ObjectiveTo understand the epidemiological characteristics and post-exposure prophylaxis of rabies exposure cases in Suqian City of Jiangsu Province from 2021 to 2024, providing a reference for optimizing the allocation of health resources and formulating scientific prevention and control measures. MethodsData on individuals exposed to rabies and treated at Suqian’s rabies post-exposure prophylaxis (PEP) clinics from 2021 to 2024 were collected. Descriptive epidemiological methods were used to analyze patient characteristics, exposure classification, animal species responsible for injuries, wound management, and vaccination status. ResultsBetween 2021 and 2024, the number of outpatient visits for rabies PEP clinics in Suqian City totaled 333 450. The median age and the 25th and 75th percentiles of exposed individuals was 23 (9, 47) years. The highest proportion of exposed individuals was recorded in 2023 (27.09%); the majority were female (52.22%), aged 5‒9 years (17.49%), and in other occupations (37.05%). The rabies exposure rate in Suqian City from 2021 to 2024 was 16.75‰. The overall rabies exposure rate showed an upward trend (χtrend2=1 994.80, P<0.001). The exposure rate among males was lower than that among females (χ²=890.43, P<0.001). The highest exposure rate was observed in the 5‒9 age group (χ²=67 063.20, P<0.001). The number of individuals seeking medical care for rabies exposure exhibited a weak bimodal distribution, with the primary peak occurring in August and the secondary peak in January. The primary animal responsible for injuries was the cat (53.70%), and the source of these animals was predominantly domestic pets (88.90%). The proportion of exposed individuals bitten by cats showed an upward trend from 2021 to 2024 (χtrend2=548.44, P<0.001). Grade Ⅲ exposure accounted for the highest proportion (53.53%), and 301 652 cases (90.46%) presented within 24 hours of exposure. The coverage rate of rabies vaccine was 98.18% (13 625/13 877) for those with Grade Ⅰ exposure and 99.95% (319 413/319 573) for those with Grade Ⅱ and Ⅲ exposures; 64 042 individuals received rabies immunoglobulin or anti-rabies serum; 8 360 exposed individuals received tetanus vaccine, with the usage rate of tetanus vaccine among exposed individuals was only 2.51%, though the rate was on the rise (χtrend2=618.26, P<0.001). ConclusionBetween 2021 and 2024, the overall incidence of rabies exposure in Suqian City showed an upward trend, with a higher incidence among women than men. The incidence was particularly high among children and adolescents aged 14 and under, with the majority of injuries caused by cats; most injuries were inflicted by domestic animals. The overall uptake of tetanus vaccines showed an upward trend. Suqian City should step up health education on rabies exposure during January and August each year, with a particular focus on raising awareness of rabies exposure prevention among people aged 14 and under and women. It should also strengthen the management of domestic animals and ensure that they receive regular rabies vaccinations, particularly for pet cats. Preventive measures against tetanus should be strengthened for individuals exposed to rabies. Medical staff at rabies PEP clinics should receive enhanced training on the management of rabies exposures and the completion of information system reports to ensure the standardized operation of these clinics.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

This study aims to investigate the changes in blood biochemical indicators of tongue roll-ing(TR)behavior in cattle and their correlation with changes in oral microbiota,laying a founda-tion for further exploring the relationship between animal oral microbiota,biochemical indicators,and behavioral changes.It also provides theoretical basis for preventing and treating TR behavior through regulating oral microbiota.This study intends to analyze and compare the blood biochemi-cal indicators and changes in oral microbiota of cattle with TR behavior and healthy cattle without TR behavior(healthy control,H),in order to explore the blood biochemical indicators of TR cattle and their correlation with changes in oral microbiota.Blood samples from the caudal vein of cattle in each group were collected for the detection of blood biochemical indicators and stress-related hormone indicators.Oral swabs from cattle in each group were collected for 16S rRNA gene se-quencing to analyze the composition,structure,and functional changes of their oral microbiota.The results of blood biochemical indicators in H and TR groups showed that the concentrations of al-bumin(ALB),aspartate aminotransferase(AST),calcium ion(Ca2+),and cortisol in TR group were significantly higher than those in H group(P＜0.05).There were significant differences in beta diversity of oral microbiota between TR and H groups(P＜0.05).At the genus level,the rela-tive abundances of Pseudomonas,Enterobacter,Xanthomonas,and other genera in the oral micro-biota of TR group were significantly higher than those in H group(P＜0.05).However,the rela-tive abundances of Tessaracoccus,Turicibacter,Monoglobus,Dietzia,Bifidobacterium,and other genera in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).In the KEGG metabolic pathway at the third level,the relative abundances of thiamine me-tabolism,lipoate metabolism,cysteine and methionine metabolism in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).Spearman correlation analysis showed that ALB and AST were significantly positively correlated with the relative abundances of Pseudomonas and Stenotrophomonas.Therelative abundances of Pseudomonas,Stenotrophomonas,and Sphingomonas were significantly positively correlated with fatty acid metabolism,phosphate and phosphonate metabolism,and lipoate metabolism.ALB was significantly positively correlated with inositol phosphate metabolism and phosphate and phosphonate metabolism.The study found that there were significant differences in blood biochemical indicators and oral microbiota between TR and H groups.In addition,there is a certain correlation between the composition,structure,and function of oral microbiota and the biochemical function of the host.This indicates that TR behav-ior may be associated with changes in the biochemical indicators of the host and the composition,structure,and function of oral microbiota.

