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.

OBJECTIVES: To conduct a comprehensive analysis of the global burden of diarrheal diseases in children under 5 years. METHODS: The data from the Global Burden of Disease (GBD) 2021 were analyzed to assess the incidence, mortality rates and average annual percentage changes (AAPC) of diarrhea among children under 5 years across nations(regions) and GBD regions from 1990 to 2021 using joinpoint regression. Smoothed curve regression was employed to explore the correlation of diarrheal disease burden with the Social Development Index (SDI) and for analyzing the burden of specific diarrheal pathogens. The Slope and Concentration Indices quantified disparities across SDI levels and the future trend were projected by the Bayesian Age-Period-Cohort (BAPC) model. RESULTS: From 1990 to 2021, the global incidence (AAPC: -3.65) and mortality (AAPC: -5.15) rates of diarrheal diseases declined steadily in children below 5 years. In 2021, neonates (<28 days) were the most affected, with an incidence rate of 138 058.74 per 100 000 and a mortality rate of 251.14 per 100 000. Rotavirus was the leading cause of death. The incidence rate of diarrheal diseases was negatively correlated with SDI, and the Concentration Index decreased from -0.293 in 1990 to -0.314 in 2021 without a significant gender difference. The BAPC model suggested that the global incidence rate of diarrheal diseases tends to decrease progressively from 2022 to 2050, with a predicted rate of 23 448.04 per 100 000 for male and 29 932.59 per 100 000 for female by 2050. CONCLUSIONS Despite the reduction in the global burden of diarrhea and the projection of its further decline, diarrheal diseases disproportionately affect neonates and low-SDI regions. While rotavirus remains the primary etiological agent worldwide, the predominant pathogens vary by nations (regions) and GBD regions, and strengthened interventions targeting vulnerable populations are needed.
Humans ; Child, Preschool ; Diarrhea/mortality* ; Infant ; Incidence ; Infant, Newborn ; Global Burden of Disease/trends* ; Global Health ; Male ; Bayes Theorem ; Female

Objective:To analyze factors associated with timely vaccination of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023.Methods:Children born in Shanghai between 2019 and 2023 were selected using a stratified random sampling method, and their vaccination data were obtained from the Shanghai Vaccine Management and Vaccination Service Information System. The vaccination rates, timely vaccination rates, and the proportions of diphtheria-tetanus-acellular pertussis-haemophilus influenzae type b combination vaccine (DTaP-Hib) and diphtheria-tetanus-acellular pertussis-inactivated poliovirus-haemophilus influenzae type b combination vaccine (DTaP-IPV-Hib) for the substitution of diphtheria- tetanus-acellular pertussis vaccine (DTaP) were calculated. Also, the factors associated with timely vaccination rate was analyzed with multivariate logistic regression analysis.Results:The average vaccination coverage rate of pertussis-containing vaccines in children born in Shanghai from 2019 to 2023 ranged from 94.71% to 99.53%. There were significant differences in the vaccination coverage of the 1 st-4 th doses of pertussis-containing vaccines among children born in different years (all P<0.05), but no gender and area specific significant differences were observed (all P>0.05). Non-national immunization program (non-NIP) vaccines were used to substitute DTaP vaccines in some children, with the proportion of DTaP-IPV-Hib vaccine accounting for 50.11%-52.69% and the proportion of DTaP-Hib vaccine accounting for 27.22%-28.43%. The proportions of DTaP-Hib and DTaP-IPV-Hib for the substitution of DTaP had increasing trends over the years. The overall timely vaccination rate of pertussis-containing vaccine vaccination was 84.09%. Analysis on the factors affecting the timely vaccination rate showed that the rate gradually decreased with the increase of the doses. Children who received the self-paid quadrivalent or pentavalent vaccines were less likely to have vaccination delays. Birth year had a significant impact on the timely vaccination rate, while the area had less impact. Additionally, the timely vaccination rate was also influenced by the degree of non-pharmaceutical intervention measures. Conclusions:The substitution of pertussis- containing vaccines with non-NIP vaccines was common in Shanghai. The coverage and timeliness of pertussis-containing vaccine vaccination were relatively high. The timely vaccination rate was significantly associated with gender, dose, vaccine type, and the degree of non-pharmaceutical interventions. There was a certain proportions of delayed and missed vaccinations, and it is necessary to pay attention to children who are not vaccinated timely and conduct high-quality catch-up vaccination to ensure timely and complete vaccination of pertussis-containing vaccines.

