Objective:To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD).Methods:A child who was admitted to the Linyi People′s Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46, XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c. 323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 ( NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion:The NR5A1: c. 323delA variant probably underlay the pathogenesis of 46, XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.

Objective To investigate the pathogenic bacteria distribution,clinical features and risk factors of urinary tract infection in patients with ischemic stroke. Methods A retrospective study was conducted on 634 patients with ischemic stroke in Beijing Bo'ai Hospital from Janu-ary,2020 to December,2023.They were divided into control group(n=551,without urinary tract infection)and observation group(n=83,with urinary tract infection)according to whether they developed urinary tract infec-tion.The incidence of urinary tract infection,the distribution of pathogenic bacteria and the resistance of main pathogenic bacteria to different antibacterial drugs were analyzed.The clinical characteristics of the two groups were compared and analyzed.The independent risk factors of urinary tract infection in patients with ischemic stroke were analyzed with multivariate Logistic regression. Results A total of 83 cases of 634 patients with ischemic stroke developed urinary tract infection,and incidence was 13.09%.A total of 127 strains of pathogenic bacteria were isolated from the urine samples of the observation group,of which Gram-negative bacteria accounted for 62.99%(80/127),Gram-positive bacteria accounted for 20.47%(26/127)and strains of fungi accounted for 16.54%(21/127).The main Gram-negative pathogens were Escherichia coli and Klebsiella pneumoniae,which were high resistant to second-generation and third-generation cephalosporins,co-trimoxazole,and levofloxacin;moderately resistant to carbapenems,β-lactamase inhibitor compound preparation and aminoglycosides,etc.;and highly sensitive to tigecycline and polymyxin,etc.The main Gram-positive pathogens were Enterococcus faecalis and Enterococcus faecalis,which were a high resistant to erythromycin and gentamicin,and highly sensitive to linezolid,daptomycin,teicoplanin and vancomycin.The pathogenic fungi detected were not obviously resistant to common antifungal drugs.The proportion of female,di-abetes,indwelling catheter and neurogenic bladder were significantly higher in the observation group than in the control group(χ2>5.043,P<0.05).The female,diabetes,indwelling catheter and neurogenic bladder were inde-pendent risk factors for urinary tract infection in patients with ischemic stroke(P<0.05). Conclusion The pathogenic bacteria of patients with ischemic stroke with urinary tract infection are mainly Gram-nega-tive bacteria,followed by Gram-positive bacteria and fungi.The Gram-negative bacteria showed multiple drug re-sistance.Meanwhile,female,diabetes,indentured catheter and neurogenic bladder are the independent risk fac-tors for urinary tract infection.