This study aims to investigate the changes in blood biochemical indicators of tongue roll-ing(TR)behavior in cattle and their correlation with changes in oral microbiota,laying a founda-tion for further exploring the relationship between animal oral microbiota,biochemical indicators,and behavioral changes.It also provides theoretical basis for preventing and treating TR behavior through regulating oral microbiota.This study intends to analyze and compare the blood biochemi-cal indicators and changes in oral microbiota of cattle with TR behavior and healthy cattle without TR behavior(healthy control,H),in order to explore the blood biochemical indicators of TR cattle and their correlation with changes in oral microbiota.Blood samples from the caudal vein of cattle in each group were collected for the detection of blood biochemical indicators and stress-related hormone indicators.Oral swabs from cattle in each group were collected for 16S rRNA gene se-quencing to analyze the composition,structure,and functional changes of their oral microbiota.The results of blood biochemical indicators in H and TR groups showed that the concentrations of al-bumin(ALB),aspartate aminotransferase(AST),calcium ion(Ca2+),and cortisol in TR group were significantly higher than those in H group(P＜0.05).There were significant differences in beta diversity of oral microbiota between TR and H groups(P＜0.05).At the genus level,the rela-tive abundances of Pseudomonas,Enterobacter,Xanthomonas,and other genera in the oral micro-biota of TR group were significantly higher than those in H group(P＜0.05).However,the rela-tive abundances of Tessaracoccus,Turicibacter,Monoglobus,Dietzia,Bifidobacterium,and other genera in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).In the KEGG metabolic pathway at the third level,the relative abundances of thiamine me-tabolism,lipoate metabolism,cysteine and methionine metabolism in the oral microbiota of TR group were significantly lower than those in H group(P＜0.05).Spearman correlation analysis showed that ALB and AST were significantly positively correlated with the relative abundances of Pseudomonas and Stenotrophomonas.Therelative abundances of Pseudomonas,Stenotrophomonas,and Sphingomonas were significantly positively correlated with fatty acid metabolism,phosphate and phosphonate metabolism,and lipoate metabolism.ALB was significantly positively correlated with inositol phosphate metabolism and phosphate and phosphonate metabolism.The study found that there were significant differences in blood biochemical indicators and oral microbiota between TR and H groups.In addition,there is a certain correlation between the composition,structure,and function of oral microbiota and the biochemical function of the host.This indicates that TR behav-ior may be associated with changes in the biochemical indicators of the host and the composition,structure,and function of oral microbiota.

