ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveThis study aimed to investigate the optimal compatibility ratio of the Chuanxiong Rhizoma-Carthami Flos （CR-CF） couplet medicines in ischemic stroke （IS） therapy and its pharmacological action mechanism， providing a scientific basis for the clinical application of CR-CF couplet medicines in IS therapy. MethodsThe chemical composition of CR-CF was analyzed using liquid chromatography mass spectrometry （LC-MS/MS）. The contents of eight characteristic chemical components in aqueous extracts of CR-CF with common clinical compatibility ratios （1∶1， 1∶2， 1∶3， 3∶2， 2∶1） were determined by ultra-high performance liquid chromatography（UHPLC）. An oxygen-glucose deprivation/reoxygenation （OGD/R）-induced mouse hippocampal neuron HT22 cell injury model was established， and cells were treated with different CR-CF compatibility ratios. The collaborative index （CI） was calculated by using CompuSyn software. A cerebral artery occlusion/reperfusion （MCAO/R） model of rats was induced by using the modified Longa suture method. The rats were divided into the sham group， model group， Chuanxiong Rhizoma （CR） group （1.3 g·kg^-1）， Carthami Flos （CF） group （3.9 g·kg^-1）， CR-CF group （5.2 g·kg^-1）， and edaravone group （5 mg·kg^-1）. Neuronal defect scores were assessed by the Longa scoring method. Cerebral infarction volume was measured by 2，3，5-triphenyltetrazolium chloride（TTC） staining. Neuronal damage was observed via hematoxylin-eosin （HE） staining. Neuronal apoptosis of rats was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， and the expression of apoptosis-related proteins was analyzed by Western blot. Label-free proteomics was employed to screen differentially expressed proteins， and Western blot was used to examine the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway-related proteins. Finally， molecular docking was performed to predict the binding affinity of eight active constituents in CR-CF （1∶3） with PI3K. ResultsWhen CR-CF was combined at a 1∶3 ratio， the total content of the eight active constituents in the extract was the highest， and the synergistic protective effect on OGD/R-injured HT22 cells was the strongest （CI=0.308）. Animal experiments showed that compared with the sham group， the model group exhibited increased neuroecological score points （P<0.01）， larger cerebral infarction volumes （P<0.01）， aggravated brain tissue damage， elevated neuronal apoptosis （P<0.01）， and increased B-cell lymphoma-2（Bcl-2）-associated X protein （Bax）/Bcl-2 and cleaved Cysteinyl aspartate specific proteinase-3/Cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3/Caspase-3） ratios （P<0.01）. Compared with the model group， CR-CF （1∶3） significantly reduced neurological scores （P<0.01）， significantly decreased cerebral infarction volume （P<0.01）， alleviated brain tissue damage， inhibited neuronal apoptosis （P<0.01）， and significantly lowered the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios （P<0.01）. The therapeutic effect of CR-CF （1∶3） was superior to that of CR or CF alone. Proteomic analysis revealed that CR-CF （1∶3） activated the PI3K/Akt signaling pathway. Validation experiments demonstrated that compared with the sham group， the model group showed obviously reduced p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Compared with the model group， p-PI3K/PI3K and p-Akt/Akt ratios （P<0.05） obviously increased. Compared with the CR-CF group， the 2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-one LY294002 inhibitor+CR-CF group exhibited obviously decreased p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Molecular docking results indicated that the active constituents of CR-CF （1∶3） had strong binding affinity with PI3K. ConclusionThe CR-CF couplet medicines at a 1∶3 ratio exhibit optimal synergistic effects， and their anti-IS mechanism is closely related to activation of the PI3K/Akt signaling pathway and inhibition of neuronal apoptosis.

Objective: To explore the relationship between serum homocysteine (Hcy), interleukin-5 (IL-5), folate and core symptoms in children with autism spectrum disorders, so as to provide potential biomarkers for early diagnosis and intervention of diseases. Methods: A total of 106 children with autism spectrum disorders and 106 healthy children with matched sex and age in Lu an People s Hospital were enrolled as autism group and healthy group between May 2020 to December 2023. On the day of admission, levels of serum Hcy, IL-5 and folate were detected. The core symptoms in autism group were evaluated by Autism Behavior Checklist (ABC), Wechsler Preschool and Primary Scale of Intelligence-fourth edition(WPPSI-IV), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). The levels of serum Hcy, IL-5 and folate in the two groups were compared by t- test. The relationship between serum Hcy, IL-5, folate and core symptoms in children with autism spectrum disorders was determined by Pearson correlation analysis. Results: The levels of serum Hcy and IL-5 in autism group were (7.48±0.32) μmol/L and (345.77±32.51) pg/mL, higher than those in healthy group [(6.11±0.54) μmol/L, (274.04±25.17) pg/mL], while folate level was lower than that in healthy group [(15.24±3.47) ng/mL, (22.51±4.69) ng/mL], the differences were statistically significant ( t =22.47, 17.96, 12.83, all P < 0.05 ). In autism group, levels of serum Hcy and IL-5 were positively correlated with scores of ABC, CARS and SRS ( r =0.29, 0.53 , 0.54; 0.45, 0.41, 0.50), while negatively correlated with WPPSI-IV score ( r =-0.28, -0.26)(all P <0.05). The folate level was negatively correlated with scores of ABC, CARS and SRS ( r =-0.55, -0.40, -0.25), while positively correlated with WPPSI-IV score ( r =0.41) (all P <0.05). Conclusion Children with ASD show elevated serum Hcy and IL-5 alongside decreased folate,and three markers correlate with core symptoms and intellectual level.