Objective:To analyze the epidemiological and etiological characteristics of a death case of meningococcal meningitis in Hengyang city, Hunan Province in 2024.Methods:Epidemiological investigation of the death case was performed, and samples from the patient and close contacts were collected. Following cultivation and isolation, Neisseria meningitidis ( Nm) strains were analyzed by antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE), and whole-genome sequencing for analyzing epidemiological and etiological characteristics. Phylogenetic analysis was carried out using core genomic multilocus sequence typing (cgMLST). Results:The case was a 16-year-old high school boarding student with fulminant meningococcal meningitis. He had shock symptoms, and died within 24 h of the onset of symptoms. Six Nm strains were isolated from the patient and his roommates, belonging to two distinct clades. Isolate 144569 from the patient was highly homologous to isolate 144572 from a close contact, both belonging to the highly pathogenic sublineage L44.1 of CC4821. The typical molecular features was C: P1.7-2, 14: F5-101: ST4821 (CC4821). The two strains carried the antimicrobial resistance genes of gyrA-71 and penA-552, indicating reduced susceptibility to quinolone and penicillin, which was with their resistance phenotype. The isolates from four close contacts clustered within the same clade, characterized by the molecular features of B: P1.18-25, 9-18: ST5829 (UA). Conclusions:The death case is caused by Nm serogroup C from highly pathogenic sublineage L44.1 of CC4821. The spread of this isolate has the potential risk of outbreaks of invasive meningococcal disease. It is necessary to enhanced the molecular epidemiological surveillance, particularly focusing on the transmission of multiple serogroups of Nm among adolescents and the increasing exposure risk.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To investigate the effect of psychological support during perithrombotic period on post-stroke depression (PSD) in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Affiliated Lianyungang Hospital of Xuzhou Medical University from January 1, 2021 to July 31, 2021 were enrolled prospectively. The intervention group received one-to-one individual psychological support therapy in the perithrombolytic period on the basis of receiving standard intravenous thrombolytic therapy. At 30 d after onset, Hamilton Depression Scale was used to assess whether PSD occurred. Multivariate logistic regression analysis was used to evaluate the independent influencing factor of PSD. Results:A total of 126 patients with AIS were enrolled, and 86 of them were male (68.25%). Their age was 63.65±10.46 years; 65 were in the intervention group and 61 were in the control group. The incidence of PSD in the intervention group was significantly lower than that in the control group (20.00% vs. 36.07%; χ2=4.049, P=0.044). Multivariate logistic regression analysis showed that psychological intervention (odds ratio [ OR] 0.333, 95% confidence interval [ CI] 0.132-0.838; P=0.020] was an independent protective factor for PSD, while ischemic heart disease ( OR 4.510, 95% CI 1.181-17.217; P=0.028), alcohol consumption ( OR 3.421, 95% CI 1.317-8.888; P=0.012), anticoagulation therapy ( OR 3.145, 95% CI 1.155-8.567; P=0.025) and modified Rankin Scale score before thrombolysis ( OR 1.627, 95% CI 1.142-2.317; P=0.007) were the independent risk factors for PSD. Conclusion:Perithrombolytic psychological support may reduce the incidence of PSD.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To analyze and summarize the characteristics of liver pathology and their relation to clinical markers and further explore noninvasive markers of liver fibrosis in children with chronic hepatitis B.Methods:Data of 80 hospitalized children with chronic hepatitis B who underwent liver biopsy without antiviral treatment from 2011 to 2020 were retrospectively analyzed. Inflammation and liver fibrosis characteristics were analyzed in children of different ages and genders. Variables with good correlation with liver fibrosis stage were selected to establish a non-invasive diagnostic score of liver fibrosis in children. Measurement data was used to compare the t-test or rank sum test. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data. Spearman’s rank correlation test was used for rank correlation analysis. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of the newly established diagnostic score in children with liver fibrosis. Results:The median age of the children was 6.4 years. HBV DNA level was high (P50 = 7.6 log 10 IU/ml), and serum alanine aminotransferase (ALT) in P50 was 171 U/L (< ULN: 5 cases, ULN-2ULN: 10 cases, > 2 ULN: 65 cases). Pathological analysis showed that the incidence of liver tissue inflammation was 97.5%, and the proportion of patients with G≥2 was 42.5%, while S≥2 was 36.3%. The incidence rate of liver fibrosis and liver cirrhosis was 81.3%, and 1.3%, respectively. The changes in liver tissue inflammation and fibrosis were gradually aggravated with the increase of age, and the proportion of high-grade inflammation and liver fibrosis in male children was higher than that in female children. Serum levels of glutamyl transpeptidase (GGT), γ-glutamyltransferase/platelet ratio (GPR) and HBeAg had a good correlation with fibrosis stage ( rs = 0.397, 0.389, and - 0.311) in children with chronic hepatitis B. The combination of GGT, GPR and HBeAg can establish a non-invasive diagnostic score for evaluating liver fibrosis in children. When the score is less than 1.5, it can be diagnosed as S0, and 1.5 ≤ score < 3.5, it can be diagnosed as S1; 3.5 ≤ score < 5.5, the diagnosis of fibrosis is S2; score≥ 5.5, the diagnosis of fibrosis is S≥3. The sensitivity and specificity were 80%, 83%, 86%, and 53%, 55%, 67%, respectively. Conclusion:The incidence of liver tissue inflammation in children with chronic hepatitis B with elevated and fluctuating transaminase levels is high, and the pathological changes of liver tissue aggravate with the age of the children. GGT, GPR and HBeAg have a good correlation with liver fibrosis in children with chronic hepatitis B. Therefore, combining the above-mentioned markers to establish a new noninvasive diagnostic score has certain diagnostic value for liver fibrosis stage S0-S3 in children with chronic hepatitis B.

