Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE-/-mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/-mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

Objective To assess effect of ultrasound-guided erector spinae plane block(ESPB)combined with patient controlled intravenous analgesia(PCIA)on postoperative analgesia after cesarean section.Methods A total of 120 full-term singleton pregnant women who underwent cesarean section under spinal anesthesia at Jiaxing Maternal and Child Health Care Hospital from May 2022 to August 2023 were selected.Participants were randomly divided into three groups using a random number table:Group E(ESPB combined with PCIA),group T[transversus abdominis plane(TAP)block combined with PCIA],and control group(PCIA alone),with 40 women in each group.Visual analogue scale(VAS)and Bruggrmann comfort scale(BCS)scores during rest and coughing were recorded at 4h,8h,12h,24h,and 48h postoperatively.Number of effective PCIA presses,total sufentanil dosage,proportion of rescue analgesia and maternal satisfaction were also documented within 48h.Additionally,adverse reactions and neonatal outcomes were observed within the same 48h period.Results Postoperatively,VAS scores for rest and coughing in group E at 8h,12h,24h were significantly lower than those in group T,those in two groups were lower than those in control group(P＜0.05).Postoperatively at 8h,12h,and 24h,BCS scores in group E were significantly higher than those in group T,with both higher than those in control group(P＜0.05).Within 48h after surgery,the number of effective PCIA presses,proportion of rescue analgesia and total sufentanil dosage in group E were lower than those in group T,both lower than those in control(P＜0.05).Moreover,maternal satisfaction score in group E was significantly higher than that in group T,that in two groups was significantly higher than that in control group(P＜0.05).Within 48h after surgery,there were no significant differences in adverse reactions or neonatal outcomes among the three groups(P＞0.05).Conclusion Ultrasound-guided ESPB combined with PCIA outperforms TAP block combined with PCIA,with reducing analgesic dose and enhancing maternal satisfaction and comfort.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

BACKGROUND: It is controversial whether prophylactic endotracheal intubation (PEI) protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding (UGIB). The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy. METHODS: Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database (eICU-CRD). The composite cardiopulmonary outcomes included aspiration, pneumonia, pulmonary edema, shock or hypotension, cardiac arrest, myocardial infarction, and arrhythmia. The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups. Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes. Moreover, restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes (yes/no) in the PEI group. RESULTS: A total of 946 patients were divided into the PEI group (108/946, 11.4%) and the non-PEI group (838/946, 88.6%). After propensity score matching, the PEI group (n=50) had a higher incidence of cardiopulmonary outcomes (58.0% vs. 30.3%, P=0.001). PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders (odds ratio [OR] 3.176, 95% confidence interval [95% CI] 1.567-6.438, P=0.001). The subgroup analysis indicated the similar results. A shock index >0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI (P=0.015). The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index (OR 1.465, 95% CI 1.079-1.989, P=0.014) and shock index >0.77 (compared with shock index ≤0.77 [OR 2.981, 95% CI 1.186-7.492, P=0.020, AUC=0.764]). CONCLUSION: PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy. Furthermore, a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

AIM: To observe the effect of paricalcitol on intestinal ischemia-reperfusion injury, and to explore the relationship with HMGB1/TLR4/NF-κB signaling pathway. METHODS: Twenty-four SPF-grade healthy adult male C57BL/6J mice were divided into 4 groups (n=6) by random number table: sham operation group (S group), paricalcitol pretreatment+sham operation group (SP group), intestinal ischemia-reperfusion group (IR group) and paricalcitol ischemic preconditioning group (P group). S group and SP group were separated the superior mesenteric artery, IR group and P group were clamped the superior mesenteric artery for 45 minutes and then followed by reperfusion for 2 hours to establish the intestinal ischemia-reperfusion model; SP group and P group were intraperitoneally injected with 0.3 μg/kg paricalcitol 24 hours before surgery, and the other two groups were given equal volume of normal saline. The mice were sacrificed at 2 h after reperfusion, and the intestinal tissue was obtained 5 cm from the terminal ileum. The pathological results were observed under light microscope. The intestinal mucosal injury was scored according to the Chiu's scoring standard. The intestinal tissue diamine oxidase (DAO) and tumor were detected by ELISA. Necrosis factor α (TNF-α) and interleukin 6 (IL-6) content; Western blot was used to detect the expression levels of HMGB1, TLR4 and NF-κB p65 protein in small intestine tissues.RESULTS: Compared with S group and SP group, Chiu's score was increased, the expression of Dao, TNF-α and IL-6 were increased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein increased significantly in IR group (P< 0.05); Compared with IR group, Chiu's score was decreased, the expression of Dao, TNF-α and IL-6 were decreased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein decreased significantly in P group (P< 0.05). CONCLUSION: Paricalcitol can alleviate intestinal ischemia-reperfusion injury by inhibiting HMGB1/TLR4/NF-κB signaling pathway and playing an anti-inflammatory role.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

Hospital culture plays an important role in the orderly operation of large shelter hospitals as well as epidemic prevention and control.From April to May 2022, the shelter hospital of the National Convention and Exhibition Center(Shanghai) had created the large shelter hospital culture co-built by doctors and patients with a greater sense of belonging by taking measures such as joint party building between doctors and patients, giving play to the vanguard force of party members, carrying out various forms of cultural, sports and science popularization activities, encouraging enthusiastic patients to participate in activity planning, focusing on key groups, formulating shelter " residents convention", and so on. These measures ultimately formed cultural adaptation, cultural synchronization and cultural shaping, which were conducive to enhancing the empathy of doctors and patients, improving the effectiveness of medical implementation, and promoting the standardization of shelter management system. This harmonious, warm and autonomous culture co-built by doctors and patients effectively ensures the safe and orderly operation of the shelter hospital, and provides reference for the construction of the cultural system of large shelter hospitals in China.