Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still...BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.展开更多
βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regu...βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regulated by various factors,among which neurotransmitters make an important contribution.This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves onβcells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion.Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized byβcells themselves,allowing them to synergistically regulate insulin secretion.Almost all of these neurotransmitters depend on the presence of glucose to function,and their actions are mostly related to the Ca^(2+)and cAMP concentrations.Although neurotransmitters have been extensively studied,many of their mechanisms remain unclear and require further exploration by researchers.展开更多
Objective Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that uses the type Ⅲ secretion system (TTSS) to inject effector proteins directly into the cytosol of target cells to subvert the host cel...Objective Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that uses the type Ⅲ secretion system (TTSS) to inject effector proteins directly into the cytosol of target cells to subvert the host cell's functions. Specialized bacterial chaperones are required for effective secretion of some effectors. To identify the chaperone of ExoS, the representative effector secreted by the TTSS of P aeruginosa, we analyzed the role of a postulated chaperone termed Orfl. Methods By allelic exchange, we constructed the mutant with the deletion of gene Orfl. Analysis of secreted and cell-associated fractions was performed by SDS-PAGE and Western blotting. Using strain expressing in trans Orfl, tagged by V5 polypeptide and histidine, protein-protein interaction was determined by affinity resin pull-down assay in combination with MALDI-TOF The role of Orfl in the expression of exoS was evaluated by gene reporter analysis. Results Pull-down assay showed that Orfl binds to ExoS and ExoT. Secretion profile analysis showed that Orfl was necessary for the optimal secretion of ExoS and ExoT. However, Orfl had no effect on the expression of exoS. Conclusion Orfl is important for the secretion of ExoS probably by maintaining ExoS in a secretion-competent conformation. We propose to name Orfl as SpcS for "specific Pseudomonas chaperone for ExoS".展开更多
In order to enrich the research about type III secretion system (T3SS) injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis...In order to enrich the research about type III secretion system (T3SS) injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis. Specific primers were designed according to the full-length geanme sequence of V. alginolyticus in GenBank. vscX gene (C, enBank accession number: FR780679) contained a 378 bp open reading frame (ORF), encoding a putative protein of 125 amino acids. The theoretical molecular weight was 14.209 2 kD and theoretical pI was 5.75. By using Signal 4.1 Server and TMHMM Server 2.0, it was predicted that VscX protein had no transmembrane domain or signal peptide. The results of prediction using SoftBerry-Psite software showed that VscX protein contained three casein ki- nase lI phosphorylation sites, one N-myristoylation site and three C-terminal targeting signal sites. Subcellular localization revealed that VscX might be located in cytoplasm with the possibility of 56.5%. According to SMART prediction, VscX had one Pfam ( 1 - 125 aa) domain. Phylogenetic analysis revealed that VscX from V. alginolyticus and VscX from E parahemolyticus were clustered into the same group. Network interaction analysis showed that vscX was adjacent to vseY, vopB and sycN. By real-time fluorescent quantitative PCR technique and 2-△△△ method, the differences in expression levels of VscX mRNA in V. alginolyticus strain HY9901, T3SS deletion strain AvscO and complementary strain C-vscO at different growth stages were analyzed. The results showed that the expression levels of VscX mRNA in V. algianlyticus strain HY9901 and C-vscO were significantly up-regulated at stable growth stage ( P 〈0.01 ) ; the expression levels of VscX mRNA in deletion strain △vscO were significantly up-regulated at late growth stage ( P 〈0.01 ). This study provided the basis for revealing the transport mechanism of T3SS injectisome of E alginolyticus.展开更多
Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one ...Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one of the secretion systems and it usually consists of 12 genes: VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island (PAl) was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.展开更多
目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方...目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。展开更多
OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, C...OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.展开更多
AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological sta...AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.展开更多
Dickeya fangzhongdai, the causal agent of bleeding canker of pear, is a new member of the Dickeya genus and the only one that infects woody plants. Recent studies have reclassified several Dickeya isolates as D. fangz...Dickeya fangzhongdai, the causal agent of bleeding canker of pear, is a new member of the Dickeya genus and the only one that infects woody plants. Recent studies have reclassified several Dickeya isolates as D. fangzhongdai, which were isolated from various environments, including water, Phalaenopsis sp. and Aglaonema sp. To provide genomic characterization of D. fangzhongdai isolates from pear, the genomes of D. fangzhongdai strain JS5(=China General Microbiological Culture Collection Center, CGMCC 1.15464 ~T=DSM 101947 ~T), along with two other isolates, LN1 and QZH3, were sequenced and compared to those of other Dickeya spp. Homology greater than 99% was observed among three D. fangzhongdai strains. Plasmid, type IV secretion system(T4 SS) and type IV pili(TFPs) were found in genomes of D. fangzhongdai isolates. Comparative analysis of the type Ⅲ secretion systems(T3 SS), type Ⅲ secretion effectors(T3 SE), plant cell wall degradation enzymes(PCWDE) and membrane transport proteins of Dickeya spp. showed some differences which might reflect the variations of virulence, phylogenetic and phenotypic characteristics of Dickeya spp. In addition, deletion mutant of TFP in D. fangzhongdai JS5 showed no twitching motility and reduced virulence and biofilm formation. The fingdings of the distinctive plasmid, T4 SS and TFPs, as well as the differences of T3 SE, PCWDE and membrane transport proteins make D. fangzhongdai isolates unique. These results also suggested that acquisition of virulence genes by horizontal gene transfer might play some role in the genetic variation of D. fangzhongdai.展开更多
