The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective To explore the pharmacokinetics/pharmacodynamics(PK/PD)parameters and influencing factors in patients with augmented renal clearance(ARC)to provide the basis for the rational use of meropenem.Methods Using the method of retrospective study,the patients with increased renal clearance who used meropenem monitored the concentration from January 2018 to December 2021.The PK/PD parameters of meropenem were analyzed,and multiple linear retrospective analyses discussed the influencing factors of meropenem valley concentration.Results A total of 58 patients were included in the study,and the trough concentration was 1.35[0.23,1.86]μg·mL-1,taking 100%fT＞MIC as PK/PD target value,the compliance rate was 20.69%.The compliance rate of daily dose＜3 g·d-1 was 8.70%,and≥3 g·d-1 was 31.43%,the difference was statistically significant.With MIC of 0.5,1,2,4,and 8 μg·mL-1,PK/PD compliance rates were 62.07%,48.28%,20.69%,8.62%and 0.Respectively.Multiple linear retrospective analyses showed that dose was an independent factor affecting meropenem valley concentration.Conclusion The PK/PD compliance rate of meropenem in patients with augmented renal clearance is low,even if MIC≤0.5 μg·mL-1,the routine dose is difficult to achieve the ideal PK/PD,so the clinical should recognize ARC and perform TDM as soon as possible,and use TDM to guide the medication regimen of meropenem for ARC patients.

Objective:To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries.Methods:General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared.Results:(1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group ( OR=1.76, 95% CI: 1.50-2.08; P<0.001), GDM 0+1 group ( OR=2.29, 95% CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group ( OR=1.98, 95% CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant ( P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions:In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Objective:To investigate whether intestinal rehabilitation therapy (IRT)could optimize the effectiveness of IRT in patients with short bowel syndrome (SBS) caused by acute mesenteric ischemia (AMI) with chronic multivessel lesions.Methods:Clinical data of 18 hospitalized patients diagnosed with AMI leading to SBS and undergoing IRT at the Eastern Theater General Hospital of the People's Liberation Army from Jan 2012 to Oct 2023 was retrospectively analyzed.Result:Following IRT, the revascularization group showed significantly greater increases in ASMI and grip strength compared to the control group [(0.28±0.26) kg/m 2vs. (0.02±0.21) kg/m 2, P=0.033, and (0.97±0.33) kg vs. (0.48±0.34) kg, P=0.007, respectively]. Similarly, the increase in EN intake was significantly higher in the revascularization group compared to the control group [(572.5±93.6) ml/d vs. (375.2±176.3) ml/d, P=0.012], accompanied by a greater improvement in intestinal nitrogen absorption rate [(25.06±14.06)% vs. (13.84±4.62)%, P=0.034] and a more substantial decrease in GSRS scores [(-15.88±3.94) vs. (-6.33±5.13), P=0.030]. Moreover, there were significant differences in the composition of EN formulations between the two groups after IRT ( P=0.046). Additionally, SF-36 scores at discharge were significantly higher in the revascularization group than that in the control group for five indicators including BP, GH, VT, SF, and MH ( P<0.05). Conclusions:For patients with SBS resulting from AMI by chronic multivessel lesions, revascularization therapy may not leading to higher growth in weight and hematological nutritional indicators during IRT, but it is beneficial for improving muscle function, improving EN absorption, increasing the likelihood of PN independence, relieving gastrointestinal symptoms, and enhancing overall quality of life.

Objective: To investigate the longitudinal association of plasma Irisin concentrations with changes in blood pressure (BP) levels among children,and to assess the moderating effect of physical activity (PA) or sedentary behavior (SB) on the relationship between Irisin levels and BP. Methods: Based on a cohort study, a cluster sampling method was used to select 3 651 school aged children from five schools in Guangzhou in 2017 at the baseline survey and follow up in 2019. Both at baseline and during follow up, PA and SB were assessed by validated questionnaires, and BP levels were measured by an electronic sphygmomanometer. A final sample of 521 children were enrolled based on the PA and SB at baseline. Plasma Irisin concentrations were measured by ELISA at baseline. Logistic regression analysis was recruited for exploring the associations of plasma Irisin concentrations with changes in BP. Moderating effects of PA and SB on the relationship between Irisin concentrations and BP were estimated using stratified analysis. Results: Logistic regression analysis indicated that there was no significant association between Irisin concentrations and changes in BP levels among children ( OR =0.98, P >0.05). After stratification for SB, Irisin levels in the low SB subgroup were inversely associated with changes in diastolic blood pressure ( OR=0.87, 95%CI=0.77-0.98, P =0.02). In addition, SB level had a moderating effect on the relationship between Irisin levels and the DBP changes ( P =0.01). Conclusion Increased Irisin concentration is associated with the decrease of DBP level among low SB children. Furthermore, SB level shows moderating role in the relationship between Irisin concentrations and changes in DBP levels.

