ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte（Th17/Treg） cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium （DSS） method. Forty-eight C57BL/6 mice were randomly allocated into normal， model， Western drug control （mesalazine， 0.39 g·kg^-1·d^-1）， Shaoyaotang （15.54 g·kg^-1·d^-1）， inhibitor （2-deoxy-D-glucose， 2-DG， 100 mg·kg^-1·d^-1）， and inhibitor （2-DG， 100 mg·kg^-1·d^-1） + Shaoyaotang （15.54 g·kg^-1·d^-1） groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin （IL）-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were performed to determine the protein and mRNA levels， respectively， of hypoxia-inducing factor-1α （HIF-1α）， lactate dehydrogenase （LDHA）， and hexokinase 2 （HK2） in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10， IL-17， and IL-6 in the serum. ResultsCompared with the normal group， the model group showed decreases in body weight and disease activity index （DAI） （P<0.05）， elevations in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and declines in the levels of of IL-10 and Treg cells （P<0.05）. Compared with the model group， the drug administration groups showed increases in body weight and DAI （P<0.05）， declines in levels of HIF-1α， LDHA， HK2， IL-17， IL-6， Th17 cells， lactic acid， and glucose in the colon tissue （P<0.05）， and rises in levels of IL-10 and Treg cells （P<0.05）. Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming， thus playing a role in the treatment of ulcerative colitis.

ObjectiveTo explore the regulation of Shaoyaotang on glucose metabolism reprogramming of macrophages and the mechanism of this decoction in inhibiting macrophage polarization toward the M1 phenotype. MethodsHuman monocytic leukemia-1 （THP-1） cells were treated with 100 ng·L^-1 phorbol myristate acetate for induction of macrophages as the normal control group. The cells treated with 100 ng·L^-1 lipopolysaccharide combined with 20 ng·L^-1 interferon （IFN）-γ for induction of M1-type macrophages were taken as the M1 model group. M1-type macrophages were treated with the blank serum， Shaoyaotang-containing serum， 0.5 mol·L^-1 2-deoxy-D-glucose （2-DG）， and Shaoyaotang-containing serum + 2-DG， respectively. After intervention， the expression of CD86 and CD206 was examined by flow cytometry. The levels of interleukin （IL）-6， tumor necrosis factor （TNF）-α， IL-10， and transforming growth factor （TGF）-β were assessed by ELISA. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of hypoxia-inducible factor-1 alpha （HIF-1α）， glucose transporter 1 （GLUT1）， hexokinase 2 （HK2）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， and 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）. ResultsCompared with that in the normal control group， the expression of CD86， the marker of M1-type macrophages， increased in the M1 model group and blank serum group （P<0.01）， which indicated that the M1 inflammatory model was established successfully. In addition， the M1 model group was observed with up-regulated mRNA and protein levels of proinflammatory cytokines IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 （P<0.01）. Compared with the M1 model group， the Shaoyaotang-containing serum， 2-DG， and combined intervention groups showed decreased expression of CD86 （P<0.01）， down-regulated mRNA and protein levels of proinflammatory factors IL-6 and TNF-α and glycolysis-related factors HIF-1α， GLUT1， HK2， GAPDH， and PFKFB3 produced by M1-type macrophages （P<0.01）， increased expression of CD206 （marker of M2-type macrophages） （P<0.01）， and elevated levels of IL-10 and TGF-β produced by M2-type macrophages （P<0.01）. ConclusionShaoyaotang inhibits macrophage differentiation toward pro-inflammatory M1-type macrophages and promotes the differentiation toward anti-inflammatory M2-type macrophages by regulating glucose metabolism reprogramming. The evidence gives insights into new molecular mechanisms and targets for the treatment of ulcerative colitis with Shaoyaotang.

Objective To develop a system for retrieving information from clinical records of Traditional Chinese Medicine(TCM)based on generative large language models(LLMs).Methods Applicational needs of the system were analyzed,and entity types to be retrieved were identified.The functions,workflows,and architecture of the system were designed by combining the automatic retrieval capabilities of LLMs with human-in-the-loop(HITL).The software was developed using such frameworks as vLLM and Node.js.Interaction of multiple commercial/open source LLMs was implemented using OpenAI-compatible interfaces.The quality of information retrieved from LLMs was enhanced by prompt engineering.Results This system supported task allocation,automatic retrieval of structured information,and manual review.To evaluate its performance,the moonshot-v1-8k model was used to retrieve clinical records of TCM before manual edition was performed.Combining large language model pre-annotation with meticulous annotator edits improved accuracy by 26.6％compared to the BERT-BiLSTM-CRF model,and enhanced extraction efficiency by 1.6-fold relative to purely manual methods.Conclusion General generative LLMs can retrieve a wide range of entity information from TCM records with high accuracy and scalability.The design and implementation of this system approach may provide a useful reference for developing other biomedical information retrieval systems.

