Analysis of influencing factors on surgical outcome and exploration of technical principles during pancreaticojejunostomy / 中华外科杂志

Pancreaticojejunostomy is the most common anastomosis following pancreaticoduodenectomy and middle pancreatectomy. The detailed surgical technics of pancreaticojejunostomy vary dramatically, but none of them can achieve zero fistula rate. In recent years,with the development of new surgical concept,application of new surgical technology, high-tech materials and instruments,the incidence of pancreatic fistula has decreased. At the same time,researches on investigating the risk factors of pancreaticojejunostomy are gradually deepening. Based on years of surgical experience on pancreaticojejunostomy and current literatures, this paper analyzes the factors affecting the effect of pancreaticojejunostomy, such as the patient's basic physical state,pancreatic texture and diameter of the pancreatic duct,pathology and course of the disease,surgical technology and perioperative management,and summarizes six technical principles for pancreaticojejunostomy to be shared with surgical comrades:appropriate tension,protection of blood supply,hermetic closure of pancreatic section,accurate connection of pancreatic duct and intestinal mucosa,individualization,learning and accumulation of experience.

Analysis of the relationship between Clostridium genus and neonatal necrotizing enterocolitis / 公共卫生与预防医学

Objective To analyze the correlation between intestinal flora changes and neonatal necrotizing enterocolitis (NEC)through 16S rRNA metagenomic sequencing and bacterial culture. Methods From September 2018 to March 2019, 10 NEC cases and 6 controls were randomly selected in the neonatal ICU ward of Nanjing maternal and child health care hospital to analyze the 16S rRNA metagenomic diversity of the for intestinal flora. The fecal samples and corresponding environmental samples were corrected from 51 cases of NEC children and their case controls to isolate and culture Clostridium. Results The dispersion of samples within the case group was smaller than that of the control group, and the sample diversity was higher than that of the control group. In the isolation and culture of Clostridium, the overall detection rate of Clostridium in the case group was 43.14% (22/51), and the detection rate of Clostridium butyricum was the highest (19.61%, 10/51). There was a statistical difference between the two groups (χ2=5.85, P=0.015 58). All Clostridium strains did not carry the A, B and E type neurotoxin genes. Conclusion: Increased intestinal flora diversity, intestinal flora abundance and changes in the abundance of Clostridium may be closely related to the intestinal environment of children with NEC; Clostridium, especially Clostridium butyricum, may be related to the occurrence of NEC.

Non-technical skills for surgeons / 中华外科杂志

The rapid development of professional technology not only brings great benefits to patients, but also reveals the problem of non-technical skills. Technical competence is not enough to avoid the occurrence of adverse medical events or to get optimal post-operative outcomes. The development of technology is endless, we are desperately in need of non-technical skills, such as situation awareness, decision making, communication and teamwork, leadership. The only way we could achieve in the assistance of the perfect surgical operation with the combination of excellent surgical techniques and solid non-technical skills, and therefore relieve the patients as much as possible.

What can we do for the recurrent-tumor patients who underwent hepatectomy for hepatocellular carcinoma / 中国实用外科杂志

Some of the patients with hepatocellular carcinoma could be performed hepatectomy and get optimal postoperative outcomes with tumor-free long-term survival which encourage surgeon to carry on the surgery with tremendous enthusiam.Unfortunately the others are not the case even though surgeons have done their best routinely and standardly and the tumor recurs in the liver in short time after surgery. For the sake of the patient treatment,the confidence should not be lost,there are a lot of things to be done which include re-resection, radio freuquency ablation,transcatheter arterial chemoembolization,liver transplantation respectively and individualizedly in order to receive better prognosis and longer-term survival.

Suggestion of grade judgment and selection of surgical methods for splenomegaly / 中国实用外科杂志

Laparoscopic splenectomy(LS) is superior to open splenectomy(OS) because of advantages of minimal invasion,such as small trauma,rapid recovery,and short hospitalizing time,widely used in the resection of normalsized or moderately enlarged spleens. With the wide application of LS,the indications have been extended to the excision of massive spleens. However,there is still a tremendous controversy about the upper limit of splenic size which can be in accord with a requirement of LS and selection of surgical indications. Taking the issues into account,the authors recommended that the splenomegaly should be divided into“four degrees”rather than“three degrees”used today widely in order to guide the selection of appropriate surgical methods.