BACKGROUND Although Borrmann type Ⅳ(B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no di...BACKGROUND Although Borrmann type Ⅳ(B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis(PPCM), which is important for selecting an appropriate therapeutic strategy.AIM To identify factors related to the prognosis and PPCM of B-4 patients.METHODS A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan–Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0.RESULTS Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the longterm survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes(n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor(P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy.CONCLUSION Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.展开更多
Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired...Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N;77 ± 5 and 254 ± 65% in IGT;and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.展开更多
AIM: To determine factors predictive for esophageal varices in severe alcoholic disease (SAD). METHODS: Abdominal ultrasonography (US) was performed on 444 patients suffering from alcoholism. Forty-four patients found...AIM: To determine factors predictive for esophageal varices in severe alcoholic disease (SAD). METHODS: Abdominal ultrasonography (US) was performed on 444 patients suffering from alcoholism. Forty-four patients found to have splenomegaly and/ or withering of the right liver lobe were defined as those with SAD. SAD patients were examined by upper gastrointestinal (UGI) endoscopy for the presence of esophageal varices. The existence of esophageal varices was then related to clinical variables. RESULTS: Twenty-five patients (56.8%) had esophageal varices. A univariate analysis revealed a significant difference in age and type Ⅳ collagen levels between patients with and without esophageal varices. A logistic regression analysis identified type Ⅳ collagen as the only independent variable predictive for esophageal varices (P = 0.017). The area under the curve (AUC) for type Ⅳ collagen as determined by the receiver operating characteristic (ROC) for predicting esophageal varices was 0.78. CONCLUSION: This study suggests that the level of type Ⅳ collagen has a high diagnostic accuracy for the detection of esophageal varices in SAD.展开更多
BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism...BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.展开更多
The regenerating islet-derived members (Reg ),a group of small secretory proteins,which are involved in cell proliferation or differentiation in digestive organs,are upregulated in several gastrointestinal cancers,fun...The regenerating islet-derived members (Reg ),a group of small secretory proteins,which are involved in cell proliferation or differentiation in digestive organs,are upregulated in several gastrointestinal cancers,functioning as trophic or antiapoptotic factors.Regenerating islet-derived type Ⅳ (RegⅣ ),a member of the Reg gene family,has been reported to be overexpressed in gastroenterological cancers.RegIV overexpression in tumor cells has been associated with carcinogenesis,cell growth,survival and resistance to apoptosis.Cancer tissue expressing RegⅣ is generally associated with more malignant characteristics than that without such expression,and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers.We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorectal cancer.The biologic functions of RegⅣ protein in cancer tissue,associated with carcinogenesis,antiapoptosis and invasiveness,are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegⅣ,and the feasibility of antibody therapy targeting RegⅣ is being assessed.These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegⅣ .This review article summarizes the current information related to biological functions as well as clinical importance of RegⅣ gene to clarify the significance of RegⅣ expression in gastroenterological cancers.展开更多
BACKGROUND Liver resection is an effective treatment for benign and malignant liver tumors.However,a method for preoperative evaluation of hepatic reserve has not yet been established.Previously reported assessments o...BACKGROUND Liver resection is an effective treatment for benign and malignant liver tumors.However,a method for preoperative evaluation of hepatic reserve has not yet been established.Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve.When determining eligibility for hepatectomy,the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy.AIM To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery.METHODS This study was a retrospective cohort study.We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016.Early post-hepatectomy liver failure(PHLF)was defined using the International Study Group of Liver Surgery’s definition of PHLF.Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of<2 mg/dL and>2.8 g/dL,respectively,and the time taken for Child-Pugh score to return to Child-Pugh class A.RESULTS Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function.Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S≤6 ng/mL than in those with type IV collagen 7S>6 ng/mL.In additional analyses,similar results were observed in patients without chronic viral hepatitis associated with fibrosis.CONCLUSION Preoperative type IV collagen 7S is a preoperative predictor of PHLF and longterm postoperative liver function recovery.It can also be used in patients without chronic hepatitis virus.展开更多
Based on x-type entangled states and the two-step protocol [Deng F G, Long G L and Liu X S 2003 Phys. Rev. A 68 042317], a quantum secret sharing protocol of secure direct communication based on x-type entangled stat...Based on x-type entangled states and the two-step protocol [Deng F G, Long G L and Liu X S 2003 Phys. Rev. A 68 042317], a quantum secret sharing protocol of secure direct communication based on x-type entangled states |X00〉3214 is proposed. Using some interesting entanglement properties of this state, the agent entirety can directly obtain the secret message from the message sender only if they collaborate together. The security of the scheme is also discussed.展开更多
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
基金Supported by the Health Research Program of Anhui,No.AHWJ2022b032 and No.AHWJ2023A30034.