Abstract Mental health problems in adolescents often emerge alongside incidents of peer bullying, negatively affecting their development. In order to develop intervention measures for peer bullying among Chinese adolescents, the article elaborates on the current research progress in the theoretical basis, evidence based approaches, and practical models of peer bullying intervention, summarizes strengths and limitations of existing approaches, and proposes future research directions for intervention, with the aim of preventing and reducing peer bullying and creating a favorable environment for the healthy adolescent develpment.

ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

ObjectiveTo investigate the regulatory effects of Huanglian Jiedutang （HLJDT） on immune cell migration， blood-brain barrier protection， and cellular functional recovery in a model of ischemic stroke. MethodsA transient middle cerebral artery occlusion （tMCAO） model was established in mice to induce ischemic stroke. Cerebral blood flow and neurological function were evaluated using laser speckle imaging and neurological deficit scoring. Histopathological damage in brain tissues was assessed by hematoxylin-eosin （HE） and Nissl staining. Mice were divided into a sham group， a model group， an HLJDT group， and a Ginkgo biloba extract （GBE） group. After one week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the HLJDT group received HLJDT at 1.82 g·kg^-¹， and the GBE group received GBE at 0.432 g·kg^-¹. Administration was continued for 5 consecutive days， and the tMCAO model was established after the final dose on day 6. Single-cell RNA sequencing was performed on brain tissues and peripheral immune cells. UMAP and odds ratio （OR） indices were used to analyze cell distribution. Differential expression analysis was conducted to evaluate the effects of HLJDT on endothelial cells， pericytes， and macrophages， combined with CellChat and decoupler to analyze cell-cell communication and transcription factor regulation. Finally， PCR and ELISA were used to validate the mRNA and protein expression of relevant genes. ResultsCompared with the sham group， the model group showed significantly increased neurological deficit scores （P<0.01） and significantly decreased cerebral blood flow （P<0.01）， accompanied by cortical structural disorder， aggravated cytoplasmic vacuolization， and increased numbers of Nissl bodies. Compared with the model group， both the HLJDT and GBE groups exhibited significantly reduced neurological deficit scores （P<0.01） and markedly improved cerebral blood flow （P<0.01）， along with amelioration of cortical structural disorder， alleviated cytoplasmic vacuolization， and reduced numbers of Nissl bodies. Single-cell analysis showed that HLJDT protected endothelial cells and pericytes by preventing their reduction， restored the expression of functional genes in these cells （e.g.， PECAM1 and NOS3）， and downregulated the expression of chemokines and adhesion-related factors （e.g.， CCL2 and CXCL2）. In macrophages， HLJDT reduced their recruitment to the central nervous system and downregulated the expression of chemokine receptors and inflammatory factors （e.g.， IL-6， CCR2， and CXCR2）. Cell-cell communication analysis further indicated that HLJDT， through the above mechanisms， alleviated damage to pericytes and endothelial cells， reduced their recruitment of macrophages， and decreased ligand-receptor interactions in chemokine signaling pathways （including CCL， CXCL， and CSF3） between pericytes/endothelial cells and macrophages， thereby preventing secondary injury. Compared with the sham group， the model group showed significantly upregulated mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， while mRNA expression levels of endothelial- and pericyte function-related genes （RGS5， PECAM1， VEGFB， and NOS3） were significantly downregulated （P<0.01）. In contrast， compared with the model group， the HLJDT and GBE groups exhibited significantly decreased mRNA expression levels of IL-1β， IL-6， TNF-α， CCL2， CXCL2， and CSF3 （P<0.01）， and significantly increased expression of RGS5， PECAM1， VEGFB， and NOS3 （P<0.01）. At the protein level， compared with the sham group， the model group showed significantly increased expression of IL-1β， IL-6， and TNF-α （P<0.01）， whereas these protein levels were significantly reduced in the HLJDT and GBE groups compared with the model group （P<0.01）. ConclusionHLJDT reduces neuronal damage in ischemic stroke by protecting endothelial cells and pericytes， while inhibiting their interaction with macrophages， thereby mitigating secondary injury in the central nervous system.

