Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

Objective The monosaccharide composition of Abelmoschus Manihot Radix polysaccharide was identified and then we evaluated the therapeutic effect on slow transit constipation.Finally,the pharmacodynamic substances and molecular mechanisms in the polysaccharide from Abelmoschus Manihot Radix to improve slow transit constipation were explored by network pharmacology and molecular docking techniques.Methods The polysaccharide from Abelmoschus Manihot Radix has been prepared by aqueous-alcoholic precipitation and has been determined by HPAEC method;The mice model of slow transit constipation was made by sc loperamide(10 mg?kg-1)and the therapeutic effect for the treatment of constipation was evaluated by two indicators:fecal water content and small intestinal propulsion rate;Pathological changes in the colon tissue of STC mice were observed by HE.Immunohistochemical method was used to detect zonula occludens-1(ZO-1)and claudin-1 expression in colon tissue of STC mice;qRT-PCR method was used to detect mRNA expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 in each group;Network pharmacology and molecular docking technology were used to explore the potential targets and pathways of the polysaccharide from Abelmoschus Manihot Radix in treating slow transit constipation.Results The Polysaccharide from Abelmoschus Manihot Radix significantly increased fecal water content and intestinal propulsion rate in mice caused by slow transit constipation,decreased the expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 mRNA(P<0.01,P<0.001),protected the integrity of the colonic barrier in STC mice,and increased the protein expressions of ZO-1 and claudin-1 in colon tissues of STC mice.By network pharmacology,it was found that monosaccharides such as rhamnose,fucose and glucuronic acid could mainly act on key targets such as STAT3,JUN,CASP3,HSP90AA1,VEGFA and IL-1β and regulate the Inflammatory mediator regulation of TRP channels,EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications to improve the symptoms of constipation in mice.Western blot results showed that intervention with polysaccharides from the roots of Solanum palmatum significantly reduced the expression of CASP3,VEGFA and IL-1β protein in the colon tissue of constipated mice.Conclusion The polysaccharide from Abelmoschus Manihot Radix can treat slow transit constipation through multi-component,multi-target and multi-pathway therapy.It provides a scientific basis for the further clinical application of Abelmoschus Manihot and drug development(National patent ZL202310894613.3.has been authorized)and it is expected to promote the efficient utilisation of resources from the non-medicinal parts of Abelmoschus Manihot.

Objective The monosaccharide composition of Abelmoschus Manihot Radix polysaccharide was identified and then we evaluated the therapeutic effect on slow transit constipation.Finally,the pharmacodynamic substances and molecular mechanisms in the polysaccharide from Abelmoschus Manihot Radix to improve slow transit constipation were explored by network pharmacology and molecular docking techniques.Methods The polysaccharide from Abelmoschus Manihot Radix has been prepared by aqueous-alcoholic precipitation and has been determined by HPAEC method;The mice model of slow transit constipation was made by sc loperamide(10 mg?kg-1)and the therapeutic effect for the treatment of constipation was evaluated by two indicators:fecal water content and small intestinal propulsion rate;Pathological changes in the colon tissue of STC mice were observed by HE.Immunohistochemical method was used to detect zonula occludens-1(ZO-1)and claudin-1 expression in colon tissue of STC mice;qRT-PCR method was used to detect mRNA expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 in each group;Network pharmacology and molecular docking technology were used to explore the potential targets and pathways of the polysaccharide from Abelmoschus Manihot Radix in treating slow transit constipation.Results The Polysaccharide from Abelmoschus Manihot Radix significantly increased fecal water content and intestinal propulsion rate in mice caused by slow transit constipation,decreased the expressions of AQP3,AQP4,TNF-α,IL-1β and IL-6 mRNA(P<0.01,P<0.001),protected the integrity of the colonic barrier in STC mice,and increased the protein expressions of ZO-1 and claudin-1 in colon tissues of STC mice.By network pharmacology,it was found that monosaccharides such as rhamnose,fucose and glucuronic acid could mainly act on key targets such as STAT3,JUN,CASP3,HSP90AA1,VEGFA and IL-1β and regulate the Inflammatory mediator regulation of TRP channels,EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications to improve the symptoms of constipation in mice.Western blot results showed that intervention with polysaccharides from the roots of Solanum palmatum significantly reduced the expression of CASP3,VEGFA and IL-1β protein in the colon tissue of constipated mice.Conclusion The polysaccharide from Abelmoschus Manihot Radix can treat slow transit constipation through multi-component,multi-target and multi-pathway therapy.It provides a scientific basis for the further clinical application of Abelmoschus Manihot and drug development(National patent ZL202310894613.3.has been authorized)and it is expected to promote the efficient utilisation of resources from the non-medicinal parts of Abelmoschus Manihot.

