OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.

Objective To investigate the association between cerebrospinal fluid(CSF)oligoclonal band(OCB)positivity and clinical manifestations in patients with neuromyelitis optica spectrum disorder(NMOSD).Methods A retrospective analysis of clinical data from patients with NMOSD treated at our hospital from May 2019 to January 2024 was conducted.Based on OCB test results,patients were categorized into OCB-positive and OCB-negative groups.We compared baseline characteristics between the two groups and analyzed the relationship between clinical features and OCB positivity.Results This study included a total of 62 patients,comprising 17 in the OCB+group and 45 in the OCB-group.Compared with the OCB-group,patients in the OCB+group exhibited more pronounced central nervous system inflammatory features.Specifically,OCB+group had significantly higher proportions of patients with cerebrospinal fluid white blood cell counts>8×10?/L(64.7%vs.26.7%,P=0.003)and elevated immunoglobulin indices(0.72 vs.0.61,P=0.037).Additionally,the OCB+group exhibited more complex and diverse clinical presentations.Specifically,this group showed a higher incidence of mild consciousness impairment during the acute phase(P=0.005)and a greater tendency to present with multiple core symptoms(≥3 core symptoms)occurring concurrently(52.9%vs.20.0%,P=0.025)and misdiagnosis(29.4%vs.8.9%,P=0.101).This was particularly notable when comparing to acute myelitis involving the cervical spinal cord(82.4%vs.53.3%,P=0.036)and acute diencephalic syndrome[41.2%vs.6.7%,P=0.004,including hyponatremia(35.3%vs.8.9%,P=0.033)].Multivariate logistic regression analysis demonstrated that OCB positivity(OR=3.895,95%CI:1.065-14.249)was significantly associated with the presence of multiple core symptoms.Conclusion In acute-phase NMOSD patients,OCB+is associated with significantly higher rates of co-occurrence of multiple core symptoms(≥3 core symptoms)and misdiagnosis.Notably,acute myelitis involving the cervical spinal cord and acute diencephalic clinical syndrome are particularly prevalent in this OCB+subgroup.The clinical manifestations are complex and diverse,suggesting the need for enhanced clinical identification and timely intervention.

Objective To explore the circRNA expression level in the urine of patients with lupus nephritis(LN),to construct a diagnostic model for LN,and to evaluate and verify its diagnostic efficacy.Methods A total of 120 patients with LN admitted from January 2022 to January 2024 were selected as the observation group and divided into the training group(n=84)and the validation group(n=36)at a ratio of 7:3.Another 100 healthy individuals who underwent physical examination were selected as the control group.The expression levels of circRNA-0001445,circRNA-002059,hsa-circ-0007385 and hsa-circ-0000006 in urine specimens of patients in the training group and the control group were detected by gene sequencing.Multivariate Logistic regression analysis was used to construct a diagnostic model for LN based on the urinary circRNA expression level.The diagnostic value of individual indicators and combined predictive models were evaluated by receiver operating characteristic(ROC)curve analysis,and then the predictive efficacy of the model was verified by the validation group.Results The expression levels of circRNA-0001445,circRNA-002059,hsa-circ-0007385 and hsa-circ-0000006 in the urine of patients in the training group were all higher than those of the control group(P<0.01).Multivariate Logistic regression analysis found that The expression levels of circRNA-0001445(OR=1.094),circRNA-002059(OR=1.040),hsa-circ-0007385(OR=1.033),and hsa-circ-0000006(OR=1.130)in theurine were independent factor for the diagnosis of LN(P<0.01).ROC curve analysis showed that the areas under the curve of combined model constructed based on the circRNA expression level in the urine were 0.985 and 0.911 in the training group and the validation group,respectively,with sensitivities of 95.00%and 91.67%,and specificities of 99.00%and 89.00%,all of which were higher than the diagnostic efficacy of a single urinary circRNA expression level.Conclusion The diagnostic model of LN constructed based on the expression level of circRNA in the urine has a high diagnostic efficacy,which has been confirmed by internal tests and may provide strong support for clinicians in the early diagnosis of LN.