Correlation between microalbuminuria and subclinical atherosclerosis in patients with essential hypertension / 心血管康复医学杂志

Objective: To explore the correlation among carotid atherosclerosis, ankle-brachial index (ABI) and urinary microalbumin (UMA) level in patients with essential hypertension (EH). Methods: A total of 215 EH patients treated in our hospital from Apr 2014 to Aug 2015 were selected. According to 24h UMA level, patients were divided into normal UMA group (n=116) and microalbuminuria (MAU) group (n=99). General data, UMA level, carotid intima-media thickness (CIMT), carotid artery lumen diameter, incidence rate of plaque and ABI were measured and compared between two groups. Correlation among CIMT, ankle-brachial index (ABI) and urinary microalbumin (UMA) level was analyzed in EH + MAU patients. Results: There were no significant difference in age, gender, levels of blood pressure, fasting blood glucose, blood lipids and serum creatinine between two groups, P＞0. 05 all. Compared with normal UMA group, there were significant rise in UMA level [21. 25 (15. 75, 25. 75) mg/d vs. 86. 50 (56. 50, 104. 50) mg/d], CIMT [(1. 20± 1. 09) mm vs. (1. 76±0. 81) mm]and incidence rate of plaque (55. 17％ vs. 75. 76％), and significant reduction in ABI [(1. 12±0. 11) vs. (0. 97±0. 11)] in MAU group, P＜0. 01 all. Linear correlation analysis indicated that UMA level was significant positively correlated with CIMT (r=0. 551, P=0. 001), and significant inversely correlated with ABI (r=-0. 266, P=0. 008) in EH + MAU patients. Conclusion: In EH+ MAU patients, MAU is significant positively correlated with CIMT, and significant inversely correlated with ABI, suggesting MAU is not only related to hypertensive renal disease, but also an early sign of subclinical atherosclerosis.

miR-130b-3p may serve as a marker for human bladder cancer / 基础医学与临床

Objective To further understand potential mechanism of miRNAs in bladder cancer .Mtehods Human microarray was used to analyze the expression of miRNAs in four pair human BC cancer tissues and adjacent normal tissues.Then RT-Qpcr was used to verified that the expression of two most up -regulated miRNAs and target genes for results of miRNA/Mrna microarray.Subsequently, it was deduced that miR-130b-3p could target at PTEN through a bioinformatics approach and dual-luciferase reporter assay.CCK8, EDU, flow cytometry, wound healing, Transwell and cytoskeleton assay were applied to prove that miR-130b could affect proliferation, apoptosis, migration and invasion of BC cells.The effects of PTEN regula-ted by miR-130b-3p on the key target protein expression of PI 3K/AKT and integrin β1/FAK signaling pathway were determined by Western blot.Resulst miR-130b-3p was significantly up-regulated and nega-tively correlated with PTEN expression in clinical bladder cancer specimens as compared with normal urothelial tissue.miR-130b-3p mimics could down-regulate PTEN expression, which leads to the activation of PI3K/AKT and integrinβ1/FAK signaling pathway related to cell proliferation , migration and invasion in bladder cancer EJ cells.When the cells were transfected with miR-130b-3p inhibitors, they could be sur- veyed with rearranging cytoskeleton.Conclusions miR-130b/PTEN may be used as a marker for bladder cancer.

