Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.

BackgroundThe functional changes of the default mode network （DMN） are closely related to the onset of major depressive disorders. However， the relationship between the DMN subsystem （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and symptoms of first-episode major depressive disorder remains unclear. ObjectiveTo investigate abnormal functional connectivity between DMN subsystems and the whole brain in first-episode major depressive disorder patients during the resting-state， and to analyse the correlations between these functional connectivity patterns and clinical symptoms， so as to reveal the potential neural mechanisms from the perspective of DMN subsystem. MethodsFrom September 2020 to September 2023， a total of 64 first-episode outpatients and inpatients meeting the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Inner Mongolia Autonomous Region Mental Health Center as the study group. During the same period， 54 healthy volunteers matched for age， gender， and years of education were recruited from the community as the control group. Both groups were assessed using the Hamilton Depression Scale-24 item （HAMD-24）. Resting-state functional magnetic resonance images （rs-fMRI） of the two groups were acquired using a Siemens 3.0 T scanner， and differences in functional connectivity between DMN subsystems （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and the whole brain were compared. The functional connectivity values of brain regions with statistically significant differences between the two groups were extracted. Spearman's rank correlation coefficient analysis was used to investigate the correlation between these functional connectivity values and HAMD-24 scores of the study group. ResultsUltimately， 46 patients and 43 controls completed the study. Compared with the control group， the study group exhibited significantly stronger functional connectivity in the following pathways： between the right superior parietal lobule （core subsystem） and right cerebellar lobule VIII （t=3.954， P<0.05， GRF-corrected）， between the right lateral temporal cortex （dorsomedial prefrontal cortex subsystem） and right cerebellar lobule VIII， right and left hippocampi， right medial， and paracingulate gyrus （t=4.595， 4.208， 5.200， 4.038， P<0.05， GRF-corrected）， and between the temporoparietal junction （dorsomedial prefrontal cortex subsystem） and left lingual gyrus and right cerebellar lobule VIII （t=3.557， 4.274， P<0.05， GRF-corrected）. Conversely， weaker functional connectivity was observed between the right inferior frontal gyrus and left gyrus rectus （t=-3.824， P<0.05， GRF-corrected）. Furthermore， within the study group， the functional connectivity values between the right lateral temporal cortex and right hippocampus， as well as between the temporoparietal junction and right cerebellar lobule VIII， were both negatively correlated with the HAMD-24 cognitive impairment factor score （r=-0.306， -0.318， P<0.05）. ConclusionIncreased functional connectivity between the DMN （specifically its core and dorsomedial prefrontal cortex subsystems） and cerebellum， partial limbic system， and lingual gyrus may be associated with the neuropathology of first-episode major depressive disorder. Furthermore， alterations in functional connectivity between the dorsomedial prefrontal cortex subsystem and both the cerebellum and hippocampus in these patients may be related to cognitive function. ［Funded by 2019 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2019MS03038）； 2023 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2023MS08028）］

Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.

PROPOSE: To investigate the molecular mechanisms underlying the protective effects of ischemic preconditioning (IPC) in patients undergoing total knee arthroplasty. METHODS: GSE21164 was extracted from an online database, followed by an investigation of differentially expressed genes (DEGs) between IPC treatment samples at 2 time points (T0T and T1T). Function and pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed to identify hub genes according to 5 different algorithms, followed by enrichment analysis. In addition, long noncoding RNAs (lncRNAs) were identified between the T0T and T1T samples. Furthermore, a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA (mRNA), lncRNA-microRNA (miRNA), and mRNA-miRNA relationships revealed in this study. Finally, a drug-gene network was investigated. Statistical analyses were performed using GraphPad Prism 8.0. Differences between groups were determined using an unpaired t-test. p < 0.05 was considered significant. RESULTS: A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respective control groups, followed by 100 DEGs between T0T and T1T. Based on these 100 DEGs, protein-protein interaction network analysis revealed 9 hub genes, mainly with mitochondria-related functions and the carbon metabolism pathway. Six differentially expressed lncRNAs were investigated between T0T and T1T. A competing endogenous RNA network was constructed using 259 lncRNA-miRNA-mRNA interactions, including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold. Finally, 13 chemical drugs associated with the hub genes were explored. CONCLUSION Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis. Moreover, IPC may induce a protective response after total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway, which should be further validated in the near future.
Humans ; Arthroplasty, Replacement, Knee ; Ischemic Preconditioning ; RNA, Long Noncoding/genetics* ; Protein Interaction Maps ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Gene Regulatory Networks

Disseminated mucormycosis is a life-threatening fungal infection with high mortality, particularly in immunocompromised patients. Early diagnosis and prompt intervention are crutial but often delayed due to nonspecific presentations. Many studies have highlighted the challenges in emergency settings, where atypical symptoms may lead to misdiagnosis. We report a rare case of disseminated mucormycosis originating from the stomach in a pregnancy-induced thrombocytopenia (PITP) patient, emphasizing rapid gastroscopy examination, histopathological confirmation, multidisciplinary management, and high-risk factors for hospital-acquired gastrointestinal mucormycosis infection.