Objective To investigate the association between cerebrospinal fluid(CSF)oligoclonal band(OCB)positivity and clinical manifestations in patients with neuromyelitis optica spectrum disorder(NMOSD).Methods A retrospective analysis of clinical data from patients with NMOSD treated at our hospital from May 2019 to January 2024 was conducted.Based on OCB test results,patients were categorized into OCB-positive and OCB-negative groups.We compared baseline characteristics between the two groups and analyzed the relationship between clinical features and OCB positivity.Results This study included a total of 62 patients,comprising 17 in the OCB+group and 45 in the OCB-group.Compared with the OCB-group,patients in the OCB+group exhibited more pronounced central nervous system inflammatory features.Specifically,OCB+group had significantly higher proportions of patients with cerebrospinal fluid white blood cell counts>8×10?/L(64.7%vs.26.7%,P=0.003)and elevated immunoglobulin indices(0.72 vs.0.61,P=0.037).Additionally,the OCB+group exhibited more complex and diverse clinical presentations.Specifically,this group showed a higher incidence of mild consciousness impairment during the acute phase(P=0.005)and a greater tendency to present with multiple core symptoms(≥3 core symptoms)occurring concurrently(52.9%vs.20.0%,P=0.025)and misdiagnosis(29.4%vs.8.9%,P=0.101).This was particularly notable when comparing to acute myelitis involving the cervical spinal cord(82.4%vs.53.3%,P=0.036)and acute diencephalic syndrome[41.2%vs.6.7%,P=0.004,including hyponatremia(35.3%vs.8.9%,P=0.033)].Multivariate logistic regression analysis demonstrated that OCB positivity(OR=3.895,95%CI:1.065-14.249)was significantly associated with the presence of multiple core symptoms.Conclusion In acute-phase NMOSD patients,OCB+is associated with significantly higher rates of co-occurrence of multiple core symptoms(≥3 core symptoms)and misdiagnosis.Notably,acute myelitis involving the cervical spinal cord and acute diencephalic clinical syndrome are particularly prevalent in this OCB+subgroup.The clinical manifestations are complex and diverse,suggesting the need for enhanced clinical identification and timely intervention.

Objective To explore the circRNA expression level in the urine of patients with lupus nephritis(LN),to construct a diagnostic model for LN,and to evaluate and verify its diagnostic efficacy.Methods A total of 120 patients with LN admitted from January 2022 to January 2024 were selected as the observation group and divided into the training group(n=84)and the validation group(n=36)at a ratio of 7:3.Another 100 healthy individuals who underwent physical examination were selected as the control group.The expression levels of circRNA-0001445,circRNA-002059,hsa-circ-0007385 and hsa-circ-0000006 in urine specimens of patients in the training group and the control group were detected by gene sequencing.Multivariate Logistic regression analysis was used to construct a diagnostic model for LN based on the urinary circRNA expression level.The diagnostic value of individual indicators and combined predictive models were evaluated by receiver operating characteristic(ROC)curve analysis,and then the predictive efficacy of the model was verified by the validation group.Results The expression levels of circRNA-0001445,circRNA-002059,hsa-circ-0007385 and hsa-circ-0000006 in the urine of patients in the training group were all higher than those of the control group(P<0.01).Multivariate Logistic regression analysis found that The expression levels of circRNA-0001445(OR=1.094),circRNA-002059(OR=1.040),hsa-circ-0007385(OR=1.033),and hsa-circ-0000006(OR=1.130)in theurine were independent factor for the diagnosis of LN(P<0.01).ROC curve analysis showed that the areas under the curve of combined model constructed based on the circRNA expression level in the urine were 0.985 and 0.911 in the training group and the validation group,respectively,with sensitivities of 95.00%and 91.67%,and specificities of 99.00%and 89.00%,all of which were higher than the diagnostic efficacy of a single urinary circRNA expression level.Conclusion The diagnostic model of LN constructed based on the expression level of circRNA in the urine has a high diagnostic efficacy,which has been confirmed by internal tests and may provide strong support for clinicians in the early diagnosis of LN.

