Erratum: Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction: Erratum.

[This corrects the article DOI: 10.7150/ijms.26954.].

Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction.

Renal tubule cell apoptosis plays a pivotal role in the progression of chronic renal diseases. The previous study indicates that Sirolimus is effective on unilateral ureteral obstruction (UUO)-induced renal fibrosis. However, the role of Sirolimus in renal tubular apoptosis induced by UUO has not yet been addressed. The aim of this study was to determine the role of Sirolimus in renal tubular apoptosis induced by UUO. Male Sprague-Dawley rats were divided into three groups, sham-operated rats, and after which unilateral ureteral obstruction (UUO) was performed: non-treated and sirolimus-treated (1mg/kg). After 4, 7 and 14 d, animals were sacrificed and blood, kidney tissue samples were collected for analyses. Histologic changes and interstitial collagen were determined microscopically following HE and Masson's trichrome staining. The expression of PCNA was investigated using immunohistochemistry and the expression of Bcl-2, Bax, caspase-9, and caspase-3 were investigated using Western blot in each group. Tubular apoptotic cell deaths were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Sirolimus administration resulted in a significant reduction in tubulointerstitial fibrosis scores. After UUO, there was an increase in tubular and interstitial apoptosis in untreated controls as compared to Sirolimus treatment rats (P<0.05). In addition, the expression of PCNA, Bcl-2, Bax, caspase-9, and caspase-3 in obstructed kidney was characterized by immunohistochemistry and Western blot analyses demonstrating that sirolimus treatment significantly reduced PCNA, Bax, caspase-9 and cleaved caspase-3 expression compared to those observed in controls (P<0.05), whereas, Bcl-2 in the obstructed kidney were decreased in untreated controls compared to Sirolimus treatment rats subjected to the same time course of obstruction (P<0.05). We demonstrated a marked renoprotective effect of sirolimus by inhibition of UUO-induced renal tubular apoptosis in vivo.

A nomogram based on preoperative inflammatory markers predicting the overall survival of pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Developing a preoperative prediction model for estimating the risk of pancreatic ductal adenocarcinoma (PDAC) patients before pancreaticoduodenectomy is a difficult task. The purpose of current study was to develop a prognostic nomogram based on inflammatory markers for PDAC patients. METHODS: Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors based on 265 PDAC patients undergone surgery. The nomogram was built to estimate the probability of 1-year, 3-year, and 5-year OS. The predictive accuracy of nomogram was determined by concordance index, calibration curve, and time dependent receiver operating characteristics. RESULTS: In multivariable Cox analysis, vascular invasion, Tumor Grade, TNM stage, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and albumin/globulin ratio were significantly associated with OS, which were all assembled into nomogram. The calibration curves for probability of survival showed optimal agreement between nomogram prediction and actual observation. The concordance index for 1-year, 3-year and 5-year OS prediction were 0.860 (95% confidence intervals (CI): 0.837-0.885), 0.837 (95%CI: 0.819-0.856), and 0.809 (95%CI: 0.787-0.829), respectively. The area under time dependent receiver operating characteristics curve of 1-year, 3-year, and 5-year OS prediction were 0.938 (95%CI: 0.886-0.989), 0.844 (95%CI: 0.782-0.906), and 0.884 (95%CI: 0.792-0.976), suggesting high discriminative ability of nomogram. It allowed significant distinction survival outcomes by grouping the patients evenly into three subgroups after sorting by total points. CONCLUSIONS: Based on clinicopathology characteristics and inflammatory markers, we developed a nomogram providing an individualized risk estimate for PDAC patients.

BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin.

BACKGROUND & AIMS: BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma (HCC). METHODS: RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with shRNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. RESULTS: BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2 /M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2 /M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. CONCLUSION: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.

Risk factors for postoperative fatigue after gastrointestinal surgery.

