Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.

OBJECTIVE: To investigate the efficacy and safety of chidamide combined with DICE regimen (cisplatin+ ifosfamide + etoposide + dexamethasone) for relapsed/refractory diffuse large B-cell lymphome(R/R DLBCL). METHODS: The clinical data of 31 R/R DLBCL patients treated by chidamide combined with DICE regimen in the Hematology Department of the Fourth Hospital of Hebei Medical University from October 2016 to October 2020 were retrospectively analyzed. The clinical efficacy and adverse events were observed. RESULTS: Among the 31 patients, 20 were male and 11 were female. The median age of the patients was 55 (range: 27-71) years old, 21 cases were < 60 years old, 10 cases were ≥60 years old. 26 cases were refractory and 5 cases were relapsed. There were 13 cases of germinal center B-cell like (GCB), 17 cases of non-GCB, and 1 case had missing Hans type. There were 17 cases of double-expression lymphoma (DEL) and 14 cases of non-DEL. The complete response rate of patients was 38.7%(12/31), the overall response rate was 67.7%(21/31). The median progression-free survival time and the median overall survival time were 9.8(95%CI : 4.048-15.552) months, 13.9(95%CI : 9.294-18.506) months, respectively. Multipvariate analysis showed that GCB and DEL reduced the risk of disease recurrence in R/R DLBCL patients. The main grade 3/4 hematological adverse events in this study were thrombocytopenia, agranulocytosis, anemia and leukopenia. CONCLUSION The chidamide combined with DICE regimen is effective in the treatment of R/R DLBCL, and hematological adverse events should be closely monitored.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Female ; Male ; Adult ; Aged ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Benzamides/administration & dosage* ; Aminopyridines/administration & dosage* ; Etoposide/therapeutic use* ; Cisplatin/administration & dosage* ; Ifosfamide/administration & dosage* ; Dexamethasone/therapeutic use*

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

Objective To investigate the longitudinal clinical manifestations of acute radiation dermatitis(ARD)induced by particle therapy in nasopharyngeal carcinoma patients and to analyze associated risk factors.Methods A longitudinal study design was employed,encompassing nasopharyngeal carcinoma patients who underwent particle therapy at the Shanghai Proton and Heavy Ion Center from Mar to Sept 2023.Participants were assessed weekly(1-12 weeks)following the commencement of radiotherapy and at baseline,prior to the start of treatment.Data collection included the patient demographic questionnaire,the Radiation Therapy Oncology Group(RTOG)grading criteria for acute radiation injury,and the radiation-induced skin reaction assessment scale(RISRAS).Photographic documentation was utilized to capture changes in the irradiated skin area.The enrolled patients with nasopharyngeal carcinoma were grouped according to different particle therapy regimens.Survival data were analyzed by Log-rank and Cox regression methods,while a linear mixed-effects model was applied to repeated measures data.Results A total of 119 patients with nasopharyngeal carcinoma were enrolled.The overall incidence of ARD was 89.1%,which included 39.5%of grade 1,45.4%of grade 2 and 4.2%of grade 3.With the extension of time,the severity of ARD peaked at week 7(RISRAS=13.26±4.512),then began to decrease,ultimately reaching a lower level.Multiple Cox proportional hazards models were constructed,revealing that proton/heavy ion radiotherapy was associated with a lower risk of ARD compared to photon/proton plus heavy ion radiotherapy(HR=0.19,95%CI:0.04-0.92,P=0.039).Additionally,concurrent cisplatin/nedaplatin chemotherapy was identified as a risk factor for the development of ARD.Least squares(LS)mean differences were calculated at different time points,and the results demonstrated that the RISRAS scores of the photon/proton plus heavy ion group were consistently and significantly higher from week 5 to week 7 compared with the proton plus heavy ion group,and despite a decrease by week 8,statistical differences remained(week 5:LS mean difference 3.35,95%CI:0.94-5.76,P=0.007;week 6:LS mean difference 5.23,95%CI:2.20-8.26,P=0.001;week 7:LS mean difference 7.13,95%CI:3.67-10.59,P<0.001;week 8:LS mean difference 4.04,95%CI:0.74-7.34,P=0.017).Patients undergoing concurrent cisplatin chemotherapy had higher RISRAS scores from week 7 to week 8 of radiotherapy compared with those not receiving chemotherapy[week 7:adjusted mean difference(Adj.MD)4.20,95%CI:1.96-6.57,P=0.006;week 8:Adj.MD 2.79,95%CI 0.55-5.03,P=0.015].Similarly,patients on concurrent nedaplatin chemotherapy had higher RISRAS scores from weeks 6 to 7 compared with those not on chemotherapy(week 6:Adj.MD 3.75,95%CI:1.54-5.96,P=0.001;week 7:Adj.MD 4.41,95%CI:2.12-6.70,P<0.001).Skin care measures during treatment and accompanying symptoms such as weight loss were not statistically associated with the development of ARD.Conclusion Proton/heavy ion radiotherapy has a lower risk of ARD,while concurrent cisplatin/nedaplatin chemotherapy is a risk factor for ARD.