As the largest microbial community in human body,gut microbiota is involved in many important physiological processes,and gut microbiota dysbiosis is associated with various diseases in humans.Due to the interaction and mutual effect between the liver and the gastrointestinal tract,gut microbiota plays an important role in the development and progression of hepatobiliary diseases.Metagenomic studies can achieve a comprehensive understanding of the features of gut microbiota and its effect on human health and diseases.This article introduces the research advances in the changes of gut microbiota among patients with nonalcoholic fatty liver disease,liver cirrhosis,hepatocellular carcinoma,and autoimmune liver diseases and related mechanisms of action.

Objective:To investigate the expression and clinical significance of cell division cycle 42 (Cdc42) and WASP family verprolin-homologous protein l (WAVE1) in non-small cell lung cancer (NSCLC). Methods:The expression of Cdc42 and WAVE1 was detected in 106 paraffin-embedded NSCLC tissues and 46 adjacent normal lung tissues (control group) using immunohistochemis-try. Results:The expression levels of Cdc42 and WAVE1 was distinctly higher in NSCLC than in the control group. The expression of Cdc42 in NSCLC significantly correlated with tumor differentiation, TNM stage, and lymph node metastasis (P<0.05). The expression of WAVE1 in NSCLC was significantly correlated with TNM stage and lymph node metastasis (P<0.05 or P<0.01). The expression of Cdc42 was significantly correlated with WAVE1 in NSCLC (r=0.469, P<0.01). The 3-year survival rates were significantly lower in the group with high Cdc42 expression (44.16%) than in the low expression group (72.41%;P<0.01). Similarly, the 3-year survival rates were significantly lower among patients with high WAVE1 expression (39.44%) than in those with low expression (77.14%;P<0.01). Lymph node metastasis and the common high Cdc42 and WAVE1 expression were independent prognostic factors for NSCLC. Conclu-sion:The Cdc42 expression is correlated with WAVE1 expression. They may act together and have an important function in NSCLC. The expression of both Cdc42 and WAVE1 in NSCLC tissue may be used as markers for assessing the clinicopathologic features and prognosis.

In order to obtain high yield of the HrpNEcc protein with a lower total cost,fermentation and lactose induction conditions for recombinant E.coli BL21(DE3)/pET30a(+)hrpN Ecc were optimized in flasks and the recombinant E.coli was fermentated in 7L fermenter.The optimized incoulum concentration was 5% and the optimized nutrient medium was TB medium.The HrpNEcc protein yield reached 417.60mg/L by adding 3g/L exogenous inducer lactose in the growth prophase of log-phase for the recombinant E.coli.The HrpNEcc protein yield was higher 36.73% than that of the case of no any inducer,and was higher 16.85% than that of the case of adding IPTG.The wet weight of cell pellet of the recombinant E.coli reached 57.24g/L after fermentation in 7L fermenter,the HrpNEcc protein reached 3.29g/L,about 50.2% of total cellular protein.

A sensitive and effective method for determination of 16 kinds of antibiotics, including tetracycline, sulfonamide, fluoroquinolone and macrolide, in livestock and poultry manure using solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.Aiming at the chemical properties and sample impurities of the target, the parameters such as mass spectrum conditions, types of extraction and ultrasonic power were optimized.Finally, the samples were extracted with 50% acetonitrile in phosphate buffer solution (pH =4) for three times, followed by ultrasonic steaming, centrifugal and rotary, dilution, and purified by SAX-HLB.After sample loading, the solid phase was washed with 10 mL of methanol-acetone (80∶20, V/V), evaporated to near dryness at 35℃, and then re-dissolved and vortex mixed in 1 mL of 0.1% formic acid∶methanol (1∶1, V/V).The extracts were analyzed with UPLC-MS/MS and calculated by external standard method based on the monitored product ion.The results indicated that the average spiked recoveries of tetracycline, sulfonamide, fluoroquinolone and macrolide in manure were 56.4%-94.6% with relative standard deviations (RSDs) of 2.6%-19.8%, the LODs (S/N=3) were 0.01-2.50 μg/kg, and the LOQs (S/N=10) were 0.05-7.90 μg/kg.The method was simple with high stability, high sensitivity and good reproducibility, and suitable for the simultaneously determination of many antibiotics in animal and poultry manure.

