BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

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.

Objective To investigate the detection conditions,risk factors and preventive measures of colorectal polyps in health examination population undergoing painless colonoscopy.Methods A total of 2 680 people who underwent painless colonoscopy at the Health Management Center of the First Affiliated Hospital of Naval Medical University from January to December 2023 were enrolled in this retrospective study.They were assigned into polyp group and non-polyp group according the examination results.The general information of the two groups was collected to explore the risk factors of colorectal polyps,so as to provide reference for the prevention strategy of colorectal polyps.Results The colorectal polyps were detected in 1 223 people(45.63%),including 633 cases(51.76%)of adenomatous polyps,587 cases(48.00%)of non-adenomatous polyps,and 3 cases(0.25%)of colorectal cancer.Logistic regression analysis indicated that male,smoking history,alcohol drinking history,age 40-59 years old,hyperlipidemia,and CRP>10 mg/L were risk factors of colorectal polyps(P<0.05).Conclusion There is a high detection rate of colorectal polyps in physical examination population.Men,aged 40-59 years old,hyperlipidemia,smoking history,alcohol drinking history,and CRP>10 mg/L are high risk factors of colorectal polyps,which should be paid more attention for the prevention and monitoring of colorectal polyps.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective The objective of this study is to investigate whether there is a correlation between a high TyG index(serum triglyceride glucose index)and higher mortality rates among patients undergoing peritoneal dialysis(PD).Methods This study utilized a single-center retrospective cohort as the basis for its methods..From January 1,2007 to December 31,2015,a total of 519 PD patients kept under observation until December 31,2018.There searchers employed the Kaplan-Meier method and Cox proportional hazards modelsto examine the cor-relation between TyG index levels and mortality.Results Over a period of 40.5 months,104(20.0%)individuals with Parkinson's disease passed away,with 55(52.9%)of these deaths attributed to cardiovascular disease(CVD).The serum median TyG index at baseline was 8.44(6.48,11.94).Through Cox regression analysis subject to the adjustments of such parameters as gender,age,body mass index(BMI),presence of cardiovascular disease,hypertension,diabetes mellitus,hemoglobin,serum albumin,serum Ferritin,total cholesterol,renal residual function(RRF),An increased risk of all-cause mortality(HR = 2.22,95%CI:1.43～3.44,P＜0.001)and CVD mortality(HR = 2.50,95%CI:1.34～4.65,P = 0.004)was observed with a higher baseline TyG index(8.44).A comparable impact was observed in the correlation between the average TyG index over time(TA-TyG index)and both all-cause mortality and CVD mortality.(HR = 1.90,95%CI:1.25～2.90,P = 0.003;HR = 2.05,95%CI:1.14～3.70,P = 0.017,respectively).Conclusion PD patients with a higher serum TyG index have a greater risk of all-cause mortality and mortality related to cardiovascular disease.

Systemic lupus erythematosus（SLE）is an autoimmune disease characterized by an unclear etiology，the presence of multiple autoantibodies，and dysfunction in various systems and organs.The disease tends to recur and primarily affects women of childbearing age，potentially leading to adverse pregnancy outcomes（APO）.The main impacts of SLE on the health of offspring from pregnant mothers include fetal growth restriction，premature birth，small size for gestational age，neonatal lupus，as well as long-term health issues，such as neurocognitive disorders，mental or motor development disorders，allergic diseases，and cardiovascular diseases.By establishing a precise prediction model for APO in SLE combined pregnancies and implementing early interventions accordingly，it is possible to minimize APO occurrences and improve both short-term and long-term effects on offspring health.This article provides a comprehensive review about the effects of SLE on the health of offspring from pregnant mothers along with related prediction models.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective:To explore the effects of curcumin on the biological characteristics and expressions of NF-κB pathway-related proteins in glucocorticoid-resistant acute lymphoblastic leukemia (ALL) cell line Jurkat.Methods:The drug-resistant ALL cell line Jurkat was selected, and 1 μmol/L dexamethasone was used as the optimal concentration for drug resistance of Jurkat cells, and the cells were passaged and cultured. The cells were divided into 10, 25 and 50 μmol/L curcumin groups, as well as 50 μmol/L pyrrolidinedithiocarbamate (PDTC) group, and control group (equal volume of culture medium without drug was added). The cells in each group were cultured for 72 h, and the cell morphology was observed under an inverted microscope. The CCK-8 method was used to detect the proliferation ability of Jurkat cells, flow cytometry was used to detect the apoptosis ability and cell cycle of Jurkat cells, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expressions of NF-κB p65, NF-κB p50, IκBα, and A20 mRNA, and Western blotting was used to detect the expressions of NF-κB p65, NF-κB p50, IκBα, caspase-8, caspase-3, bcl-2, and A20 proteins.Results:Jurkat cells were treated with 10, 25, 50 μmol/L curcumin and 50 μmol/L PDTC for 72 h. In the control group, the cell membranes were basically intact, the size was uniform, the cell was round and transparent, and the cell nucleus had uniform fluorescence; a large number of deformed cells and cell fragments were observed in curcumin groups with different concentrations and 50 μmol/L PDTC group, with concentrated and fragmented nuclei and obvious apoptosis. After treating Jurkat cells with different concentrations of curcumin and 50 μmol/L PDTC for 24, 48 and 72 h, respectively, the cell proliferation inhibition rates in curcumin groups with different concentrations and PDTC group were higher than those in the control group (all P < 0.01). The apoptosis rates at 72 h in the control group, 10 μmol/L curcumin group, 25 μmol/L curcumin group, 50 μmol/L curcumin group, and 50 μmol/L PDTC group were (4.9±0.1)%, (99.2±0.1)%, (99.9±0)%, (100.0±0)%, and (100.0±0)%, respectively, and the difference was statistically significant ( F = 2 876 604.40, P < 0.001); compared with the control group, the apoptosis rates in curcumin groups with different concentrations and 50 μmol/L PDTC group were higher, and the differences were statistically significant (all P < 0.01). Compared with the control group, the proportions of S-phase and G 2-phase cells were lower and the proportion of G 1-phase cells was higher in curcumin groups with different concentrations and 50 μmol/L PDTC group at 72 h, and the differences were statistically significant (all P < 0.01). Compared with the control group, the protein and mRNA expressions of NF-κB p65 and NF-κB p50 in curcumin groups with different concentrations and 50 μmol/L PDTC group were lower (all P < 0.01), while the protein expressions of IκBα, caspase-8 and caspase-3 were higher (all P < 0.01), the protein expression of bcl-2 was lower ( P < 0.01), and the protein and mRNA expressions of A20 were higher (both P < 0.01). Conclusions:Curcumin can effectively reverse glucocorticoid resistance and promote apoptosis in Jurkat cells, which may be related to the influence of curcumin on NF-κB pathway-related proteins.