BACKGROUND: Postoperative fatigue (POF) is an important complication that is commonly observed postoperatively and is also one of the most serious obstacles to postoperative convalescence. However, the risk factors for POF have not been fully addressed, and there is no effective method to predict POF. The aim of the present study was to investigate the risk factors for POF and to explore prediction of the degree of POF. METHODS: A prospective observational study was conducted of patients undergoing elective gastrointestinal surgery. Fatigue score, grip strength, length of postoperative hospital stay (LOS), as well as preoperative and intraoperative factors were collected. χ(2) was used to compare categorical variables, and multivariate logistic regression analysis was used to further analyze correlation between POF and preoperative and intraoperative factors. RESULTS: A total of 155 patients were included in our analysis without loss in follow-up. Multivariate logistic regression analysis after adjustment for factors with severe POF in univariate analysis including preoperative fatigue, plasma albumin and hemoglobin level, and cardiopulmonary function demonstrated that old age, gastrectomy, and a nutritional risk screening 2002 score ≥ 3 were associated with a higher relative risk of severe POF. Moreover, laparoscopic-assisted surgery was associated with lower relative risk of severe POF. CONCLUSIONS: Old age, nutritional risk screening 2002 score ≥ 3 and gastrectomy were risk factors for POF in patients undergoing elective gastrointestinal surgery. POF was reduced in laparoscopic-assisted surgery. Consideration of these factors could be important for the prevention and treatment of POF.

Laparoscopic versus open colorectal surgery within enhanced recovery after surgery programs: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) -1.92 days; 95 % confidence interval (CI) -2.61--1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. CONCLUSIONS: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs.

Prevention of postoperative fatigue syndrome in rat model by ginsenoside Rb1 via down-regulation of inflammation along the NMDA receptor pathway in the hippocampus.

Postoperative fatigue syndrome (POFS) is a common complication which decelerates recovery after surgery. The present study investigated the anti-fatigue effect of ginsenoside Rb1 (GRb1) through the inflammatory cytokine-mediated N-methyl-D-aspartate (NMDA) receptor pathway. A POFS rat model was created by major small intestinal resection and assessed with an open field test. Real-time quantitative polymerase chain reaction, western blot analysis, high performance liquid chromatography and a transmission electron microscopic analysis were used to determine typical biochemical parameters in the hippocampus. Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. Degenerated neurons were found in the hippocampus of POFS rats. The NMDA receptor antagonist MK801 had a significant effect on central fatigue on postoperative day 1. GRb1 had no effect on IDO or tryptophan metabolism, but exhibited a significant effect on POFS by inhibiting the expression of inflammatory cytokines and NMDA receptor 1. These data suggested that inflammatory cytokines could activate tryptophan metabolism to cause POFS through the NMDA receptor pathway. GRb1 had an anti-fatigue effect on POFS by reducing inflammatory cytokines and NMDA receptors.

[Sedum sarmentosun bunge extraction ameliorated severe acute pancreatitis-induced lung injury: an experimental research]].

OBJECTIVE: To explore the effect of Sedum sarmentosum Bunge Extract (SSBE) on severe acute pancreatitis (SAP) induced acute lung injury (ALI) model rats and their excessive inflammatory reactions. METHODS: Forty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the sham-operated control group (C), the SAP group (SAP), and the SSBE treated group (SSBE), 14 in each group. SAP induced ALl rat model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. SSBE (100 m/kg) was administrated subcutaneously after the establishment of the SAP model. Equal dose of SSBE was injected again 12 h later. Equal volume of normal saline was administrated in the same way for rats in the C group and the SAP group. Rats were sacrificed after successful modeling and samples taken at 12 and 24 h. Pathological changes in the pancreas and the lung tissue were observed under light microscope. The ascites, serum amylase (AMS), wet/dry proportion (W/D) of the lung tissue, activities of myeloperoxidase (MPO), interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ascites and serum AMS activities significantly increased; MPO, IL-1, IL-6, TNF-alpha contents, and W/D ratio also significantly increased in the SAP group, when compared with the C group (P<0.05). Compared with the SAP group, those parameters were all attenuated in the SSBE group at 12 and 24 h (P<0.05, P<0.01). Pathological changes in the pancreas and the lung tissue were alleviated in the SSBE group under light microscope. The injury degree ranged between that of the C group and the SAP group. CONCLUSION: SSBE could relieve the ALl in SAP model rats, which could be achieved through alleviating inflammation responses of SAP rats.

Ginsenoside Rb1 improves energy metabolism in the skeletal muscle of an animal model of postoperative fatigue syndrome.