Objective To explore the epidemiological characteristics of voluntary blood donors with enzyme-linked im-muno-sorbent assay(ELISA)negative and nucleic acid testing(NAT)positive in Hainan from 2012 to 2022,so as to pro-vide reference for developing rational blood screening strategies.Methods The screening results for transfusion-transmitted disease markers in 1 161 042 blood samples in Hainan from 2012 to 2022 were retrospectively analyzed.All samples have been measured twice by ELISA and once by NAT.Statistical methods were used to analyze the proportion of ELISA negative and NAT positive(ELISA-/NAT+)among voluntary blood donors and its relation with factors including gender,age,eth-nicity and region.Results Among the voluntary blood donors in Hainan from 2012 to 2022,the overall proportion of ELISA-/NAT+was 0.19%(2 151/1 161 042),and the difference was statistically significant(P＜0.05).The ELISA-/NAT+rate in hepatitis B virus(HBV)DNA,hepatitis C virus(HCV)RNA,human immunodeficiency virus(HIV)RNA and non-discriminating reactive(NDR)was 0.10%,0.000 3%,0.000 4%and 0.09%respectively.The ELISA-/NAT+rate of voluntary blood donors varied among different age groups and gradually increased with age(P＜0.05).The ELISA-/NAT+rate of male donors(0.22%,1 729/795 032)was significantly higher than that of female donors(0.12%,422/366 010,P＜0.05).The ELISA-/NAT+rate of Han blood donors was significantly lower than that of Li and Miao blood donors(P＜0.05).The ELISA-/NAT+rate was the highest of 0.32%(301/94 046)in the eastern region,followed by 0.30%(341/113 783)in western region,and 0.16%in both southern and northern region,which also presented a significant difference(P＜0.05).Conclusion The ELISA-/NAT+rate of voluntary blood donors in Hainan fluctuated from 2012 to 2022,which was related to factors such as age,gender,ethnicity and region.

Objective To analyze the nucleic acid testing(NAT)results of voluntary blood donors in Hainan and evalu-ate the residual risk in the window period of NAT for hepatitis B virus(HBV),hepatitis C virus(HCV)and human immu-nodeficiency virus(HIV).Methods A retrospective analysis on the NAT results of voluntary blood donors at our center from January 2012 to December 2022 was conducted.The new infection rate-window period residual risk model was used to assess the residual risk of HBV,HCV and HIV among blood donors.Results From January 2012 to December 2022,a-mong the blood donated by voluntary blood donors in Hainan,45.02％(522 684/1 161 042)were collected from first-time donors,54.98％(638 358/1 161 042)were from repeat donors(including regular donors),and 30.48％(354 227/1 162 042)were from regular donors.The total reactive rate of NAT was 0.19％(2 151/1 161 042).After NAT,the residual risk in the window period of HBV,HCV and HIV was 62.54 per million,0.431 per million and 0.791 per million,respective-ly.Conclusion The implementation of NAT among voluntary blood donors in Hainan significantly reduces the residual risk of HCV,and the residual risk of HBV,HCV and HIV transmission in the window period is at a relatively low level.

[Objective] To investigate the prevalence of human T-lymphotropic virus (HTLV) infection among voluntary blood donors and provide reference for the development of blood safety screening strategy in Hainan Province. [Methods] Enzyme linked immunosorbent assay (ELISA) was used to screen for HTLV, and the reactive samples were confirmed by Western blot (WB). [Results] A total of 326 269 blood samples from 2016 to 2023 in Hainan were screened, among which 117 samples showed reactive results for initial screening, with a reactive rate of 0.036% (117/326 269), and 9 were confirmed positive by WB, with a positive rate of 0.002 7%(9/326 269). The prevalence of HTLV antibody varied among different demographic groups, with a significantly higher rate among males compared to females (P<0.05). [Conclusion] There are HTLV antibody positive blood donors in the voluntary blood donors in Hainan. Although it is a low prevalence area for HTLV, it is necessary to continue to expand the blood screening and conduct epidemiological investigations on positive blood donors for blood safety.

