Nonalcoholic fatty liver disease （NAFLD） is a multisystem disease associated with obesity， insulin resistance， and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD， and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota， the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD， and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota， in order to provide new ideas for the treatment of NAFLD.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

OBJECTIVETo observe the protective effect of acupuncture preconditioning at "Jiaji" (EX-B 2) on acute myocardial ischemia-reperfusion injury (MIRI) in the rats and explore the mechanism.

METHODSFifty Wistar rats were randomly divided into a control group, a model group, a Jiaji group, a Neiguan group and a Quchi group, 10 rats in each one. In the Jiaji group, the Neiguan group and the Quchi group, electroacupuncture was given for preconditioning at "Jiaji" T4~T5 (EX-B 2), "Neiguan" (PC 6) and "Quchi" (LI 11) for 7 days before modeling. In the control group and the model group, the regular feeding was given, without any acupuncture. At the end of acupuncture, except the control group, ligating the left anterior descending coronary artery (LAD) was adopted to duplicate MIRI models in the rest groups. Electrocardio-gram (ECG) was monitored and ST-segment shift was analyzed. HE staining method was adopted to observe the morphology of cardiac tissue in the rats of the groups. The transmission electron microscope was used to observe myocardial cell ultrastructure. WST-1 method was used to determine the activity of serum superoxide dismutase (SOD), TBA method was used to determine the content of serum malondialehyde (MDA) and the real-time fluorescent quantitative PCR method to determine the expressions of Nrf 2 in ischemic myocardial tissue and downstream HO-1 gene.

RESULTSCompared with the control group, after LAD ligation, ST-segment was elevated and depressed in ECG apparently after reperfusion in the rest groups (all<0.05). The ST-segment elevation in the Jiaji group and the Neiguan group was less than that in the model group (both<0.05). Compared with the model group, SOD activity was increased apparently in the Jiaji group and the Neiguan group (both<0.05), and MDA content was reduced apparently (both<0.05). The effects in the Jiaji group were better than those in the Neiguan group (both<0.05). Pathologically, "Jiajia" (EX-B 2) and "Neiguan" (PC 6) all improved the morphology of cardiac tissue and cell ultrastructure. The effects in the Jiaji group were much more significant and the improvements in the Quchi group were not apparent. Compared with the control group, the expressions of Nrf 2 and HO-1 gene in myocardial tissue were down-regulated in the model group (both<0.05). Those were up-regulated apparently in the Jiaji group and the Neiguan group as compared with the model group (<0.05,<0.01). The up-regulation times of the expressions of Nrf 2 and HO-1 gene in the Jiajia group were the highest in comparison.

CONCLUSIONSAcupuncture preconditioning at "Jiaji" (EX-B 2) has the protective effect on cardiac ischemia and reperfusion damage, which is probably relevant with the up-regulation of Nrf 2-ARE pathway expression, the activation of endogenous anti-oxidative pathway, the improvement of oxygen free radical scavenging capacity and the alleviation of lipid peroxide damage.

G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility.
Animals ; Computational Biology ; Crystallography, X-Ray ; Gene Expression ; Humans ; Plasmids ; genetics ; metabolism ; Protein Domains ; Receptors, Adrenergic, beta-1 ; Receptors, G-Protein-Coupled ; classification ; genetics ; metabolism ; Receptors, Odorant ; metabolism ; Receptors, Purinergic P1 ; genetics ; metabolism ; Sf9 Cells ; Spodoptera

Objective To study effect of rubescens on inflammatory cytokines and liver function of alcoholic liver injury rat model.Methods 120 SD rats were chosed for studied, randomly divided into control group, model group and treatment group,40 rats per group.Alcoholic liver injury rat model was made by ethanol feeding approach, rubescens were given for treatment.Then serum AST, ALT, α-GST, GLDH content and liver tissue NF-κB, TNF-α, IL-6, IL-8 levels were detected by electrochemiluminescence and fluorescent quantitation PCR,respectively.Results Model group serum AST, ALT,α-GST, GLDH contents and NF-κB, TNF-α, IL-6, IL-8 contents in liver tissue were higher than control group(t=12.030~37.417, P<0.05). Treatment group serum AST,ALT, α-GST, GLDH contents and NF-κB, TNF-α, IL-6, IL-8 contents in liver tissue were lower than model group (t=5.128~32.325, P<0.05).Conclusion Alcohol feeding can cause liver damage, rubescens therapy can reduce liver injury, relieve inflammation.

Background and purpose: Uridine diphosphoglucu-ronosyl transferase 1A1 (UGT1A1) is an important enzyme for metabolism of irinotecan. The activity of UGT1A1 enzyme was significantly affected by the gene polymorphism. This study aimed to investigate the correlation of UGT1A1*28 and *6 gene polymorphisms with irinotecan-based chemotherapy in colorectal cancer(CRC). Methods: Analysis of UGT1A1*28 and *6 gene polymorphisms was performed in 160 gastrointestinal cancer patients admitted to Zhongshan Hospital Fudan University from Apr. 2013 to Dec. 2013 by amplifying the gene fragments using PCR, STR and Sanger sequencing. Eighty-two cases with CRC treated with irinotecan were chosen to observe the adverse events during chemotherapy. The incidence of different genotypes was compared. Results:The distribution of the genotypes in 160 gastrointestinal cancer patients was as followed:UGT1A1*28 wild-type genotype TA6/6 (124, 77.5%), heterozygous genotype TA6/7 (33, 20.5%), and homozygous genotype TA7/7 (3, 2.0%);UGT1A1*6 wild-type genotype GG (105, 65.6%), heterozygous genotype GA (48, 30.0%), and homozygous genotype AA (7, 4.4%). In the 82 CRC cases, the incidences of grade 3 and 4 neutropenia in the patients carrying UGT1A1*28 (TA6/7+TA7/7 ) were higher than those in the WT genotype (TA6/6) (58.3%vs 0.0, P<0.001), and increased the total incidence of adverse events (76.0%vs 45.6%, P<0.001). There was no signiifcant relevance between UGT1A1*6 genotype, age, gender chemotherapy and adverse events. Conclusion:In the CRC cases with irinotecan-based chemotherapy, the UGT1A1*28 (TA6/7+TA7/7) genotype signiifcantly increased the risk of grade 3 and 4 neutropenia. Detecting UGT1A1 gene polymorphisms may guide individualized treatment and predict adverse events.

