Objectives To evaluate the efficacy and safety of single-incision versus conventional laparoscopic cholecystectomy.Methods We searched electronic databases (PubMed,EMBASE,Cochrane Library,Chinese Biomedicine databases) from January 2000 to April 2012.Personal contact with experts in the field of laparoscopic cholecystectomy was performed to identify further potentially relevant clinical trials.Randomized controlled trials conducted on single-incision versus conventional laparoscopic cholecystectomy were analysed to compare conversion rates,blood loss,operation time,postoperative complications,wound satisfaction score,postoperative pain score and postoperative duration of hospitalization.Data were extracted by two reviewers independently.Statistical analysis was performed by using the RevMan 5.1 software.Results Twelve studies involving 915 patients met the inclusion criteria.When compared with conventional laparoscopic cholecystectomy (LC),the singleincision laparoscopic cholecystectomy (SILC) group showed no significant difference in conversion rate (OR=0.70,95％CI: 0.13～3.77,P=0.68),postoperative complications (OR=1.13,95％CI:0.72～1.78,P＝0.59) and postoperative pain scores (WMD＝-0.18,95％CI:-0.78～-0.43,P=0.57) . There was a significant increase in operative blood loss (WMD ＝ 1.43,95 ％ CI: 0.09 ～2.78,P＜0.05),increase in operative time (WMD=16.79,95％CI: 9.05～24.52,P＜0.01),but an increase in wound satisfaction score (WMD=1.28,95％CI..1.09～1.47,P＜0.01).The postoperative duration of hospitalization was significantly shorter (WMD =-0.30,95％ CI:-0.58 ～-0.02,P＜0.05).Conclusions Current evidence suggests that there is no significant difference in conversion rate or postoperative complications between SILC and LC.Although SILC requires a longer operative time and there is more blood loss when compared with LC,the SILC is superior in wound satisfaction score and in duration of hospitalization.

Objective To study the relationship between expression of G-protein-coupled bile acid receptor 1 (GPBAR1) in gallbladder mucosa and formation of lithogenic bile in patients with gallstones.Methods Gallbladder mucosa,gallbladder wall,bile and plasma were collected from 34 patients with gallstone (GS) and 15 individuals who were gallstone free (GSF).The gallbladder wall was stained with hematoxylin-eosin (HE) and immunohistochemistry to detect pathologic changes and expressions of GPBAR1,mucin 1 (MUC1) and mucin 5AC (MUC5AC).Reverse-transcription polymerase chain reaction (RT-PCR) was used to test mRNA expressions of GPBAR1,MUC1 and MUC5AC in the gallbladder mucosa.The contents of total cholesterol (TC),total bile acid (TBA),triglyceride (TG),low density lipoprotein (LDL) and high density lipoprotein (HDL) in plasma and cholesterol,TBA,phospholipid (PL) and mucin in the bile of gallbladder were measured.Results The gallbladder mucosa in all GS patients showed chronic inflammation on hematoxylin-eosin staining.The expressions of GPBAR1 and MUC5AC were more markedly increased in the GS group than in the GSFgroup (61.34±8.06 vs.43.05±7.83,P＜0.01; 52.11±9.62 vs.45.05±9.27,P＜0.05).The mRNA expressions of GPBAR1 and MUC5AC in the GS group were also more markedly increased than in the GSR group (0.87±0.07 vs.0.80±0.09,P＜0.05; 1.04±0.22 vs.0.8±0.17,P＜0.01).Serum cholesterol,as well as biliary cholesterol,cholesterol mol percentage,cholesterol saturation index and mucin in the GS group were more significantly higher than in the GSF group (5.07±1.64 vs.3.62±1.42,P＜0.01; 17.23±3.67 vs.12.47±2.31,P＜0.01; 7.47±0.65 vs.5.05±0.24,P＜0.01; 1.03±0.58 vs.0.69±0.38,P＜0.01; 92.02±20.89 vs.76.36±19.71,P＜0.05).Biliary total bile acids and bile acids mol percentage were lower in the GS group than in the GSF group (162.68±20.19 vs.180.21±26.05,P＜0.05; 71.28±1.84 vs. 73.29±0.96,P＜0.01). In the GS group,there were negative correlations between the mRNA expression of GPBAR1 and biliary TBA (γ=-0.341,P＜0.05).There were negative correlations in the GS group between the GPBAR1 expression and the level of biliary TBA (γ=- 0.403,P＜0.05),and between the GPBAR1 expression and the level of biliary total lipid (γ=-0.365,P＜0.05).Conclusions This study shows an increase in expression of GPBAR1 in gallbladder mucosa in patients with GS.It is suggested that GPBAR1 may accelerate formation of lithogenic bile by inducing re-absorption of bile acid.

