Hepatolithiasis is a common bile duct disease in China.Chinese scholars in the biliary tract surgery field earnestly comply with the famous twelve-word policy of obstruction clearance,lesion removal and free drainagewhich was put forward by academician Huang Zhiqiang,meanwhile,persist in doing the clinical and basic researches on the pathogenesis,pathology,pathophysiological characteristics and strategies of surgical treatment for decades.Diagnosis and Treatment Guidelines of Hepatolithiasis (2007 edition) and Expert Consensus of Laparoscopic Treatment of Hepatolithiasis (2013 edition) are highest standardization literatures about the diagnosis and treatment of hepatolithiasis at present and in the future.In the 21st century,Chinese scholars in the biliary tract surgery field will make full use of minimally invasive techniques,biotechnology,information technology and other advanced technologies under the guidance of the precise surgery concept to constantly improve the treatment of hepatolithiasis as well as bring well-being to the people.

The rapid development of bacterial resistance is a serious threat to the patients' life and health,and it's also a focus in the field of anti-infection in the world.Surgeons should pay special attention to the antibiotic resistance in highrisk patients.Many subjective and objective factors caused antibiotic resistance,including increase of conditional pathogenic bacteria due to the dysfunction of barrier of digestive tract; enhancement of virulence of bacteria and susceptibility of patients owing to dysfunctional and low immunity; increased risk of antibiotic resistance because of application of various medical and nursing measures for severe patients (especially patients in ICU) ; unreasonable application of antibiotics due to insufficient knowledge of the medical staff and the concern of disease severity.In order to prevent the prevalence of antibiotic resistance,scientific and medical treatment under a variety of provisions should be adopted to prevent the abuse of antibiotics; safeguard the gastrointestinal barrier and immune function of patients; use fine operation,drainage and other specialized technology and timely detect the pathogenic bacteria and give targeted therapy; aseptic manipulation of medical and nursing technology should be applied.

Huang Zhiqiang,the academician of Chinese Academy of Engineering,is the father of biliary tract surgery beloved by the vast number of medical workers in China.He not only has made outstanding contributions to hepatobiliary surgery in China and possess noble medical esthic,but also the Publicity Department of the Central Committee awarded the honorable title of model in the era to him.In this article,through the study of the important works of academician Huang Zhiqiang,there was an in-depth understanding of the concept of the core essence and the fundamental goal in the new era of surgery the academician Huang Zhiqiang advocated should bepeople-oriented,medicine with reduced damage.And in this era of rapid development of bioinformatics,the cultivation of surgeons should pay more attention to help doctors to establish the idea that the interests of patients is the best interests and to in-depth first-line clinical work,make unremitting efforts to carry out clinical research,master the basic and modem knowledges,cultivate team work spirit,lay the foundation in everything.The immortal Zhiqiang spirit will always guide us forward.

Gallstone is a common and multiple benign disease,that has become an important public health problem.Focusing on the recent dispute about cholelithotomy or cholecystectomy and analysis of recent literatures,the author put forward to grasp the treatment principles performed by academician Huang Zhiqiang and discuss the crucial problems of treatment strategy about benign gallbladder disease from the following four aspects:(1) The key point of Cholelithotomy is to protect the gallbladder,not only to preserve the gallbladder.(2) The training,guidance and practice of clinical research on benign gallbladder diseases such as gallstones need to be further standardized.(3)The operation of gallstones is relatively easy while the and patients' prognosis is relatively complex.The choice of surgical indications is very important,and both of over treatment and inadequate treatment should be emphasized.(4) The epidemiological investigation and prevention of gallstones need to be strengthened.

