ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

To explore the effects of different exercise prescriptions on glycemic metabolism in East Asian patients with type 2 diabetes mellitus (T2DM) and to compare the differences in the impact of population characteristics and exercise components on glycemic metabolism.

Objective: High-risk psychosis before schizophrenia includes individuals at clinical high risk (CHR) and genetic high risk (GHR). Methylenetetrahydrofolate Reductase (MTHFR) gene variants have been identified as risk factors for schizophrenia onset and symptom severity, though the effects of these polymorphisms in high-risk individuals remain unexplored. This study investigated the impact of MTHFR polymorphisms on clinical features of high-risk psychosis. We hypothesized that MTHFR variants may influence the progression of high-risk psychosis before schizophrenia. Methods: A total of 163 individuals were enrolled, comprising 76 healthy controls, 31 GHR, and 56 CHR. MTHFR polymorphisms (C677T, A1298C, and G1793A) were detected. The MATRICS Consensus Cognitive Battery was administered to assess cognitive ability. Additional recorded clinical features included sex, age, family history, cognitive scores, and the Structured Interview for Psychosis Risk Syndromes (SIPS) scores. Results: Higher MTHFR polymorphism levels were observed in high-risk individuals at the C677T site (p=0.006) and in multi-site variant analysis (p=0.012) compared to controls. Stratified by sex, both males and females showed similar increases in MTHFR polymorphism. Cognitive ability scores decreased in the high-risk group with an increase in MTHFR variant allele amounts. In the CHR group, SIPS scores non-significantly increased with the number of variant alleles. Conclusion Increased MTHFR polymorphism was associated with the risk progression of schizophrenia, being more pronounced in males than in females. Higher amounts of hypofunctional MTHFR variants tended to decrease the cognitive ability in both high-risk and healthy subjects, while higher risk levels are observed in CHR subjects.

Objective: High-risk psychosis before schizophrenia includes individuals at clinical high risk (CHR) and genetic high risk (GHR). Methylenetetrahydrofolate Reductase (MTHFR) gene variants have been identified as risk factors for schizophrenia onset and symptom severity, though the effects of these polymorphisms in high-risk individuals remain unexplored. This study investigated the impact of MTHFR polymorphisms on clinical features of high-risk psychosis. We hypothesized that MTHFR variants may influence the progression of high-risk psychosis before schizophrenia. Methods: A total of 163 individuals were enrolled, comprising 76 healthy controls, 31 GHR, and 56 CHR. MTHFR polymorphisms (C677T, A1298C, and G1793A) were detected. The MATRICS Consensus Cognitive Battery was administered to assess cognitive ability. Additional recorded clinical features included sex, age, family history, cognitive scores, and the Structured Interview for Psychosis Risk Syndromes (SIPS) scores. Results: Higher MTHFR polymorphism levels were observed in high-risk individuals at the C677T site (p=0.006) and in multi-site variant analysis (p=0.012) compared to controls. Stratified by sex, both males and females showed similar increases in MTHFR polymorphism. Cognitive ability scores decreased in the high-risk group with an increase in MTHFR variant allele amounts. In the CHR group, SIPS scores non-significantly increased with the number of variant alleles. Conclusion Increased MTHFR polymorphism was associated with the risk progression of schizophrenia, being more pronounced in males than in females. Higher amounts of hypofunctional MTHFR variants tended to decrease the cognitive ability in both high-risk and healthy subjects, while higher risk levels are observed in CHR subjects.

Objective: High-risk psychosis before schizophrenia includes individuals at clinical high risk (CHR) and genetic high risk (GHR). Methylenetetrahydrofolate Reductase (MTHFR) gene variants have been identified as risk factors for schizophrenia onset and symptom severity, though the effects of these polymorphisms in high-risk individuals remain unexplored. This study investigated the impact of MTHFR polymorphisms on clinical features of high-risk psychosis. We hypothesized that MTHFR variants may influence the progression of high-risk psychosis before schizophrenia. Methods: A total of 163 individuals were enrolled, comprising 76 healthy controls, 31 GHR, and 56 CHR. MTHFR polymorphisms (C677T, A1298C, and G1793A) were detected. The MATRICS Consensus Cognitive Battery was administered to assess cognitive ability. Additional recorded clinical features included sex, age, family history, cognitive scores, and the Structured Interview for Psychosis Risk Syndromes (SIPS) scores. Results: Higher MTHFR polymorphism levels were observed in high-risk individuals at the C677T site (p=0.006) and in multi-site variant analysis (p=0.012) compared to controls. Stratified by sex, both males and females showed similar increases in MTHFR polymorphism. Cognitive ability scores decreased in the high-risk group with an increase in MTHFR variant allele amounts. In the CHR group, SIPS scores non-significantly increased with the number of variant alleles. Conclusion Increased MTHFR polymorphism was associated with the risk progression of schizophrenia, being more pronounced in males than in females. Higher amounts of hypofunctional MTHFR variants tended to decrease the cognitive ability in both high-risk and healthy subjects, while higher risk levels are observed in CHR subjects.

