OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The chan-ges of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed.MI rats were in-jected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy re-lated protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fi-brosis,and the cardiac function were observed in different groups.Results After treatment with H2O2 on cardiac fi-broblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P＜0.001),NLRP3 was significantly in-creased(P＜0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P＜0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P＜0.001),NLRP3 was significantly down-regulated(P＜0.001),serum IL-1β and IL-18 levels were significantly decreased(P＜0.001),fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced(P＜0.001),myocardial fibrosis was significantly relieved(P＜0.001),and cardiac function was sig-nificantly improved(P＜0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

Objective:To analyze and compare the risk factors for hemorrhagic stroke and ischemic stroke and understand the exposure levels in population.Methods:A cohort study of risk factors of stroke was conducted in a rural community in Fengxian District of Shanghai in 2003, and the common risk factors of stroke were investigated at baseline survey, the cerebrovascular hemodynamics indexes were detected, the cerebrovascular function score was calculated according to the unified integral rule, and the incidence of stroke was observed in follow up. The risk factors for hemorrhagic stroke and ischemic stroke were analyzed by cohort study. The risk factors for two subtypes of stroke were compared.Result:A total of 10 565 participants were included in the study, with a mean follow-up period of (11.15±2.26) years, and 103 hemorrhagic stroke cases and 268 ischemic stroke cases were observed during follow-up period. The independent risk factors of hemorrhagic stroke included decreased cerebrovascular function score [hazard ratio ( HR)=1.56, 95% CI: 1.23-1.98], history of alcohol consumption ( HR=2.46, 95% CI: 1.39-4.34), hypertension ( HR=1.75, 95% CI: 1.00-3.07) and older age ( HR=1.07, 95% CI: 1.04-1.10). The independent risk factors of ischemic stroke included decreased cerebrovascular function score ( HR=1.43, 95% CI: 1.25-1.65), smoking history ( HR=1.52, 95% CI: 1.13-2.05), hypertension ( HR=1.51, 95% CI: 1.10-2.07), family history of stroke ( HR=1.89, 95% CI: 1.13-3.15), left ventricular hypertrophy ( HR=1.74, 95% CI: 1.07-2.81) and older age ( HR=1.07, 95% CI: 1.05-1.08). Conclusions:Decreased cerebrovascular function score, hypertension, and older age were common independent risk factors of both types of stroke, alcohol consumption history was an independent risk factor of hemorrhagic stroke, and smoking history, and family history of stroke and left ventricular hypertrophy were independent risk factors of ischemic stroke.

Objective:To prepare cisplatin-loaded anti-progastrin-releasing peptide (ProGRP) monoclonal antibody targeted nanobubbles, and to explore the proliferation inhibition effect and anti-cancer molecular mechanism of them on small cell lung cancer (SCLC).Methods:The cisplatin targeted nanobubbles were prepared by thin film hydrating method, and the physicochemical property were explored. The subcutaneous xenograft tumor models of SCLC in 10 nude mice were established, and the ultrasound molecular targeting development effect of cisplatin targeted nanobubbles was analyzed by using blank nanobubbles as control. Another 24 tumor-bearing nude mouse models were established and randomly divided into four groups: blank nanobubbles group, cisplatin group, cisplatin nanobubbles group, cisplatin targeted nanobubbles group. The tumor inhibition rate was calculated. The effect on SCLC proliferation was detected by CCK8 method. RT-PCR and Western blotting methods were used to detect SCLC proliferation related genes the P53, Rb, c-myc protein and mRNA expression level of change, the molecular regulatory mechanism was analyzed.Results:The cisplatin targeted nanobubbles were successfully prepared. The particle size was (467.3±42.3)nm, the structure was stable. The cisplatin targeted nanobubbles had a good effect of ultrasonic molecular development in SCLC xenograft.Compared with the control group, the proliferation of SCLC cells was significantly inhibited by cisplatin targeted nanobubbles. The RT-PCR and Western blotting analysis showed that compared with the control group, the mRNA and protein levels of the proliferation-related gene P53 and Rb in the cisplatin targeted nanovesicles group were significantly up-regulated, and the mRNA and protein levels of c-myc were significantly down-regulated (all P<0.05). Conclusions:The cisplatin targeted nanobubbles can inhibit the proliferation of SCLC, and may be used as a new potential targeted drug for the treatment of SCLC.

