Objective To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Shanxi Province from 2012 to 2024, and predict the incidence trend for 2025, and to provide a scientific basis for the formulation of prevention and control strategies. Methods Based on the surveillance data of HFMD in Shanxi Province from 2012 to 2024, the spatial and temporal distribution characteristics and time trends of the disease were analyzed. The ARIMA model was constructed and used to predict the incidence trend in 2025. Results From 2012 to 2024, a total of 254 028 HFMD cases were reported in Shanxi Province, with an average annual incidence rate of 54.17 per 100 000 population, a severe case rate of 0.56%, and a case fatality rate (CFR) of 12.60 per 100 000 population. Joinpoint regression analysis showed that the incidence rate, severe case rate, mortality rate, and case fatality rate all presented a downward trend. The epidemic exhibited obvious seasonal distribution characteristics, with the peak period from April to November, and two incidence peaks in June-July and October-November. The male-to-female incidence ratio was 1.41:1. Children aged 1-5 years accounted for 89.24% of the total cases, among which scattered children (58.48%) and nursery children (33.54%) were the high-risk groups. Linfen City (96.06 /100 000) and Taiyuan City (88.54 /100 000) had relatively high incidence rates. After 2017, the proportion of enterovirus A71 (EV-A71) decreased, while coxsackievirus A16 (Cox-A16) and other enteroviruses became the main epidemic strains. The ARIMA(1,0,1)(0,1,1)₁₂ model predicted that the incidence of HFMD in 2025 would remain at the level of 2023-2024, and the dual-peak characteristic would continue. Conclusion From 2012 to 2024, the overall HFMD epidemic in Shanxi Province generally shows a significant downward trend. The high-risk population includes scattered children and nursery children under 5 years old, with high-incidence areas concentrated in the central and southern regions, requiring focused attention. The seasonal ARIMA model can effectively fit the evolutionary trend of HFMD incidence in Shanxi Province and possesses short-term predictive capability.

BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective:To strengthen the management of low-value consumables in public hospitals by introducing the Supply Processing Distribution(SPD)management model,and to explore refined operational management strategies and path optimization for low-value consumables.Methods:The SPD management model was introduced,and the entire process of hospital consumables was refinedly managed using third-party supply chain information management platforms,visualized tertiary department warehouses,Radio Frequency Identification(RFID)technology and intelligent cabinet systems,Unique Device Identification(UDI)coding,"four-code integration"and other supporting technologies.Results:Based on the analysis of the current situation in the target Hospital,specific measures related to the management of low-value consumables were introduced after the introduction of the SPD model.Conclusion:It provides a reference and guidance for the hospital's medical consumables management department to promote refined management of medical consumables under the SPD model.

Objective:To explore the clinical characteristics and prognostic risk factors of Mycoplasma pneumoniae pneumonia(MPP)in adults across different age groups,providing evidence for age-stratified management strategies.Methods:A retrospective analysis was conducted on 80 MPP patients admitted to the Respiratory Department of a hospital between January 2023 and December 2024.Patients were divided into three groups based on age:young adults(18-40 years),middle-aged adults(41-60 years),and elderly adults(≥ 61 years).Demographic features,clinical indicators,and mixed infections were analyzed.Univariate and multivariate Logistic regression were used to identify risk factors for disease severity.Results:The severity rate was significantly higher in the elderly group(41.2％)compared to the young adult group(7.1％)and middle-aged group(20.0％)(P=0.022).Elderly patients also exhibited significantly higher rates of underlying diseases(chronic lung disease:35.3％vs.3.6％in young adults),elevated inflammatory markers(C-reactive protein:68.3±19.5 mg/L vs.32.5±8.4 mg/L in young adults),mixed infections(52.9％vs.14.3％),and prolonged hospital stays(8.61±2.22 days vs.5.01±1.11 days)(P＜0.05).Multivariate analysis identified age(OR=1.79 per 10 years),chronic lung disease(OR=3.25),blood urea nitrogen ≥6 mmol/L(OR=2.44),and mixed infections(OR=4.26)as independent risk factors for severe MPP(P＜0.05).Conclusion:Clinical manifestations and prognoses of MPP in adults vary significantly across age groups.Elderly patients are characterized by high mixed infection rates,intense inflammatory responses,and renal function impairment,necessitating individualized monitoring and intervention strategies.