Background and Purpose:Lung cancer is the most malignant tumour in the world.Its incidence is growing and NSCLC is predominent(80%) in lung cancer.Most patients with lung cancer were diagnosed in late stages.The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following,operation could be improved,micrometastasis could be annihilated and survival could be extended.Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC.Methods:98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC,stageⅠ~Ⅲ,were collected retrospectively in our hospital from 1995 to 1997.35 cases were stageⅠ.21 cases were stage Ⅱ.42 cases were stage Ⅲ.83 cases had 1 cycle of chemotherapy pre-operatively.15 cases had 2 cycles chemotherapy pre-operatively.Regimes of chemotherapy were MVP,MOP and MAP et al.Response rate(RR) of chemotherapy was:45 cases had partial response(PR) and 53 cases were stable disease(SD).Operative mode was lobectomy and pneumectomy with lymph nodes dissection.Pathologic type was squamous,adeno,adeno-squamous and others.All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stageⅠin 1996~1997.After being followed-up for more than 5 years,data were examined using life table,KaplanMeier method,Log Rank statistic and Cox-mantel test.The possible factors affecting survival were tested with univariate and multivariate analysis.Results:The median followed-up time of 98 cases for NSCLC was 41.2 months.36 cases were alive.62 cases were dead.The 1-,3-,5-year survival rate of 98 cases for NSCLC was 88.78%、49.63% and 18.46%.The 5-year survival rates of stageⅠ、ⅡandⅢ were 33.23%、20.26% and 5.52% respectively(P=0.0002).The 5-year survival rates of N_(0)、N_(1)、N_(2) were 35.49%、19.08% and 4.90% respectively(P=0.0004).In the 98 cases of NSCLC,better prognosis was correlated with earlier stage.The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy,lung hila activity,thorax lymph nodes negativity and squamous cancer was better.The prognosis was poorer if the tumor had invaded big vessels,viscera,chest wall,pericardium and quantity bleeding during≥400ml.The prognosis was better if the tumor was fibrotic.The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle.The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better.Conclusions:The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage,the period from last chemotherapy before operation to operation,operation mode,lung hila activity,thorax lymph nodes,site of tumor invasion,bleeding quantity,pathologic type,tumor fibrosis and necrotis,cycles chemotherapy pro-operation and chemotherapy post-operation.

BACKGROUNDTo compare the effect and toxicity between gemcitabine and cisplatin (GP) with vinorelbine, ifosfamide and cisplatin (NIP) combined chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC).

METHODSEighty patients received either gemcitabine 1 000 mg/m² on days 1, 8, or 15 plus cisplatin 70-80 mg/m² on day 1, or vinorelbine 25 mg/m² on days 1, 8, ifosfamide 1.2 g/m² on days 1-4 plus cisplatin 70-80 mg/m² on day 1, every 28 days as a cycle.

RESULTSThe objective response rate was 40.0% in GP goup, compared with 52.5% in NIP group (P > 0.05). Median survival time of GP and NIP groups was 13.68 and 15.34 months respectively, and 1-year survival rates were 54.29% and 59.46% respectively (P > 0.05). Leukopenia at grade III+IV was significantly lower in GP arm (27.5%) than that in NIP arm (55.0%) (P < 0.05). Non-hematological toxicities were less frequent in GP group than those in NIP group (P < 0.05).

CONCLUSIONSAlthough the response rate tends to be higher in three-drug than in two-drug combined chemotherapy, but no significant difference is observed. Three-drug combinations often result in more toxicities. Two-drug combination GP may be the standard protocol for chemotherapy of advanced NSCLC. Three-drug combination NIP should be given to young patients with good performance status.