AIM: To investigate the protective effect of five natural anti-oxidants (schisandrin B, Sch B; silibinin, SIB; propyl gallate, PG; sodium ferulate, SF; total flavonoids of hippophase, TFH) on experimental oxidative injuries of lens. METHODS: All fresh transparent lenses of rabbit eyes except control group were bathed in Fenton reaction system in order to produce a model of oxidative damages of lens, meanwhile Sch B, SIB, PG, SF, TFH and pirenoxine sodium (PS) were added in the reaction system in different groups respectively. Lenses were incubated for 24 hours. Then total protein (TP), soluble protein (SP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), vitamin C (Vit C), total activities of anti-oxidation (TAO) and malondiaoldehyde (MDA) in homogenized lenses were measured to observe the effects of five anti-oxidants on above index. RESULTS: Five anti-oxidants increased the anti-oxidative index and decreased MDA in lens of oxidative damages in different levels, the effects are better than that of PS, especially in group SF and Sch B. CONCLUSION: The five natural anti-oxidants protected lens against experimental oxidative injuries very well. There are wide prospects to pursue effective anti-cataract drugs from natural anti-oxidants.

AIM: To investigate the effects of Co-SZ eye drop on galactose cataract in rats. METHODS: Based on folk remedy, SZ eye drop was made from leech, as a modified SZ eye drop, Co-SZ eye drop was enriched in Zinc and Vitamin C. In the present study, animal model of galactose cataract in SD rats was used. All animals were randomly divided into 3 groups : control group(using 0.9 % NaCl instead of SZ and Co SZ), SZ group and Co-SZ group. Lens opacities were examined dynamically in each groups via FS-3V slit-lamp microscope. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH) and soluble protein (SP) in the lenses were measured in 15 days. RESULTS: Both the Co-SZ and SZ eye drops could significantly delay and alleviate galactose cataract in rats, with better effect of Co-SZ than SZ eye drop. The antioxidant index indicated that SOD, GSH-Px, GSH in Co-SZ and SZ group were significantly higher than that in control group. Furthermore, SOD, GSH-Px in Co-SZ group were higher than that in SZ group significantly. CONCLUSION: Co-SZ eye drops could significantly delay and alleviate galactose cataract in rats, the effect is much better than SZ eye drops. The different effect between SZ and Co-SZ eye drops could be raised from the different content of Zinc, which is involved in anti-oxidation.

Objective To design and synthesize a series of new type four hydrogen quinoline-benzyl/benzimidazole amine derivatives as a potential new inhibitor targeting auxiliary receptor CXCR 4, and determine their inhibitory activities to HIV-1.Methods Based on HIV-1 receptor CXCR4 inhibitors containing three nitrogen structure-activity motif and CCR5 partial hydrophobic pharmacophore , a series of new compounds were designed , synthesized and characterized by 1 HNMR and MS.The inhibitory activities of these compounds were determined using HIV-1 IIIB virus.Results and Conclusion Ten target compounds are synthesized .Four hydrogen quinoline-benzimidazole amine derivatives exhibit good anti-HIV activity(IC50 <1 μmol/L), but four hydrogen quinoline-benzyl amine compounds are less active ((IC50 >8 μmol/L).

OBJECTIVETo investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC).

METHODSThe role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively.

RESULTSWestern blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109.

CONCLUSIONmiR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Esophageal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; metabolism ; Receptor, ErbB-4 ; metabolism

OBJECTIVE: To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice. METHODS: Sixty C57BL/6 mice were divided equally into sham-operated group, saline adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay. RESULTS: The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, < 0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) ( < 0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, < 0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, < 0.05), and the levels TNF-α and IL-1β were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, < 0.05). No significant differences were found in these parameters between the empty vector group and the control group (>0.05). CONCLUSIONS SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.
Animals ; Apoptosis ; Liver ; Methyltransferases ; Mice ; Mice, Inbred C57BL ; NF-kappa B ; Reperfusion Injury ; Serine

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

Objective: To analyze the prognostic factors of adult nonclear cell renal cell carcinoma (nccRCC). Methods: The clinical data of 286 patients with pathologically diagnosed one specific type of nccRCC after radical nephrectomy and nephron sparing surgery(NSS) in the affiliated hospital of Qingdao university followed up from January 2012 to January 2019 were retrospectively analyzed.There were 159 males and 127 females. Their age ranged from 17 to 81 years old, with an average age of 53. Based on the AJCC combination stage, 218 cases were in stage Ⅰ, 56 cases were in stage Ⅱ, 9 cases were in stage Ⅲ, 3 cases were in stage Ⅳ. Assay indicators were collected, including lymphocyte percentage(LY%)(31.5±10.5), neutrophil-lymphocyte ratio(NLR)(2.6±2.8), albumin(40.9±4.7)g/L, prealbumin(255.0±74.3)mg/L, lactate dehydrogenase (LDH)(201.0±174.0)U/L, creatine kinase isoenzyme (CK-MB)(20.0±62.1)U/L, total cholesterol(4.9±1.0)mmol/L, blood urea nitrogen/creatinine (BUN/Cr)(12.9±9.9), blood glucose(5.4±1.3)mmol/L, triglyceride(1.4±1.1)mmol/L, low-density lipoprotein cholesterol (LDL-C)(2.9±0.8)mmol/L. The optimal cut-off value of the above indexes were obtained by the receiver operating characteristic curve(ROC) in the SPSS software, and difference between high cut-off and low cut-off divided basing on the optimal cut-off value were evaluated respectively. The prognostic factors of adult nccRCC were evaluated by univariate and multivariate Cox proportional hazards regression analysis. Kaplan-Meier survival curve was used to study the survival relationship. The log-rank test were used to compare survival rate in two groups. The prognostic factors of nccRCC were analyzed after the results above were presented. Prognostic factors in renal chromophobe cell carcinoma and papillary cell carcinoma were analyzed by the same method. Results: The 286patients were followed up from 1 to 87 months, with an average of 43.9 months. The 3-year and 5-year survival rates were 93.8% and 89.3%, respectively. Results of univariate and multivariate Cox regression model revealed that AJCC combined staging (HR=2.38, 95%CI1.48-3.83), LDH(HR=2.99, 95%CI1.16-7.69), blood glucose (HR=4.13, 95%CI 1.74-9.78), CK-MB (HR=3.85, 95%CI1.63-9.08) were independent prognostic factors of nccRCC. NLR(HR=8.28, 95%CI1.66-41.35) and LDH(HR=9.82, 95%CI2.94-32.82) were the independent prognostic factor in the renal chromophobe cell carcinoma subgroup and the papillary renal cell carcinoma subgroup, separately. Conclusions AJCC combination stage, LDH, blood glucose and CK-MB are independent prognostic factors of adult nccRCC. Patients with low LDH, hypoglycemia, CK-MB and early AJCC stage have better prognosis. NLR is an independent predictor of renal chromophobe cell carcinoma, and the low NLR group has a better prognosis and higher survival rate. LDH is an independent predictor of papillary renal cell carcinoma and low LDH is beneficial to patients' prognosis. NLR and LDH can be used as a prognostic indicator for clinical evaluation in renal chromophobe cell carcinoma and papillary renal cell carcinoma, respectively.

ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription， their clinical symptoms were observed， and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry （LC-MS） were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine （TCM） syndromes of patients after drug administration decreased significantly （P<0.01）. The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration， and a total of 106 differential metabolites were screened out （P<0.05）. The Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis revealed that arginine-proline metabolism， ferroptosis， glycine， and serine and threonine metabolism were significantly enriched metabolic pathways （P<0.05）. Notably， L-4-hydroxyglutamate semialdehyde， glutathione， isopentenyl pyrophosphate， creatinine， 4-acetamido-2-aminobutanoic acid， and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore， the association between these metabolites and different intestinal flora was analyzed， and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium， Eggerthella， and Dialister （P<0.05）. ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria， reducing the abundance of harmful bacteria， and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.