ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo evaluate the antipyretic effect of the Qingwen Baiduling prescription in a dry yeast-induced rat fever model and to investigate its antipyretic mechanism， providing a theoretical basis for its clinical application. MethodsSPF-grade male SD rats were randomly assigned to six groups （n=6 per group）： control， model， aspirin （20 mg·kg^-1）， and high-， medium-， and low-dose Qingwen Baiduling prescription groups （14.40， 7.20， 3.60 g·kg^-1）. The fever model was established by subcutaneous injection of dry yeast suspension on the back. After model induction， body temperature was recorded every 1 hour. Drugs were administered at 6 hours after modeling， and body temperature was continuously recorded hourly for 12 hours. Record the body temperature of rats to observe the trend of changes in body temperature. Serum interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） levels， as well as hypothalamic prostaglandin E₂ （PGE₂） and cyclic adenosine monophosphate （cAMP）， were measured using enzyme-linked immunosorbent assay （ELISA）. Hypothalamic tissue morphology was examined by hematoxylin and eosin （HE） staining. Western blot was used to detect hypothalamic expression of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， nuclear factor-κB p65 （NF-κB p65）， inhibitor κBα （IκBα）， phosphorylated IκBα （p-IκBα）， IκB kinase α （IKKα）， IKKβ， phosphorylated IKKα/β （p-IKKα/β）， and cyclooxygenase-2 （COX2）. ResultsCompared with the control group， the model group showed a significant increase in body temperature 6 hours after modeling （P0.01）， confirming successful fever induction. Serum IL-6， IL-1β， TNF-α， and hypothalamic cAMP and PGE₂ levels were significantly elevated （P0.01）. Hypothalamic neurons exhibited irregular morphology and disordered distribution， accompanied by inflammatory cell infiltration and microglial aggregation. Expression levels of TLR4/NF-κB pathway-related proteins and phosphorylated proteins were significantly increased （P0.05， P0.01）. Compared with the model group， 2-3 hours after administration， all Qingwen Baiduling prescription dose groups significantly reduced body temperature （P0.01）. All dose groups significantly decreased serum IL-6， IL-1β， TNF-α， and hypothalamic cAMP and PGE₂ levels （P0.05， P0.01）. Neuronal morphology was markedly improved in the high- and medium-dose groups， with narrowed intercellular spaces and reduced inflammatory infiltration. The prescription effectively inhibited hypothalamic expression of TLR4， MyD88， NF-κB p65， p-IκBα， p-IKKα/β， and COX2 proteins （P0.05， P0.01）. ConclusionQingwen Baiduling prescription effectively reduces body temperature in rats by mitigating the further effects of inflammatory cytokines on the hypothalamic thermoregulatory center through the blood-brain barrier. Its antipyretic mechanism may be related to inhibition of NF-κB pathway activation.

ObjectiveTo compare the diagnostic accuracy of five different weighting methods of Chinese medicine syndrome and then analyze their diagnostic efficacy and characteristics， by taking Diagnostic Standard for Type 2 Diabetes Mellitus （T2DM） with Dampeness-heat Syndrome （abbreviated as diagnostic standard） as an example. MethodsData from expert questionnaire on the diagnostic standard and a cross-sectional survey of 1021 patients were collected. The comparative diagnostic test accuracy （CDTA） method was used to calculate the area under the ROC curve （AUC）， area under the PR curve （AUPR）， accuracy （ACC）， sensitivity， and specificity of five commonly used weighting methods in two categories， including knowledge-driven weighting methods （expert scoring synthesis method， analytic hierarchy process， and precedence chart method） and data-driven weighting methods （logistic regression contribution method and entropy weighting method）. ResultsAmong 1021 patients with T2DM， 389 cases were diagnosed as dampness-heat syndrome. The expert scoring synthesis method， analytic hierarchy process method， and precedence chart method were basically consistent in the weight scores of each item. The expert scoring comprehensive method， analytic hierarchy process method， and entropy weighting method have a smaller difference in the weight scores of each item， while there was larger difference in the weight scores of each item of the precedence chart method and the logistic regression contribution method. The AUC （95% CI）， AUPR， ACC， sensitivity， and specifi-city of the expert scoring synthesis method were 0.913 （0.893， 0.932）， 0.851， 0.870， 0.868 and 0.875， respectively； while those of the analytic hierarchy process method were 0.910 （0.890， 0.930）， 0.838， 0.879， 0.848 and 0.896； of the precedence chart method were 0.919 （0.900， 0.937）， 0.858， 0.875， 0.871 and 0.875； of the logistic regression contribution method were 0.867 （0.842， 0.891）， 0.792， 0.853， 0.769 and 0.898； and of the entropy weighting method were 0.895 （0.873， 0.916）， 0.820， 0.869， 0.802 and 0.908. ConclusionThe knowledge-driven weighting methods are better than the data-driven weighting methods in terms of diagnostic efficacy and reflecting expert experience.