BACKGROUNDTo detect dendritic cells (DC)in the peripheral blood and plasma concentration of vascular endothelial growth factor (VEGF) of patients with non-small cell lung cancer (NSCLC) and to evaluate their relationship.

METHODSThe quantitation of DC in the blood was performed in 55 patients with NSCLC, 13 patients with pulmonary benign diseases, and 12 healthy volunteers by a novel flow cytometric assay. The concentration of VEGF in the plasma was measured by ELISA kit.

RESULTSNo significant difference was found in the levels of DC and VEGF between the patients with pulmonary benign diseases and healthy volunteers (P>0.05). In comparison with subjects of healthy volunteers and pulmonary benign diseases, the level of DC was significantly decreased, while that of VEGF was significantly increased in the patients with NSCLC(P < 0.05 to 0.01). The levels of DC and VEGF in the peripheral blood of NSCLC were closely associated with TNM stages and lymph node metastasis. However, no correlation was found among the levels of DC and VEGF and age, gender, cell differentiation and histologic classification. There was a negative correlation between the VEGF concentration and the DC counts.

CONCLUSIONSThe decline of DC count in peripheral blood and the enhancement of plasma VEGF are remarkably related to the malignancy of NSCLC. And VEGF overexpression may be one of mechanisms of DC maturation and differentiation inhibition in patients with NSCLC.

BACKGROUNDDendritic cell (DC)-based immunotherapy is a new approach and effective for some malignant tumors. The aim of this study is to observe the efficacy and toxicity of immunotherapy with carcinoembryonic antigen (CEA) peptide-pulsed DCs in patients with refractory advanced lung cancer.

METHODSLung cancer patients with high CEA expression were enrolled into this project. Autologous DCs were generated from patients' plastic-adherent peripheral blood mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells (CIK) were cultured from non-adherent peripheral blood mononuclear cells. DCs and CIK were transfused to patients. Responses and toxicities were observed.

RESULTSA total of 22 patients with lung cancer received DCs immunotherapy. DCs doses were 2.5×10⁶-9.6×10⁷ (5.03×10⁶). CIK doses were 3.4×10⁸-46×10⁸. CD3, CD8, NK and IFN-γ levels obviously increased after treatment (P < 0.05). The 1-year survival rate was 68.2% (15/22). Main toxicities were fever and rash.

CONCLUSIONSDCs-based immunotherapy is feasible and safe to patients with lung cancer.