The operation assistant work team of public hospitals is an important bridge and link to realize the integration of industry and finance,and an important practitioner to promote the realization of lean operation management.It examines the service model of the operation assistant team engaged in Similar Multi-disciplinary Treatment,focusing on organizational structure,job responsibilities,and service mechanisms.Build a four-tiered lean operational management system and set up an operation assistant work team that combines production,university and research.Based on specific management matters,establish an operation assistant service mechanism such as problem assessment and classification management mechanism,project standardization management mechanism,reward and punishment assessment mechanism,etc.,to promote the optimization and integration of hospital medical education,research,prevention and management and core elements such as human,talent,material and technology resources.Help public hospitals to continuously improve their lean operation management level.

Objective: High-risk psychosis before schizophrenia includes individuals at clinical high risk (CHR) and genetic high risk (GHR). Methylenetetrahydrofolate Reductase (MTHFR) gene variants have been identified as risk factors for schizophrenia onset and symptom severity, though the effects of these polymorphisms in high-risk individuals remain unexplored. This study investigated the impact of MTHFR polymorphisms on clinical features of high-risk psychosis. We hypothesized that MTHFR variants may influence the progression of high-risk psychosis before schizophrenia. Methods: A total of 163 individuals were enrolled, comprising 76 healthy controls, 31 GHR, and 56 CHR. MTHFR polymorphisms (C677T, A1298C, and G1793A) were detected. The MATRICS Consensus Cognitive Battery was administered to assess cognitive ability. Additional recorded clinical features included sex, age, family history, cognitive scores, and the Structured Interview for Psychosis Risk Syndromes (SIPS) scores. Results: Higher MTHFR polymorphism levels were observed in high-risk individuals at the C677T site (p=0.006) and in multi-site variant analysis (p=0.012) compared to controls. Stratified by sex, both males and females showed similar increases in MTHFR polymorphism. Cognitive ability scores decreased in the high-risk group with an increase in MTHFR variant allele amounts. In the CHR group, SIPS scores non-significantly increased with the number of variant alleles. Conclusion Increased MTHFR polymorphism was associated with the risk progression of schizophrenia, being more pronounced in males than in females. Higher amounts of hypofunctional MTHFR variants tended to decrease the cognitive ability in both high-risk and healthy subjects, while higher risk levels are observed in CHR subjects.

Objective: High-risk psychosis before schizophrenia includes individuals at clinical high risk (CHR) and genetic high risk (GHR). Methylenetetrahydrofolate Reductase (MTHFR) gene variants have been identified as risk factors for schizophrenia onset and symptom severity, though the effects of these polymorphisms in high-risk individuals remain unexplored. This study investigated the impact of MTHFR polymorphisms on clinical features of high-risk psychosis. We hypothesized that MTHFR variants may influence the progression of high-risk psychosis before schizophrenia. Methods: A total of 163 individuals were enrolled, comprising 76 healthy controls, 31 GHR, and 56 CHR. MTHFR polymorphisms (C677T, A1298C, and G1793A) were detected. The MATRICS Consensus Cognitive Battery was administered to assess cognitive ability. Additional recorded clinical features included sex, age, family history, cognitive scores, and the Structured Interview for Psychosis Risk Syndromes (SIPS) scores. Results: Higher MTHFR polymorphism levels were observed in high-risk individuals at the C677T site (p=0.006) and in multi-site variant analysis (p=0.012) compared to controls. Stratified by sex, both males and females showed similar increases in MTHFR polymorphism. Cognitive ability scores decreased in the high-risk group with an increase in MTHFR variant allele amounts. In the CHR group, SIPS scores non-significantly increased with the number of variant alleles. Conclusion Increased MTHFR polymorphism was associated with the risk progression of schizophrenia, being more pronounced in males than in females. Higher amounts of hypofunctional MTHFR variants tended to decrease the cognitive ability in both high-risk and healthy subjects, while higher risk levels are observed in CHR subjects.