Objective To establish a method for determining oxalate and citrate in urine simultaneously by capillary electrophoresis.The components,the concentration and pH of the buffer solution,the separation voltage and the injection time on theseparation were studied in detail.Methods The separations were carried out using potassium dihydrogen phosphatebuffer ina fused-silica capillary tubeby capillary zone electrophoresis (CZE) and the detection were monitored by UV.24 h-urine samples from patients (n =5) and health control (n =5) were collected from Zhongshan Hospital of Fudan University for systematically validating the method developed.Results The optimized separations were carried out using a 50 mmol/L potassium dihydrogen phosphatebuffer solution (pH 6.5) in a fused-silica capillary tube of 50 cm × 50 μm I.D.Injections were made by using the pressure mode for 10 s at 34 mbar.The detections were monitored by a UV at 200 nm after samples were separated at avohage of 30 kV.Under the seconditions,urinary oxalate and citrate were separated completely within 5 min.The relative standard deviations of migration time and peak area within-run foroxalate and citrate were less than 1％ and 3.0％ and the betweenrun relative standard deviations were less than 2.0％ and 4.0％,respectively.The detection limits were 1 mg/L for both oxalate and citrate.The linearity ranges of oxalate and citrate were both 0-500 mg/L with the correlation coefficient between 0.999 5 and 0.995 4 (P ＜ 0.05),respectively.The average recoveries were 102.38％ for oxalate and 92.74％ for citrate.Conclusion This method is proved to be simple,sensitive and accurate,and also applied to determine oxalate and citrate in urine samples with satisfactory results.

Objective To observe the clinical effect of acupuncture plus ginger-partitioned moxibustion in treating diarrhea-predominant irritable bowel syndrome (D-IBS). Method Ninety D-IBS patients were randomized into an acupuncture-moxibustion group (acupuncture plus ginger-partitioned moxibustion), an acupuncture group, and a Western medication group (Pinaverium bromide), 30 patients in each group. The clinical effect, symptom score, and quality of life in the 3 groups were observed. Result The general clinical effect of the acupuncture-moxibustion group was significantly higher than that of the acupuncture group and Western-medication group (P＜0.05), but there was no significant difference in comparing the total effective rate between the acupuncture group and acupuncture-moxibustion group (P>0.05). After treatment, the Western medication group showed marked decreases in abdominal pain, abdominal distension and discomfort, defecation property, and defecation frequency (P＜0.01);the acupuncture group showed significant decreases in abdominal pain, abdominal distension and discomfort, mucous stool, and appetite (P＜0.05, P＜0.01); the acupuncture-moxibustion group had significant decreases in abdominal pain, abdominal distension and discomfort, defecation property, defecation frequency, mucous stool, and appetite (P＜0.01). The quality of life score changed significantly in all groups after treatment (P＜0.05, P＜0.01);the changes of quality of life score in the acupuncture group and acupuncture-moxibustion group were both significantly higher than that in the Western-medication group (P＜0.01);the change of quality of life score in the acupuncture-moxibustion group was significantly higher than that in the acupuncture group (P＜0.01). Conclusion Acupuncture plus ginger-partitioned moxibustion and acupuncture alone both can produce a higher therapeutic efficacy than Pinaverium bromide in treating D-IBS; acupuncture plus ginger-partitioned moxibustion is superior to acupuncture alone.

The increased level of fibrinogen (Fg) is an independent factor that resulting in the occurrence of ischemic cardio-cerebrovascular diseases. The Fg level is correlated with heredity, age, sex, obesity, lipid, smoke, inflammation and infection, and the pathogenic effect of genetic factor has been increasingly receiving attention. In recent years, more than 10 FgBβ gene polymorphisms have been reported, among them, - 148C/T, - 455G/A, and - 854G/A are considered to be significantly correlated with the increased level of Fg, and may be one of the most key factors in influencing the genetic risk factors of the occurrence of ischemic cerebrovascular disease.

[Objective]To contrast the influence of using the electro-needling machine on the Zusanli(ST36) or Shangjuxu(ST37) ,or on the two points both to treat the postoperative distension of the abdomen.And simultaneously to obverse whether using the two points together has the coordination effect or antagonistic effect.[Method] Adopting the stochastic grouping contrastive technique,dividing the 100 patients into the Zusanli group,the Shangjuxu group,the cooperative group and the blank group. To contrastively observe each situation,including the abdominal rumbles sound,the abdominal pain,the transformation of the incidental symptoms and the first time of exhaust,before and after the acupuncture treatment in each group.[Result]The treatment group has the therapeutic effect,with the blank group comparison,having the significant difference(P0.05)with each other.There's no obvious coordination effect or antagonistic effect during the treatment in the cooperative group. [Conclusion] Using the electro-acupunture on Zusanli,Shangjuxu can play an important part in improving the recuperation of the gastrointestinal function after surgical treatment. It also can obviously relieve uncomfortable postoperative symptoms.