Objective To investigate the role of mitochondrial antiviral signaling protein(MAVS)in viral infection-triggered generalized pustular psoriasis(GPP)in children.Methods This retrospective case-control study enrolled 80 GPP patients aged 0～18 years from Children's Hospital of Chongqing Medical University(from October 2013 to April 2019).Whole-exome sequencing identified rare MAVS variants associated with GPP.Pathogenicity of variants was predicted using Mutation Taster,Disease Association,SIFT,and CADD bioinformatics tools.Sanger sequencing validated variants,followed by construction of wild-type(WT)and mutant MAVS expression plasmids transfected into HEK 293 cells.Protein expression was assessed by Western blot.Dual-luciferase reporter gene assays measured IFNB1 and NF-κB transcriptional activity.Genotype distribution of the MAVS c.171dupT/p.H57fs variant was analyzed using Fisher's exact test.Results This study enrolled 80 pediatric GPP patients(aged 0～18 years).Whole-exome sequencing identified five rare MAVS variants,with bioinformatics analyses predicting deleterious effects on protein stability and function.Western blot demonstrated that the c.171dupT mutation in GPP patients significantly reduced full-length MAVS expression(P<0.001);dual-luciferase assays further revealed this variant impaired MAVS-mediated IFNB1 transcriptional activation by 85%(P<0.001),abrogated NF-κB signaling pathway activation(P<0.001),but exhibited no dominant-negative effect on wild-type MAVS function(P>0.05).Conclusion The MAVS c.171dupT frameshift variant may contribute to infection-triggered GPP in children,suggesting its potential as a genetic biomarker for GPP susceptibility.

CD8+T cell-based immune-therapeutics,including immune checkpoint inhibitors and adoptive cell therapies(tumor-infiltrating lymphocytes(TILs),T cell receptor-engineered T cells(TCR-T),chimeric antigen receptor T cells(CAR-T)),have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases.However,immunotherapy resistance and tumor insusceptibility frequently occur,leading to treatment failure.Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites,immune-inhibitory cytokines,and alteration of gene expression,which suppress the activity of immune cells,particularly CD8+T cells to evade immune surveillance.Therefore,targeting tumor cell metabolic adaptations to reshape the immune microenvi-ronment holds promise as an immunomodulatory strategy to facilitate immunotherapy.Here,we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming,focusing on the regulatory mechanisms underlying tumor cell glucose metabolism,amino acid meta-bolism,and lipid metabolism in influencing CD8+T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

Objective To explore the risk of preeclampsia(PE)and construct an individualized column chart predictive model.Methods A total of 209 PE patients admitted to Huzhou Maternal and Child Health Hospital from January 2020 to July 2023 were selected as research group,and 162 healthy pregnant women who underwent prenatal examination during the same period were selected as control group.Logistic regression model was used for data analysis,and nomogram prediction model based on Logistic regression results was constructed by R statistical software,receiver operating characteristic(ROC)curve and calibration curve were drawn,and Hosmer-Lemeshow goodness-of-fit test was conducted to evaluate prediction efficiency.Results The occurrence of PE had no correlation with body mass index(BMI),gestational age,pregnancy times,abortion history and whether there are multiple pregnancies(P＞0.05),but age,education level,gestational diabetes,gestational hypertension and standardized prenatal examination of pregnant women are related factors(P＜0.05).Age≥30 years old,education below senior high school,gestational diabetes,pregnancy-induced hypertension and irregular prenatal examination were risk factors for PE(P＜0.05).The area under ROC curve of nomograph model was 0.813(95％CI:0.770-0.855).Conclusion The nomogram model based on age,education level,diabetes in pregnancy,hypertension in pregnancy and irregular prenatal examination screened by Logistic regression model has a good predictive effect on the occurrence of PE.

Objective To explore the risk of preeclampsia(PE)and construct an individualized column chart predictive model.Methods A total of 209 PE patients admitted to Huzhou Maternal and Child Health Hospital from January 2020 to July 2023 were selected as research group,and 162 healthy pregnant women who underwent prenatal examination during the same period were selected as control group.Logistic regression model was used for data analysis,and nomogram prediction model based on Logistic regression results was constructed by R statistical software,receiver operating characteristic(ROC)curve and calibration curve were drawn,and Hosmer-Lemeshow goodness-of-fit test was conducted to evaluate prediction efficiency.Results The occurrence of PE had no correlation with body mass index(BMI),gestational age,pregnancy times,abortion history and whether there are multiple pregnancies(P＞0.05),but age,education level,gestational diabetes,gestational hypertension and standardized prenatal examination of pregnant women are related factors(P＜0.05).Age≥30 years old,education below senior high school,gestational diabetes,pregnancy-induced hypertension and irregular prenatal examination were risk factors for PE(P＜0.05).The area under ROC curve of nomograph model was 0.813(95％CI:0.770-0.855).Conclusion The nomogram model based on age,education level,diabetes in pregnancy,hypertension in pregnancy and irregular prenatal examination screened by Logistic regression model has a good predictive effect on the occurrence of PE.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

Objective:To explore the influencing factors of fetal growth restriction (FGR) in patients with preeclampsia (PE) and construct a Nomogram prediction model.Methods:From Aug. 2021 to May. 2023, 273 PE patients admitted to our hospital were regarded as the study subjects, and grouped into a modeling group (n=191) and a validation group (n=82). Multivariate logistic regression analysis was applied to determine the influencing factors of FGR in PE patients. R4.3.1 was applied to construct a Nomogram model for predicting FGR in PE patients. Receiver operating characteristic (ROC) curve and the Hosmer Lemeshoe (H-L) goodness of fit test were applied to evaluate the discrimination and consistency of the Nomogram model in predicting FGR in PE patients.Results:There was no statistically obvious difference in gestational age, blood pressure, hemoglobin, urinary protein (UP), uric acid, umbilical artery systolic/diastolic blood pressure (S/D), D-dimer (D-D), or birth frequency between the modeling group and the validation group ( P>0.05). Compared with no concurrent FGR group, the onset of pregnancy in the concurrent FGR group was earlier, the levels of UP, S/D, and D-D, and the proportion of oligohydramnios were obviously higher, and the platelet count (PLT) was obviously lower ( t/χ 2=2.588, 1.437, 6.262, 5.464, 9.881, 3.326, P<0.05). Multivariate Logistic regression analysis showed that UP, S/D, D-D, and oligohydramnios were risk factors for FGR in PE patients ( OR=1.004, 3.807, 1.006, 4.348, P<0.05), while PLT was a protective factor ( OR=0.980, P<0.05). Nomogram model showed that when the total score of the above 5 influencing factors in PE patients was 149, the probability of concurrent FGR was 60%; when the total score was 167, the probability of concurrent FGR was 90%, and the probability of exceeding 167 was over 90%. Modeling group H-L test χ 2=6.736, P=0.565, validation group χ 2=5.812, P=0.668. The area under the ROC curve (AUC) of the modeling group and the validation group was 0.924 (95% CI: 0.883-0.965) and 0.932 (95% CI: 0.880-0.984), respectively. The sensitivity was 83.93% and 90.48%, and the specificity was 89.63% and 81.97%, respectively. Decision curve analysis (DCA) was applied to evaluate the clinical application value of the Nomogram model in predicting FGR in PE patients. Conclusion:The Nomogram model constructed based on the five indicators of UP, S/D, D-D, PLT, and oligohydramnios for predicting the risk of FGR in PE patients has high discrimination and consistency.

Background: Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Methods: Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Results: Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Conclusions Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.