Analysis of current status of mouse euthanasia methods based on the publications in China(2015-2016) / 中国比较医学杂志

Objective To investigate the current status of mouse euthanasia methods in China,and to provide the reference and basis for the administrative authorities of laboratory animal management to master the implementation of"euthanasia"and formulate related policies. Methods Research papers containing the terms of"mouse"and"execution"in Chinese characters during the period from 2015 to 2016 were searched in Wanfang database,and statistical analysis was performed with the articles meeting the searching criteria. Results A total of 890 research articles met the searching criteria,of which 351 articles clearly described the killing method, accounting for only 39.44%. The mouse-killing methods included cervical dislocation, decapitation, exsanguination and sampling after anesthesia, excessive anesthesia,abdominal aorta bleeding and carbon dioxide asphyxiation, among them cervical dislocation accounted for the highest rate,75.78%. Conclusions The current implementation of mouse euthanasia methods in our country has been far from optimistic. The mouse euthanasis methods have often been ignored in scientific articles and the description of the methods is not standardized. In order to promote the effective implementation of the regulations related to mouse euthanasia,it is needed to promote the study of related techniques and to strengthen personnel training.

The clinical analysis of a step-up approach for severe acute pancreatitis: report of 121 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and clinical value of the step-up approach for severe acute pancreatitis (SAP).</p><p><b>METHODS</b>Clinical data of 121 SAP patients admitted between January 2002 and December 2011 were retrospectively analyzed. Fifty-eight patients (37 males and 21 females, aged from 20 to 72 years, mean 47.6 years) in the group of direct open necrosectomy from January 2002 to December 2006 were performed laparotomy through removal of all necrotic tissue. Sixty-three patients (42 males and 21 females, aged from 19 to 78 years, mean 46.2 years) of step-up approach from January 2007 to December 2011 underwent percutaneous catheter drainage through retroperitoneum or omental bursa guided by B-type ultrasonography for the first therapy, and then, according to the pathogenetic condition, if necessary, followed by a small incisional necrosectomy along the drainage tube. The two groups were compared for the rates of postoperative complications, death, transfusion and length of stay, medical costs.</p><p><b>RESULTS</b>The rates of total postoperative complications, organ dysfunction, alimentary tract fistula and incisional hernia in step-up approach group were significantly lower than those of direct open necrosectomy group (31.7% vs. 62.1%, 14.3% vs. 37.5%, 6.3% vs. 19.0%, 9.5% vs. 29.3%; χ(2) = 4.43 to 11.17, P = 0.001 to 0.035). The other complications had no significant differences between the two groups (P > 0.05). Patients in step-up approach group had a lower rates of transfusion (44.4% vs. 70.7%, χ(2) = 8.488, P = 0.004), fewer medical costs of transfusion and hospital stay, compared with those in direct open necrosectomy group ((2525 ± 4573) yuan vs. (4770 ± 6867) yuan, t = 2.131, P = 0.035; (171 213 ± 50 917) yuan vs. (237 874 ± 67 832) yuan, t = 2.496, P = 0.014). There were no significant differences of length of stay and mortality between two groups (P > 0.05).</p><p><b>CONCLUSION</b>Step-up approach for SAP which can reduce the rates of postoperative complications, transfusion and medical costs has significant feasibility and great clinical value.</p>

Analysis of predisposing factors for pancreatic fistula after pancreaticoduodenectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the predisposing factors for pancreatic fistula after pancreaticoduodenectomy.</p><p><b>METHODS</b>The clinical data of 323 patients undergoing pancreaticoduodenectomy from January 2007 to March 2012 were analyzed retrospectively. There were 185 male and 138 female patients, aging from 27 to 82 years. All the patients were devided into pancreatic fistula group (n = 52) and non-pancreatic fistula group (n = 271). Twenty variables, such as age, sex, primary disease, alcohol abuse, cholangitis, bilirubin, albumin, hemoglobin, operating time, blood loss, transfusion, texture of the remnant pancreas, diameter of wirsung, drainages of pancreatic duct, specialized group which potentially affect the incidence, were analyzed by t test for continuous variables and χ(2) test for discrete variables. The variables with significance (P < 0.05) were then analyzed with Logistic regression model.</p><p><b>RESULTS</b>Of all the 323 patients, the overall morbidity rate was 30.3% (98/323), and the mortality was 3.7% (12/323). Pancreatic fistula rate was 16.1% (52/323), 7 patients died for pancreatic fistula PF. In univariate analysis, primary disease, preoperative high bilirubin level, intraoperative blood loss and transfusion, texture of the remnant pancreas, diameter of wirsung, drainages of pancreatic duct, specialized group had significant difference between two groups (χ(2) = 4.072 to 9.008, P < 0.05). Multivariate logistic regression analysis revealed that primary disease (OR = 2.091, P = 0.001), texture of the remnant pancreas (OR = 7.715, P = 0.040), diameter of wirsung (OR = 5.405, P = 0.006), pancreatic duct stent (OR = 4.313, P = 0.001) and specialized group (OR = 6.404, P = 0.006) were independent risk factors in pancreatic fistula.</p><p><b>CONCLUSIONS</b>Primary disease, texture of the remnant pancreas, diameter of wirsung, pancreatic duct stent and specialized group are independent risk factors in pancreatic fistula. With the purpose of decreasing pancreatic fistula rate after PD, it is necessary to operate meticulously and precisely, place external pancreatic duct stent and establish pancreatic center or specialized group.</p>