Objective:To investigate endothelial cell heterogeneity in diabetic cardiomyopathy (DCM) and identify potential therapeutic targets of dapagliflozin in cardiac vascular endothelial cells.Methods:ePharmaLib reverse virtual screening was performed on 15 148 protein crystals to identified the binding interactions between human-derived proteins and dapagliflozin. Subsequently, single-cell RNA sequencing data (PRJNA1069235) from wild-type mice (control group) and db/db mice (DCM group) were integrated, then dimensionality reduction and clustering analysis were performed to identify endothelial cell subpopulations in the heart tissue of DCM mice, followed by functional annotation. Cell-cell communication analysis was explored to investigate fibroblast-endothelial cell interactions. The Agilent Mouse ceRNA Microarray chip was used to perform transcriptomic analysis of heart tissue from mice fed a high-fat diet and treated with dapagliflozin. Intersection analysis of reverse virtual screening results, single-cell RNA sequencing results and chip analysis data was performed to identify common differentially expressed genes. In vitro, human umbilical vein endothelial cells were divided into blank control group, tumor necrosis factor-α (TNF-α) group (TNF-α 10 mg/L), dapagliflozin low concentration group (TNF-α 10 mg/L+dagliazin 2 μmol/L), dapagliflozin medium concentration group (TNF-α 10 mg/L+dagliazin 5 μmol/L) and dapagliflozin high concentration group (TNF-α 10+dagliazin 10 μmol/L). Western blot and real-time reverse transcriptase polymerase chain reaction were used to detect the expression of inflammatory factors and differential genes.Results:ePharmaLib reverse virtual screening identified 168 human-derived proteins with potential binding affinity to dapagliflozin, and single-cell analysis identifiedf 6 types of endothelial cell subpopulations. Compared with the control group, the abundance of capillary endothelial cells was significantly lower in DCM group, while the abundance of microvascular and venous endothelial cells was significantly higher ( P all<0.05). Cell-cell communication analysis showed significant expression of Pgf-Vegfr1 ligand-receptor pair. In addition, 15 differentially expressed genes were identified by intersection analysis of 168 dapagliflozin-binding proteins. Including Bcl2, Baz2b, Nos3, Ephb4, Cdk8, Pparg, Pde2a, Fgfr2, Fto, Stk24, Dlg1, Gsk3b, Pdpk1, Fas and Tnks2. Notably, Baz2b, Pparg, Fto and Gsk3b were differentially expressed in all cell subpopulations. Six differential genes, including Pde7a, Dlg1, Gsk3b, Nampt, Met and Adk, were obtained by the intersection of the chip analysis data with the virtual screening results of dapagliflozin. In vitro, compared to the human umbilical vein endothelial cells of TNF-α group, the expression levels of interleukin-6, interleukin-1β and p-P65 proteins and messenger RNA of Bcl2, Nos3, Cdk8, Pde2a, Dlg1, Pdpk1, Tnks2, Baz2b, Pparg, Fas, Pde7a and Nampt were significantly lower than dapagliflozin high concentration group ( P all<0.05). Conclusions:Dapagliflozin may inhibit endothelial cell inflammatory responses and improve endothelial dysfunction in DCM by regulating key genes such as Dlg1, Bcl2, Nos3, Pde7a and Nampt.

The operation assistant work team of public hospitals is an important bridge and link to realize the integration of industry and finance,and an important practitioner to promote the realization of lean operation management.It examines the service model of the operation assistant team engaged in Similar Multi-disciplinary Treatment,focusing on organizational structure,job responsibilities,and service mechanisms.Build a four-tiered lean operational management system and set up an operation assistant work team that combines production,university and research.Based on specific management matters,establish an operation assistant service mechanism such as problem assessment and classification management mechanism,project standardization management mechanism,reward and punishment assessment mechanism,etc.,to promote the optimization and integration of hospital medical education,research,prevention and management and core elements such as human,talent,material and technology resources.Help public hospitals to continuously improve their lean operation management level.