BACKGROUND: Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. Ginsenoside Rb1 (GRb1), a principle ginsenoside in ginseng, could exert a potent anti-fatigue effect on POFS. However, the mechanism is still unknown. Previous studies revealed that alterations in the energy metabolism in the skeletal muscle may play a vital role in the development and progression of fatigue. In the present study, we investigate the effect of GRb1 on energy metabolism in the skeletal muscle of a rat model of POFS induced by major small intestinal resection. METHODS: GRb1 (10 mg/kg) was intraperitoneally administrated once daily for 1, 3, 7, and 10 d from the operation day, respectively. The locomotor activity was recorded every day, and total food intake was calculated starting from 24 h after surgery. After GRb1 treatment was completed, blood and skeletal muscle were sampled. The level of blood glucose was determined by an automatic biochemical analyzer. The content of adenosine triphosphate (ATP) in skeletal muscle was determined by high-performance liquid chromatography. The activity of energy metabolic enzymes Na(+)-K(+)-ATPase, pyruvate kinase, and succinate dehydrogenase (SDH) was assessed by commercially available kits. RESULTS: The results revealed that GRb1 could increase locomotor activity of POFS rats and significantly increase their total food intake postoperatively (P < 0.05). Furthermore, GRb1 also significantly increased ATP content in the skeletal muscle of POFS rats (P < 0.05). Meanwhile, the activity of Na(+)-K(+)-ATPase and SDH in the skeletal muscle of POFS rats was enhanced by GRb1 (P < 0.05). However, no significant differences in blood glucose and pyruvate kinase were found between the POFS and GRb1 treatment rats (P > 0.05). CONCLUSIONS: These results suggest that GRb1 may improve skeletal muscle energy metabolism in POFS, and the underlying mechanism may be associated with an increase in the content of ATP and an enhancement in the activity of energy metabolic enzymes such as Na(+)-K(+)-ATPase ATPase and SDH in the skeletal muscle.

Fast-track surgery in gastrectomy for gastric cancer: a systematic review and meta-analysis.

PURPOSE: Fast-track surgery aims to attenuate the surgical stress response, reduce complications, and shorten hospital stay. The goal of the present meta-analysis is to assess the safety and effectiveness of fast-track surgery in patients undergoing gastrectomy for gastric cancer compared with conventional perioperative care. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared fast-track surgery with conventional perioperative care in patients undergoing gastrectomy for gastric cancer. RESULTS: Five studies with a total of 400 patients were included in the meta-analysis. Meta-analysis shows that postoperative hospital stay (weighted mean difference (WMD) -1.87 days, 95 % confidence interval (CI), -2.46 to -1.28 days, P < 0.00001), time to first passage of flatus (WMD -0.71 days, 95 % CI, -1.03 to -0.39 days, P < 0.0001), and hospital costs (WMD -505.87 dollars, 95 % CI, -649.91 to -361.84 dollars, P < 0.00001) were significantly reduced for fast-track surgery. No significant differences were found for readmission rates (relative risk (RR), 1.97 95 % CI, 0.37 to 10.64, P = 0.43) and total postoperative complications (RR, 0.99 95 % CI, 0.56 to 1.76, P = 0.97). CONCLUSIONS: Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions.

Enhanced recovery after surgery programs versus traditional care for colorectal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Enhanced recovery after surgery programs in colorectal surgery aim to attenuate the surgical stress response, reduce complications and shorten hospital stay. OBJECTIVE: This study aimed to assess the safety and efficacy of enhanced recovery after surgery programs in colorectal surgery in comparison with traditional care. DATA SOURCES: PubMed, Embase, and Cochrane databases were electronically searched (date range, January 1966 to July 2012). STUDY SELECTION: Randomized controlled trials were selected that compared enhanced recovery after surgery programs with traditional care in elective colorectal surgery. INTERVENTION: Articles were reviewed independently by 2 reviewers, who extracted the data and assessed the quality of the included studies. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation system. MAIN OUTCOME MEASURES: The primary outcome measures were primary and total postoperative hospital stay, readmission rates, total postoperative complications (including general and surgical complications), and mortality. RESULTS: Thirteen studies (total, 1910 patients) were included in the meta-analysis. In comparison with traditional care, enhanced recovery after surgery programs were associated with significantly decreased primary hospital stay (weighted mean difference, -2.44 days; 95% CI, -3.06 to -1.83 days; p < 0.00001), total hospital stay (weighted mean difference, -2.39 days; 95% CI, -3.70 to -1.09 days; p = 0.0003), total complications (relative risk, 0.71; 95% CI, 0.58-0.86; p = 0.0006), and general complications (relative risk, 0.68; 95% CI, 0.56-0.82; p < 0.0001). No significant differences were found for readmission rates, surgical complications, and mortality. LIMITATIONS: This study was limited by the risk of bias in most included studies. CONCLUSIONS: Enhanced recovery after surgery programs are safe and effective, and increased implementation is justified for perioperative care in colorectal surgery. Future studies may examine the benefits of enhanced recovery after surgery programs in elderly patients and in other GI surgery.

