±3.18, 25.54±2.25, 33.44±4.05, and there was a statistically significant difference ( F=324.58, P<0.001). Compared with 0 mg/L DCN, 5, 10, 20, 30, 40 and 50 mg/L DCN could significantly inhibited the expression of TGF-β1 (all P<0.001). Compared with 0 mg/L DCN, P21 protein was upregulated 72 h after treatment with 40 mg/L DCN. Conclusion:DCN can inhibit proliferation and induce apoptosis of T24 cells in vitro, and has the effect of anti-metastasis of T24 cells.

The investigation of environmental radioactivity level is an important basic work of ecological environment protection. It can provide basic data and scientific basis for the evaluation of radioactive environment quality and the formulation of radiation safety regulations and standards. Based on many years of practical experience of environmental radioactivity level investigation, combined with relevant regulations and standards, this paper summarizes the common investigation methods in the investigation and research of environmental radioactivity level at home and abroad, summarizes a set of environmental radioactivity level investigation scheme with strong applicability, and gives detailed suggestions on the ideas, methods, technical routes and other key points of the investigation scheme. The research results of this paper can provide a reference for the preparation of environmental radioactive level investigation scheme.