ABSTRACT
Gallbladder carcinoma （GBC） is a type of malignant tumor with an extremely poor prognosis， and at present， surgical operation is the most effective treatment method for this disease. Unfortunately， due to a lack of typical symptoms in the early stage， most patients have progressed to the advanced stage at the time of confirmed diagnosis and lost the opportunity for radical surgery. Among the currently available adjuvant treatments， targeted therapy has higher specificity and fewer side effects and has improved the prognosis of a variety of malignancies. With reference to the latest research advances in targeted therapy for GBC， this article reviews the current research status， potential targets， and targeted medications of targeted therapy for GBC， in order to provide a reference for the clinical treatment of GBC patients.
ABSTRACT
Objective:To investigate the effects and molecular mechanism of neuropilin and tolloid-like 2 (NETO2) on proliferation, migration, cell cycle, and apoptosis in gallbladder cancer (GBC).Methods:The NETO2 mRNA and protein expression in GBC-SD, ZJU-0430, NOZ GBC cells were detected by quantitative real-time polymerase chain reaction and Western blot. NETO2 overexpression and knockdown stable cell lines were constructed by plasmid transfection. Cell counting kit-8 assay, colony formation assay, transwell assay, flow cytometry and WB assay were performed to evaluate proliferation, migration, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT) and changes of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway.Results:GBC-SD and ZJU-0430 cells with NETO2 gene overexpression and NOZ cells with NETO2 gene knockdown were effectively constructed. NETO2 overexpression in gallbladder cancer cell lines significantly improved cell proliferation and migration, advanced cell cycle progression from G0/G1 to S phase, and inhibited cell apoptosis. In the ZJU-0430 and GBC-SD cells, the clone number increased from (78.5±9.2), (217.0±6.4) to (213.5±10.3), (296.3±9.3)( t=10.98, 6.51; P=0.008, 0.023); The number of migrating cells increased from (198.6±8.4), (233.3±11.0) to (382.7±12.4), (379.0±7.3) ( t=16.98, 16.85, both P<0.001); The total apoptosis rate reduced from (29.7±0.9)%, (35.6±1.1)% to (19.2±0.5)%, (29.1±0.4)% ( t=9.74, 9.05; both P<0.001); The expression of EMT related proteins such as N-cadherin, Vimentin, Snail, and Slug were upregulated, while E-cadherin expression was downregulated. Phosphorylated PI3K (p-PI3K) and Akt (p-Akt) protein expression were significantly increased (all P<0.05). In contrast, NETO2 knockdown had the opposite effect on all these parameters. Conclusion:NETO2 influences the EMT process by regulating the PI3K/Akt signaling pathway, thus promotes GBC cell proliferation, migration and cell cycle progression, and inhibits cancer cell apoptosis.
ABSTRACT
Objective:The safety and effectiveness of the enhanced recovery after surgery (ERAS) in the treatment of distal pancreatectomy (DP) were evaluated by meta-analysis.Methods:Pancreatic body and tail resection, distal pancreatic resection, ERAS, rapid recovery after surgery, pancreatectomy, DP and ERAS were used as key words, and the network database such as Chinese journal full-text database, Wanfang data knowledge service platform, Weipu database, Chinese biomedical literature database, Pubmed, Embase, Cochrane library, Web of science, Sciencedirect and so on were searched. The retrospective literatures published from the database establishment to May 2022 were retrieved from the network database, and the papers were screened and the quality was evaluated according to the pre-set inclusion and exclusion criteria; and important data were extracted. The software Review Manager 5.4 was used for meta-analysis.Results:9 papers were finally included, and a total of 650 patients with DP were enrolled (311 in the ERAS group and 339 in the NO-ERAS group). Meta-anaysis showed that compared with NO-ERAS group, ERAS group could reduce intraoperative bleeding ( MD=-73.88, 95% CI -121.21--26.55, P=0.002), decrease the incidence of postoperative complications ( OR=0.48, 95% CI 0.32-0.72, P<0.001) and pulmonary complications ( OR=0.47, 95% CI 0.24-0.93, P=0.030), shorten the postoperative exhaust time (MD=-8.76, 95% CI -11.23--6.29, P<0.001), postoperative length of hospital stay ( MD=-2.65, 95% CI -3.06--2.07, P<0.001) and abdominal drainage tube removal time ( MD=-1.45, 95% CI -1.81--1.09, P<0.001). However, ERAS could not shorten the operative time ( MD=6.25, 95% CI -4.56-17.07, P=0.260), reduce the incidence of postoperative pancreatic fistula ( OR=0.92, 95% CI 0.53--1.60, P=0.780) and the re-admission rate within 30 days after surgery ( OR=1.00, 95% CI 0.47-2.11, P=0.990). Conclusions:ERAS is safe and effective for patients undergoing DP, because it can reduce intraoperative bleeding and postoperative complications, shorten postoperative hospital stay and postoperative abdominal drainage tube removal time.