Objective To construct and validate a predictive model for the risk of deep vein thrombosis(DVT)after lower extremity orthopedic surgery.Methods Clinical records of hospital-ized patients who underwent lower extremity orthopedic surgery in Wuxi Traditional Chinese Medicine Hospital from January 2017 to October 2019 were collected.The univariate and multivariate analysis with the backward stepwise method were applied to screen variables and build a nomogram prediction model,and the performance of the nomogram was evaluated with respect to its discriminant capabili-ty,calibration ability,and clinical utility.Results A total of 5 773 hospitalized patients with ortho-pedic surgery of lower extremity were included in the study,with the incidence of DVT of 0.9％.Through single factor and multi-factor stepwise regression analysis,5 variables were selected from 31 variables to construct the prediction model,including age,mean corpuscular hemoglobin concentra-tion(MCHC),D-dimer,platelet distribution width(PDW),and thrombin time(TT).The receiver operating characteristic(ROC)curve showed that areas under the ROC curve in the training and vali-dation cohort were 0.859 and 0.857,respectively.The model had good calibration ability and clini-cal practicability.Conclusion The DVT risk prediction model constructed in this study has good dif-ferentiation ability,calibration ability and clinical practicability,which is helpful for doctors to classi-fy DVT patients after lower extremity orthopedic surgery and formulate early treatment plan.

Objective To construct and validate a predictive model for the risk of deep vein thrombosis(DVT)after lower extremity orthopedic surgery.Methods Clinical records of hospital-ized patients who underwent lower extremity orthopedic surgery in Wuxi Traditional Chinese Medicine Hospital from January 2017 to October 2019 were collected.The univariate and multivariate analysis with the backward stepwise method were applied to screen variables and build a nomogram prediction model,and the performance of the nomogram was evaluated with respect to its discriminant capabili-ty,calibration ability,and clinical utility.Results A total of 5 773 hospitalized patients with ortho-pedic surgery of lower extremity were included in the study,with the incidence of DVT of 0.9％.Through single factor and multi-factor stepwise regression analysis,5 variables were selected from 31 variables to construct the prediction model,including age,mean corpuscular hemoglobin concentra-tion(MCHC),D-dimer,platelet distribution width(PDW),and thrombin time(TT).The receiver operating characteristic(ROC)curve showed that areas under the ROC curve in the training and vali-dation cohort were 0.859 and 0.857,respectively.The model had good calibration ability and clini-cal practicability.Conclusion The DVT risk prediction model constructed in this study has good dif-ferentiation ability,calibration ability and clinical practicability,which is helpful for doctors to classi-fy DVT patients after lower extremity orthopedic surgery and formulate early treatment plan.

Objective:To explore the experience of teachers from Guangdong and Macao in nursing teaching cooperation, the existing problems in current teaching cooperation and suggestions for improvement.Methods:From January to April 2021, using descriptive qualitative method to conduct in-depth among eight clinical tutors from The Third Affiliated Hospital of Guangzhou Medical University who teach Macao nursing students, and four teachers from Kiang Wu Nursing College of Macao using the purposive sampling method. And adopted content analysis for data analysis.Results:A total of 4 themes and 2 sub-themes were analyzed: the positive impact of cross-border teaching cooperation projects including developed the nursing business of the two places and deepened the cooperative relationship between the two places; limiting the depth and breadth of knowledge transfer because of the short cross-border learning time; the imbalance between students′ abilities and teachers′ expectations; expectations for homogeneous internships for heterogeneous groups.Conclusions:Cross-border nursing teaching cooperation is an important promoter for the development of nursing education between Guangdong and Macao, but there are still deficiencies in cooperation, and it is necessary for the two places to strengthen the construction of a sharing platform for teaching resources to promote the development of nursing education in the Guangdong-Hong Kong-Macao Greater Bay Area.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People