Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.

Objective To identify the pathogen causing bloodstream infection(BSI)in an elderly patient and to de-scribe its pathogenic characteristics.This study also reviews recent relevant literatures on Trichoderma longibra-chiatum(T.longibrachiatum)infections.Methods Blood specimens from central and peripheral veins were co-llected for blood culture.The morphological characteristics and drug susceptibility of the isolated filamentous fungus were analyzed.The sequences of the isolated strains were detected using the internal transcribed spacer(ITS)re-gion,and then analyzed using MEGA software.Results Both morphological observation and ITS sequencing su-ggested that the pathogen was T.longibrachiatum.The minimum inhibitory concentration(MIC)against the strain detected in accordance with the M38-A2 Guideline for the Drug Susceptibility of Filamentous Fungi issued by the Clinical and Laboratory Standards Institute(CLSI)of the United States showed that the MICs of micafungin,caspofungin,5-fluorocytosine,posaconazole,voriconazole,itraconazole,fluconazole,anidulafungin and amphoteri-cin were 8,8,64,2,0.5,2,64,8 and 4 μg/mL respectively.The patient recovered well after anti-fungal treat-ment with voriconazole.A total of 15 cases of T.longibrachiatum infection were reported in the literature.The main underlying disease was transplantation(n=5),and the main clinical manifestation was pulmonary infection(n=5).Of these,9 cases survived,3 died,and 3 had an unknown prognosis.Conclusion T.longibrachiatum in-fection is more common in patients with low immunity and more underlying diseases,with a high fatality rate,lack standardized clinical treatment guidelines,lack break points in drug sensitivity results,and is resistant to common antifungal drugs.It is of guiding significance to isolate and identify pathogens in time and provide corresponding drug sensitivity testing results for clinical drug use.

Objective To identify the pathogen causing bloodstream infection(BSI)in an elderly patient and to de-scribe its pathogenic characteristics.This study also reviews recent relevant literatures on Trichoderma longibra-chiatum(T.longibrachiatum)infections.Methods Blood specimens from central and peripheral veins were co-llected for blood culture.The morphological characteristics and drug susceptibility of the isolated filamentous fungus were analyzed.The sequences of the isolated strains were detected using the internal transcribed spacer(ITS)re-gion,and then analyzed using MEGA software.Results Both morphological observation and ITS sequencing su-ggested that the pathogen was T.longibrachiatum.The minimum inhibitory concentration(MIC)against the strain detected in accordance with the M38-A2 Guideline for the Drug Susceptibility of Filamentous Fungi issued by the Clinical and Laboratory Standards Institute(CLSI)of the United States showed that the MICs of micafungin,caspofungin,5-fluorocytosine,posaconazole,voriconazole,itraconazole,fluconazole,anidulafungin and amphoteri-cin were 8,8,64,2,0.5,2,64,8 and 4 μg/mL respectively.The patient recovered well after anti-fungal treat-ment with voriconazole.A total of 15 cases of T.longibrachiatum infection were reported in the literature.The main underlying disease was transplantation(n=5),and the main clinical manifestation was pulmonary infection(n=5).Of these,9 cases survived,3 died,and 3 had an unknown prognosis.Conclusion T.longibrachiatum in-fection is more common in patients with low immunity and more underlying diseases,with a high fatality rate,lack standardized clinical treatment guidelines,lack break points in drug sensitivity results,and is resistant to common antifungal drugs.It is of guiding significance to isolate and identify pathogens in time and provide corresponding drug sensitivity testing results for clinical drug use.

BACKGROUND:Stem cells from human exfoliated deciduous teeth are widely used in the field of tissue repair and regeneration,but the tissue regeneration effect has limitations in practical applications.Using miRNA to intervene in the directional differentiation of stem cells from human exfoliated deciduous teeth is an important development direction fortissue repair and regeneration in the future.OBJECTIVE:To investigate the effect of miR-26b on the neurogenic and angiogenic differentiation of stem cells from human exfoliated deciduous teeth.METHODS:Dental pulp stem cells were isolated and extracted from human exfoliated deciduous teeth,and induced to differentiate into nerves and blood vessels.The expressions of neurogenic markers Nestin,NSE,βⅢ-Tubu lin,and angiogenic markers CD31,VEGFR2,ANG-1 and miR-26b were detected.Dental pulp stem cells were divided into blank control group,miR-26 overexpression group,and negative control group.RT-qPCR,cell immunofluorescence staining,and western blot assay were used to detect the expression changes of related markers of neurogenic and angiogenic induction of stem cells from human exfoliated deciduous teeth in each group.RESULTS AND CONCLUSION:(1)Stem cells from human exfoliated deciduous teeth had multi-directional differentiation potential and could differentiate into osteogenesis,adipogenesis,neurogenesis,and vasculogenesis.(2)The expression level of miR-26b increased during the neurogenic and angiogenic differentiation of stem cells from human exfoliated deciduous teeth.(3)Compared with the blank control group and negative control group,the mRNA expression of neuroblast-related genes βⅢ-Tubulin,Nestin,NSE and angiogenesis-related genes CD31,VEGFR2,and ANG-1 in stem cells from human exfoliated deciduous teeth in the miR-26b overexpression group was significantly increased(P＜0.01),βⅢ-Tubulin,Nestin,CD31,and VEGFR2 protein expression was significantly increased(P＜0.01).The above results show that overexpression of miR-26b can promote the neurogenic and angiogenic differentiation of stem cells from human exfoliated deciduous teeth.