Objective:To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children.Methods:The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8 + memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8 + memory T lymphocyte subsets was analyzed. Pearson’s Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman’s rank correlation analysis was used for the correlation between continuous variables. Results:Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log 10IU/ml] than the non-response group children [4.54 (4.45~4.64) log 10IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group ( P < 0.05). The proportion of CD8 + Tem, CD38 +CD8 + Tem and CD38 +CD8 + Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group ( P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8 + T lymphocytes between the two groups ( P > 0.05). Spearman’s correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8 + Tem, CD38 +CD8 + Tem, CD38 +CD8 + Temra cells and the level of IFNγ secreted by CD8 +T lymphocytes ( P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38 +CD8 + TEM and CD38 + CD8 + Temra cells ( P < 0.05). Conclusion:Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.

Objective:To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B.Methods:Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study. Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status. Then, in the longitudinal study (60 cases), the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors.Results:In this cross-sectional study, 64.4% of preC/C and 68.2% of S mutations had occurred in the epitope region. There were ten mutation sites (PreC/C50, 55, 79, 84, 103, 126, 145, 184 and s110, s213) correlated with HBeAg negative status ( P < 0.05). After adjusting for confounding factors such as age, gender, HBV genotype, serum alanine aminotransferase level and precw28 * mutations in the longitudinal studies, the results showed that TC cell epitope (prec47-56, prec117-125, s208-216) and Th cell epitope (prec176-185) were the main independent risk factors affecting the host HBeAg serological status. Conclusion:HBV preC/C region (PreC47-56, PreC117-125 and PreC176-185) and S region (s208-216) epitope mutations are the main independent factors affecting the host HBeAg status, suggesting that these epitope mutations may be involved in the HBeAg seroconversion.

Objective: To analyze non-alcoholic steatohepatitis (NASH)-related differentially expressed genes (DEGs) by bioinformatics methods to find key pathways and potential therapeutic targets for NASH. Methods: GSE61260 chip was downloaded from the public microarray database and liver biopsy samples from 24 NASH cases and 38 healthy controls were included. The Limma software package in R language was used to screen DEGs under the condition of difference multiple > 1.5 and adj. P < 0.05. The clusterProfiler software package was used for GO analysis and KEGG analysis. The STRING online database was used for protein-protein interaction analysis, and the L1000 and DrugBank databases were used for drug prediction. Results: Compared with healthy control group, 857 DEGs were screened out in NASH group including 167 up-regulated genes and 690 down-regulated genes. GO analysis showed that DEGs were mainly involved in inflammation and cholesterol metabolism. KEGG analysis showed that DEGs were mainly enriched in PPAR, non-alcoholic fatty liver disease, oxidative phosphorylation and other signaling pathways. Among them, eight genes of ACSL4, CYP7A1, FABP4, FABP5, lipoprotein lipase, ME1, OLR1 and PLIN1 were enriched in PPAR signaling pathway, and 165 interaction nodes were formed with 47 DEGs-encoded proteins. Lipoprotein lipase interacted with 21 DEGs, and its up-regulated expression had improved lipid metabolism, insulin resistance and anti-inflammatory effects. Four drugs (gemfibrozil, bezafibrate, omega-3 carboxylic acid and glycyrrhizic acid) were screened by L1000 and DrugBank to activate lipoprotein lipase. Presently, these four drugs are clinically used to treat hypertriglyceridemia or to improve inflammation. In this regard, we speculated that the pharmacological effects of these four drugs had improved NASH by activating lipoprotein lipase to promote liver lipid metabolism and alleviate inflammation. Conclusion PPAR signaling pathway is closely associated to the occurrence and development of NASH, and thereby lipoprotein lipase agonist is a new attempt to treat NASH.