Objective To analyse whether Resveratrol can inhibit the inflammatory response in septic cardiomyopathy by modulating the mammalian target of rapamycin-transcription factor EB(mTOR-TFEB)signaling pathway.Methods A total of 32 clean-grade male Sprague-Dawley(SD)rats were selected and divided into sham operation group(Sham group),sepsis model group[cecal ligation and puncture(CLP)group],Resveratrol group(Res group)and mTOR inhibitor group(Torin1 group),with 8 rats in each group.Sepsis was induced by CLP.The sham group only underwent laparotomy and did not perform CLP.In the Torin1 group,20 mg·kg-1·d-1 of mTOR inhibitor Torin l injection was injected intraperitoneally 10 days before molding,once a day for 10 days.The Sham group and the CLP group were given the same amount of normal saline through the same route before molding.The Res group was injected intraperitoneally with 60 mg/kg Resveratrol injection before molding.At 6 hours after model establishment,the heart function was evaluated by echocardiography;Serum cardiac troponin I(cTnI)levels were detected by enzyme linked immunosorbent assay(ELISA).The mRNA expressions of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The protein expressions of phosphorylation-mTOR(p-mTOR),TFEB(nuclear),TFEB(total)and light chain 3-Ⅱ(LC3-Ⅱ)of myocardial tissue were detected by Western blotting.The interaction between Resveratrol and mTOR was simulated using a network pharmacology approach.Results Compared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening rate(FES)were significantly reduced in the CLP group[LVEF:0.37±0.02 vs.0.69±0.01,FES(%):17.8±3.1 vs.33.9±2.8,both P<0.01],serum cTnI levels were elevated(ng/L:1 935.96±47.78 vs.87.95±7.98,P<0.01),the mRNA expression levels of IL-6 and TNF-α were significantly up-regulated[IL-6 mRNA(2-ΔΔCt):26.10±2.08 vs.1.61±0.03,TNF-α mRNA(2-ΔΔCt):12.80±1.51 vs.1.26±0.22,both P<0.01),serum levels of inflammatory cytokines IL-6 and TNF-α mRNA were increased[IL-6 mRNA(2-ΔΔCt):26.10±2.08 vs.1.61±0.03,TNF-α mRNA(2-ΔΔCt):12.80±1.51 vs.1.26±0.22,both P<0.01),the expression level of p-mTOR protein in myocardial tissue was significantly increased(p-mTOR/β-actin:0.60±0.07 vs.0.30±0.05),while the protein levels of TFEB(total),TFEB(nuclear)and LC3-Ⅱwere significantly decreased[TFEB(total)/β-actin:0.52±0.08 vs.0.80±0.09,TFEB(nuclear)/H3:0.36±0.06 vs.0.09±0.07,LC3-Ⅱ/β-actin:0.25±0.08 vs.0.48±0.08,all P<0.01];Compared with the CLP group,the Res group and the Torin1 group had significantly higher LVEF and FES[LVEF:0.66±0.02,0.67±0.03 vs.0.37±0.02;FES(%):32.5±3.5,33.7±3.3 vs.17.8±3.1,both P<0.01],serum cTnI level was decreased(ng/L:1 216.88±36.66,1 225.78±35.64 vs.1 935.96±47.78,both P<0.01),mRNA levels of serum inflammatory cytokines IL-6 and TNF-α were decreased[IL-6 mRNA(2-ΔΔCt):3.91±0.46,4.14±0.39 vs.26.1±2.08,TNF-α mRNA(2-ΔΔCt):4.67±1.16,5.16±1.25 vs.12.8±1.51,both P<0.01],the p-mTOR protein expression in myocardial tissue was significantly decreased(p-mTOR/β-actin:0.22±0.05,0.24±0.06 vs.0.60±0.07,all P<0.01),the protein levels of TFEB(total),TFEB(nuclear),LC3-Ⅱwere significantly increased[TFEB(total)/β-actin:0.86±0.06,0.84±0.07 vs.0.52±0.08;TFEB(nuclear)/H3:0.96±0.08,0.86±0.07 vs.0.36±0.06;LC3-Ⅱ/β-actin:0.57±0.07,0.55±0.06 vs.0.25±0.08,all P<0.01].Network pharmacology was used to verify that resveratrol binds well to mTOR.Conclusion Resveratrol enhanced cardiac autophagy via the mTOR-TFEB pathway,thereby attenuating myocardial inflammation and subsequent cardiac injury in septic rats.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.