Objective:To explore the application effect of transitional care mode (CTM) based on protective motivation theory (PMT) in patients with urinary calculus.Methods:A total of 156 patients with urinary calculus who were admitted to Henan Provincial People's Hospital from January to December 2019 were selected by the convenient sampling method. According to random number table method, they were divided into the control group and the observation group, with 78 cases in each group. The control group received routine nursing, while the observation group received CTM nursing based on PMT. The two groups were followed up for 1 year. The self-care ability, self-management efficiency score and recurrence rate of calculus were compared between the two groups before and after nursing intervention.Results:After 1 year of follow-up, the recurrence rate of calculus in the observation group was 1.28% (1/78) , lower than 8.97% (7/78) in the control group, and the difference was statistically significant ( P<0.05) . After nursing intervention, the self-care ability and self-management efficacy of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The implementation of PMT based CTM in patients with urinary calculus can reduce the recurrence rate of calculus and improve the self-care ability and self-management efficiency of patients.

Objective:To establish a 10-year comparison table of cerebrovascular function score and first stroke risk, and to provide a new method for screening of high-risk population of stroke.Methods:In the beginning of 2003, a cohort for studing stroke risk factors in those aged 40 years and over was established in a community of Shanghai by cluster sampling. The common risk factors of stroke were investigated with a unified questionnaire, and the cerebrovascular function (cerebral vascular hemodynamic indexes, CVHI) was measured. The baseline study was completed from April to June 2003 and December 2004 to January 2005, respectively. The incident of first stroke and all cause of death were followed up year by year. The follow-up period was up to December 31, 2014. The 10-year incidence of first stroke was calculated according to the baseline score of cerebrovascular function, and the score-risk control table was established to estimate 10-year first stroke risk in each score group. The role of cerebrovascular function score in stroke was also estimated.Results:The follow-up term of 10 565 participants was (10.26±2.00) years, and 350 patients had first stroke during the follow-up. The trend 10-year incidence of first stroke both in men and women was significantly increased with the decrease of the score of cerebrovascular function (trend χ2=296.125, P<0.01). As the 10-year risk of first stroke was higher than 5% and higher than 10%, the corresponding CVHI score was lower than 70 and 40 points in males and lower than 30 and 20 points in females. When the scores of cerebral vascular function were divided by every 25 points, incidence of first stroke in each group from top to bottom was 1.9%, 4.7%, 10.8%, 15.2% in males and 1.6%, 4.4%, 4.8%, 11.4% in females, respectively. As compared to the top, the relative risk (95% CI) of first stroke in the lower groups was 2.61(1.67-4.07), 6.46(4.22-9.89), 9.74(6.53-14.52) for males and 2.82(1.93-4.12), 3.15(1.99-4.99), 8.12(5.65-11.68) for females, respectively. Multivariate analysis showed that the factors being selected into the regression equation were cerebrovascular function score, age, hypertension history, stroke family history and smoking history, among which the role of cerebrovascular function score was the strongest. Conclusion:The risk of first stroke increases significantly with the decrease of cerebrovascular function score, which can be used to assess the 10-year risk of first stroke.