Objective To study the expression levels and clinical significance of histone H3 trimethylation at lysine 4(H3K4me3),histone H3 trimethylation at lysine 27(H3K27me3)and modifying enzyme in placental tissue of patients with premature rupture of membranes(PROM)with chorioamnionitis.Methods Clinical data of 95 pregnant women treated in the Xi'an Gaoxin Hospital due to PROM from June 2021 to December 2023 were retrospectively collected,and they were divided into infected group and a non-infected group according to whether they were complicated with histological chorioamnionitis(HCA).Another 30 normal pregnant women were selected as the control group.Placental tissues of all subjects were collected and H3K4me3 and H3K27me3 levels were detected,and the expression levels of H3K4me3,H3K27me3 specific methyltransferase[mixed lineage leukemia protein-1(MLL1),Zeste enhancer homolog 2(EZH2)]and demethyltransferase[lysine-specific demethylase 5B(KDM5B),Jumonji domain-containing protein 3(JMJD3)]were detected by quantitative real-time PCR(qRT-PCR).The expression differences of H3K4me3,H3K27me3 and specific modifiers among the three groups and the correlation with the histological stage of HCA were analyzed.The Receiver operating characteristic curve(ROC)was plotted,the Area under curve(AUC)value was calculated,and H3K4me3 was evaluated.Predictive value of H3K27me3 for concurrent HCA infection.Result Compared with the control group,the levels of H3K4me3(0.08%±0.02%,0.12%±0.03%vs 0.25%±0.06%),MLL1 mRNA(1.32±0.16,1.44±0.23 vs 2.02±0.31),and JMJD3 mRNA(0.78±0.13,0.91±0.15 vs 1.53±0.23)in the infected and non-infected groups were significantly decreased(t=10.939～19.062),while the levels of H3K27me39(0.23%±0.05%,0.15%±0.03%vs 0.10%±0.02%),EZH2 mRNA(1.96±0.26,1.85±0.25 vs 1.15±0.29)and KDM5B(1.46±0.15,1.35±0.18 vs 0.94±0.12)were significantly increased(t=6.077～14.974),and the levels in the infected group were lower/higher than those in the non-infected group(t=2.017～10.688),with statistically significant differences(all P<0.05).There was a significant negatively correlation between H3K4me3 and H3K27me3 levels in placenta tissue of PROM(r=-0.604,P<0.05).The levels of H3K4me3,MLL1 and JMJD3 were negatively correlated with the histological stages of HCA(r=-0.646,-0.489,-0.503,all P<0.05).The levels of H3K27me3,EZH2 and KDM5B were positively correlated with the histological stages of HCA(r=0.632,0.515,0.520,all P<0.05).The cutoffvalues of H3K4me3 and H3K27me3 were 0.10%and 0.19%,respectively.The AUC(95%CI)value of the combined prediction of PROM combined with HCA infection was 0.896(0.882～0.947),and the sensitivity and specificity were 92.14%and 86.23%respectively,which was significantly higher than the diagnosis of a single index.Conclusion The levels of H3K4me3,H3K27me3 and modifying enzymes in the placenta tissue of PROM are closely related to HCA infection and histological stage,which has high clinical prediction value for HCA infection and is expected to be a new biomarker for clinical diagnosis.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

BACKGROUND:Basement membrane genes are closely related to the occurrence and development of rheumatoid arthritis,but the role of basement membrane-related genes in the pathogenesis of rheumatoid arthritis under different traditional Chinese medicine patterns is not yet clear.OBJECTIVE:To explore the differences in the pathogenesis of rheumatoid arthritis with five different traditional Chinese medicine syndromes based on the analysis of basement membrane-related genes and transcriptomics,and to predict potential therapeutic drugs.METHODS:Rheumatoid arthritis-related traditional Chinese medicine syndrome microarray data and basement membrane-related genes were collected from the GEO database.The differentially expressed genes were screened using the R-limma package,and the expression trends were analyzed using the Mfuzz package.The protein-protein interaction network was constructed using the STRING database and key genes were selected using UPset.The differentially expressed genes were subjected to gene set enrichment analysis(GSEA)and enrichment analysis using the R-clusterProfiler package.Receiver operating characteristics curves were plotted to evaluate the diagnostic value of core basement membrane-related targets for each of the five syndromes.The immune infiltration of each syndrome was calculated using the CIBERSORT algorithm.Finally,potential traditional Chinese medicines and small molecule drugs targeting core basement membrane-related genes for the treatment of different traditional Chinese medicine syndromes of rheumatoid arthritis were predicted using SymMap and COREMINE databases.RESULTS AND CONCLUSION:(1)67,47,59,57,and 55 basement membrane-related differentially expressed genes were screened for the five traditional Chinese medicine syndromes of rheumatoid arthritis(obstruction syndrome,cold-dampness obstruction syndrome,liver-kidney deficiency syndrome,qi-blood deficiency syndrome,and blood stasis obstructing collaterals syndrome),with 5,7,5,3,and 5 key targets identified,respectively.(2)The most enriched biological processes in each syndrome were extracellular matrix adhesion,immune cell migration,collagen metabolism,and extracellular matrix receptor interaction,PI3K-Akt,focal adhesion,and Rap1 signaling pathways.(3)According to the predictions,Smilax glabra,Sargentodoxa cuneata,and Polygonatum sibiricum have the most potential as traditional Chinese medicines for the treatment of the five traditional Chinese medicine syndromes of rheumatoid arthritis by affecting basement membrane-related genes.(4)These results indicate that abnormal expression of basement membrane-related genes may affect the occurrence and development of rheumatoid arthritis through the regulation of cell adhesion,immune cell migration,and inflammatory reactions,among other pathways.These effects vary among different syndromes,with ITGA6 serving as a common diagnostic marker for the five traditional Chinese medicine syndromes of rheumatoid arthritis.Traditional Chinese medicines with heat-clearing and detoxifying properties may be potential effective drugs for the treatment of different syndromes of rheumatoid arthritis.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.

Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.