Aim To investigate the role of mesence-phalic astrocyte-derived neurotrophic factor(MANF)in the inhibitory effect of rhynchophylline(Rhy)on the malignant biological behaviors of gastric cancer cells and its underlying regulatory mechanisms.Meth-ods SGC-7901 gastric cancer cells were transfected using adenovirus and liposome transfection techniques.The experimental groups included:Control group,Rhy group,Rhy+NC group(Rhy+adenovirus-transfected MANF-irrelevant fragment),Rhy+si-MANF group(Rhy+adenovirus-transfected MANF siRNA),Vec-tor group(empty vector),OVE-MANF group(recom-binant plasmid overexpressing MANF).After 24 hours of intervention,cell proliferation,apoptosis,migra-tion,and invasion were assessed using the MTT assay,Hoechst staining,and Transwell assays,respectively.The expressions of MANF,Cyclin D1,and cleaved caspase-3 proteins were measured using Western blot.NF-κB transcriptional activity was evaluated via a lucif-erase reporter assay.Results Compared to the control group,Rhy treatment significantly inhibited gastric cancer cell growth in a dose-dependent manner(P＜0.05),induced typical apoptotic morphological chan-ges,and increased the expression of MANF and cleaved caspase-3 proteins(P＜0.05),while reduc-ing Cyclin D1 protein expression and NF-κB transcrip-tional activity(P＜0.05).Additionally,Rhy treat-ment markedly decreased cell migration and invasion capabilities(P＜0.05).In comparison to the Rhy group,adenovirus-mediated transfection of MANF siR-NA suppressed apoptosis,promoted gastric cancer cell proliferation,migration,and invasion,inhibited MANF and cleaved caspase-3 expression(P＜0.05),and enhanced Cyclin D1 protein levels and NF-κB transcriptional activity(P＜0.05).Compared to the Vector group,OVE-MANF(overexpression of MANF)induced apoptosis,suppressed proliferation,invasion,and metastasis of gastric cancer cells,upregulated MANF and cleaved caspase-3 expression(P＜0.05),and inhibited Cyclin D1 protein levels and NF-κB tran-scriptional activity(P＜0.05).Conclusion Rhy in-hibits the proliferation,migration,and invasion of gas-tric cancer cells and induces apoptosis,with its mecha-nism linked to the promotion of MANF expression and suppression of NF-κB transcriptional activity.

Objective To observe the clinical efficacy and safety of hydrocortisone injection combined with continuous blood purification in the treatment of sepsis patients.Methods Sepsis patients were randomly divided into control group and treatment group.The control group received continuous blood purification treatment;on the basis treatment of control group,the treatment group received hydrocortisone 200 mg,qd,intravenous infusion.Two groups were treated for 1 week.The clinical efficacy,levels of inflammatory cytokines,cellular immune function indicators,and safety were compared between two groups.Results Fifty-six cases were enrolled in the treatment group,5 cases were excluded,and ultimately 51 cases were included in the statistical analysis.Fifty-five cases were enrolled in the control group,4 cases were excluded,and ultimately 51 cases were included in the statistical analysis.After treatment,the total effective rates of the treatment and control groups were 94.12％(48 cases/51 cases)and 74.51％(38 cases/51 cases)with statistical significant difference(P＜0.05).After treatment,the levels of C-reactive protein in the treatment and control groups were(12.21±2.35)and(15.18±2.25)mg·L-1,the levels of procalcitonin were(0.49±0.13)and(0.78±0.21)ng·mL-1,the levels of CD3+were(58.72±5.13)％and(54.21±4.47)％,the CD4+/CD8+ratios were 1.71±0.23 and 1.43±0.17,respectively.The differences were statistically significant(all P＜0.05).The adverse drug reactions of treatment group were chest tightness,nausea,and vomiting,while those in the control group were hypotension,nausea,and vomiting.The total incidences of adverse drug reactions in the treatment and control groups were 9.80％and 5.88％,without significant difference(P＞0.05).Conclusion Hydrocortisone injection combined with continuous blood purification have a definitive clinical efficacy in the sepsis patients,which can improve the patients'immune function,reduce inflammatory reactions,without increasing the incidences of adverse drug reactions.

Dark plum can be used to treat symptoms such as consumptive thirst due to deficiency-heat and chronic cough due to lung deficiency.Its active ingredients have auxiliary effects on lowering blood glucose,antibacterial and anti-inflammatory activities.Insulin resistance is mainly characterized by the weakening of the physiological effects of insulin in the body,with a relatively complex mechanism that can lead to various metabolic-related diseases and seriously affect health.The active ingredients of dark plum can improve insulin resistance by regulating insulin signaling pathways,endoplasmic reticulum stress,antioxidant stress,inflammatory signaling pathways,levels of related inflammatory mediators,and free fatty acid levels.By reviewing the relevant literature on the improvement of insulin resistance by the active ingredients of dark plum,this article summarizes and analyzes its mechanism of action,aiming to provide new ideas and scientific evidence for in-depth research on insulin resistance and the development and application of drugs.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.