Objective To observe the adverse reactions of different anesthesia methods used in bronchoscopic diagnosis and treatment,and provide ideas for clinical selection of the best anesthesia methods.Methods 150 patients from June 2022 to June 2023 for bronchoscope were randomly divided into group W(atomization with lidocaine combined with intravenous sedation),group Q(laryngeal mask general anesthesia)and group H(lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia),with 50 cases in each group.Heart rate(HR),mean arterial pressure(MAP)and percutaneous arterial oxygen saturation(SpO2)values were recorded at different time points,adverse reactions during recovery,recovery time and dosage of anesthetic drugs were recorded.Results At T1 and T2,SpO2 in group W(89.4±0.7)%and(91.8±0.3)%were lower than that(99.6±0.8)%in T0,and lower than those(98.6±1.3)%and(98.5±1.6)%in group Q and(99.7±0.3)%and(98.4±1.6)%in group H,the difference were statistically significant(P<0.05).At T1 and T2,the MAP of group W were(108.5±7.8)and(105.6±7.3)mmHg,which were significantly higher than those of T0(87.5±8.6)mmHg,and higher than those of group Q(92.6±8.5)and(85.8±11.3)mmHg,respectively,higher than those(85.7±9.2)and(85.2±10.8)mmHg in group H,the differences were statistically significant(P<0.05).The MAP of group Q at T1 and T3 was(92.6±8.5)and(91.4±8.6)mmHg,respectively,higher than that of T0(87.8±7.5)mmHg,and higher than those of group H(85.7±9.2)and(86.5±7.2)mmHg,with statistical significance(P<0.05).At T1 and T2,the HR of group W was(92.7±9.6)and(91.3±9.2)times/min,higher than that of T0(72.3±8.4)times/min,and higher than those of group Q(75.3±11.6)and(78.5±12.8)times/min,respectively,and higher than those of group H(76.6±10.7)and(77.2±8.5)times/min,and the differences were statistically significant(P<0.05).The hypoxemia,arrhythmia and cough rates in group Q were higher than those in group W and group H,and the differences were statistically significant(P<0.05).The recovery time of group H was(11.5±7.2)min,which was significantly lower than that of group W(16.8±8.5)min and group Q(17.6±6.4)min,and the differences were statistically significant(P<0.05).The dosage of propofol in group H was(314.3±12.7)mg and remifentanil was(211.6±12.5)μg,both lower than those in group W(390.5±12.4)mg and(268.4±13.6)μg,and lower than those in group Q(387.6±15.2)mg and(372.5±15.3)μg.The differences were statistically significant(P<0.05).The dosage of micuronium chloride was(23.7±3.8)mg in group H,lower than(32.5±4.3)mg in group Q,and the difference was statistically significant(P<0.05).Conclusion Lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia is the best anesthesia method for bronchoscopic diagnosis and treatment,which is beneficial to respiratory management and less adverse reactions in perioperative period.

Objective:To systematically review the correlation between frailty and postoperative adverse outcomes in ovarian cancer patients.Methods:The research on frailty and postoperative adverse outcomes in ovarian cancer patients was systematically searched in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine. The search period was from database establishment to March 27, 2023. Two researchers independently conducted literature screening, quality evaluation, and data extraction, and conducted Meta-analysis using Stata 15.0 software.Results:A total of 17 studies were included. Meta-analysis showed that frailty increased the risk of total postoperative complications [ OR=1.84, 95% CI (1.53, 2.21), P<0.001], severe postoperative complications [ OR=2.34, 95% CI (1.80, 3.03), P<0.001], postoperative 30 day mortality [ OR=1.96, 95% CI (1.68, 2.28), P<0.001], and decreased overall survival [ OR=1.45, 95% CI (1.24, 1.69), P<0.001] in ovarian cancer patients, and it also increased the risk of Intensive Care Unit (ICU) transfer rate [ OR=2.11, 95% CI (1.97, 2.26), P<0.001], non-home discharge [ OR=1.57, 95% CI (1.48, 1.67), P<0.001], and readmission 30 days after surgery [ OR=1.12, 95% CI (1.03, 1.21), P=0.009]. Subgroup analysis showed that age, frailty assessment tools, and whether or not covariates were corrected had no effect on outcomes. Sensitivity analysis showed that all results were reliable. Conclusions:Frailty is a risk factor for postoperative complications, postoperative 30 day mortality, poor overall survival, ICU transfer rate, non-home discharge, and readmission 30 days after surgery in ovarian cancer patients. However, the research findings still need to be further validated through large-scale prospective cohort studies.