Objective To investigate the application value of hepatectomy via anterior approach in the surgery of primary liver cancer. Methods Clinical data of 138 patients with primary liver cancer undergoing hepatectomy in Sun Yat-sen Memorial Hospital and Lingnan Branch, the Third Afifliated Hospital of Sun Yat-sen University from June 2011 to June 2014 were retrospectively analyzed. There were 97 males and 41 females, aged 36 to 87 years with a median age of 52 years. The informed consents of all patients were obtained and the local ethical committee approval had been received. The patients were divided into the anterior approach hepatectomy group (anterior group, n=63) and traditional approach hepatectomy group (traditional group, n=75). Preoperative general data, intra-, post-operative parameters of two groups were compared using t test or Chi-square test. Results In the anterior group, the percentage of patients with Child-Pugh liver function grade B and C, multiple tumors and tumor diameter>10 cm was 73%(46/63), 44%(28/63) and 16%(16/63) respectively, which were signiifcantly higher compared with 37%(28/75), 17%(13/75) and 5%(4/75) in the traditional group (χ2=20.444, 12.051, 8.144;P<0.05). In the anterior group, the average intraoperative blood loss, transfusion volume of plasma and red blood cells were (428±17), (470±14) and (300±7) ml, which were signiifcantly lower compared with (517±11), (630±15) and (420±11) ml in the traditional group (t=-6.097,-2.927,-8.928;P<0.05). The rate of postoperative complications in anterior group was 10%(6/63), which was signiifcantly lower compared with 17%(13/75) in the traditional group (χ2=1.759, P<0.05). Conclusion For patients with poor liver function, multiple and large tumors, hepatectomy via anterior approach is a preferential surgical procedure rather than the traditional approach hepatectomy.

Objective To evaluate the value of ultrasound-guided core needle biopsy(US-CNB) in diagnosing malignant and benign thyroid nodule by meta-analysis.Methods A computer-based online retrieval on the accurate tests of US-CNB for diagnosing thyroid nodule was conducted in PubMed,Cochrane Library (Issue 5,2016),EMbase,CBM,CNKI,VIP,Wangfang Data databases.The retrieval time limit was from the database establishment to June 8,2016.The quality of included articles was assessed by using the quality assessment of diagnostic accuracy studies (QUADAS).The puncture success rate,diagnosis sensitivity (Sen),specificity (Spe),positive likelihood ratio (+LR),negative likelihood ratio (-LR),diagnostic odds ratio (DOR) and area under the curve (AUC) of summary receiver operating characteristic curve (SROC) were served as the outcome indicators.The included data were performed the statistical analysis by using STATA12.0 and Meta-Disc 1.4 softwares.Results A total of 29 diagnostic accuracy trials were finally included,involving 4 213 patients with 4 391 thyroid nodules.The meta-analysis results suggested that the US-CNB puncture success rate was 98.7 ％ [95％ CI (98.3 ％,99.0 ％)];Sen of US-CNB for diagnosing thyroid nodule was 0.94 [95％CI(0.93,0.95)],Spe=0.98[95 ％CI(0.98,0.99)],+LR=33.96[95％CI(20.31,56.78)],-LR=0.06[95％CI(0.04,0.10)],DOR=581.44[95 ％CI(335.08,1 007.87)],and the AUC of SROC was 0.99.Conclusion The current evidences indicate that UG-CNB has high diagnostic accuracy in benign and malignant thyroid nodules,and is worth promotion and application in clinic.

Objective To investigate the clinical value of magnetic resonance cholangiopancreatography (MRCP) in the preoperative evaluation of patients with biliary calculus. Methods Clinical data of 70 patients with biliary calculus in Sun Yat-sen Memorial Hospital and the Third Afifliated Hospital of Sun Yat-sen University from June 2012 to June 2013 were retrospectively analyzed. There were 38 males and 32 females with age ranging from 18 to 87 years old and the median age of 52 years old. The informed consents of all patients were obtained and the ethical committee approval was received. The patients underwent ultrasound examination and MRCP before operation. The surgical procedures were cholecystectomy+bile duct exploration and the intraoperative exploration result was the gold standard of diagnosis for biliary calculus and biliary tract variations. The detectable rate of biliary calculus and biliary tract variations by two methods were compared using Chi-square test and Fisher's exact probability test. Results The detectable rate of gallstones was 93%(62/67) by ultrasound and was 79%(53/67) by MRCP, where signiifcant difference was observed (χ2=4.968, P<0.05). The detectable rate of common bile duct stones was 61%(17/28) by ultrasound and was 86%(24/28) by MRCP, where signiifcant difference was observed (χ2=4.462, P<0.05). The detectable rate of the left and right hepatic duct stones was 2/5 by ultrasound and was 4/5 by MRCP, where no signiifcant difference was observed (P>0.05). The detectable rate of intrahepatic bile duct stones was 36%(4/11) by ultrasound and was 73%(8/11) by MRCP, where no signiifcant difference was observed (P>0.05). The detectable rate of biliary tract variations was 2/8 by ultrasound and was 7/8 by MRCP, where signiifcant difference was observed (P<0.05). Conclusions MRCP is superior to ultrasound examination in the detection of common bile duct stones and biliary tract variations. It can be a common practice in the preoperative evaluation of patients with biliary calculus when circumstances allow.