Experimental study of the function of nuclear factor-κB-dependent epithelial to mesenchymal transition in pancreatic cancer cells under hypoxic conditions / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the function of nuclear factor (NF)-κB in the epithelial to mesenchymal transition induced by hypoxia in pancreatic cancer cells.</p><p><b>METHODS</b>For cultured pancreatic cancer cells (BxPC-3 and Panc-1) under hypoxic and normoxic conditions, the differences in the morphology were observed by optical microscope. The expression of markers of epithelial and mesenchymal phenotypes, E-cadherin, vimentin and N-cadherin, were determined by Western blot. NF-κB P65 activity was measured by electrophoretic mobility shift assay. Invasion and gemcitabine resistance of pancreatic cancer cells were evaluated in matrigel invasion assay and cell counting kit-8 assay. Both molecular and pharmacologic means of inhibiting NF-κB P65 were used in these hypoxic cells and then the above resulting phenotypes were compared with those of the control-treated cells.</p><p><b>RESULTS</b>After cultured pancreatic cancer cells under hypoxic conditions for 48 h, normoxic cells exhibited a polygonal shape and formed tight clusters of cells, whereas hypoxic cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character and resistance to gemcitabine; hypoxic cells exhibited an suppression of E-cadherin and increase in vimentin and N-cadherin expression. NF-κB P65 activity was elevated in hypoxic cells. On the contrary, on molecular or pharmacologic inhibition of NF-κB P65, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.</p><p><b>CONCLUSIONS</b>Pancreatic cancer cells underwent epithelial to mesenchymal transition exposed to hypoxia, exhibited highly invasive and drug resistant phenotype. Inhibition of NF-κB P65 under hypoxic conditions, pancreatic cancer cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.</p>

Experimental study of the function and mechanism combining dihydroartemisinin and gemcitabine in treating pancreatic cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the anti-tumor activity of combined gemcitabine with dihydroartemisinin, and the mechanism of the anti-tumor effect of gemcitabine enhanced by dihydroartemisinin on pancreatic cancer.</p><p><b>METHODS</b>For cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis and confocal laser scanning microscope stained with Annexin V-FITC/PI. The nuclear extract for determining NF-kappaB DNA-binding activity was analyzed by EMSA, while nuclear P65 and its downstream gene expression was determined by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to agents. TUNEL assay was used to assess tumor cell apoptosis in tumor tissue.</p><p><b>RESULTS</b>After combination of gemcitabine and dihydroartemisinin treatment, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and Panc-1 reached up to (81.1 +/- 3.9)% and (76.5 +/- 3.3)%, and the apoptosis rates were up to (53.6 +/- 3.8)% and (48.3 +/- 4.3)%, the differences were significantly (P < 0.01) compared with gemcitabine [(24.8 +/- 2.9)% and (21.8 +/- 3.5)%]. All the treatment groups inhibited the growth of pancreatic xenograft tumors in nude mice. The tumor volume and apoptosis index were (262 +/- 37) mm(3) and (50 +/- 4)% respectively in the combined treatment, compared to those of [(384 +/- 56) mm(3) and (25 +/- 3)%] in gemcitabine, the differences were significantly (P < 0.05). EMSA showed that gemcitabine alone obviously enhanced its DNA-binding activity compared to control. However, dihydroartemisinin significantly reduced its DNA-binding activity, so that abrogated the inducing effect of gemcitabine on NF-kappaB activation. Western blot assay indicated that dihydroartemisinin downregulated expression of nuclear P65, and combined treatment not only downregulated the expression of Cyclin D1, Bcl-xL and Bcl-2 while upregulated Bax, thus reduced the Bcl-2/Bax ratio, but also increased the caspase-3 activation, all of which increased apoptosis in both BxPC-3 and Panc-1 cells.</p><p><b>CONCLUSION</b>Dihydroartemisinin significantly abrogated the inducing effect of gemcitabine on NF-kappaB activation and downregulated the expression of NF-kappaB targeted gene products, which may be one possible mechanism by which dihydroartemisinin augments the anti-tumor effect of gemcitabine on pancreatic cancer.</p>