Objective:To investigate the diagnostic value of contrast-enhanced ultrasonography (CEUS) in evaluating the severity of renal artery stenosis.Methods:Eighty six patients with suspected renal artery stenosis admitted to Shanxi Provincial People′s Hospital from January 2018 to July 2021 were enrolled in the study. All patients underwent digital subtraction angiography (DSA), Doppler ultrasonography (DUS) and CEUS examinations. With DSA results as gold standard the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CEUS and DUS in the diagnosis of renal artery stenosis were analyzed. The consistency between CEUS and DSA in the diagnosis of renal artery stenosis was evaluated. The accuracy of DUS and CEUS in diagnosis of renal artery stenosis was assessed by the area under receiver operating characteristic (ROC) curve (AUC) and compared between groups.Results:Among 153 renal arteries from 86 patients examined by DSA, 101 showed the stenosis ≥30% (49 left and 52 right renal arteries), and there were 31, 45, 20 and 5 renal arteries with grade I, II, III and IV stenosis. The sensitivity and specificity of DUS in the diagnosis of renal artery stenosis were 74.3% (75/101) and 76.9% (40/52),respectively. DUS showed 21, 42, 20 and 4 renal arteries with grade Ⅰ, Ⅱ, Ⅲ and Ⅳ stenosis, respectively. The sensitivity and specificity of CEUS in the diagnosis of renal artery stenosis were 88.1% (89/101) and 86.5%(45/52), respectively. CEUS showed 26, 43, 23 and 4 renal arteries with grade Ⅰ, Ⅱ, Ⅲ and Ⅳ stenosis, respectively. There was a significant difference between DUS and DSA in grading of renal artery stenosis (χ2=4.447, P=0.03),and there was a moderate consistency between DUS and DSA ( Kappa=0.480). There was no significant difference between CEUS and DSA in grading renal artery stenosis (χ2=0.842, P=0.36) with a good consistency ( Kappa=0.730). The AUC of CEUS in diagnosis of renal artery stenosis was higher than that of DUS [0.873 (95% CI: 0.808-0.938) vs. 0.756 (95% CI:0.673-0.839); Z=4.361, P<0.01]. Conclusion:The study suggests that contrast-enhanced ultrasonography may be used as a diagnostic method for grading renal artery stenosis.

Autophagy is a highly conservative cellular self-protective behavior dependent on lysosomes, and can be used as an important factor in promoting or preventing cancer, and its effect is related to the type and development of tumors. A full understanding of autophagy pathway is helpful to improve the diagnosis and treatment of tumors. Studies have shown that autophagy is closely related to the occurrence and development of oral tumors. Autophagy-related genes and signal pathways play a dual regulatory role on oral tumors. This article reviews the latest progress in the regulatory mechanism and therapeutic effect of autophagy on oral tumors.

Objective: This study aimed to analyze and summarize the implementation of the primary prevention program for stroke in Shanghai rural community and evaluate its preventive effect. Methods: A cluster sampling method was used to select approximately 50 000 community natural population from a town in Fengxian District of Shanghai. A primary stroke prevention program was established and implemented in the community from 2008 to 2010 and from 2012 to 2015. The prevention program inclueded stroke health education for the whole population, screening of high risk population of stroke, and therapeutic intervention and management plan for individuals aged≥50 years. The intervention measures were followed up every 2 months. From 2008 to 2015, new stroke cases were monitored dynamically and reviewed annually with classification of stroke diagnosis. The effect of community primary prevention of stroke program was evaluated by the dynamic changes in stroke incidence. Results: From 2008 to 2015, a total of 422 600 individuals were monitored, including 20 500 men and 217 600 women. In 2008, 7 828 individuals were screened and 2 129 individuals were at high risk of stroke were screened, with a high risk rate of 27.2%. In 2012, 2 877 individuals were screened, and 725 individuals were at high risk of stroke were screened, with a high risk rate of 25.2%. The standardized incidence of stroke in this community was 158.1, 105.4, 86.6, 77.6, 89.3, 77.4, 50.7, and 42.3 per 100 000 respectively. The overall incidence image roughly showed a downward trend except 2012(trend test P<0.01). There was no significant difference in the incidence of stroke between men and women in each year. The incidence of stroke increased significantly with age (trend test P<0.01). The age composition of stroke patients is slightly different between different sexes. The proportion of male patients with stroke aged <70 years was significantly higher than that of female patients with stroke, while the proportion of female patients with stroke age>70 years was significantly higher than that of male patients with stroke (P<0.01). Cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage accounted for 20.76%, 75.14%, and 4.10%, respectively. Conclusion Based on lifestyle intervention and treatment and control of risk factors, screening high-risk individuals for therapeutic intervention in community population can significantly reduce the incidence of stroke.

Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. AntiSOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with antiSOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients.SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.