Objective: To investigate the prevalence and influencing factors of the co-occurrence of elevated blood pressure and depressive symptoms among junior and senior high school students in Anhui Province, so as to provide evidence for comprehensive interventions on physical and mental health among adolescents. Methods: From September to December 2024, a multi stage random cluster sampling method was used to select 103 225 junior and senior high school students from 16 prefecture level cities in Anhui Province. Data were collected through questionnaire surveys and physical measurements. Elevated blood pressure was determined according to the Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years. Depressive symptoms among middle school students were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Chi-square test, Chi-square test for trend, and multivariate Logistic regression model were used to analyze the risk factors for the co-occurrence of elevated blood pressure and depressive symptoms. Results: The detection rate of elevated blood pressure was 15.22%, the detection rate of depressive symptoms was 18.56%, and the co-occurrence rate of the two conditions was 2.67% among junior and senior high school students. Multivariate Logistic regression analysis showed that after controlling for gender, school stage, household registration, and overweight and obesity status,compared with those who don t drink sugary drink and eat fried food, and get enough sleep, sugar sweetened beverage intake <1 and ≥1 time/d( OR =1.28,1.61), fried food consumption ≥1 time/d( OR =1.37), and insufficient sleep ( OR =1.54) were all associated with an increased risk of the co-occurrence of elevated blood pressure and depressive symptoms(all P <0.05). Daily fresh vegetable intake ≥1 time/d( OR =0.78) and fresh fruit intake ≥1 time/d( OR =0.85) were both associated with a decreased risk of the co-occurrence(both P <0.05). Compared with students who did not eat breakfast, students who ate breakfast sometimes and every day ( OR =0.62,0.36) had a lower co-occurrence risk(both P < 0.05). Junior and senior high school students with daily outdoor activity duration≥1 h ( OR =0.81) had a lower risk of the co-occurrence of elevated blood pressure and depressive symptoms ( P <0.05). Conclusions Sugar sweetened beverage drink and fried food consumption, inadequate consumption of fresh vegetables, fruits and breakfast, lack of outdoor activity, and insufficient sleep are risk factors for the co-occurrence of elevated blood pressure and depressive symptoms among junior and senior high school students in Anhui Province. It is necessary to establish school health promotion strategies integrating nutrition, exercise and sleep management as intervention targets to reduce the co-occurrence risk of elevated blood pressure and depressive symptoms among junior and senior high school students.

ObjectiveTo investigate the mechanism of Dipeptidyl peptidase 7 （DPP7） in hepatocellular carcinoma （HCC）. MethodsThe expression of DPP7 protein in hepatocellular carcinoma tissues and liver benign tissues was detected by UALCAN and GEPIA database， immunohistochemical， and Western blot， and its relationship with clinicopathological characteristics was analyzed. The expression of DPP7 was silenced by siRNA and the protein expression of DPP7 in MHCC97H cells was detected by Western blot and qRT-PCR. MTT assay， colony formation assay and wound healing assay were used to detect cell proliferation. Transwell assay was used to detect the invasion and migration ability of cells. Western blot was used to detect the changes of protein markers related to epithelial-mesenchymal transition （EMT）. ResultsIn UALCAN， GEPIA and clinical liver tissue samples， DPP7 expression was upregulated and it was closely related to TNM stage （P=0.002）， lymph node metastasis （P=0.038） and depth of tumor invasion （P=0.027）. The downregulation of DPP7 protein expression in MHCC97H cells was detected after transfection of siRNA in the experimental group （P<0.01）； furthermore， the results of the MTT， colony formation， wound healing and Transwell assay demonstrated that knockdown of DPP7 expression in the MHCC97H cell line significantly inhibited the proliferative and metastatic capabilities of these cells. Consistent with this phenotypic change， analysis of epithelial-mesenchymal transition （EMT） related proteins revealed a significant upregulation of the epithelial marker E-cadherin （P<0.001） and downregulation of the mesenchymal markers Vimentin and N-cadherin （P<0.01）. ConclusionDPP7 is highly expressed in hepatocellular carcinoma tissues and cell lines， and this is associated with poor prognosis in patients. The downregulation of DPP7 protein expression can inhibit the proliferation and metastasis of hepatocellular carcinoma cell line MHCC97H， and its mechanism is closely related to EMT.