Diseases of glucose and lipid metabolism disorder,presented rather complicated pathological mechanism,often with clinical pattern of multiple concurrent diseases.Therefore,the traditional single-disease based on treatment methods need improving.In view of plenty of clinical practice,theatrical and fundamental researches,the pathological mechanisms of some chronic disorders,such as hyperlipidemia,nonalcoholic fatty liver disease,type 2 diabetes,hypertension,atherosclerosis and severe cardiovascular complications,resulted from the impairment in the metabolism of glucose and lipid were investigated using the method of integrated Chinese and western medicine.Overall,the features of these diseases and their common characteristics were discovered,and accordingly we defined the new concept of glucolipid metabolic disease (GLMD) and put forward the concept of pivot liver of metabolic regulation system.In addition,we developed the therapeutic strategy of modulating liver,starting pivot and cleaning turbidity,for the comprehensive and integrated treatment and prevention of these diseases.The theory of GLMD shared the critical characteristics with precision medicine,taking its own specialty.Finally,the content and approaches for the research of GLMD were proposed,and some essential and core fields in the precision medical research for GLMD were profoundly analyzed and prospected.

Humans ; Metabolic Syndrome

Objective To explore the mechanism of Borneolum combined with Rhizoma Chuanxiong in counteracting cerebral ischemia with reperfusion injury.Methods Rat Model of cerebral ischemia with reperfusion injury was set up by occlusion of bilateral carotid arteries.The effect of Borneolum combined with Rhizoma Chuanxiong on the content of nitric oxide(NO)and free radicals of model rat brain tissue was observed.Results Borneolum combined with Rhizoma Chuanxiong decreased the lipid peroxide(LPO)content and increased the activity of superoxidase(SOD)in model rat brain tissue(P

Objective To explore the mechanism of Fudoidan for regulating the disorder of lipid metabolism in rats. Methods Rat hyperlipidemic model was established. The effect of Fudoidan on rats levels of blood lipids, lipid metabolic enzyme, and the lipid contents in the stool, as well as bile metabolismand LDL-R mRNA expression in the liver were observed. Results Fudoidan can notably restrain the concentration of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) of hyperlipidemic rats and increase the concentration of high-density lipoprotein cholesterol (HDL-C) and activities of 1ipoprotein lipase (LPL), hepatic lipoprotein (HL) and lecithin cholesterol acyltransferase (LCAT).Fucoidan can remarkably increase the contents of cholesterol, TG, bile acid , but has no effect on the secretion of bile, the concentration of cholesterol and bile acid in bile. The results of RT-PCR experiment showed that Fudoidan can notably improve the expression level of low-density lipoprotein receptor (LDL-R) mRNA in the liver of hyperlipidemic rats. Conclusion Fucoidan can regulate the disorder of lipid metabolism probably by restraining the absorption of lipids (TC, cholesterol, bile acid) , activating the activities of lipid metabolic enzyme (LPL, HL and LCAT), and promoting the expression of LDL-R mRNA in the liver.

Objective To study the protective effects of aqueous extract and alcohol-soluble extract of Isodon lophanthoides var.gerardianus (Benth.)Hara (ILVG) on immunity hepatic injury induced by concanavalin A (Con A) in mice.Methods One hundred and eight NIH mice were allocated into normal control group,model group,ILVG groups of aqueous extract and alcohol-soluble extract (low-,middle-and high-dosage),and bifendate group randomly.In the experimental groups,mice received either ILVG aqueous extract or alcohol-soluble extract (18.20 g?kg-1,9.10 g?kg-1,4.55 g?kg-1 respectively) or Bifendate (45 mg?kg-1) by gastric perfusion daily for consecutive 5 days.In the 5th day,Con A (20 mg?kg-1) was injected into mice via the tail vein 4h after administration.And then the blood was obtained by picking out the eyeball and the serum was separated after 8-hour fasting.The serum levels of ALT and AST were analyzed,the body weight as well as the weight of liver,spleen and thymus were measured,and pathological features of hepatic tissue were observed.Results ILVG can decrease the ALT and AST,restrain the enlargement of liver and the shrinkage of thymus and reduce the necrosis of hepatic tissue.Conclusion Aqueous extract and alcohol-soluble extract of ILVG possess the effects of protecting liver from immunity injury induced by Con A in NIH mice.

Objective To observe the effect of Weichangshu Capsule (WCSC) in inhibiting experimental gastric ulcer and the damage of gastric mucosa in SD rats. Methods The experimental gastric ulcer rat models were established by ligation of pylorus, water immersing method and subcutaneous injection of indometacin, and rat models with acute damage of gastric mucosa were induced by hydrochloric acid- ethanol (HAE).Then the effect of WCSC in inhibiting experimental gastric ulcer and the damage of gastric mucosa in SD rats were observed. Results WCSC had obviously inhibitory effects on stress gastric ulcer, indometacin- induced gastric ulcer and HAE- induced acute damage of gastric mucosa. WCSC also inhibited the secretion of gastric juice and increased pepsase activity. Conclusion WCSC has counteraction on experimental gastric ulcer.