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.

ObjectiveTo investigate the association of Modified Response Evaluation Criteria in Solid Tumors (mRECIST) response with the prognosis of patients with unresectable hepatocellular carcinoma (HCC) after transarterial embolization (TACE). MethodsA retrospective analysis was performed for the clinical data of 190 patients with unresectable HCC who were consecutively admitted to Department of Liver Disease and Digestive Interventional Radiology, The First Affiliated Hospital of Air Force Medical University, and treated with TACE from January 2010 to December 2014. The mRECIST criteria were used to evaluate imaging response after TACE; the patients with complete response (CR) or partial response (PR) were enrolled as response group(n=89), and those with progressive disease (PD) or stable disease (SD) were enrolled as non-response group(n=101). The Kaplan-Meier method was used to calculate median survival time, and the log-rank test was used for comparison between groups; the Cox regression model was used to identify the influencing factors for prognosis. ResultsAccording to the mRECIST criteria, 39 patients (20.5%) achieved CR, 50 (26.3%) achieved PR, 67 (35.3%) had SD, and 34 (17.9%) had PD. The objective response rate based on mRECIST was 46.8% for the whole population. The response group had a significantly longer survival time than the non-response group, and the median survival time was 29.9 (95% confidence interval ［CI］: 25.0-34.8) months for the response group and 7.5 (95% CI: 5.7-9.3) months for the non-response group (P＜0.001). The multivariate analysis showed that mRECIST response (hazard ratio ［HR］=2.02, P＜0.001), hepatitis B (HR=4.03, P＜0.001), and portal invasion (HR=2.12, P=0.008) were independent risk factors for survival. ConclusionThe mRECIST response has a certain value in predicting the prognosis of patients with unresectable HCC after TACE.

Objective To assess the effectiveness of a novel mobile health patient management system involving doctors, nurses, and patients ( TRIO mode) on glycemic control and self-monitoring of blood glucose (SMBG) compliance among the type 2 diabetes mellitus ( T2DM) patients using basal insulin standardization treatment in China. Methods From April 2014 to April 2015, 416 hospitals in 110 cities of 30 provinces, municipalities, and autonomous regions across China were selected to participate in the program. A Online-to-Offline ( O2O) integrated mobile health patients management system with mobile terminals for the doctors, nurses, and patients was applied in the program for patient education, follow-up, and data collection. For all the newly recruited patients, the baseline information was collected and a first-day patient education program were provided by a designated nurse. In the 12-week follow-up period, data of basal insulin doses and fasting plasma glucose ( FPG) values were collected from the patients by text messages or tracking phone call by the nurse. The patients also received timely standardized patients health education and glycemic control guidance by participating in thepatient education forum anddoctors' hotline in order to help them achieve the glycemic control goals. Results A total of 102 524 patients using basal insulin treatment were eligible and enrolled in the program. 64 420 patients completed the 12 weeks follow-up and provided at least one FPG value at all five follow-ups. In total, 62. 6% (40 334 / 64 420) of the patients reached the FPG control target(FPG≤7. 0 mmol/ L) at the end of follow-up period. The weekly average FPG for patients with complete SMBG data decreased from 10. 58 mmol/ L to 6. 91 mmol/ L while the FPG control rates increased from 13. 4% to 69. 2% . The weekly average FPG for the patients provided incomplete SMBG data decreased from 10. 54 mmol/ L to 7. 13 mmol/ L while the FPG control rates increased from 13. 6% to 62. 2% . The FPG control rates for the patients provided complete SMBG were 1. 74 times higher than those patients provided incomplete SMBG. Based on a GEE model, the average decline of the FPG and the increase of the FPG control rates were significantly better for patients who provided complete SMBG as compared to the patients with incomplete SMBG data. The results of the multivariate logistic regression analysis showed that factors such as receiving the first-day education, participating in the follow-up patient education forum, and the doctors' hotline were significantly associated with the improvement of the SMBG compliance, the treatment adherence, and the FPG control rates. The SMBG compliance and the treatment adherence for patients who completed first-day education were 1. 68 times and 1. 22 times higher, respectively. For the patients who participated in follow-up education activities, their SMBG compliance and treatment adherence were 3. 17 times and 3. 36 times higher, respectively. Conclusion The innovativeTRIOmobile health patient management mode was feasible and effective for better managing the type 2 diabetes patients initiated on basal insulin treatment in China. Active participation in the first-day education program and the follow-up patient education activities can effectively improve the SMBG compliance and the treatment adherence, and therefore play an important role in helping patient achieving FPG control in a faster manner.

Objective To compare diabetes(pre-diabetes) prevalence and awareness between Province Shanxi and Fujian .Meth-ods Study data was from China National Diabetes and Metabolic Disorders Study 2007-2008 .5 926 individuals(Shanxi 3 254 ,Fu-jian 2 672) were included as study participants .Standardized questionnaire was used to obtain demographic and lifestyle data .All participants were administered a glucose tolerance test .Results Overall diabetes prevalence was 9 .6% .The diabetes prevalence in Shanxi was lower compared with Fujian(8 .2% vs .11 .3% ,P<0 .001) .Overall pre-diabetes was 15 .4% and no significant differ-ence was found between the two provinces .The awareness of diabetes and pre-diabetes in Shanxi was lower compared with Fujian , although both provinces were not satisfactory .Conclusion Regional differences were showed in diabetes (pre-diabetes) prevalence and awareness between Province Shanxi and Fujian .

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.

Objectives:To determine the expressions of decoy receptors (DcR1 and DcR2) of TRAIL in carcinoma of endometrium. Methods:The expressions of DcR1 and DcR2 in endometrium tissues from 13 carcinoma of endometrium and 7 normal endometrium were detected by immunohistochemical staining.Results: The expressions of DcR1 and DcR2 in carcinoma of endometrium were much lower than in normal endometrium. Conclusions:The decreasing of DcR1 and DcR2 in carcinoma of endometrium may be concerned with its pathogenesis, which may be related to the prevention of endometrium from carcinomatous change.