Objective To systematically evaluate the impact of continuous renal replacement therapy(CRRT)on the pharmacokinetics of polymyxin B,explore its possible impacting factors.Methods PubMed,Embase,Co-chrane Library,Web of Science,VIP database,China National Knowledge Infrastructure(CNKI),SinoMed,and Wanfang data were retrieved.The study subjects were patients receiving CRRT and polymyxin B.Observational studies,case reports,and reviews were included.The outcome indicators included therapeutic drug monitoring re-sults,pharmacokinetic parameters,and CRRT parameters.The retrieval time was from the inception of each data-base to January 2025.The quality of literatures was evaluated with ClinPK tool.Two researchers independently conducted literature screening,data extraction,and quality evaluation.Results A total of 12 literatures were ulti-mately included in analysis,including 1 review,3 case reports,and 8 observational studies.Five studies showed that the clearance rate during CRRT period(1.3-6.66 L/h)was higher than that during non-CRRT period(0.5-3.9 L/h).Five studies reported that the area under the steady-state 24-hour drug concentration-time curve(AUCss,24h)during CRRT period(21.58-75.1 mg·h/L)was lower than that during non-CRRT period(60.6-118 mg·h/L).Two studies detected drugs in ultrafiltrate or dialysate,with in vitro drug recovery rates ranging from 5.62％to 24.0％.Two studies reported a decrease in drug concentration after passing through a blood filter.Conclusion During CRRT period,polymyxin B presents higher clearance rate and lower blood drug concentration,and some patients have lower AUCss.24h than the therapeutic target.The mechanism of this change during CRRT is not yet clear,the therapy mode and filter type may be potential impacting factors,further research are needed to promote precise anti-infective treatment.

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5％ CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.

Background and Aims:Mucinous adenocarcinoma of the colorectum(MAC)is a distinct histologic subtype of colorectal cancer characterized by high malignancy and low diagnostic accuracy of preoperative biopsy,posing challenges for clinical decision-making.Given the critical role of the inflammatory microenvironment in tumor progression,this study aimed to develop and validate a nomogram model integrating preoperative systemic inflammatory indicators and clinical features to improve the preoperative diagnosis of MAC.Methods:Clinical data of 293 patients with colorectal cancer who underwent radical resection between June 2017 and June 2022 at the First Affiliated Hospital of the University of South China were retrospectively analyzed.Based on postoperative pathology,patients were classified into the mucinous adenocarcinoma(MAC)group and the non-specific adenocarcinoma(AC)group.Propensity score matching(PSM,1∶1)was used to balance age,T stage,and N stage.Differences in preoperative inflammatory indices were compared between groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of MAC,which were incorporated into a diagnostic nomogram.The model's discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration plots,and decision curve analysis(DCA).Results:Among the 293 patients,46 had MAC and 247 had AC,with a preoperative colonoscopic diagnostic rate of 54%for MAC.After PSM(43 pairs),platelet count,platelet lymphocyte ratio(PLR),systemic immune inflammation index(SII),inflammation related prognostic index(IPI),and systemic inflammation score(SIS)were significantly higher in the MAC group,while lymphocyte monocyte ratio(LMR)was lower(all P<0.05).Multivariate analysis identified tumor location,maximum tumor diameter,and preoperative IPI as independent predictors.The AUCs of the nomogram in the training(n=206)and validation(n=87)cohorts were 0.759(95%CI=0.662-0.856)and 0.776(95%CI=0.649-0.903),respectively.Calibration plots showed good agreement between predicted and observed probabilities,and DCA demonstrated satisfactory clinical applicability.Conclusion:A nomogram model integrating tumor location,tumor size,and preoperative IPI was successfully developed and validated for preoperative diagnosis of colorectal MAC.This model provides a practical,quantitative tool with good predictive performance to assist clinicians in individualized treatment planning,particularly for patients ineligible for surgical biopsy.