Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels (pLGICs) that mediate rapid cholinergic synaptic transmission throughout the central and peripheral nervous systems. These receptors are integral to neuromuscular junction signaling, autonomic regulation, cognitive learning, reward-related behavior, and neuroplasticity. The nAChR family exhibits remarkable functional diversity through combinatorial assembly of seventeen identified subunits (α1-α10, β1-β4, γ, δ, and ε). Among these, the α9 subunit occupies a distinctive phylogenetic position, exhibiting greater sequence divergence from other neuronal α subunits and possessing unique biochemical properties that distinguish it from all other family members. α9 can form homopentamers and also co-assemble with the α10 subunit to form functional heteropentamers, primarily in (α9)₂(α10)₃ and (α9)₃(α10)₂ stoichiometries. This dual assembly strategy generates functional heterogeneity, as distinct subunit compositions confer differential ion permeation, ligand sensitivity, and desensitization kinetics. The structural determinants governing this stoichiometric variability remain incompletely resolved, representing a critical gap in our mechanistic understanding. Unlike most other nAChR subtypes, traditional agonists of nAChRs (such as nicotine) elicit virtually no agonistic effect on α9* nAChRs (α9-containing receptors, including α9 homopentamers and α9α10 heteropentamers). This pharmacological divergence reflects structural differences within the orthosteric site, particularly in regions at complementary subunit interfaces. As cation-selective channels, α9* nAChRs exhibit high permeability to Ca²⁺. In cochlear outer hair cells, α9α10 nAChRs mediate cholinergic efferent modulation by the medial olivocochlear (MOC) bundle. Acetylcholine-evoked Ca²⁺ influx activates functionally coupled SK2 potassium channels, generating net hyperpolarization that dampens electromechanical amplification through a tightly constrained signaling microdomain. This Ca²⁺-dependent excitatory-to-inhibitory conversion exemplifies sophisticated sensory gain control, and its disruption contributes to noise-induced hearing loss, age-related hearing loss, and tinnitus. Beyond canonical ionotropic signaling, α9* nAChR engages metabotropic transduction pathways. In macrophages, receptor activation modulates cytokine production and inflammatory responses. In keratinocytes, it regulates wound healing by modulating cell migration and differentiation. In dorsal root ganglion sensory neurons, α9* signaling contributes to nociceptive processing and inflammatory hyperalgesia. This functional pleiotropy, spanning both ionotropic signaling and metabotropic transduction, positions α9* nAChR as an exemplary model for investigating signal polymorphism within the pLGIC superfamily. Pathophysiologically, α9* nAChR dysfunction is implicated across multiple organ systems. In the auditory system, disruption of α9α10 nAChR-mediated MOC efferent feedback impairs cochlear gain control, predisposing to noise-induced synaptopathy and age-related hearing loss. In immune cells, dysfunctional α9* nAChR signaling disrupts cholinergic anti-inflammatory pathway activity, exacerbating pro-inflammatory responses. In the peripheral sensory system, aberrant α9* nAChR signaling has been implicated in neuropathic and inflammatory pain states. In skin, impaired receptor function compromises keratinocyte migration and re-epithelialization through disrupted signaling pathways, leading to chronic wound healing defects and inflammation. These pathophysiological associations have catalyzed pharmacological interest, yielding promising chemical entities including α‑conotoxins, small-molecule antagonists/agonists, and allosteric modulators.α-Conotoxin peptides, in particular, demonstrate remarkable subunit selectivity and potent antinociceptive effects in preclinical pain models. However, therapeutic translation faces substantial challenges: the broad tissue distribution of α9* nAChR risks on-target adverse effects in non-target organs; pronounced species differences between rodent and human receptors complicate preclinical validation; and the complexity of ionotropic-metabotropic signaling crosstalk demands pharmacological strategies that extend beyond conventional orthosteric agonism or antagonism. Looking forward, integrating cryo-electron microscopy of full-length receptors in distinct conformational states with single-channel electrophysiology and systems-level circuit analysis promises to illuminate the molecular mechanisms governing α9* nAChR function and regulation. The development of signal pathway-biased ligands and tissue-selective delivery strategies may ultimately harness the therapeutic potential of this receptor while mitigating safety liabilities. As a paradigm for understanding pLGIC signaling diversification, α9* nAChR research will continue to inform broader questions regarding ion channel evolution, allosteric regulation, and pathophysiological mechanisms of chronic pain and autoimmune inflammatory diseases.

