OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.
Aging ; Brain/metabolism* ; Energy Metabolism ; Humans ; Hypothalamus/metabolism* ; Obesity/metabolism*

Objective To realize the distribution and characteristics of Mycobacterium leprae (M.leprae) species and its single nucleotide polymorphisms (SNPs) spreading currently in China.Methods A total of 171 cutaneous lesion specimen of leprosy patients from 22 provinces were collected.The 16S rRNA conservative region of Mycobacterium leprae was amplified by nest PCR and the positive products were sequenced directly and aligned by BLAST.The SNPs of M.leprae were genotyped by restricted fragment length polymorphism for the PCR products.Results The 171 specimen were all Mycobacterium leprae since the amplified fragments of DNA samples were 99％ similar to the Br4923 of M.leprae from Brazil.No new species (M.lepromatosis) was found.Among the 85 samples genotyped for SNPs,SNP3,SNP1 and SNP2 accounted for 78.8％ (67/85),20％ (17/85) and 1.2％ (1/85) respectively.There was no sample with SNP4 genotype to be detected.Among the 171 sequencing specimen,130 showed mutation C-T at 251 bp of 16S rRNA.There was no difference for mutant rate of 16S rRNA gene and SNP genotype among the samples with different clinical pathological types.Certain associations between 16S rRNA C251T mutation and SNP genotype were found.Most of the samples with C251T mutations of 16S rRNA sequence were SNP3,only a few were SNP1 but not SNP2.There was significant difference of SNP genotype distribution among the patients from different regions.The distribution rate of SNP3 genotype in the samples from inland region (97.1％,34/35)was significantly higher than that from coastal region (66％,33/50) (x2 =11.96,P ＜ 0.01) . There was significant difference of the gene mutation rate of 16S rRNA sequence among the patients from different regions.The mutation rate of 16S rRNA in the samples from inland region (94.8％,92/97) was significantly higher than that from coastal region (51.4％,38/74) (x2 =43.56,P ＜0.01).Conclusion C251T mutation in 16S rRNA gene sequence of M.leprae may associate with SNP type suggesting that the characteristics of geographical distribution presented in different genotypes of M.leprae.No new species of M.leprae was found in this study.

Objective To produce the biological calcium citrate cement with fresh oyster shells, and investigate its compressive strength and biocompatibility so as to provide the experimental basis for clinical application of the material.Methods The compressive strength of biological calcium citrate cement was measured and its surface morphology was observed by SEM.The calcium release curve and pH value were measured in the simulated body fluid.Last, its biocompatibility was detected by cytotoxicity test.Results Biological calcium citrate cement produced by 0.33mL/g liquid solid ratio had the maximum compressive strength, and the crystal structure of the material was uniform and orderly.The determination of pH value showed that the degradation and absorption of biological calcium citrate cement did not significantly change the pH value of the body fluid.With gradual degradation of the material, the concentration of Ca2+ in the solution increased gradually.Cytotoxicity test showed that this material had good biocompatibility and no cytotoxicity.Conclusion Biological calcium citrate cement possesses strong compressive strength and good biocompatibility, and it can form a microenvironment with low in alkaline and high in calcium.

Objective To investigate the expression of pro-irtilammatory mediator in peripheral blood of patients with severe sepsis treated by different therapeutic dose of high-volume hemofiltration (HVHF). Methods According to the standard of severe sepsis, 83 cases were randomly divided into three groups, A group [60 ml/(kg·h)], S group[80 ml/(kg·h)], C group[100 ml/(kg·h)], respectively. The levels of TNF-α, IL-1, IL-8 in plasma of patients were measured by enzyme-linked immunosorbent assay (ELISA) before treatment and at 2, 4, 6, 8, 10 h after treatment, and the grades of APACHEⅢ were evaluated at every time-point simultaneously. Results The grades of APACHEⅢ were lower after treatment than those before treatment (P<0.05), but the decreases between every group had no significant deviation (P>0.05). The levels of TNF-Ⅲ, IL-1, IL-8 in plasma of patients were all decreased gradually after treatment. Compared with those before treatment, the levels of TNF-α,IL-1 and IL-8 at 2, 4 and 6 h after HVHF were obviously decreased (P<0.05). The levels of TNF-α, IL-1 and IL-8 were lightly increases at 4 and 6 h after HVHF, but they were lower that those before treatment (P<0.05). At every time-point, the levels of TNF-α, IL-1, IL-8 trended to decrease following the increase, of displacement liquid volume, the mean levels of pro-inflammatory mediator in C group were markedly reduced compared with the levels in A group (P<0.05). Conclusion HVHF can decrease the levels of pro-inflammatory mediator in peripheral blood of patients with severe sepsis and the grades of APACHEⅢ, the more the therapeutic dose of HVHF, the lower the levels of pro-inflammatory mediator.

0.05).As compared with pre-treatment,The bcore of the two gromps were significantly decreased,but were more quickly decreased in group B(P0.05).Conclusions Xuebijing Zhusheye can improve curative effect and degrade the case-fatality rates in the elderly with sepsis.The possible mechanism may be associated with the decreased serum TNF?,IL-1? and IL-6 levels and the increased IL-10 levels.