Protection of CSE/H2S system in hepatic ischemia reperfusion injury in rats / 中华外科杂志

<p><b>OBJECTIVE</b>To study the protective function and pathophysiology of cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) system in hepatic ischemia-reperfusion injury (HIRI) in rats.</p><p><b>METHODS</b>Wistar rats were randomly distributed into sham group (n = 18), ischemia-reperfusion (IR) group (n = 18), IR + NaHS group (n = 18) and IR + DL-propargylglycine (PAG) group (n = 18). The hepatic IR model was established by Pringle's hepatic vascular occlusion. At each of the indicated time points (1, 3 and 6 hours after IR), the serum levels of H(2)S and the hepatic CSE activity were measured. The serum levels of inflammatory factors, including TNF-α, IL-10 were determined by ELISA methods. The expression of apoptotic protein, TNF-α, in liver tissue was tested by Western blot assay, cell apoptosis was examined by TUNEL and the histological changes were examined in each group.</p><p><b>RESULTS</b>The serum levels of H(2)S and CSE activity were significantly increased in group IR compared with group sham at all indicated time points (P < 0.05). The serum level of inflammatory factors (P < 0.01) and the hepatic expression of TNF-α protein (P < 0.05) were elevated obviously in group IR than that in group sham. Administration of NaHS could reduce the production of inflammatory factors in serum (P < 0.01), inhibit hepatic protein expression of TNF-α (P < 0.05) and attenuate the liver histological scores of IR injury (P < 0.05), whereas PAG aggravated them.</p><p><b>CONCLUSION</b>The endogenous CSE/H(2)S system maybe involved in the pathogenesis of hepatic IR injury, which suggests that CSE/H(2)S system can protect liver from IR injury in rats by intervening in inflammatory reaction, attenuating the injury severity and inhibiting expression of apoptotic protein TNF-α.</p>

Experience of the surgical comprehensive treatment on severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To summary the experience of the surgical comprehensive treatment of severe acute pancreatitis (SAP).</p><p><b>METHODS</b>From July 1999 to December 2009, a total of 506 patients suffered SAP were admitted with a mean APACHE II score 12.8 ± 4.6. There were 270 male and 236 female, aged from 16 to 89 years, mean age 43 years. SAP patients were treated by the SAP treatment team which consisted of pancreatic specialized and multidisciplinary doctors. Two hundreds and thirty-four cases (46.2%) received non-operative treatment and 272 cases (53.8%) received surgical intervention.</p><p><b>RESULTS</b>In 506 cases, 445 patients were cured and 52 patients died (31 died in early stage, 21 died in later stage), 9 cases discharged automatically. The overall incidence of complication, overall mortality and overall curative rate were 29.4% (149/506), 10.3% (52/506) and 87.9% (445/506), respectively. The incidences of complication in non-operative group and in surgical intervention group were 27.8% (65/234) and 30.9% (84/272), respectively (P > 0.05). The mortality in non-operative group and in surgical intervention group were 9.4% (22/234) and 11.0% (30/272), respectively (P > 0.05). The curative rates in non-operative group and in surgical intervention group were 90.6% (212/234) and 85.7% (233/272), respectively (P > 0.05).</p><p><b>CONCLUSIONS</b>Patients should be treated in ICU in the early phase of the disease when APACHE II score > 10. Pancreatic specialized and multidisciplinary team treatment, appropriate choice of timing, indication and procedure of surgical intervention and details of drainage are vital to the prognosis of SAP.</p>