Objective To observe the effects of silencing IGF-1 receptor on the expression of Caspase12 , a endoplasmic reticulum specificity apoptosis protein of the peroxidation damage in L02 cells. Methods Four the recombined plasmids expressing short hairpin RNA (shRNA) specific for sileincing IGF-1R gene were constructed and these shRNAs were potentially targeted on different mRNA sequences of the IGF-1 receptor gene (Sh-H-IG1R- 1108, Sh-H-IGF1R-2797, Sh-H-IGF1R-3215 and Sh-H-IGF1R-3787). These constructs were classed as the experimental group. Another two constructs containing an irrespective sequence and no sequence were defined as a positive control group a negative control group , respectively. All these constructs were transfected into the L02 cells by Lipefectamine 2000. The interference effect was detected by RT-PCR after 24 h and the plasmid stably silencing the expression of IGF-1 receptor was selected for further analysis which was divided into four groups: the blank control group(Group A), the peroxidation damage group(Group B), the negative plasmid transfection group (Group C) and the positive plasmid transfection group (Group D). The expression of Caspase12 was detected by Westen Blot after 12 h. Results The amplification folds of experimental groups were statistically significantly lower than those of the Sh-H-IGF1R-V1 group and Sh-H-IGF1R-V2 group (P < 0.05). The silence effect of the Sh-H-IGF1R-3215 group (0.02 ± 0.01) and the Sh-H-IGF1R-3787 group (0.05 ± 0.05) were most stable and the repeatability of the later was better. The expressions of Caspase12 in Group B (2.41 ± 0.03), Group C (2.45 ± 0.02) and Group D (3.60 ± 0.06) were higher than Group A (0.34 ± 0.02) (P < 0.01). The Group Cexpression was higher than that of the Group B (P > 0.05). The Caspase12 expression in Group D was higher than that in Group B and C (P < 0.01). Conclusion (1) Of all the four constructs in this study, Sh-H-IGF1R-3787 is the most suitable for silencing IGF-1 receptor. (2) Silencing IGF 1R expression using shRNA plasmids can aggravate the L02 cells apoptosis, suggesting that the IGF-1/IGF 1R signal pathway might be involved in regulating the activation of apoptosis in L02 cells with peroxidation damag via endoplasmic reticulum stress.

Intrahepatic cholangiocarcinomas (ICCA) are primary intrahepatic malignancies originating from biliary epithelia.While both hepatocellular cancer and ICCA can present as mass lesions within the liver,these cancers are distinct in their morphology,etiology,pathology,natural history and response to therapy.There is a need for accurate and sensitive molecular markers for the diagnosis of ICCA.Recent advances in elucidating molecular and genetic characteristics of ICCA offer the potential of molecular-based diagnosis of ICCA.Specific genetic mutations of IDH1/2,BAP1,p53,and KRAS,FGFR gene fusions and alterations in microRNA have all been described in ICCA.Although there are no accurate serum or biliary biomarkers currently available for diagnosis of ICCA,several potential candidates have been identified.Knowledge of specific genetic or molecular abnormalities offers potential for individualized approaches for the treatment of patients with ICCA in the future.

Objective To investigate the influences of Radix salvia miltiorrhiza (RSM) preconditioning on the expressions of phosphorylated eukaryotic initiation factor 2α (p-eIF-2ot) and caspase12 in hepatic ischemia reperfusion in rats.Methods Eighty Wistar rats were randomly divided into the control group (5 rats),sham operation group (25 rats),ischemia reperfusion (IR) group (25 rats) and RSM pretreated group (25 rats).Rats in the sham operation group,IR group and RSM pretreated group were subdivided into 5 groups at different time intervals (0,3,12,24 and 72 hours).Mter midline laparotomy,all structures in the hepatic portal were clamped for 45 minutes followed by different periods of reperfusion.Rats in the control group did not receive any treatment; rats in the sham operation group only received anatomy of the hepatic portal without clamping; rats in the RSM pretreated group received RSM by intravenous injection 30 minutes before ischemia at a dose of 6 ml/kg.Rats in the sham operation group and the IR group received a dose of normal saline as RSM pretreated group.The protein expressions of p-eIF-2α and caspase12 in the hepatic tissues of each group were detected by the Western blot,and the pathological changes of hepatic tissues in each group were detected by hematoxylin and eosin staining.All data were analyzed using the analysis of variance,LSD test or Games-Howell method.Results The relative expression of p-eIF-2α in the control group was 0.296 ± 0.038,and the relative expressions of p-eIF-2α in the sham operation group at different time points were 0.304 ± 0.048,0.298 ± 0.038,0.272 ± 0.042,0.266 ± 0.076 and 0.296 ± 0.043,with no significant difference between the 2 groups (P ＞ 0.05).The relative expression of p-eIF-2α in the IR group at 0 hour was 0.310 ± 0.034,which had no significant difference compared with the control group and the sham operation group (F =0.15,P ＞0.05).The relative expressions of p-eIF-2α in the IR group at 3,12,24 hours were 0.386 ± 0.021,0.710 ± 0.034,0.474 ± 0.017,which had no significant difference compared with the control group and the sham operation group (F =11.90,211.52,25.15,P ＜ 0.05).The relative expression of p-eIF-2α in the IR group at 72 hours was 0.336 ± 0.043,which was back to the level of the control group and the sham operation group (F =1.57,P ＞ 0.05).The relative expressions of p-eIF-2α in the RSM pretreated group at different time intervals were 0.278 ± 0.044,0.800 ± 0.079,1.056 ± 0.125,0.736 ±0.087 and 0.442 ± 0.047,which were significantly lower than the group at 3,12,24,72 hours (P ＜ 0.05).The relative expression of caspase12 in the control group was 0.983 ± 0.003,and the relative expressions of caspase12 in the sham operation group at different time intervals were 0.974 ± 0.004,0.983 ± 0.005,0.985 ± 0.003,0.981 ± 0.004 and 0.978 ± 0.004,with no significant difference between the 2 groups (P ＞ 0.05).The relative expression of caspase12 in the IR group at 0 hour was increased to 1.018 ± 0.076,while it had no significant difference compared with the control group and the sham operation group (F =1.43,P ＞ 0.05).The relative expressions of caspase12 in the IR group began to rise at 3 hours (2.056 ±0.067),and peaked at the 12 hours (2.804 ± 0.050),still at a relative higher level at 24 hours (1.882 ± 0.037),and began to decrease at 72 hours (1.282 ± 0.066),it had significant difference compared with the control group and the sham operation group (F=1290.69,6490.84,2898.71,103.61,P ＜ 0.05).The relative expressions of caspase12 in the RSM pretreated group at different time intervals were 0.998 ± 0.056,1.442 ± 0.066,1.990 ± 0.068,1.364 ± 0.056and 0.962 ±0.054.The relative expressions of caspase12 in the RSM pretreated group at 3,12,24,72 hours were significantly lower than the IR group (P ＜ 0.05).The results of pathomorphological examination showed that the hepatic lobules were integrated and the nucleuses were large and round in the control group an d the sham operation group; deformation of the hepatic lobule,smaller cell volume,nuclear condensation and necrosis were observed in the IR group; cell swelling and slight spotty necrosis were detected in the RSM pretreated group.Conclusions RSM could protect liver from damages during IR through up-regulating the expression of p-eIF-2α,reducing the apoptosis induced by endoplasmic reticulum stress.