Early versus traditional postoperative oral feeding in patients undergoing elective colorectal surgery: a meta-analysis of randomized clinical trials.

BACKGROUND: The safety and effectiveness of early oral feeding after colorectal surgery has not been determined. We performed a meta-analysis to evaluate surgical outcomes following early oral feeding compared with traditional oral feeding in patients undergoing elective colorectal surgery. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials comparing the outcomes following early oral feeding versus traditional oral feeding in patients undergoing elective colorectal surgery. The trials must have reported at least one of the following end points: anastomotic dehiscence, pneumonia, wound infection, nasogastric tube reinsertion, vomiting, mortality, length of hospital stay, hospital costs, and quality of life. RESULTS: Seven trials, which included a total of 587 patients, met our inclusion criteria. Compared with traditional oral feeding, early oral feeding reduced the length of hospital stay (weighted mean difference -1.58 days; 95% CI -2.77 to -0.39; p = 0.009) and the total postoperative complications (relative risk 0.70; 95% CI 0.50-0.98; p = 0.04). There were no significant differences in the risk of anastomotic dehiscence, pneumonia, wound infection, rate of nasogastric tube reinsertion, vomiting, or mortality. CONCLUSIONS: Early oral feeding is safe and effective in patients undergoing elective colorectal surgery.

[Study on KIR gene polymorphisms in 416 renal transplantation recipients from southern Zhejiang].

OBJECTIVE: To investigate polymorphisms of killer cell immunoglobulin-like receptor gene (KIR) in renal transplant recipients from southern Zhejiang. METHODS: KIR genotypes were analyzed by PCR-SSP in 416 renal transplant recipients, and the genotype frequencies were compared with populations from Eastern China and worldwide. RESULTS: All 16 known KIR genes were detected in the renal transplant recipients, and KIR2DL4, 3DL2-3, 3PD1 were found in all. As a pseudogene, 2DP1 has a high genotype frequency (99%). The frequencies of KIR2DL1, 2DL3, 3DL1, 2DS4 have ranged from 92.1% to 98.8%. Compared with 11 groups in Eastern China and other countries, the KIR2DL2 phenotype frequency was higher (34.6%) than those of Shanghai, Zhejiang and Jiangsu populations (P<0.05). Among 41 genotypes, three have not been reported previously. The most common genotype was AA1, with a frequency of 43.51%, which was significantly lower than those of Jiangsu and Northern Zhejiang. CONCLUSION: Renal transplant recipients from southern Zhejiang share similar features with Eastern China Han population with regard to KIR polymorphisms, but also have unique frequencies for KIR genotypes.

[Expression of miRNA-29b and its clinical significances in primary hepatic carcinoma].