Objective: Some regions in China have lowered the minimum interval for whole blood donation to 3 months through local regulations: Hainan, effective from March 1, 2012, allows men to donate at intervals of≥3 months and women at intervals of≥4 months; Shenzhen, effective from November 1, 1995, allows whole blood donation at intervals of≥3 months. The aim of this study was to evaluate the impact of shortening the whole blood donation interval on blood donation adverse reactions and donation behavior, thereby providing scientific evidence for policy evaluation and revision of relevant regulations. Methods: This was a multicenter, retrospective cohort study based on blood donation registry data from Shenzhen and Hainan. Data were obtained from the blood information management systems of Hainan Province (1991-2025) and Shenzhen City (2018-2024). Eligible participants were donors aged 18-65 years who had donated whole blood at least twice and met health eligibility criteria. The exposure was defined as a shorter donation interval (whole-blood interval≥3 months and<6 months) and was treated as a time-varying variable. The primary outcome was blood donation adverse reactions. Negative binomial regression with person-years as an offset was used to estimate incidence rate ratios for adverse reactions. Marginal standardization was used to estimate the adjusted incidence rate difference, and donor-level bootstrap resampling was used to estimate the 95% confidence interval of the adjusted incidence rate difference. Non-inferiority was assessed by comparing the upper limit of the 95% confidence interval with the prespecified non-inferiority margin of Δ=0.00 070 per person-year. In addition, Andersen-Gill models were used to analyze adverse reaction-free probability for recurrent events. Secondary outcomes were donation behavior, including annual repeat donation rate, annual donation frequency, mean donation interval, and annual whole-blood donation volume. These were analyzed using logistic regression, negative binomial regression, and linear regression models, respectively, with adjustment for age, sex, region, and donation site. This study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (Approval No.2025011) and registered in the Chinese Clinical Trial Registry (ChiCTR2500114968). Results: A total of 375 075 repeat whole-blood donors were included, contributing 1 292 748 whole-blood donations. Among them, 119 993 had ever donated at a shorter interval and 255 082 had never done so. Over 1 281 842 person-years of follow-up in the dynamic cohort, 2 100 blood donation adverse reactions were recorded. The incidence rates of adverse reactions were 1.76 and 1.58 per 1 000 person-years in the ever-short interval and never-short interval groups, respectively. After adjustment for age, sex, province, and donation site, the ever-short interval group had a slightly higher adverse reaction rate than the never-short interval group (IRR=1.28, 95%CI: 1.15-1.41, P<0.001). Marginal standardization showed that the adjusted incidence rates were 1.73 and 2.21 per 1 000 person-years in the never-short interval and ever-short interval groups, respectively. The adjusted incidence rate difference was 0.000 48 per person-year, with a bootstrap 95%CI of 0.000 26-0.000 69 per person-year; the upper limit of the 95%CI was below the prespecified non-inferiority margin. Andersen-Gill recurrent-event analysis showed that the ever-short interval group had a higher probability of remaining adverse reaction-free. Analysis of donation behavior showed that among donors followed for at least 365 days, the ever-short interval group had a higher annual repeat donation rate than the never-short interval group (74.2% vs 18.3%; adjusted OR=12.5, 95%CI: 12.3-12.7, P<0.001). They also had a higher annual whole-blood donation rate (adjusted RR=1.98, 95%CI: 1.97-1.98, P<0.001), a shorter mean whole-blood donation interval (β=-239 days, 95%CI: -242 to -237 days, P<0.001), and a higher annual whole-blood donation volume (adjusted RR=2.14, 95%CI: 2.13-2.15, P<0.001). Conclusion: Based on real-world data from repeat whole-blood donors in Shenzhen and Hainan, lowering the minimum whole blood donation interval to 3 months did not show an absolute increase in blood donation adverse reactions exceeding the prespecified margin within the scope of this outcome. Shorter whole-blood donation interval behavior was also associated with greater repeat-donation activity, higher annual donation frequency, and higher annual whole-blood donation volume. Given the observational nature of this study and the lack of long-term donor health indicators such as iron status and longitudinal hemoglobin changes, the long-term safety of setting the minimum whole blood donation interval at 3 months requires further evaluation.