This study aims to establish an antibody detection method for porcine deltacoronavirus (PDCoV). The recombinant proteins PDCoV-N1 and PDCoV-N2 were expressed via the prokaryotic plasmid pColdII harboring the N gene sequence of the PDCoV strain CH/XJYN/2016. The reactivity and specificity of PDCoV-N1 and PDCoV-N2 with anti-PEDV sera were analyzed after the recombinant proteins were analyzed by SDS-PAGE and purified by the Ni-NTA Superflow Cartridge. Meanwhile, Western blotting and indirect immunofluorescence assay were carried out separately to validate the recombinant proteins PDCoV-N1 and PDCoV-N2. Finally, we established an indirect ELISA method based on the recombinant protein PDCoV-N2 after optimizing the conditions and tested the sensitivity, specificity, and reproducibility of the method. Then, the established method was employed to examine 102 clinical serum samples. The recombinant protein PDCoV-N2 showed low cross-reactivity with anti-PEDV sera. The optimal conditions of the indirect ELISA method based on PDCoV-N2 were as follows: the antigen coating concentration of 1.25 μg/mL and coating at 37 ℃ for 1 h; blocking by BSA overnight at 4 ℃; serum sample dilution at 1:50 and incubation at 37 ℃ for 1 h; secondary antibody dilution at 1:80 000 and incubation at 37 ℃ for 1 h; color development with TMB chromogenic solution at 37 ℃ for 10 min. The S/P value ≥ 0.45, ≤0.38, and between 0.45 and 0.38 indicated that the test sample was positive, negative, and suspicious, respectively. The testing results of the antisera against porcine epidemic diarrhea virus (PEDV), porcine circovirus 2 (PCV2), transmissible gastroenteritis virus (TGEV), foot-and-mouth disease virus (FMDV), and African swine fever virus (ASFV) showed that the S/P values were all less than 0.38. The testing results of the 800-fold diluted anti-PDCoV sera were still positive. The results of the inter- and intra-batch tests showed that the coefficients of variation of this method were less than 10%. Clinical serum sample test results showed the coincidence rate between this method and neutralization test was 94.12%. In this study, an ELISA method for the detection of anti-PDCoV antibodies was successfully established based on the truncated N protein of PDCoV. This method is sensitive, specific, stable, and reproducible, serving as a new method for the clinical diagnosis of PDCoV.
Animals ; Enzyme-Linked Immunosorbent Assay/methods* ; Swine ; Antibodies, Viral/blood* ; Recombinant Proteins/genetics* ; Deltacoronavirus/isolation & purification* ; Coronavirus Infections/virology* ; Swine Diseases/diagnosis* ; Coronavirus Nucleocapsid Proteins ; Sensitivity and Specificity

OBJECTIVE:There are many kinds of biological scaffolds used for pulp revascularization in clinical practice,and the difference of efficacy between different scaffolds is controversial.The efficacy of nine kinds of biological scaffolds in endodontic revascularization was evaluated by Bayesian network meta-analysis.METHODS:The computer was used to search the literature in CNKI,VIP,WanFang,China Biomedical Literature Service System,PubMed,Cochrane Library,Web of Science,Embase,and Scopus databases.Randomized controlled trials of different biological scaffolds for the treatment of pulp revascularization in young permanent teeth meeting inclusion criteria were collected from each database up to April 1,2024.Two researchers sifted through the literature,data collection,sorting and extraction were completed independently,and the quality of the included literature was assessed for risk of bias.A network meta-analysis was performed using BUGSnet1.1.1 package of R4.2.0 software.RESULTS:A total of 22 studies with 926 affected teeth and 9 different interventions were included in this study.The results of network meta-analysis showed that:(1)Clinical success rate(primary goal):platelet-rich fibrin was superior to blood clot[OR=1.45,95％CI(0.32,2.69)],and the top three ranking results were:concentrated growth factor(82.77％)＞platelet-rich fibrin(75.38％)＞modified platelet-rich fibrin(62.39％).(2)Increased root length(secondary goal):There was no difference among the 7 biological scaffolds at 1-6 months of follow-up(P＞0.05),the top 3 ranking results of rank probability were:concentrated growth factor(86.25％)＞platelet-rich plasma(53.76％)＞platelet-rich fibrin(51.11％).When followed up for＞6 months and＜12 months,concentrated growth factor was superior to blood clot[MD=9.59,95％CI(0.52,18.40)],the top 3 ranking results of rank probability were:concentrated growth factor(92.42％)＞platelet-rich plasma(56.03％)＞platelet-rich fibrin(55.76％).When followed up for more than 12 months,concentrated growth factor was superior to modified platelet-rich fibrin[MD=11.01,95％CI(0.02,22.72)],the top 3 ranking results of rank probability were:concentrated growth factor(86.95％)＞platelet-rich fibrin(68.61％)＞blood clot combined with collagen(52.5％).(3)Increased root wall thickness(secondary goal):at 1-6 months of follow-up,platelet-rich fibrin was superior to blood clot[MD=11.37,95％CI(4.74,17.71)],the top 3 ranking results of rank probability were:platelet-rich fibrin(93.66％)＞concentrated growth factor(63.11％)＞modified platelet-rich fibrin(50.48％).At＞6 months and＜12 months of follow-up,there was no difference among the 6 biological scaffolds(P＞0.05),the top 3 ranking results of rank probability were:modified platelet-rich fibrin(73.63％)＞platelet-rich fibrin(62.36％)＞concentrated growth factor(56.25％).When followed up for more than 12 months,there was no difference among the 9 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(81.9％)＞platelet-rich plasma(62.67％)＞modified platelet-rich fibrin(59.49％).(4)Pulp vitality(third-level goal):there was no difference among the 6 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(84.22％)＞concentrated growth factor(67.71％)＞platelet-rich fibrin(48.79％).CONCLUSION:Existing evidence shows that the clinical success rate of different scaffolds is higher in pulp revascularization,among which platelet-rich fibrin is better than blood clots.In terms of comprehensive comparison of root length and root wall thickness increase,concentrated growth factor performs best in the follow-up period of 1-6 months and＞6 months and＜12 months,while blood clot combined with collagen performs best after follow-up of more than 12 months;concentrated growth factor performs outstandingly in all levels of goals,and may be more conducive to the continued development of the tooth root than other scaffolds,and has great potential in pulp regeneration treatment.Limited by the quality and quantity of literature,the above conclusions still need to be verified by more high-quality studies.