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 lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

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.

Purpose: This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. Methods: This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change.Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Results: Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Conclusion Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

AIM: Previous studies have suggested that big stick design (BSD) method can only be used in clinical trials of two treatments with equal proportion, which has good statistical performance and has become the recommended choice of randomized methods. This study expands BSD method, so that it can be applied to three groups, and provides more randomized methods for clinical trials. METHODS: On the basis of BSD method used in two treatments with equal proportion, the derivation conditional allocation probability of BSD method used in three treatments with equal proportion was carried out. BSD method was compared with simple randomization (SR) method, permuted block design (PBD) method and block urn design (BUD) method by Monte-Carlo simulation in balance and randomness. RESULTS: In terms of balance, PBD method was the best, followed by BUD method, BSD method, and SR method was the worst. In terms of randomness, SR method was the best, followed by BSD method, BUD method and PBD method. The comprehensive performance showed that BSD method was better than BUD method, PBD method and SR method. CONCLUSION: The expanded BSD method used in three treatments with equal proportion has good comprehensive performance, and it can be the recommended randomization method for clinical trials of three treatments with equal proportion.

OBJECTIVE To investigate the effects of nasal administration of non-mitogenic acid fibroblast growth factor(NMFGF1) loaded nanoparticles(NMFGF1-NPs) on the improvement of cognitive function in vascular dementia(VD) mice and its mechanism. METHODS Nanoparticles containing NMFGF1(NMFGF1-NPs) were prepared by water-in-water emulsion technique and characterized. The mice were divided into sham group, VD model group, blank-NPs group, NMFGF1 solution group and NMFGF1-NPs group after repeated cerebral ischemia-reperfusion to establish VD test model, and then given the corresponding form of drug intervention by nasal cavity. After drug intervention, Morris water maze was used to evaluate the learning and memory function of the animals in each group from the perspective of behavior. Meanwhile, the morphology, arrangement and apoptosis index(AI) of hippocampal neurons in each group were evaluated by pathological methods such as HE staining, FJB staining and Tunel apoptosis staining. In addition, ELISA and Western blotting were used to investigate the molecular mechanism of NMFGF1-NPs improving VD by nasal administration. RESULTS The morphology of NMFGF1-NPs was round. The encapsulation rate of NMFGF1-NPs respectively was (87.76±5.89)%. Morris water maze results showed that the behavioral indexes of mice in VD model group were significantly different from those in sham operation group(P<0.01). At the same time, the pathological results showed that the neurons in the CA1 region of the hippocampus in the VD model group were disordered, the cells morphology and structure were missing, and the AI was significantly increased compared with that in the sham operation group(P<0.01). Meanwhile, compared with the VD model group, the NMFGF1-NPs treatment group showed significant improvement in various behavioral indexes, and the hippocampal neuron cells were intact and orderly, and the AI index was significantly decreased(P<0.01). ELISA and Western blotting analysis showed that compared with that of VD model group and other intervention groups, the content of MDA in the brain of NMFGF1-NPs treatment group was significantly decreased. While the content of SOD, NO and the expressions of Nrf2, SOD-1 and GSTO1/2 was significantly increased (P<0.01). CONCLUSION Nasal administration of NMFGF1-NPs can play the role of antioxidant stress damage by activating Nrf2/ARE signal pathway, and ultimately improve the learning and cognitive function of VD mice.

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.