Objective To understand serotypes and clinical manifestation of children with invasive pneumococcal disease (IPD) in Suzhou,so as to find a better strategy for reducing the incidence and mortality of IPD. Methods Eighty children with IPD were enrolled into our study from January 2011 to December 2015. The data of epidemiology,serotype,clinical manifestation,laboratory results and prognosis were collected and analyzed. Results The mortality of 80 children with IPD was 17. 5%(14/80). Sixty percent of them were younger than 2 years old,and 78. 6% of 14 dead cases were younger than 2 years old,the median age of dead group 0. 68 (0. 45,2. 07) years was younger than 1. 61 (0. 85,3. 45) years of survival group ( P <0. 05). The incidence rates of hyperpyrexia,vomiting and somnolence in dead group were higher than those in survival group before admission ( P <0. 05), the incidence rates of shock, DIC, respiratory failure, AKI, seizure or coma in dead group were higher than those in survival group ( P<0. 05). The coincidence rate between choice of antibiotics before admission and drug sensitivity test was 15. 0%(12/80),the mortality of coincident group (coincidence between choice of antibiotics and drug sensitivity test) 8. 3% was lower than 16. 2% of non-coincident group with no statistical differences ( P>0. 05). The drug resistance rates of 80 pneumococcus to Erythromycin,Clindamycin,Tetracycline,Sulfamethoxazole,Penicillin,Cefotaxime,Amoxi-cillin,Chloramphenicol,Vancomycin and Levofloxacin were 100% (80/80),98. 8% (79/80),88. 8%(71/80),71. 3%(57/80),48. 8%(39/80),32. 5%(26/80),8. 8%(7/80),5. 0%(4/80),0(0/80) and 0(0/80) respectively. Eight serotypes of 80 IPD cases were listed in descending order:6B(25. 5%,20/80),14 (23. 8%,19/80),19F(15. 0%,12/80),19A(15. 0%,12/80),23F(8. 8%,7/80),20(5. 0%,4/80),9V (5. 0%,4/80) and 15B/C(2. 5%,2/80),and 6 serotypes of 14 dead cases were:6B(35. 7%,5/14),14 (28. 6%,4/14),19F(14. 3%,2/14),19A(7. 1%,1/14),23F(7. 1%,1/14) and 20(7. 1%,1/14); the coverage of IPD serotypes of 7-valent pneumococcal conjugate vaccine (PCV7) 77. 5%(62/80) was lower than 92. 5%(74/80) of 13-valent pneumococcal conjugate vaccine (P <0. 05). Conclusion Majority of dead cases of IPD is always younger than 2 years. The low coincidence rate of choices of antibiotics to inva-sive pneumococcus outpatient and low rate of PCV immunization in China are responsible for the high mortal-ity of IPD. Timely recognition of continuous hyperpyrexia, vomiting and somnolence in early stage and appropriate use of antibiotics is the key to improve the outcome of IPD. Thirteen-valent pneumococcal conju-gate vaccine immunization provides a robust strategy for reducing the incidence and mortality of IPD.

Objective:To compare the efficacy and safety of different dosages of new drugs in the treatment of PsA by using network meta-analysis.Methods:Three medical databases (PubMed, Web of Science, Cochrane Library) were searched for the studies that compared the efficacy and safety of 4 new drugs (secukinumab, ixekizumab, apremilast, tofacitinib) with different dosages in the treatment of PsA. Data from included studies were analyzed by Stata 15.0.Results:A total of 16 RCTs were included. The results of the network meta-analysis showed that: (1) Among the overall patients, in terms of ACR20 response rate, the larger the surface under the cumulative ranking (SUCRA), the more effective it is. Secukinumab 300 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q4W(79.0%), ixekizumab 80 mg Q2W(75.1%), secukinumab 150 mg Q4W(73.2%), apremilast 30 mg BID(50.6%), apremilast 20 mg BID(38.6%), tofacitinib 5 mg BID(18.1%), tofacitinib 10 mg BID(17.7%) and placebo(2.0%). (2) In terms of PASI75 response rate, the larger the area under the SUCRA curve, the more effective it is. Ixekizumab 80 mg Q4W(96.1%) had the best efficacy, followed by ixekizumab 80 mg Q2W(88.7%), secukinumab 300 mg Q4W(75.6%), secukinumab 150 mg Q4W(63.3%), apremilast 30 mg BID(44.5%), apremilast 20 mg BID(38.4%), tofacitinib 10 mg BID(30.0%), tofacitinib 5 mg BID(12.5%) and placebo(1.0%). (3) Among the overall patients, in terms of safety, the smaller the area under the SUCRA curve, the higher the safety it is. Secukinumab 300 mg Q4W (17.3%) has the best safety. (4) The results of subgroup analysis showed that in terms of ACR20 response rate, ixekizumab 80 mg Q2W(85.3%) had the best efficacy in bDMARDs-na?ve patients, while in bDMARDs-IR patients, secukinumab 300 mg Q4W(83.9%) had the best efficacy.Conclusion:Among all patients, secukinumab 300 mg Q4W is the best in terms of ACR20 response rate and safety, but ixekizumab 80 mg Q4W is more effective in improving PsA lesions comparing yo other drugs.