ABSTRACT
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
ABSTRACT
Objective:To systematically evaluate the efficacy and clinical value of early enteral nutrition (EEN) combined with microecological agents in the treatment of severe acute pancreatitis (SAP).Methods:China National Knowledge Infrastructure, Chinese biomedical literature database, Wanfang Database, VIP, Cochrane Library, PubMed, Embase, and Web of Science were analyzed, and the retrieval time range is from the establishment of the datebase to November 1, 2019. To compare the clinical efficacy of EEN combined with microecological agents (experiment group) and single EEN treatment (control group) in SAP patients, and to compare the main outcome indicators: serum C-reactive protein level, incidence of multiple organ dysfunction syndrome, incidence of pancreatic infection necrosis, incidence of other complications, mortality, and length of hospital stay. And secondary outcome measures: plasma interleukin-8 (IL-8), tumor necrosis factor-α level, gastrointestinal score, and incidence of surgical intervention. The quality of the included literature was evaluated by using the Cochrane systematic evaluator's manual 5.1.0 risk of bias assessment tool, and meta-analysis was performed by using Stata16.0 software.Results:A total of 762 patients were enrolled in 9 RCTs. The results of meta-analysis showed that: among the main outcome indicators, C-reactive protein level [Mean Difference ( MD)=-7.58, 95% CI: -23.71-8.55, P>0.05], incidence of multiple organ dysfunction syndrome [Logarithm Risk Ratio (Log RR)=-0.30, 95% CI: -0.71-0.10, P>0.05], incidence of pancreatic infection and necrosis (Log RR=-0.21, 95% CI: -0.57-0.16, P>0.05) and mortality rate (Log RR=0.13, 95% CI: -0.36-0.62, P>0.05) the differences were not statistically significant. The incidence of complications in the experimental group was significantly lower than that in the control group (Log RR=-0.29, 95% CI: -0.51-0.07, P<0.05), and the length of hospital stay in the experimental group ( MD=-4.45, 95% CI: -7.47--1.43, P<0.05) was significantly shorter than that in the control group. Plasma IL-8 levels ( MD=-7.43, 95% CI: -14.28--0.57, P<0.05), TNF-α level ( MD=-38.96, 95% CI: -72.96--4.95, P<0.05)and gastrointestinal score ( MD=-0.15, 95% CI: -0.17--0.13, P<0.05)were significantly lower in the experimental group than in the control group, and the incidence of surgical intervention was significantly lower than that of the control group (Log RR=-1.63, 95% CI: -8.96-0.57, P>0.05) no statistical significance. Conclusion:EEN combined with microecological preparations can reduce the length of hospital stay in SAP patients and the incidence of complications. Therefore, EEN combined with microecological agents may be beneficial for SAP patients.