OBJECTIVE To understand the drug resistance genes,virulence genes and molecular epidemiological characteristics of extensively drug-resistant hypervirulent Klebsiella pneumoniae(XDR-hvKP)strains causing hospital-associated infection.METHODS The clinical isolates of XDR-hvKP were collected from Tongling People's Hospital from Jul.2020 to Dec.2022.The strains were identified by matrix-assisted laser desorption ionization-time-of-flight(MALDI-TOF)mass spectrometry,the common drug resistance genes and virulence genes were an-alyzed by Sanger sequencing,the capsular serotypes were determined by wzi gene sequencing;the drug resistance genes,virulence genes and ST subtypes were observed by means of whole-genome sequencing(WGS)technique.RESULTS Totally 18 strains of XDR-hvKP were collected,55.56％(10/18)of which were isolated from blood specimens,and 61.11％(11/18)were isolated from critical care medicine department.Sanger sequen-cing analysis showed that all of the strains carried blaKPC-2 drug resistance gene;rmpA2(100.00％)and rmpA,i-roN,iutA(94.44％,17/18)were the major virulence genes carried by the strains.WGS analysis indicated that all of the 18 XDR-hvKP isolates carried multiple drug resistance genes such as blaKPC-2 carbapenemase and the viru-lence genes like capsule(rmpA/rmpA2),aerobacterin(iucABCD-iutA),Salmonella(iroN)and yersinin(ybt).All of the ST subtypes were ST 11,and all of the capsular serotypes were KL 64.CONCLUSIONS The ST11-KL64 type XDR-hvKP strains carry blaKPC-2;rmpA,rmpA2,iroN and iutA are the major virulence genes.It is necessary to strengthen the monitoring of key population of the key departments and make joint efforts of multiple departments to contain the transmission of the strains.

Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

Objective To investigate the effect of embryonic inflammatory exposure on the response of mouse offspring to interphotoreceptor retinoid-binding protein(IRBP)-induced experimental autoimmune uveitis(EAU).Methods RNA transcriptome sequencing data from eyeballs of C57BL/6J mouse offspring born to mothers with active EAU were used to screen immune-associated differentially expressed genes in the eyes of the exposed offspring.Gene fragments overlapping in the two datasets were screened using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to identify biological pathways associated with the gene fragments.Hub genes were identified from these intersecting genes by protein-protein interaction network analysis.EAU models of maternal uveitis were established by immunization with IRBP651-670,and expression levels of the pivotal genes in the offspring exposed to inflammation by maternal uveitis were examined by fluorescence quantitative polymerase chain reaction.EAU severity,T lymphocyte proliferation,and serum cytokines were detected to investigate the immune effect in offspring from mothers with an active inflammation response to IRBP induction.Results Microarray analysis identified 72 immune-related differentially expressed genes in exposed samples compared with the findings in control samples.These genes were mainly enriched in Toll-like receptor signaling,mitogen-activated protein kinase signaling,and B cell receptor signaling pathways.Protein-protein interaction network interaction analysis screened out four hub genes,Psmc5,Psmc3,Psmd4,and Psmd8,and mRNA levels of these four genes were increased in the adult offspring from mothers with active uveitis compared with the findings in healthy offspring.In addition,the group induced with 150 μg IRBP showed an increase in the severity of clinical and pathological outcomes in offspring with EAU affected by active inflammation,compared with the healthy offspring group(P=0.0087,P=0.0410).Meanwhile,T cell proliferation in the offspring was enhanced during the inflammatory activity stage and secretion of the inflammatory cytokines interleukin(IL)-17 and IL-6 was increased(P=0.0450,P=0.0300).Conclusions Psmc5,Psmc3,Psmd4,and Psmd8 may be important genes exacerbating uveitis in offspring of mothers with active uveitis,associated with increased T cell proliferation and production of IL-17 and IL-6.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase