G protein- coupled receptors (GPCRs), also known as seven- transmembrane domain receptors, constitute the largest superfamily of cell surface receptors. By coupling to heterotrimeric G proteins, arrestins and other signaling molecules, GPCRs modulate diverse signal transduction pathways under physiological and pathological conditions. Recent studies have revealed crucial roles of GPCRs in tumorigenesis and development of cancer metastasis. This review summarizes roles of GPCRs, particularly the roles of those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine and angiotensin in proliferation, invasion, metastasis and angiogenesis of hepatoma cells and development of hepatocellular carcinoma. The potential of GPCRs- based therapeutics being used for hepatocellular carcinoma is also highlighted.

Objective To evaluate the effect of four carbapenems combined with EDTA for metallobeta-lactamases (MBLs) detection.Methods Thirty MBLs-producing gram-negative bacteria ( 16 strains of Enterobacteriaceae and 14 strains of Non-fermentative),9 KPC-producing Enterobacteriaceae and 10 OXA-producing Acinetobacter baumannii strains were collected from the Second Affiliated Hospital of Zhejiang University.A double disk screening test with EDTA was performed for MBLs detection,comparing the changes of inhibition zone diameter with or without EDTA.Results When the inhibition zone diameter difference of ≥5 nn as standard,the sensitivity of panipenem (PAN) group was relatively high (66.7％,20/30),followed by meropenem group (MEM) (63.3％,19/30) and imipenem (IPM) group (60.0％,18/30),etrapenem (ETP) group was the wont (43.3％,13/30).When the inhibition zone diameter difference of ≥4 mm as standard,the sensitivity of meropenem and panipenem group was 80.0％ (24/30)respectively.When the inhibition zone diameter difference of ≥ 3 mm as standard,the sensitivity of imipenem and meropenem group was 90.0％ (27/30) respectively,while 83.3％ ( 25/30 ) for etrapenem and panipenem group.Specificity of four groups under these three interpretation was 100％ respectively.Results of screening test for 16 MBLs positive strains showed that the sensitivity of panipenem group was the highest (75.0％,12/16).While using ≥ 5 mm as the MBLs positive interpretation,the sensitivity of panipenem group was the highest (75.0％,12/16).While using ≥4 mm as the MBLs positive interpretation,the sensitivity of panipenem group (93.8％,15/16) was much higher than that of imipenem (75.0％,12/16),meropenem (68.8％,11/16) and ertapenem (68.8％,11/16).Conclusions Detection of MBLs with EDTA is easy to operate,and it shows a low false positive rate against gram-negative bacteria.Ertapenem is not recommended to screen for MBLs,the best method for screening for MBL production in gram-negative bacteria is the MEM-EDTA or PAN-EDTA with a breakpoint of ≥4 mm.As for Enterobacteriaceae,PAN-EDTA with a breakpoint of ≥4 mm is better than the other three carbapenems in screening for MBL production,but panipenem is not recommended for MBLs screening tests for nonfermentative gram-negative bacteria.

Objective To investigate the molecular epidemiology and resistance mechanism of reduced carbapenem susceptibility of Proteus mirabilis from intensive care unit (ICU).Methods Nineteen carbapenem resistance or reduced carbapenem susceptibility of Proteus mirabilis were isolated from two ICUs in Second Afiliated Hospital of Zhejiang University from August 2010 to October 2010.Pulsed-field gel electrophoresis (PFGE) was performed to analyze the molecular epidemiology of isolates.Antibiotic susceptibilities were determined by agar dilution method.Conjugation experiments were carried out in mixed broth cultures.Plasmid DNAs were obtained by using an alkalinelysis technique.Specific polymerase chain reaction (PCR) and DNA sequencing were preformed to confirm the genotype of β-lactamases. Results Nineteen Proteus mirabilis showed resistance or reduced carbapenem susceptibility,and were resistant or susceptible to cephalosporins.PFGE analysis indicated that nineteen carbapenem-non-susceptible Proteus mirabilis belonged to 3 clones,named as clone A (14 isolates),clone B (2 isolates of subclone B1 and 2 isolates of subclone B2 ) and clone C (1 isolate).Fourteen clone A isolates were indistinguishable,and subclone B1 and subclone B2 were closely related with only one fragment disparity.Escherichia coli (EC600) acquired an approximately 45 000 bp,54 000 bp and 45 000 bp plasmids from clone A,subclone B1 and subclone B2 isolates separately by conjugation studies.PCRs and DNA sequence analysis confirmed that all Proteus mirabilis isolates and their transconjugants produced the KPC-2 carbapenemase. Conclusion Carbapenem-non-susceptible Proteus mirabilis were epidemic in two ICUs in our hospital,and were clonally disseminated.