An experimental study of gemcitabine inducing pancreatic cancer cell apoptosis potentiated by nuclear factor-kappa B P65 siRNA / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of NF-kappaB P65 gene silencing by small interference RNA on the apoptosis of human pancreatic cancer cells induced by gemcitabine in vitro and in vivo.</p><p><b>METHODS</b>Human pancreatic cancer cells (BxPC-3 and PANC-1) were cultured and respectively divided into five groups: blank control group, negative control siRNA group, gemcitabine group, NF-kappaB P65 siRNA group and gemcitabine + P65 siRNA group. The ability of cell proliferation was analyzed by MTT; the expression of NF-kappaB P65 and the apoptosis related proteins were examined by Western blot assay; the apoptosis was evaluated by the flow cytometry and laser scanning confocal microscopy analysis stained with Annexin V-FITC/PI; the DNA binding activity of NF-kappaB was examined by electrophoretic mobility shift assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors. The tumor volume was monitored and TUNEL assay was used to assess the apoptosis index in tumor tissue after treatment.</p><p><b>RESULTS</b>At 72 h after transfection, the combination with gemcitabine and p65 siRNA significantly decreased the cell viability index (P < 0.05), and down-regulated the expression of Bcl-2 and procaspase-3 and up-regulated the expression of Bax compared with other groups. The combined treatment significantly increased the rate of apoptosis compared with other groups (P < 0.05). EMSA assay indicated that the DNA binding activity of NF-kappaB significantly decreased in NF-kappaB P65 siRNA group and gemcitabine+P65 siRNA group compared with Control group. The combined therapy inhibited the growth of pancreatic xenograft tumors by apoptosis induction in nude mice (P < 0.01).</p><p><b>CONCLUSIONS</b>The effect of gemcitabine inducing cell apoptosis may be potentiated through inhibiting the DNA binding activity of NF-kappaB and regulating the expression of apoptosis related proteins by NF-kappaB P65 siRNA, which can activate the mitochondria apoptosis pathway in pancreatic cancer in vitro and in vivo.</p>

The expression of caspase-10 in differentiated thyroid carcinoma and association with its development and metastasis / 中国地方病学杂志

Objective To investigate the expression of caspase-10 in differentiated thyroid carcinoma and association with its development and metastasis. Methods Thyroid samples from 37 patients in a period from January 2006 to December 2007, with differentiated thyroid carcinoma were retrospectively analyzed for caspase-10 by immunohistocbemistry(streptavidin-perosidase, S-P), compared to control group of 46 cases with nodtdar goiter. The relationship between the expression of caspase-10 and the clinical pathologic characteristics of thyroid carcinoma were also explored simultaneously. Results caspase-10 were observed as brown or yellow particles located in the cytoplasm or cell membrane of nodular goiter but there were no significant evidence for its positive expression in thyroid carcinoma, caspase-10 expression was markedly down-regulated in differentiated thyroid carcinoma(29.73%,11/37) compared with benign nodules(71.74%,33/46, χ2=14.528, P<0.01). The positive expression in 18 cases with lymph node metastasis(11.11%,2/18) was significantly lower than those in 19 patients without lymph node metastasis(47.37%,9/19; χ2=4.210, P<0.01). There was no significant correlation(P> 0.05) between the expression of caspase-10 and the clinical pathologic characteristics including male, age, TNM stage and pathologic type. Conclusion Down-regulation of caspase-10 may play a critical role in carcinogenesis and development of differentiated thyroid carcinoma.