OBJECTIVE: To explore the clinical value of miRNA-29b expression and the combined detection of serum miRNA-29b and alpha-fetoprotein (AFP) in the diagnosis of primary hepatic carcinoma(PHC). METHODS: From January 2007 to May 2010, the serum levels of miRNA-29b and AFP from 96 healthy controls and 87 PHC patients were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) respectively. The relationship of miRNA-29b and various clinical parameters was analyzed. RESULTS: Serum levels of miRNA-29b in PHC pre-operative group (0.250 (0.124 - 0.381)) significantly decreased versus the control group [0.860 (0.587 - 1.338)] and the post-operative group (0.890 (0.637 - 1.414)) (P < 0.001). Also, the levels of AFP in PHC pre-operative group (65.4 (20.1 - 212.3)) was obviously higher than that in the control group (13.3 (7.1 - 19.8)) and the post-operative group (23.2 (11.6 - 55.7)) (P < 0.001). A lower expression of miRNA-29b was correlated with lower differentiation and higher TNM stages (P < 0.045, P < 0.001). Kaplan-Meier curve analysis revealed that PHC patients with a low serum expression of miRNA-29b had a significantly shortened overall survival when compared with a high serum expression of miRNA-29b (25.52 vs 36.94 months, P = 0.008). Multivariable Cox regression analysis indicated that the serum expression of miRNA-29b was an independent risk factor for overall survival. Relative risk was 0.482 (95% confidence interval: 0.236 - 0.985). The critical values for miRNA-29b and AFP were determined at 0.38 and 23.1 µg/L through the ROC curves. Under the critical value, the sensitivity of miRNA-29b and AFP were 75.9% and 70.1% and the specificity of miRNA-29b and AFP 89.5% and 92.7% respectively. Combined detection could increase the sensitivity up to 87.3%, and achieve a specificity of 88.5%. CONCLUSION: The combined detection of miRNA-29b and AFP aids the diagnosis of PHC and the prediction of its prognosis.

[Effects of ginsenoside Rb1 on the mRNA expression of tyrosine kinase B in the hippocampus of acute immobilization stress rats].

OBJECTIVE: To observe the effects of acute immobilization stress on the mRNA expression of tyrosine kinase B (TrkB) in rats' hippocampus. METHODS: Eighteen SD rats were randomly divided into three groups, i.e., the normal control group, the model group, and the medication group, 6 in each group. The acute immobilization stress model was prepared in the model group using acute immobilization for 2 h. Ginsenoside Rb1 (40 mg/kg) was peritoneally injected to rats in the medication group 30 min before modeling, with the same procedure as those for rats in the model group. No treatment was performed to rats in the normal control group. The plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) contents were detected using ELISA. The mRNA expression of TrkB in the rats' hippocampus was detected using real-time fluorescence quantitative RT-PCR. RESULTS: Before modeling there was no statistical difference of plasma CORT or ACTH concentrations among three groups (P >0.05). The plasma CORT and ACTH concentrations increased in the model group and the medication group more significantly after modeling than before modeling, showing statistical difference (P <0.05). Besides, they were obviously higher in the model group than in the normal control group (P <0.05). They were obviously higher in the medication group than in the model control group (P <0.05). Compared with the normal control group, the mRNA expression of TrkB significantly decreased in the model group (87.73 +/- 7.62 vs 50.65 +/- 5.19, P < 0.05), showing statistical difference. The mRNA expression of TrkB was significantly higher in the medication group (78.91 +/- 18.07) than in the model group, showing statistical difference (P <0.05). CONCLUSION: Pretreatment by ginsenoside Rb1 could increase the plasma CORT and ACTH concentrations, maintain the mRNA expression of TrkB, thus relieving injury induced by acute immobilization stress.

[The role of adenosine deaminase in the electroacupuncture preconditioning induced rapid tolerance to focal cerebral ischemia].

OBJECTIVE: To observe the electroacupuncture (EA) pretreatment at Baihui (GV20) on the concentration of adenosine deaminase (ADA) and adenosine, and to evaluate its effects on the neurologic function score and the infarction volume after middle cerebral artery occlusion (MCAO) ischemia/reperfusion (I/R), thus exploring its mechanisms for relieving the ischemia/reperfusion injury. METHODS: Totally 54 male SD rats were randomly divided into 3 groups, the sham-EA group, the EA group, and the control group, 18 in each group. Rats in the control group were not intervened after anesthesia. Rats in the EA group were needled at Baihui (GV20) for 30 min. Rats in the sham-EA group received the same procedure as those performed in the EA group without electricity connected. The changes of adenosine and ADA contents were detected at 30, 60, and 120 min after EA respectively. The I/R model was established. Totally 48 male SD rats were randomly divided into 6 groups, i.e., the model group (Group A), the EA group (Group B), the EA +8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) group (Group C), the EA + DMSO group (Group D), the Deoxycoformycin (Deo) group (Group E), and the normal saline group (Group F). Rats in Group B, C, and D received EA for 30 min before modeling. Rats in Group C and D were peritoneally injected with DPCPX (1 mg/kg) and DMSO (1 mL/kg) at 30 min before EA. The neurologic function score was evaluated and the infarct volumes were detected after 24-h reperfusion. RESULTS: Compared with the sham-EA group, there was no statistical difference in the contents of the adenosine or ADA in the control group at each time point (P > 0.05). Compared with the control group at the same time point, the content of ADA significantly decreased at 60 min in the EA group [(315.0 +/- 22.9 U/L), P < 0.05], and restored to the normal level at 120 min after EA. The content of adenosine increased in the EA group at 120 min [(20.4 +/- 2.2) ng/microL, P < 0.05]. Compared with the model group, the neurologic function score decreased (P < 0.05) and the infarct volumes were obviously reduced (P < 0.01) in Group B, D and E. There was no statistical difference in the neurologic function score or the infarct volumes in other groups, when compared with the model group (P > 0.05) CONCLUSION: EA at Baihui (GV20) showed protective effects on the cerebral I/R rats, which might be achieved through lowering the ADA concentration and elevating the adenosine content, and further activating adenosine A1 receptor.