ABSTRACT
Cholecystectomy is currently the most important surgical treatment for gallbladder disease, however, the complications of cholecystectomy, especially the occurrence of intestinal tumors has gradually aroused attention of scholars. In recent years, scholars have found that bile acid metabolism changes significantly after cholecystectomy, which may be the main cause of colorectal cancer induction, but the specific mechanism of colorectal cancer induced by cholecystectomy has not been clarified. In this article, the changes of bile acid metabolism after cholecystectomy (the size and composition of bile acid pool) and the mechanism of colorectal cancer induction after cholecystectomy were summarized and discussed based on the research progress at home and abroad, aiming at providing theoretical basis for the exploration of the prevention and treatment of colorectal cancer.
ABSTRACT
Severe acute pancreatitis (SAP) is a common critical disease of the digestive system with rapid progression, multiple clinical outcomes, and high mortality rate. With the development of minimally invasive technology, the surgical intervention strategies for SAP have changed greatly, and the mode of surgical intervention is developing towards minimal invasiveness, multidisciplinary cooperation, and individualization. At present, the treatment concepts of “step-up approach” and delayed intervention have been widely accepted by clinicians. Accurately grasping the indications for surgical intervention, emphasizing the timing of surgical intervention, and selecting a reasonable mode of surgical intervention have become the key to successful surgical intervention for SAP in clinical practice. Emphasis on the principles of multidisciplinary cooperation and individualization and a correct understanding of the role and status of surgical intervention may help to further improve the overall cure rate of SAP patients.
ABSTRACT
Objective@#To analyze the genetic characteristics of Coxsackievirus A4 isolated from Taian, 2017-2018.@*Methods@#Sixty throat swab samples of the children who visited Taian Maternal and Child Health Hospital during the year 2017-2018 and were diagnosed as hand, foot and mouth disease, were collected and aseptically inoculated. Fluorescent quantitative PCR analysis was performed using the universal primer for enteroviruses. The high-throughput sequencing was applied to the enterovirus-positive samples, and the full-length genome sequences of the viruses were obtained. Phylogenetic analysis was performed using Mega5.05 and RaxML respectively, and sequence homology and amino acid mutation sites were also analyzed using Mega5.05.@*Results@#Four whole genome sequences of CV-A4 isolated from infants aged 17-19 months old were obtained. Phylogenetic analysis of the full length CV-A4 genomes showed that apart from MG550920/AA/Henan/2016, the remaining CV-A4 strains from China (97.2%), including the four strains from Taian, fell within Group 3. The VP1 genes could be classified into four genotypes and 98.5% of the Chinese strains belonged to genotype D, and the four strains from Taian belonged to D2. It was notable that the Taian isolate A1/Taian is closely related to two strains C179 and C062 from Australia both in the complete genome and the VP1 gene, as well as one strain YT184R isolated from Yantai in 2016 by us. Compared with the prototype CV-A4 strain High Point, 18 amino acid mutations were found in the P1 region.@*Conclusions@#Both phylogenetic trees estimated using the complete genome and the VP1 gene sequences revealed that the four CV-A4 isolates from Taian fell within the same clade with the majority of CV-A4 strains circulating in China. Compared with the prototype CV-A4 strain, several amino acid variations have occurred in the P1 region, which warrants further investigation.
ABSTRACT
Objectives@#To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer.@*Methods@#The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ2 test, survival analysis was carried by Kaplan-Meier and Log-rank test.@*Results@#Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ2=288.60,P<0.01),N stage(χ2=68.10, P<0.01), vascular invasion(χ2=128.70, P<0.01)and neural invasion(χ2=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ2=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05).@*Conclusion@#With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.