Down-regulation of lung resistance related protein by RNA interference targeting survivin induces the reversal of chemoresistances in hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both survivin and lung resistance related protein (LRP) are related to the chemoresistances in hepatocellular carcinoma (HCC). But the relationship between survivin and LRP is indefinite. The aim of this study was to investigate the effects of down-regulation of survivin on LRP expressions and the reversal of chemoresistances in HCC both in vitro and in vivo.</p><p><b>METHODS</b>The expressions of survivin were detected by RT-PCR and Western blotting in HCC cell line SMMC-7721 and SMMC-7721/ADM. The sensitivities of these two cell lines to ADM were evaluated by MTT assays. SiRNA which targeted survivin was transfected into SMMC-7721/ADM cells, then the sensitivity of SMMC-7721/ADM cells to ADM and the expressions of survivin and LRP were detected respectively. SMMC-7721/ADM cells were transplanted subcutaneously into nude mice to establish xenograft tumors. Antitumor activities of RNA interference (RNAi) targeting survivin, various doses of ADM and combination therapies were observed respectively. Possible toxicities were evaluated. LRP expression changes were tested. Student's t test was used for evaluating statistical significance.</p><p><b>RESULTS</b>The expressions of survivin in SMMC-7721/ADM cell line showed significant elevation compared to those in SMMC-7721 cell line (P < 0.05). Positive siRNA down-regulated the expressions of survivin significantly (P < 0.05). SiRNA targeting survivin could sensitize SMMC-7721/ADM cells to ADM and down-regulate the expressions of LRP significantly (P < 0.05). Growths of the tumors were significantly inhibited in positive siRNA group as compared with those in the control group from the 8th day (P < 0.05). Combination therapies caused significant tumor inhibitions compared with tumors of nude mice in the other three groups respectively (P < 0.05). No toxicities were found in nude mice treated by siRNA and combination therapies. The expressions of LRP were markedly reduced in tumors treated with siRNA targeting survivin (P < 0.05).</p><p><b>CONCLUSIONS</b>Down regulation of survivin gene by RNAi can increase chemosensitivity of HCC both in vitro and in vivo. The reversal of drug resistance may be reduced through the inhibitions of LRP.</p>

Study on anticancer effect of dihydroartemisinin on pancreatic cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the anti-tumor activity of dihydroartemisinin in pancreatic cancer in vitro and in vivo.</p><p><b>METHODS</b>For cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis stained with Annexin V-FITC/PI. The protein expression in BxPC-3 cells was analyzed by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to dihydroartemisinin. Ki-67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue.</p><p><b>RESULTS</b>After treatment by dihydroartemisinin in vitro, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and AsPC-1 reached up to (76.2 +/- 3.5)% and (79.5 +/- 2.9)%, and the apoptosis rates were up to (55.5 +/- 3.2)% and (40.0 +/- 3.5)%, the differences were significantly (P < 0.01) compared with control [(2.0 +/- 1.3)% and (0.9 +/- 0.4)%]. Dihydroartemisinin inhibited the growth of pancreatic xenograft tumors in nude mice. The proliferation index and apoptosis index were (49.1 +/- 3.9)% and (50.2 +/- 4.4)% respectively in dihydroartemisinin 50 mg/kg treatment group, compared to those of (72.1 +/- 3.3)% and (9.4 +/- 2.9)% in control, the differences were significantly (P < 0.01). Western blot assay indicated that dihydroartemisinin up-regulates expression of proliferation-associated protein p21(WAF1) and down-regulates expression of PCNA, increases expression of apoptosis-associated protein Bax and decreases expression of Bcl-2 and activates caspase-9 in BxPC-3 cells.</p><p><b>CONCLUSIONS</b>Dihydroartemisinin exerts anti-tumor activity in pancreatic cancer both in vitro and in vivo by proliferation inhibition and apoptosis induction. Dihydroartemisinin can be used as a potential anti-tumor drug in pancreatic cancer.</p>