Background: This study aimed to explore relationships between job stress and psychological adaptation and how they related to interpersonal needs through mood states among female migrant manufacturing workers. Methods: A cross-sectional survey was conducted in 16 factories in Shenzhen, China. Sociodemographic, job stress, psychological adaptation and other psychological information of was collected. Structural equation modeling was performed to delineate the internal relationship between variables. Results: The hypothetical structural equation model exhibited acceptable model fit among female migrant manufacturing workers (χ2 = 11.635, df = 2, χ2/df = 5.82, p = 0.003, RMSEA = 0.090, CFI = 0.972, SRMR = 0.020). Job stress was directly associated with mood states and interpersonal needs; Psychological adaptation was directly associated with mood states and indirectly associated with interpersonal needs; Bootstrapping tests demonstrated mediation effect of mood states in the way from psychological adaptation to interpersonal needs. Conclusion Female migrant manufacturing workers who suffered stress from job and the process of psychological adaptation may have worse mood states and workers with worse mood states are more likely to develop unmet interpersonal needs, a proximal factor of suicidal ideation.

Objective:To investigate the expression of connexin-43 (Cx43) in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism.Methods:The model of steroid-induced osteonecrosis of femoral head (SIONFH) of rat was established. Micro-CT and HE staining were used to observe the degree of bone trabecular destruction and the incidence of empty lacunae. The expression levels of Cx43 and PI3K/Akt signaling pathway related molecules and osteoblast-related proteins in model group and control group were detected by RT-PCT and Western blot. The osteoblast (OB) of rats was further isolated and cultured in vitro. Under treatment of dexamethasone (Dex), Cx43 expression in OB cells was detected by Western blot and immunofluorescence. Western blot was used to detect the effect of glucocorticoid (GC) on the expression of related molecules of PI3K/Akt/β-catenin signaling pathway. Akt activator (SC79) and PI3K inhibitor (LY294002) were used to study the molecular mechanism of Dex regulation on Cx43 expression in OB cells. The regulatory relationship between β-catenin and Cx43 was investigated by immunoprecipitation and small interfere RNA (siRNA) technology.Results:The model of SIONFH in rats was successfully established, which proved that Cx43 expression level in the SIONFH model group was significantly lower than that in the control group, and the expression level of Cx43 was positively correlated with the expression of PI3K/Akt signaling pathway related molecules and osteoblast-related proteins Runx2, ALP and Collagen I Type (COL). In addition, in vitro culture of isolated rat OB cells, the expression of Cx43, p-PI3K, P-Akt and β-catenin in OB cells decreased gradually as the Dex action time went on. Moreover, SC79 pretreatment could significantly reverse the inhibitory effect of GCs on Cx43 expression, while LY294002 could significantly enhance the inhibitory effect of GCs on Cx43. In addition, the immunoprecipitation results showed that β-catenin expression was closely related to Cx43 expression, and further studies showed that β-catenin-siRNA could significantly down-regulate the expression of Cx43.Conclusion:Under the action of GC, the expression level of Cx43 in bone tissue and OB cells decreased significantly, and the possible mechanism was that GCs inhibited the expression of Cx43 by inhibiting the PI3K/Akt/β-catenin signaling pathway, which laid a new theoretical foundation for the further study of the role of Cx43 in the pathogenesis of steroid-induced femoral head necrosis.

Objective To explore the effect of community comprehensive intervention on stroke-prevention-related knowledge, belief and behavior of hypertensive patients. Methods The community-based comprehensive interventions were done to 77 hypertensive patients, with the measures including archives establishment, hypertension-phased management, regular follow-up and multi-mode health education. The stroke-prevention-related knowledge, belief and behavior of them were assessed by the stroke-preventing knowledge questionnaire (SPKQ), champion′s health belief model scale (CHBMS) and (stroke-prevention behavior questionnaire,SPBQ) before and after the intervention. Results Their knowledge on daily-life and pre-stroke symptoms and part of their behaviors (health duty, physical exercises and stress management after the intervention were superior, as compared to the pre-intervention (P<0.05). There were no significant differences in other stroke-related knowledge and behaviors and health belief in comparison of the pre-and post-intervention (P>0.05). Conclusion The community-based intervention can improve parts of stroke prevention knowledge and health behavior among hypertensive patients. The intervention needs to be modified based on ecological models of health promotion and health belief model.