Ischemic reperfusion is the common mechanism of some chronic diseases such as type 2 diabetes,coronary heart disease,hypertension,and so on.Previous studies of insulin resistance is mainly focused on the relationships of these chronics,while now,in recent years,the research between the insulin resistance and ischemic reperfusion has gradually become one of the new and hot points,closely related to the patient's prognosis.In this paper,we will review the insulin resistance and ischemic reperfusion according to the reported literature review.

Early growth response gene-1 is an immediate early response gene,a transcription factor which includ three zinc finger-like domains.Recentl studies demonstrate that early growth response gene-1 is involved in regulating cell cycle,proliferation and differentiation,and plays a critical role in injuring and repairing.Early growth response gene- 1 induces Target genes,and promotes extracellular environmental signal( such as oxygen deficit,oxidative stress,mechanical injury and cytokine)link with the complex biological responses.Intensive study to early growth respnse gene-1 will contribute to further illustrate the mechanism of the ischemia-reperfusion injury.This article summarizes from protein structure,signal transduction,biological functions and the relationship with ischemia- reperfusion injury.

Objective To investigate the relationship between sonic hedgehog(SHH)signaling pathway and chronic pancreatitis.Methods Thirty Wistar rats were randomly divided into the model group,experimental control group and blank control group,and there were 10 rats in each group.Trinitrobenzene sulfonic acid was infused into the pancreatic duct of the rats to induce pancreatitis in the model group.The pancreatic duct of the rats in the experimental control group were infused with 0.9％ sodium chloride solution.No treatment was performed on rats in the blank control group.The serum levels of bilirubin and amylase of the 3 groups were determined,and the histopathological alterations were studied.Expressions of patched-1(PTCH-1),smoothened (SMO)and SHH were detected by immunohistochemistry.All data were analyzed using the analysis of variance or Student's t test.Results The levels of total bilirubin(TBil)in the model group,experimental control group and blank control group from day 1 to day 35 were(3.17 ±0.21)μmol/L-(9.28 ±2.15)μmol/L,(3.44 ±0.54)μmol/L-(3.76 ± 0.15)μmol/L,(2.45 ± 0.32)μmol/L-(3.27 ± 1.43)μmol/L,respectively.The levels of amylase in the model group,experimental control group and blank control group were(1124 ± 143)U/L-(1522 ± 169)U/L,(1123 ± 104)U/L-(1007 ± 141)U/L,(1014 ± 115)U/L-(1013 ± 142)U/L,respectively.Compared with the experimental group and the blank control group,the serum levels of TBil and amylase in the model group were increased significantly from day 7 to day 35(F =14.81,16.27,18.13,11.49,17.91;11.54,10.24,12.64,21.11,15.38,P ＜ 0.05),and fibrotic proliferation of pancreatic tissues were found at day 35;the expressions of PTCH-1,SMO and SHH in the pancreatic tissue was increased significantly in the model group.Conclusion SHH signaling pathway is activated in the tissue of pancreatitis in rats,it might play an important role in the genesis of pancreatitis.