ABSTRACT
Objective To investigate the safety and feasibility of laparoscopic pancreaticoduodenectomy (LPD). Methods Clinical data of 9 patients who underwent LPD operation from September 2014 to February 2017 in the first hospital of Shanxi Medical University were analyzed retrospectively. Results 9 patients attempted LPD, while one required conversation to open procedure. Two cases underwent hand assisted laparoscopic surgery .The average operative time was (553 ± 86.1) minutes, the average amount of bleeding was (333.3 ± 304.1) ml, and the average hospitalization time after operation was (25.3 ± 8.9) d. Postoperative bowel sound recovery time was (3.5 ± 1) d. Postoperative complications included pancreatic leakage in 4 cases (A grade pancreatic leakage in 1 cases, B grade in 3 case), lymph leakage in 1 case, abdominal hemorrhage in 1 case , gastric emptying in 2 cases , and bile leakage in 1 case. All patients with postoperative complications were cured by non operative treatment. Postoperative pathological examination showed that 5 cases had duodenal papillary adenocarcinoma, 1 case had pancreatic ductal carcinoma, 2 cases had common bile duct disruption differentiation of carcinoma, and 1 case had pancreatic head retention cyst. Patients were followed up 3 to 24 months after operation. 1 case of pancreatic duct died 17 months after operation. One case of middle bile duct carcinoma 12 months after surgery had liver and retroperitoneal lymph node metastasis. The remaining 7 cases had no complications. Conclusions laparoscopic pancreaticoduodenectomy is minimally invasive, safe and feasible.
ABSTRACT
CCAAT/enhancer binding protein β (C/EBPβ) is a critical member of C/EBP family.C/EBPβ,based on the leucine zipper located in C terminal of the protein,can regulate transcriptional activities of downstream target genes involved in diverse cellular processes,such as proliferation and differentiation.Recently published studies have identified that C/EBPβ is essential in the decidualization of endometrial stromal cells.This review summarizes the roles and mechanisms of C/EBPβ during the courses of decidualization,which is aimed at providing novel insights for dysfunctional decidualization.
ABSTRACT
Aim To investigate the effects of aspirin on Epstein-Barr virus (EBV)-transformed human B-lym-phocytes.Methods EBV-transformed human B-lym-phocytes were treated with certain concentrations of as-pirin.Cellular proliferation was analyzed by MTT as-say.Further evaluation of apoptosis of aspirin-treated cells was performed through light-field microscope, transmission electronic microscope(TEM),propidium iodide(PI)staining and flow cytometric analysis and DNA electrophoresis. Finally, immunoblot analysis was used to determine the expression levels of apopto-sis-associated proteins, proteins involved in mTOR pathway and PU.1 -Bim axis.Results Aspirin treat-ment inhibited proliferation of EBV-transformed human B-lymphocytes.We observed that aspirin treatment in-duced apoptosis in EBV-transformed human B-lympho-cytes,resulting in the decreased number and size of cells.Ultramicroscopic structural analysis via TEM in-dicated that aspirin treatment deformed the cellular nu-cleus,and led to peripheral chromatin and cytoplasmic vacuole.PI staining and flow cytometric analysis indi-cated that aspirin increased the permeability of cell membrane and decreased the viability of treated cells. Agarose electrophoresis revealed DNA smear in aspirin-treated cells.Mechanistically,mTOR signaling was in-hibited in aspirin-treated cells,as evidenced by the de-creased phosphorylation of S6K1 and S6 via immunob-lot analysis.Aspirin treatment led to the decrease of hematopoietic transcription factor PU.1 .Consequently, pro-apoptotic Bim, apoptosis-associated proteins caspase-3 and PARP were activated in aspirin-treated cells.Conclusion Aspirin may show anti-lymphoma effects via its inhibition of proliferation and induction of apoptosis of EBV-transformed human B-lymphocytes, in which mTOR signal pathway and PU.1 -Bim axis may be involved.
ABSTRACT
Objective To explore the safety of the human bone marrow‐derived mesenchymal stem cells (hBMSCs) after silencing of human leukocyte antigen A2 expression .Methods We divided the cells into three groups:normal cultured cells of the 8th passage served as control group , and hBMSCs after HLA A2 silencing expression of the 5th and 15th passage as experimental groups 1 and 2 ,respectively .The hBMSCs were recultured by sterile methods .The growth curve ,telomerase activation ,and expressions of P27 ,cyclin D2 and cyclin‐dependent kinase 4 (CDK4) were utilized to explore the safety of the hBMSCs induced by LV‐siRNA‐HLA A2 .The BMSCs were transplanted to the subcutaneous layer of nude mice .Tissue types were detected 24 weeks after transplantation . Results The cell curves had no obvious left or right shift in all the groups . The telomerease activation in experimental groups 1 and 2 did not significantly differ from those in control group . The expressions of anti‐oncogene P27 ,cyclin D2 and CDK4 had no obvious difference between the two experimental groups and control group , either . There was only ectopic osteogenesis 24 weeks after the BMSCs (HLA A2 gene silenced ) were transplanted to the subcutaneous layer of the nude mice .Conclusion There was no obvious evidence to support that hBMSCs had undergone change in safety after the silencing of HLA A 2 expression .
