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 assess the impact of albumin (Alb) administration on the prognosis of patients with acute kidney injury (AKI). METHODS: Clinical data of AKI patients in the intensive care unit (ICU) were retrospectively analyzed from the American Medical Information Mart of Intensive Care-IV (MIMIC-IV), including demographic data, acute physiology score (APS), comorbidities, vital signs, laboratory indicators, treatment status, ICU length of stay, and outcome indicators. The main outcome measure is ICU mortality. AKI patients were divided into Alb infusion group and Alb non infusion group based on whether they received Alb treatment. Multiple imputation was used to process missing data and eliminate variables that missing more than 30%. To ensure the stability of the results, propensity score matching (PSM) and inverse probability weighting (IPW) were used to correct the results. Using Kaplan-Meier survival curve and Cox proportional hazards regression model to evaluate the effect of Alb infusion on ICU survival rate in AKI patients. Perform subgroup analysis based on patient age, gender, and comorbidities to evaluate the prognostic effects of Alb on different patient subgroups. RESULTS: A total of 6 390 AKI patients were included, including 1 721 in the Alb infusion group and 4 669 in the Alb non infusion group. After adjusting for key covariates in the Cox regression model, compared with the Alb non infusion group, patients in the Alb infusion group were significantly younger in age, with APS III score, proportion of vasoactive drugs and continuous renal replacement therapy (CRRT) use, sepsis proportion, heart rate, respiratory frequency, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr), lactic acid (Lac), and arterial partial pressure of carbon dioxide (PaCO₂) levels significantly higher. The proportion of hypertension, myocardial infarction, and congestive heart failure, as well as blood pressure, urine output, platelet count (PLT), and Alb levels were significantly lower. The results of univariate and multivariate Cox regression analysis on the raw data showed that the risk of death in the Alb infusion group was significantly lower than that in the Alb non infusion group [hazard ratio (HR) = 0.69, 95% confidence interval (95%CI) was 0.60-0.80, all P < 0.05]. The results after propensity score matching (PSM) and inverse probability weighting (IPW) processing are consistent with the original data trend (both P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate during ICU stay in the Alb infusion group was significantly higher than that in the Alb non infusion group (24.48% vs. 12.17%, Log-Rank test: χ² = 74.26, P < 0.05). Subgroup analysis shows that Alb infusion has a more significant survival benefit for AKI patients who use vasoactive drugs, have concurrent sepsis, and do not have liver disease. CONCLUSION Albumin infusion can decrease the ICU mortality of AKI patients.
Humans ; Retrospective Studies ; Acute Kidney Injury/mortality* ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units ; Albumins/therapeutic use* ; Proportional Hazards Models ; Adult ; Databases, Factual

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.

Objective:To explore the value of subspecialty group collaboration combined with disease checklist-driven learning in overcoming the impact of the specialized disease treatment mode in subspecialty establishment on the cultivation of professional postgraduate students.Methods:In the teaching of general surgery and gastroenterology, sixty professional postgraduate students of grade 2019 were randomly divided into control group and experimental group, with 30 students in each group. The control group received traditional teaching, while the experimental group received the teaching mode of subspecialty group collaboration combined with disease checklist-driven learning. The teaching effectiveness and the degree of satisfaction with teaching were compared between the two groups. The data were analyzed using the t test and the chi-squared test using SPSS 20.0. Results:In actual teaching, compared with the control group, the experimental group showed significantly higher scores of theoretical assessment (71.51±11.32 vs. 87.23±10.51, P<0.05) and case analysis (73.61±6.82 vs. 92.37±6.87, P<0.05). The rates of satisfaction with theoretical knowledge learning, application of clinical thinking ability for diseases, teaching organization forms, and teaching effectiveness were 90.00%(27/30), 86.67%(26/30), 96.67%(29/30), and 93.33%(28/30) in the experimental group, respectively, which were significantly higher than those of the control group [40.00%(12/30), 23.33%(7/30), 40.00%(12/30), and 46.67%(14/30), respectively; all P<0.05]. Conclusions:The subspecialty group collaboration combined with disease checklist-driven learning mode can overcome the problems of "narrow disease spectrum and narrow knowledge scope" in specialized postgraduate education, and guide students to break the teaching barriers generated by subspecialty construction to create a new form of comprehensive and multi-disease learning, with good prospects for promotion and application.

Objective To compare the influences of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional or mechanical cardiopulmonary resuscitation (CCPR/MCPR) on survival rate and neurological outcome for adult patients with out-of-hospital cardiac arrest (OHCA), and to assess the effect of ECPR. Methods Databases such as Medline, Embase, ScienceDirect, HighWire, Cochrane Library, Wanfang Database and China National Knowledge Infrastructure (CNKI) were searched from January 2000 to October 2018 to retrieve clinical trials on comparison of the effect of ECPR and CCPR/MCPR on survival rate and neurological outcome of adult patients with OHCA. Thereafter, the studies retrieved were based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated by two researchers. A meta-analysis was performed by using RevMan 5.3 software. Sensitivity analysis was used to evaluate the stability of the results, and funnel plot was used to evaluate publication bias. Results A total of 12 studies and 2 519 patients were enrolled, including 615 patients receiving ECPR and 1 904 patients receiving CCPR/MCPR. Meta-analysis showed that compared with CCPR/MCPR, ECPR could not improve the short-term (at hospital discharge or within 1 month) survival rate in patients with OHCA [odds ratio (OR) = 2.26, 95% confidence interval (95%CI) = 0.95-5.41, P = 0.07], but could increase long-term (at more than 3 months) survival rate (OR = 3.56, 95%CI = 1.65-7.71, P = 0.001), rate of good neurological outcome at hospital discharge [Glasgow-Pittsburgh cerebral performance categories (CPC) 1-2 was defined as good neurological function; OR = 3.39, 95%CI = 1.73-6.62, P = 0.000 4], and rate of good long-term neurological outcome (OR = 3.45, 95%CI = 2.24-5.32, P < 0.000 01). Sensitivity analysis showed that the overall results did not change significantly, whether using fixed-effect model and random-effect model to analyze the differences of each effect index, or excluding one study with fewer than 50 subjects for data analysis, indicating that the results were more stable. The funnel plot suggested that there was no publication bias in the studies. But due to the small number of studies, the publication bias could not be excluded. Conclusion ECPR could not improve the short-term survival rate at hospital discharge or within 1 month in patients with OHCA, but could increase long-term survival rate at more than 3 months, good neurological outcome at hospital discharge and long-term neurological outcome.