Uch37 is a de-ubiquitinating enzyme that is activated by Rpn13 and involved in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activity and is thought to be auto-inhibited. Structural comparisons revealed that within a homo-dimer of Uch37, each of the catalytic domains was blocking the other's ubiquitin (Ub)-binding site. This blockage likely prevented Ub from entering the active site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activation mechanism of Uch37 by Rpn13, we investigated the Uch37-Rpn13 complex using a combination of mutagenesis, biochemical, NMR, and small-angle X-ray scattering (SAXS) techniques. Our results also proved that Uch37 oligomerized in solution and had very low activity against the fluorogenic substrate ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) of de-ubiquitinating enzymes. Uch37Δ(Hb,Hc,KEKE), a truncation removal of the C-terminal extension region (residues 256-329) converted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activity comparable to that of a truncation-containing the Uch37 catalytic domain only. We also demonstrated that Rpn13C (Rpn13 residues 270-407) could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 complex. Uch37 was activated in such a complex, exhibiting 12-fold-higher activity than Uch37 alone. Time-resolved SAXS (TR-SAXS) and FRET experiments supported the proposed mode of auto-inhibition and the activation mechanism of Uch37 by Rpn13. Rpn13 activated Uch37 by forming a 1:1 stoichiometric complex in which the active site of Uch37 was accessible to Ub.
Binding Sites ; Catalytic Domain ; Chromatography, Gel ; Crystallography, X-Ray ; Humans ; Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Scattering, Small Angle ; Ubiquitin Thiolesterase ; chemistry ; genetics ; metabolism ; Ultracentrifugation

Algorithms ; Crystallography, X-Ray ; Disulfides ; chemistry ; Models, Molecular ; Protein Conformation ; Proteins ; chemistry

ObjectiveTo compare the feasibility of establishing the rat model of acute coronary syndrome with combined blood stasis and poison by lipopolysacharide （LPS） injection， ligation of coronary artery and different combinations of the two methods. MethodA total of 225 male SD rats were randomly divided into sham operation group， simple coronary artery ligation group， first injected LPS group ［LPS（5 mg·kg）injection 24 h before coronary artery ligation］ and follow injected LPS group ［LPS（5 mg·kg）injection 10 min after coronary artery ligation］. The indexes of each group were detected at 3， 24， 72 h after modeling， and the model was comprehensively evaluated. The general state and macroscopic evaluation indexes of traditional Chinese medicine （TCM） syndrome （tongue and pulse） of rats in each group were observed. ECG and echocardiography were used to evaluate cardiac function， and the myocardial ischemia and infarction areas were measured by Evans blue/2，3，5-triphenyltetrazolium chloride （TTC） staining. The content of creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， creatine kinase （CK）， and troponin T （cTnT） in serum as well as interleukin-1 β （IL-1β） and IL-6 changes were determined by biochemical method or enzyme-linked immunosorbent assay （ELISA）. Hematology analyzer was adopted to determine the white blood cell （WBC） count， and the four coagulation indexes， platelet aggregation rate， hemorheology and other coagulation evaluation indexes were also detected. The myocardial tissue was observed by hematoxylin-eosin（HE）staining. ResultAfter 3 h of modeling， compared with the conditions in sham operation group， the R， G and B values of tongue of rats （P<0.01）， pulse amplitude （P<0.01）， and cardiac function in simple coronary artery ligation group were decreased， and the color of hypoglossal veins became purple（P<0.01）. The content of CK， LDH， cTnT， IL-1β and IL-6 in serum（P<0.05）， myocardial infarction area（P<0.01）， and total number of WBCs （P<0.05）were increased. Compared with simple coronary artery ligation group， first injected LPS group and follow injected LPS group had increased hypoglossal veins， decreased R value of tongue and elevated cTnT content （P<0.01）， while follow injected LPS group had reduced B value of tongue， decreased cardiac output （CO）（P<0.05）， increased IL-1β content， and thinned left ventricular anterior walls at end-systole （LVAWs）（P<0.01）. After 24 h of modeling， compared with sham operation group， simple coronary artery ligation group presented significantly decreased R， G and B values of tongue， lengthened purplish dark hypoglossal veins （P<0.01）， reduced pulse amplitude（P<0.01） and cardiac function， enlarged myocardial infarction area（P<0.01）， increased whole blood viscosity， platelet aggregation rate， fibrinogen （FIB）， shortened prothrombin time （PT） and thrombin time （TT）（P<0.01）， and elevated total number of WBCs （P<0.01）and content of CK， LDH， cTnT and IL-6 in serum（P<0.05）. Compared with the conditions in simple coronary artery ligation group， the pulse amplitude， R， G and B values of tongue （P<0.01）， and ejection fraction （EF） and fractional shortening （FS） scores （P<0.05）dropped， and hypoglossal veins were deepened and lengthened（P<0.05）， and cTnT content was increased（P<0.01）in first injected LPS group and follow injected LPS group. However， follow injected LPS group had thinned LVPWs， increased LDH content， platelet aggregation rate（P<0.05）， myocardial infarction area， and total number of WBC， level of IL-1β（P<0.05）， and shortened TT（P<0.01）. Additionally， 72 h after modeling， compared with sham operation group， simple coronary artery ligation group showed significantly reduced pulse amplitude， lowered R， G and B values of tongue， thickened and lengthened hypoglossal veins（P<0.01）， decreased cardiac function， and increased content of cTnT， FIB， whole blood viscosity（P<0.01），platelet aggregation rate， level of IL-6 and IL-1β（P<0.05）. Compared with the conditions in simple coronary artery ligation group， the hypoglossal veins of the first injected LPS group and the follow injected LPS group were more purple， and the content of cTnT was boosted（P<0.01）， whereas follow injected LPS group had decreased pulse amplitude， R， G and B values of tongue， EF and FS scores （P<0.05）， and enlarged myocardial infarction area（P<0.01）. ConclusionCompared with the other modeling methods and models at different modeling time， the established model by LPS injection 10 min after coronary artery ligation for 24 h was more consistent with the clinical characteristics of acute coronary syndrome with combined blood stasis and poison.

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.