ABSTRACT
Pancreatic cancer is one malignancy with high aggressive and extremely poor prognosis,its incidence and mortality rates are increasing gradually in our country.Although surgical techniques and adjuvant drug therapy are improving,survival of patients with pancreatic cancer still has not been significantly improved.Long non-coding RNA are a class of non-coding transcripts longer than 200 nucleotides.Recent studies show long non-coding RNA is closely related to pancreatic cancer cells,apoptosis,metastasis and drug resistance.LncRNA plays an important role in the diagnosis,treatment and prognosis of pancreatic cancer.In this article we reviewed the role of long noncoding RNA and their significance in pancreatic carcinoma.
ABSTRACT
MicroRNA (miRNA) is an endogenous nonprotein-coding short-chain RNA,and it involves in the evolution of a variety of malignant tumors through targeted inhibition of mRNA translation or mRNA cleavage of gene expression regulation cancer or tumor suppressor genes,meanwhile,is also an important molecule in the occurrence and development processes of tumor.In the recent studies,miRNA has played an important role in the proliferation,apoptosis and invasion of cholangiocarcinoma cells,and it maybe become a new biomarker for the early diagnosis,assessment of prognosis and chemotherapy of cholangiocarcinoma.
ABSTRACT
Epithelial-mesenchymal transition is not only involved in generating normal embryonic development of organs and tissues,but also helps to improve cancer cell invasion and metastasis.When epithelial-nesenchymal is stimulated,cell-cell adhesion and cell polarity are disrupted by disappearance of adhesion molecules such as Ecadherin,resulting in the acquisition of a mesenchymal phenotype.Consequently,cells which have acquired mesenchymal function activate the migratory and invasion capability in cancer.Studies have shown that part of the transcription factors,growth factors and signaling pathways involved in epithelial-nesenchymal process,and miRNA may participates in the proliferation,apoptosis,invasion and metastasis of gastric cancer cells by regulating oncogenes or tumor suppressor genes,which also relates to the regulation of epithelial-nesenchymal.This article will be reviewed in recent years specific miRNA regulatory mechanisms of gastric cancer epithelial-nesenchymal.
ABSTRACT
<p><b>OBJECTIVE</b>To identify the complete genome sequence of an echovirus 20 isolate (KM/EV20/2010) and understand its genetic variation and evolution characteristics.</p><p><b>METHODS</b>Seven overlapping clones covering the whole viral genome (excluding the poly-A tail) were obtained by RT-PCR and sequenced, and their nucleotide and amino acid sequences were aligned with other echovirus 20 isolates. Phylogenetic and pairwise alignment analyses based on genome and complete VP1 regions were conducted with software Mega 4.1, RDP3 and SimPlot 3.5.1.</p><p><b>RESULTS</b>The genome of the echovirus strain was 7 395 nucleotides in length, and contained a 744-nt non-translated region (NTR) at the 5' end and a 96-nt NTR at the 3' end. The entire open reading frame contained 6 549 nt, encoding a 2 183-aa polyprotein. In the coding region, there was no nucleotide deletion or insertion. Based on the complete genome sequence alignments, the echovirus strain showed 80.1% nucleotide and 96.7% amino acid homology to echovirus 20 prototype JV-1 strain. The phylogenetic trees constructed on the genome and complete VP1 regions all indicated that the echovirus strain was not in one cluster with echovirus 20 prototype JV-1 strain, while had a closer relationship with echovirus 30 prototype Bastianni. Genotyping results from phylogenetic analysis showed that echovirus 20 has six genotypes. The strain used in this study belonged to genotype IV. The nucleotide divergence was 9.4%-21.7% among the 6 genotypes. The possible putative recombination was detected in its non-coding sequence of the echovirus 20 strain used in this study.</p><p><b>CONCLUSION</b>Based on the bioinformatics analysis. The echovirus 20 strains isolated in China could be divided into six genotypes, and the echovirus 20 in this study belonged to genotype IV.</p>