Objective To investigate the value of bedside lung ultrasound B-line score in the diagnosis of acute heart failure (AHF). Methods A retrospectively analysis was conducted. The adult patients presenting with acute dyspnea in intensive care unit (ICU) of Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2016 to June 2017 were enrolled. An 8-zone lung ultrasound was performed and plasma B-type natriuretic peptide (BNP) level was tested in all patients. AHF was determined as the final diagnosis by two experienced ICU doctors according to the diagnostic criteria of AHF. Patients were divided into two groups: AHF group and non-AHF group. The levels of BNP and B-line score were compared between the two groups, and the diagnostic value of BNP and B-line score in AHF was evaluated. Results Fifty-six patients were included in this study, with 32 of men and 24 of women,and with an average age of 77.3±8.8. Thirty-six patients were diagnosed as AHF. The level of BNP and lung ultrasound B-line score in AHF group were higher than those in non-AHF group [BNP (ng/L): 1 640.4±1 078.4 vs. 236.9±124.9,B line score: 12.8±5.3 vs. 5.4±1.8, both 1 < 0.01]. There was a strong correlation between elevated BNP levels and an increased B-lines score (R2 = 0.712, 1 = 0.000). The receiver operating characteristic curve (ROC) showed that when the cut-off of lung ultrasound B-line score was 8.5, AHF could be discriminated from dyspnea caused by other diseases (sensitivity was 77.8%, specificity was 95%, positive likelihood ratio was 15.56, negative likelihood ratio was 0.23).The area under the ROC curve (AUC) of lung ultrasound B-line score was 0.917 [95% confidence interval (95%CI) =0.847-0.987, 1 = 0.000], slightly lower than that of plasma BNP [0.979 (95%CI = 0.951-1.008)]. Conclusion Lung ultrasound B-line score was highly specific, but moderately sensitive for identifying patients with AHF.

Objective To explore the application of holistic intervention in elderly patients with reflux esophagitis.Methods A total of 100 elderly patients with reflux esophagitis were randomly divided into observation group and control group,with 50 patients per group.The observation group was treated with holistic nursing intervention and the control group were treated with the routine nursing method for reflux esophagitis,and the incidence rate of two groups were observed and compared.Results The total response rate of the experimental group was higher than that of the control group (72.0％ vs.94.0％,P ＜ 0.05).Conclusion Holistic nursing intervention can effectively reduce the incidence of complications,and significantly improve the clinical nursing and treatment efficacy.

Objective To explore the application of holistic intervention in elderly patients with reflux esophagitis.Methods A total of 100 elderly patients with reflux esophagitis were randomly divided into observation group and control group,with 50 patients per group.The observation group was treated with holistic nursing intervention and the control group were treated with the routine nursing method for reflux esophagitis,and the incidence rate of two groups were observed and compared.Results The total response rate of the experimental group was higher than that of the control group (72.0％ vs.94.0％,P ＜ 0.05).Conclusion Holistic nursing intervention can effectively reduce the incidence of complications,and significantly improve the clinical nursing and treatment efficacy.

Objective To assess the effectiveness of pre-hospital therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) for survival and neuro-protection.Methods Databases such as Medline, ScienceDirect, Embase, Highwire, Cochrane Library, CNKI and Wanfang digital database were searched from January 2000 to March 2017 to retrieve randomized controlled trials (RCTs) on pre-hospital therapeutic hypothermia after OHCA. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A Meta-analysis was performed using the Cochrane Collaboration RevMan 4.3 software. Analysis of publication bias was depicted by funnel plot.Results Eight studies involving 3555 cases were included, among which 1804 cases were assigned to the treatment group and 1751 cases to the control group. Meta-analysis showed that compared with in-hospital therapeutic hypothermia, pre-hospital therapeutic hypothermia did not improve the survival rate of patients with OHCA [odds ratio (OR) = 1.00, 95％ confidence interval (95％CI) =0.85-1.18,P = 0.99], and neurological outcome at hospital discharge (OR = 0.97, 95％CI = 0.80-1.16,P = 0.71), but the body temperature was significantly lowered at admission [weighted mean difference (SMD) = -0.88, 95％CI = -1.03 to-0.73,P < 0.00001]. The funnel plot suggested that there was no publication bias in the 8 studies. But due to the low number of studies, the publication bias could not be completely excluded.Conclusion Pre-hospital therapeutic hypothermia after OHCA can decrease temperature at hospital admission, but cannot increase the survival rate and neurological outcome at hospital discharge.