Objective To compare the capability of ertapenem-hydrolyzing in various concentrations in KPC-producing Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry( MALDI-TOF MS).Methods Nineteen KPC-producing Enterobacteriaceae including ten Proteus mirabilis isolates,three Enterobacter aerogenes isolates,two Serratia marcescens isolates,two Citrobacter freundii isolates,one Klebsiella pneumoniae isolate and one Enterobacter cloacae isolate were isolated from 2nd Affiliated Hospital of Zhejiang University; Seven KPC-producing Morganella morganii were isolated from Hangzhou Traditional Chinese Medicine Hospital; Eleven Escherichia coli transconjugants produced the KPC-2 carbapenemase gene were conjugated from seven M.morganii and four P.mirabilis.MALDI-TOF MS was used to detect the ertapenem-hydrolyzing capability in different KPC-producing Enterobacteriaceae.Results When the concentration of ertapenem was 0.1 g/L,ertapenem can be hydrolyzed by KPC carbapenem within 1.5 h and the sensitivity was 100％,all the three peaks produced by ertapenem disappeared; when the concentration of ertapenem raised to 0.3 g/L,the sensitivity fell to 70.3％ (26/37) within 1.5 h,followed with 89.2％ ( 33/37 ) within 2.5 h and 94.6％ (35/37) within 3.5 h; when the concentration of ertapenem raised to 0.5 g/L,the sensitivity was 48.6％ (18/37) within 1.5 h,83.8％ (31/37) within 2.5 h,94.6％ (35/37 ) within 3.5 h.Two independent samples tests indicated that 0.1 g/L of ertapenem group has significant difference with 0.3 g/L and 0.5 g/L group,while there was no significant difference between 0.3 g/L group and 0.5 g/L group; As for the bacteria groups,there are no significant differences between the bacteria groups except the group of P.mirabilis and E.coli.Conclusion MALDI-TOF MS was easy to operate; it can rapidly detect KPC-producing Enterobacteriaceae with high sensitivity and a low false positive rate.0.1 g/L of ertapenem was recommended to detect KPC carbapenem rather than 0.3 g/L and 0.5 g/L; The detection time is short and can be widely applied clinically.

Objective To evaluate the safety,efficacy of interventional treatment for late postpancreaticoduodenectomy hemorrhage (LPPH).Methods From Jan 2008 to Dec 2017,678 patients underwent pancreaticoduodenectomy (PD).33 patients (4.9％) suffered from LPPH.30 of these 33 patients underwent diagnostic angiography and endovascular treatment,either transcatheter arterial embolization (TAE,n =21) or covered stent placement (CSP,n =9),and the other 3 underwent laparotomy.Results The incidence of LPPH is 4.9％ with a 12％ motality.The most common presentation is bleeding from abdominal drainage (24.2％) and melena (24.2％).The incidence of sentinel bleeding (SB) is 45.5％ and postoperative pancreatic fistula (POPF) is 69.7％.Intra-abdominal infection were identified in 24 patients (72.7％) and the most common pathogenic bacteria is pseudomonas aeruginosa (11/24,45.8％).The mean time between PD operation and LPPH was 17.4 days.In 21 patients receiving TAE,4 got liver damage and 2 with liver abscesses,1 died.The most common site of LPPH is GDA stump and re-bleeding occurred in 5 patients.9 patients by CSP got bleeding under control.In all 7 re-bleeding patients,2 were saved by CSP,1 was saved by TAE,while the other 4 died.Conclusion Early intervention plays an important role for LPPH.CSP is better than TAE.

Objective To study the compliance of forbidden depasturing livestock on the marshland with Oncomelania snails in schistosomiasis endemic areas. Methods According to 3 levels of human infection rates as > 10% ,5%-10% and <5% , 2 204 residents selected randomly from the schistosomiasis endemic villages were sampled with the stratified cluster sampling method in Hunan, Hubei, Jiangxi, Anhui, Jiangsu, Sichuan and Yunnan provinces, and investigated by questionnaire. The contents of the questionnaire included the recognition and implementation of forbidden depasturing livestock on marshland with Oncomelania snails and breeding livestock in bam. Results A total of 78.4% residents agreed forbidden depasturing livestock on marshland with snails, but 3. 7% residents disagreed it. A total of 83. 9% residents considered the relationship between breeding livestock in bam and schistosomiasis control, but 3. 1% residents thought that it was no relationship. The main reasons of depasturing livestock on marshland with Oncomelania snails were the high cost of breeding livestock in bam (36. 2% ) , unaccustomed (26.4% ) and no room for breeding livestock in bam (25.4% ). Conclusion Forbidden depasturing livestock on the marshland with Oncomelania snails should be strengthened according to the local economic, nature environment, agriculture, residents'culture degree and agriculture habit.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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