Objective:To describe the prevalence of anxiety disorders and its distribution in Inner Mongolia Autonomous Region,and to explore the relevant factors of anxiety disorders.Methods:From June 2019 to Decem-ber 2019,representative multi-stage disproportionate stratified sampling procedure was used to sample in residents aged 18 and over in the Inner Mongolia Autonomous Region.All respondents were face-to-face interviewed by trained interviewers.Composite International Diagnostic Interview-3.0(CIDI-3.0)was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ).Chi-square test and multivariate logistic regression analysis were used for statistical anal-ysis.Results:Totally 12 315 people were interviewed in the survey.The weighted 12-mouth prevalence rate of any anxiety disorder was 4.64％,and the lifetime prevalence rate was 6.25％.The weighted 12-month prevalence rate of anxiety disorders was higher in female than that in male(5.38％vs.3.92％).The rate was higher in rural resi-dents than that in urban residents(5.67％vs.3.95％).The rate was higher in people with chronic diseases than that in people without chronic diseases(6.81％vs.2.29％).Logistic regression analysis showed that unmarried(OR=2.32,95％CI:1.31-4.10),separated/divorced(OR=2.49,95％CI:1.33-4.67),in debt(OR=1.55,95％CI:1.04-2.32),chronic disease(OR=2.22,95％CI:1.39-3.53),family history of anxiety disorders(OR=12.05,95％CI:8.78-16.53),poor sleep(OR=2.64,95％CI:1.97-3.54)were risk factors of occurrence of anxiety disorders,while junior high school(OR=0.65,95％CI:0.44-0.96)was protective factor of anxiety disor-ders.Conclusion:Adults with chronic diseases,poor sleep,unmarried or separated/divorced,family history of anxi-ety disorders,and financial debt are at higher risk groups of anxiety disorder in Inner Mongolia Autonomous Re-gion.

Objective:To describe the prevalence and distributions of mood disorder in Inner Mongolia Au-tonomous Region,and analyze the related risk factors.Methods:The multistage stratified sampling method with un-equal probability was used to select permanent residents aged 18 years and over in Inner Mongolia Autonomous Re-gion.The Composite International Diagnostic Interview 3.0 was used as a diagnostic tool.Mood disorders were di-agnosed according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition(DSM-Ⅳ).Single and multivariate analyses were used to investigate the related factors of mood disorders.Results:Totally,12 315 community residents were interviewed in the survey.The weighted 12-month prevalence and lifetime prevalence of mood disorder were 5.4％and 8.7％,respectively.Weighted 12-month prevalence of depressive disorder was 4.9％,and that of bipolar disorder was 0.3％.Among all subtypes of mood disorder,the 12-month prevalence rate of major depressive disorder(3.1％)was the highest.Multivariate logistic regression analysis showed that female,unmarried,separated or divorced,unemployment,family history,other mental disorders,sleep disorders and chronic diseases(OR=1.56,2.80,2.07,1.42,13.46,7.97,3.23,2.13)were risk factors of mood disorder,while aged 65 years and over(OR=0.44)was protective factor of mood disorders.The lifetime consultation rate in patients with mood disorders was 15.5％,the rate of psychiatric consultation was 3.7％,the rate of medication was 1.8％.Con-clusion:It indicates that female residents and people who are unmarried,separated and divorced,unemployed,with family history,suffering from other mental disorders,suffering from sleep disorders,and suffering from chronic dis-eases may be high risk groups of mood disorders,and the utilization rate of health services is rather low in Inner Mongolia Autonomous Region.

The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.