Percutaneous renal denervation(RDN)is a minimally invasive interventional treatment for hypertension that has been used in clinics at home and abroad,primarily for patients with resistant hypertension or who cannot tolerate antihypertensive drugs.Current clinical studies have confirmed the safety and efficacy of this technique.As RDN is still in its promotional and popularization stage,the expert group has written this clinical pathway to promote the orderly implementation of this technology,standardize the operating process,and standardize diagnostic and therapeutic behaviors.The pathway describes the clinical assessment of patients in detail(including indications,contraindications,and the patient screening process),the standardized operating process for RDN(including perioperative medication,anaesthesia,ablation,and management of complications),and the postoperative follow-up plan(including follow-up content,methods,and timing).It is hoped that this will serve as a reference for physicians involved in RDN clinical work,standardize diagnostic and therapeutic behaviors,and promote the standardized,precise,and sustainable development of the RDN discipline.

Objective To identify potential ergonomic risk factors of works and quickly assess their risks of developing work-related musculoskeletal disorders (WMSDs) in the medical staff. Methods A total of 188 medical staff were selected as the research objects using a two-stage random sampling method. The method for the identification of musculoskeletal stress factors (PLIBEL) was used to analyze the adverse ergonomic factors in the work process, and the rapid entire body assessment (REBA) was used to quickly assess the whole-body posture load. Results The PLIBEL assessment results showed that various adverse ergonomic factors affected different parts of the body during the work process of medical staff. Specifically, 18 adverse ergonomic factors were identified in the neck, shoulders, and upper back, while 10 adverse ergonomic factors were identified in the elbow, forearm, hand, and lower back. Rehabilitation therapists and nurses engaged in patient handling in general wards and medication preparation and blood collection were exposed to ≥35 adverse ergonomic factors. The REBA assessment showed that the REBA score was 3-12 points for medical staff during their work process. Rehabilitation therapists were classified as having an extremely high ergonomic risk. High-risk occupations included ward housekeeping nurses, surgery assistant nurses, operating-room instrument nurses, and surgeons. Medium-risk occupations included general ward nurses (medication preparation and blood collection, venipuncture/infusion, and patient handling), intensive care unit (ICU) nurses, internal medicine residents, and dentists. Low-risk occupations included administrative front-desk nurses, outpatient internal medicine physicians, and technicians/physicians in ultrasonography, laboratory medicine, physical examination, and occupational health departments. Conclusion Adverse ergonomic factors of medical staff predominantly affect the neck, shoulders, upper back, elbows, forearms, hands, and the lower back during the work process. Rehabilitation therapists, ward housekeeping nurses, ICU nurses, operating-room instrument nurses, and surgeons are high-risk groups for WMSDs. Attention should be paid to the management and control of adverse ergonomic factors for medical staff to prevent the occurrence of WMSDs.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds.Search Genecards,OMIM,Drugbank,TTD,and PharmGKB databases to obtain targets for gastric cancer.The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer.The String database was utilized construct a protein-protein interaction(PPI)network.Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the shared targets.This process revealed significant regulatory pathways crucial for jolkinolide B's efficacy in treating gastric cancer.Cytoscape 3.7.1 software was utilized create the core network of"Potential Targets of Triptolide B in Gastric Cancer Treatment",and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.Results Jolkinolide B may target multiple proteins,including MAPK1,glycogen synthase kinae-3β(GSK-3β),and JUN,impacting the proliferation,invasion,and metastasis of gastric cancer,ultimately inhibiting its growth.Conclusion We predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.