Effects of early goal-directed fluid therapy on intra-abdominal hypertension and multiple organ dysfunction in patients with severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effects of early goal-directed fluid therapy with hydroxyethyl starch 130/0.4 on intra-abdominal hypertension (IAH), multiple organ dysfunction and fluid balance in severe acute pancreatitis (SAP) patients.</p><p><b>METHODS</b>According to the criteria of selection and exclusion, 120 SAP patients within 72 hours after the symptom occurred from 4 study sites were recruited. They were given standard medication according to "the guideline of diagnosis and treatment of SAP in China" in SICU or PICU. The patients were randomly divided into two groups with crystalloid (control group) and colloid plus crystalloid resuscitation (research group). The objective of fluid therapy was to keep steady hemodynamics for 8 days. IAP was measured three times daily by means of urinary bladder transduction. Function of liver, renal and lung were detected daily. APACHE II score and fluid balance were calculated daily.</p><p><b>RESULTS</b>Total 120 cases were recruited into research group (n = 59) and control group (n = 61). The demography and baseline data were comparable. IAP was lower in research group than that in control group at day 4 and day 5 (P < 0.05). There was no significant difference in APACHE II scores between two groups pre- and after admission. The decline of daily IAP to baseline (DeltaIAP) in research group was significantly higher than in research group from day 2 to day 8(P < 0.05), whilst the decline of daily APACHE II score to baseline (DeltaAPACHE II score) in research group were significantly higher from day 4 to day 8 (P < 0.05). Negative fluid balance emerged much earlier in the research group (P = 0.036). Percentage of patients with negative fluid balance within 8 days was significantly higher in research group than that in control group (94.9% vs. 62.3%). The amount of positive fluid balance was significantly lower in research group (P = 0.039). IAP correlated significantly with APACHE II score (r(2) = 0.322, P = 0.000). PaO2/FiO2 was significantly higer in research group at day 4 and day 8.</p><p><b>CONCLUSIONS</b>It is very important to pay close attention to IAP in early fluid therapy of SAP patients. Early goal-directed fluid therapy with HES130/0.4 shortens the duration of positive fluid balance, decreases the amount of positive fluid balance, reduces APACHE II score, relieves IAH, and improves PaO2/FiO2.</p>

The effect of hyperbaric oxygen on acute pancreatitis through downregulating hypoxia-inducible factor / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of hyperbaric oxygen (HBO) on acute pancreatitis (AP) by downregulating hypoxia-inducible factor (HIF).</p><p><b>METHODS</b>Forty Wistar rats were randomly divided into 4 groups (n = 10): sham group, AP group, normo-oxygen group (NP) and HBO group. At 4 hours after taurocholate-induced AP, the rats of NP group and HBO group were respectively treated with oxygen or HBO for 90 min. Several parameters were measured to evaluate oxygen stress after treatment including oxygen saturation (SaO2), partial pressure of oxygen (PO2), pH, and serum LDH. Pancreatic tissues were subjected to histopathological analysis, immunostained, and homogenized for Western blotted analysis of HIF-1alpha and VEGF, and measuring myeloperoxidase activity. The serum TNF-alpha and pancreatic histopathological scores were evaluated the severity of AP.</p><p><b>RESULTS</b>It was proved by immunohistochemisty that HIF in acinar cell and polymorphonuclear leukocytes (PMNs) was activated and transferred from cytoplasm into nucleus in AP group, NP group, and HBO group, following upregulation of VEGF. HBO therapy elevated blood SaO2 (99.6% +/- 0.7% vs. 87.7% +/- 1.8% or 91.2% +/- 2.5%, P < 0.05) and PaO2 [(369.1 +/- 67.6) mm Hg (1 mm Hg = 0.133 kPa) vs. (86.6 +/- 5.6) mm Hg or (99.9 +/- 4.0) mm Hg, P < 0.05]. HBO therapy attenuated the severity of AP through inhibiting AP-induced upregulation of HIF-1alpha and VEGF, as evidenced by reducing histopathological scores (12.40 +/- 1.21 vs. 16.45 +/- 1.10 or 16.38 +/- 1.10, P < 0.05), dry/wet weight ratio of pancreatic tissues, and myeloperoxidase activity.</p><p><b>CONCLUSIONS</b>HIF-1alpha plays a key role in the pathogenesis of AP. HBO therapy attenuates the severity of AP through downregulating the expression of HIF-1alpha.</p>