[Analysis of an hereditary protein C deficiency pedigree with compound heterozygous gene mutations].

OBJECTIVE: To analyze genetic mutations and explore its molecular pathogenesis for an hereditary protein C (PC) deficiency pedigree. METHODS: The pedigree has included 15 individuals from 4 generations. Plasma levels of PC activity (PC:A), PC antigen (PC:Ag) and other coagulant parameters were determined for members of the family. The 9 exons and intron-exon boundaries of protein C gene (PROC) of the proband were amplified with PCR and analyzed with direct sequencing. Detected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from the family members were also directly sequenced. RESULTS: Plasma PC:A and PC:Ag for the proband was 26% and 18.60%, respectively, both being lower than normal references. Seven members from the pedigree also had lower PC:A, six had lower PC:Ag. A compound heterozygous missense mutation, including a T to G transition at position 6128 of exon 7, which results in Phe139Val, and a G to C transition at position 8478 in exon 9, which results in Asp255His, were identified in the proband. The paternal grandma, father and two aunts were heterozygous for g.6128 T to G, whilst the mother, the second uncle, sister and son were heterozygous for g.8478 G to C. There were lower PC:A in family members with g.8478 G to C. CONCLUSION: The proband had inherited two independent mutations of the PROC gene including g.6128 T to G in exon 7 and g.8478 G to C in exon 9 from her father and mother, respectively. The resulting compound heterozygous mutation has caused a serious hereditary protein C deficiency.

Overexpression of Dermokine-α enhances the proliferation and epithelial-mesenchymal transition of pancreatic tumor cells.

Pancreatic cancer is a prevalent malignancy of the digestive system and a major cause of cancer-associated deaths. Previous studies have shown that mutation in the dermokine-ß (DMKN-ß) gene causes pancreatic and colorectal cancer. The role of the carboxy-terminal domain of DMKN-ß and dermokine-α (DMKN-α) genes in cancer tumorigenesis. Herein, the role of DMKN-α in pancreatic cancer (PC) tumorigenesis and the mechanisms underlying this process were investigated. Differentially expressed genes between PC and matched normal cells were identified through RNA-seq analysis, and the corresponding protein expression levels were verified using Western blot analysis. In vivo tumor formation experiment was also performed in nude mice. We found that the DMKN-α gene was overexpressed in cancerous pancreatic cell lines compared to normal pancreatic cell lines. CCK-8, colony formation, RTCA test, wound healing, as well as transwell test showed that the overexpression of DMKN-α enhanced the proliferation, migration, invasion, and EMT of PC cells. In vivo assays confirmed that DMKN-α promotes tumorigenesis. The findings of this study show that DMKN-α is a potential oncogene for pancreatic cancer.

Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats.

OBJECTIVE: Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. MATERIALS AND METHODS: Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. RESULTS: Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of α-SMA and TGF-ß1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). CONCLUSION: Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.

Establishment and assessments of a new model for the postoperative fatigue syndrome by major small intestinal resection in rats.

OBJECTIVE: Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods. MATERIAL AND METHODS: Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a "middle" small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. RESULTS: As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test (p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups (p < 0.05), as well as decreased SOD and increased MDA in serum (p < 0.05). CONCLUSIONS: Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS.