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.

Vaccines are highly effective, but rare or delayed adverse events following immunization (AEFIs) require post-licensure surveillance beyond clinical trials. Korea lacks a comprehensive, active, database-based framework, yet key assets exist: nationwide claims databases (National Health Insurance Service/Health Insurance Review and Assessment Service), the national immunization registry (Korea Disease Control and Prevention Agency’s Immunization Registry Information System) for National Immunization Program (NIP) and non-NIP vaccines, and increasingly standardized hospital electronic health records.We propose a federated, code to data architecture with data linkages between these data.Implementation should adopt a common data model (CDM), standardized case definitions, latency accounting, and transparent public reporting under strong privacy governance. Major challenges include multi step administrative approvals for data linkage, incomplete capture of adult non-NIP vaccinations, heterogeneous hospital data structures, and strict data protection constraints. Strategic priorities are to streamline statutory and administrative processes for public health use, mandate or enable claims-based capture of adult vaccinations, enhance CDM based interoperability, and develop secure hubs for aggregated outputs. With these measures, Korea will be well positioned to establish a scalable active surveillance system capable of detecting rare AEFIs, supporting transparent and evidence-based communication, and ensuring equitable injury compensation grounded in domestic data.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Objective:To explore the effect of immobility on the quality of life in older adults.Methods:This cross-sectional study included 244 consecutive elderly patients aged 60 years and older who were admitted to the Department of Geriatrics at Xuanwu Hospital of Capital Medical University from May 2022 to March 2023.Among the participants, 52.5%(128/244)were male and 47.5%(116/244)were female, with a mean age of 69.2±7.4 years.All participants underwent a series of assessments, including the Short Physical Performance Battery(SPPB), grip strength measurement, gait speed evaluation, and the Timed Up and Go test(TUG).The Barthel Index was employed to assess activities of daily living, while the Medical Outcomes Study 36-Item Short Form Health Survey(SF-36)was used to evaluate quality of life.A score of SPPB ≤ 9 was used to diagnose immobility.Results:A total of 60 older adults met the criteria for immobility.Compared to the non-immobility group, the quality-of-life scores for older adults in the immobility group were significantly lower across various dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, physical component summary, and the total SF-36 score(all P<0.05).Furthermore, a positive correlation was identified between the SPPB scores and the quality-of-life scores across the dimensions of physical functioning, bodily pain, general health, vitality, social functioning, mental health, reported health transition, physical component summary, and the total SF-36 score among patients in the immobility group(all P<0.05).Additionally, older adults in the immobility group exhibited lower grip strength, slower gait speed, and longer TUG times, as well as a higher incidence of emergencies and falls over the past year(all P<0.05). Conclusions:The poorer quality of life and physical function, along with higher rates of emergencies and falls among older adults with immobility, indicate the necessity of addressing the health consequences that immobility inflicts on this population.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

South Korea’s current vaccination policies leave a surveillance gap for non-National Immunization Program (NIP) vaccines. In this study, we proposed a sentinel surveillance approach for monitoring the safety of non-NIP vaccines. Vaccination data were collected retrospectively among patients hospitalized with pre-defined adverse events of special interest (AESI) by reviewing electronic medical records in five university hospitals. This approach incorporates expert assessment to determine the causal relationship. We confirmed that 16 patients had received non-NIP vaccines among 860 patients diagnosed with AESI.We concluded one case of preeclampsia was possibly related to tetanus-diphtheria-pertussis vaccination. We propose a multi-hospital-based, retrospective assessment system for predefined AESIs as an alternative to active vaccine safety monitoring method. These efforts are expected to enhance both the accuracy and timeliness of safety monitoring in South Korea.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female