Subject(s)
Humans , Amino Acid Sequence , Base Sequence , China , Computational Biology , Enterovirus B, Human , Genetics , Genome, Viral , Genomics , Genotype , Open Reading Frames , Phylogeny , Sequence AlignmentABSTRACT
Objective To isolate and identify viruses from fecal samples of tree shrew with diarrhea.Methods Fecal sample supernatant of tree shrew with diarrhea was inoculated to three cell lines ( Vero, LLC-MK2 and KMB17 ) , and the cytopathic effects on the cells were observed.The infectious particles in the culture supernatant were further ana-lyzed by transmission electron microscopy ( TEM) , genomic RNA-PAGE, rotavirus detection kit, amplification of S1 com-plete segment and bioinformatics analysis.Results Constant cytopathic effects were induced in Vero, LLC-MK2 and KMB17 cell lines after three passages of culture.The results from TEM, RNA-PAGE and rotavirus analysis indicated that they belong to reoviruses.Analysis of the S1 segments revealed that the S1 sequence from KMB17 cell culture had the high-est homology with that of prototype isolate T1L (85%nucleotide homology and 90%amino acid homology), therefore this isolate was named as type I reovirus.The other two S1 sequences from LLC-MK2 and Vero cell culture were identical to have 85%nucleotide homology and 92%amino acid homology with the prototype isolate T3D, named as type III reovirus. Phylogenetic analysis indicated that the isolates in this study are evolutionally adapted to tree shrews.Conclusions It is the first report here that 2 genotypes of Tupaia orthoreovirus are isolated and identified from one fecal sample via three cell lines and viral S1-specific primers, which provides useful guidelines for the isolation and identification of other reoviruses from tree shrew or other hosts.
ABSTRACT
Induced pluripotent stem cell (iPS cell) opened a new way to stem cell research,iPS cells can differentiate into hepatocytes in vitro gradually,this breakthrough makes the iPS cells have become a promising clinical application source.During the process of iPS cells to hepatocytes,a variety of cytokines regulate gene expression by coordinating various liver cell growth signal to promote iPS cells into hepatocytes differentiation and maturation.This article summarizes the relevant cytokines and their role in iPS cells in hepatocytes differentiation.
ABSTRACT
Objective To explore the changes of mTOR signaling in LPS/D-gal-induced acute hepatitis in mice . Methods Twenty-six healthy adult female ICR mice were divided into two groups:the control group and experimental group, 13 mice in each group .LPS/D-gal was used to induce acute hepatitis in the mice .The survival of mice was moni-tored within 24 hours after LPS/D-gal challenge .At 6 hours after challenge , samples of serum and liver tissue were collect-ed for further analysis.Results Injection of LPS/D-gal resulted in acute death of the mice within 24 hours.At 6 hours post LPS/D-gal injection , the blood levels of ALT and AST were significantly increased .The mRNA expression of inflammatory cytokines Tnfa and Il6 was up-regulated in LPS/D-gal-induced hapatitis , in which DNA fragmentation and activation of caspase-3 were subsequently observed .Immunoblot analysis showed that both mTOR pathway and NF-κB pathway were ac-tivated.Unexpectedly , inhibition of mTOR signaling could neither decrease the apoptosis in the liver nor increase the sur -vival of mice .Conclusions The results of the present study indicate that mTOR signaling may play pleiotropic roles in the pathogenesis of LPS/D-gal-induced hepatitis .