文摘BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.
基金Supported by National Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,China,No.2019J01010+1 种基金Xiamen Research Foundation for Science and Technology Project No.3502Z20194037Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005.
文摘βcells are the main cells responsible for the hypoglycemic function of pancreatic islets,and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body.βcells are regulated by various factors,among which neurotransmitters make an important contribution.This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves onβcells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion.Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized byβcells themselves,allowing them to synergistically regulate insulin secretion.Almost all of these neurotransmitters depend on the presence of glucose to function,and their actions are mostly related to the Ca^(2+)and cAMP concentrations.Although neurotransmitters have been extensively studied,many of their mechanisms remain unclear and require further exploration by researchers.
基金This research was supported by the association "Vaincre la Mucoviscidose" of France
文摘Objective Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that uses the type Ⅲ secretion system (TTSS) to inject effector proteins directly into the cytosol of target cells to subvert the host cell's functions. Specialized bacterial chaperones are required for effective secretion of some effectors. To identify the chaperone of ExoS, the representative effector secreted by the TTSS of P aeruginosa, we analyzed the role of a postulated chaperone termed Orfl. Methods By allelic exchange, we constructed the mutant with the deletion of gene Orfl. Analysis of secreted and cell-associated fractions was performed by SDS-PAGE and Western blotting. Using strain expressing in trans Orfl, tagged by V5 polypeptide and histidine, protein-protein interaction was determined by affinity resin pull-down assay in combination with MALDI-TOF The role of Orfl in the expression of exoS was evaluated by gene reporter analysis. Results Pull-down assay showed that Orfl binds to ExoS and ExoT. Secretion profile analysis showed that Orfl was necessary for the optimal secretion of ExoS and ExoT. However, Orfl had no effect on the expression of exoS. Conclusion Orfl is important for the secretion of ExoS probably by maintaining ExoS in a secretion-competent conformation. We propose to name Orfl as SpcS for "specific Pseudomonas chaperone for ExoS".
基金Supported by the Wilhelm-Sander-Stiftung(No.2002.025.1 to JJM)Deutsche Forschungsgemeinschaft(grants Me 2096/2-1,Na 203/6-1 and Ga 386/8-1)the Deutsche Diabetes Gesellschaft(to JJM)
基金Supported by National Natural Science Foundation of China(31402344,31572656)Major Program of Natural Science Foundation of Guangdong Province(2015A030308020)
文摘In order to enrich the research about type III secretion system (T3SS) injectisome of Vibrio alginolyticus, vscX gene was cloned from E algianlyticus strain HY9901 for bioinformatics analysis and expression analysis. Specific primers were designed according to the full-length geanme sequence of V. alginolyticus in GenBank. vscX gene (C, enBank accession number: FR780679) contained a 378 bp open reading frame (ORF), encoding a putative protein of 125 amino acids. The theoretical molecular weight was 14.209 2 kD and theoretical pI was 5.75. By using Signal 4.1 Server and TMHMM Server 2.0, it was predicted that VscX protein had no transmembrane domain or signal peptide. The results of prediction using SoftBerry-Psite software showed that VscX protein contained three casein ki- nase lI phosphorylation sites, one N-myristoylation site and three C-terminal targeting signal sites. Subcellular localization revealed that VscX might be located in cytoplasm with the possibility of 56.5%. According to SMART prediction, VscX had one Pfam ( 1 - 125 aa) domain. Phylogenetic analysis revealed that VscX from V. alginolyticus and VscX from E parahemolyticus were clustered into the same group. Network interaction analysis showed that vscX was adjacent to vseY, vopB and sycN. By real-time fluorescent quantitative PCR technique and 2-△△△ method, the differences in expression levels of VscX mRNA in V. alginolyticus strain HY9901, T3SS deletion strain AvscO and complementary strain C-vscO at different growth stages were analyzed. The results showed that the expression levels of VscX mRNA in V. algianlyticus strain HY9901 and C-vscO were significantly up-regulated at stable growth stage ( P 〈0.01 ) ; the expression levels of VscX mRNA in deletion strain △vscO were significantly up-regulated at late growth stage ( P 〈0.01 ). This study provided the basis for revealing the transport mechanism of T3SS injectisome of E alginolyticus.
基金supported by the National Natural Science Foundation of China (No. 81201322)the Priority Project on Infectious Disease Control and Prevention 2011ZX10004-001 and 2013ZX10003006-002 by the Chinese Ministry of Science and Technology and the Chinese Ministry of Healththe Foundation of State Key Laboratory for Infectious Disease Prevention and Control (Grand No. 2011SKLID303)
文摘Secretion systems, macromolecules to pass which can mediate the across cellular membranes, are essential for virulent and genetic material exchange among bacterial species[1]. Type IV secretion system (T4SS) is one of the secretion systems and it usually consists of 12 genes: VirB1, VirB2 ...VirB11, and VirD4[2]. The structure and molecular mechanisms of these genes have been well analyzed in Gram-negative strains[3] and Gram-positive strains were once believed to be lack of T4SS. However, some recent studies revealed that one or more virB/D genes also exist in some kinds of Gram-positive bacteria and play similar role, and form a T4SS-like system[3]. The VirBl-like, VirB4, VirB6, and VirD4 genes were identified in the chromosome of Gram-positive bacterium Streptococcus suis in our previous studies and their role as important mobile elements for horizontal transfer to recipients in an 89 K pathogenicity island (PAl) was demonstrated[45]. However, their structure and molecular mechanisms in other strains, especially in Gram-positive strains, are remained unclear.
文摘目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。
基金This study was supported by the grant from the Guangdong Provincial Science and Technology Foundation (No. A 1999--198).
文摘OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.
文摘AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.
基金supported by the 111 International Cooperation Grant 2.0(BP0719029)to Nanjing Agricultural University,China,from the Chinese government and Canadian Interdepartmental funding of Genomics Research and Development Initiatives(GRDI)。
文摘Dickeya fangzhongdai, the causal agent of bleeding canker of pear, is a new member of the Dickeya genus and the only one that infects woody plants. Recent studies have reclassified several Dickeya isolates as D. fangzhongdai, which were isolated from various environments, including water, Phalaenopsis sp. and Aglaonema sp. To provide genomic characterization of D. fangzhongdai isolates from pear, the genomes of D. fangzhongdai strain JS5(=China General Microbiological Culture Collection Center, CGMCC 1.15464 ~T=DSM 101947 ~T), along with two other isolates, LN1 and QZH3, were sequenced and compared to those of other Dickeya spp. Homology greater than 99% was observed among three D. fangzhongdai strains. Plasmid, type IV secretion system(T4 SS) and type IV pili(TFPs) were found in genomes of D. fangzhongdai isolates. Comparative analysis of the type Ⅲ secretion systems(T3 SS), type Ⅲ secretion effectors(T3 SE), plant cell wall degradation enzymes(PCWDE) and membrane transport proteins of Dickeya spp. showed some differences which might reflect the variations of virulence, phylogenetic and phenotypic characteristics of Dickeya spp. In addition, deletion mutant of TFP in D. fangzhongdai JS5 showed no twitching motility and reduced virulence and biofilm formation. The fingdings of the distinctive plasmid, T4 SS and TFPs, as well as the differences of T3 SE, PCWDE and membrane transport proteins make D. fangzhongdai isolates unique. These results also suggested that acquisition of virulence genes by horizontal gene transfer might play some role in the genetic variation of D. fangzhongdai.
文摘BACKGROUND Although Borrmann type Ⅳ(B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis(PPCM), which is important for selecting an appropriate therapeutic strategy.AIM To identify factors related to the prognosis and PPCM of B-4 patients.METHODS A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan–Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0.RESULTS Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the longterm survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes(n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor(P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy.CONCLUSION Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.
文摘Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N;77 ± 5 and 254 ± 65% in IGT;and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.
文摘AIM: To determine factors predictive for esophageal varices in severe alcoholic disease (SAD). METHODS: Abdominal ultrasonography (US) was performed on 444 patients suffering from alcoholism. Forty-four patients found to have splenomegaly and/ or withering of the right liver lobe were defined as those with SAD. SAD patients were examined by upper gastrointestinal (UGI) endoscopy for the presence of esophageal varices. The existence of esophageal varices was then related to clinical variables. RESULTS: Twenty-five patients (56.8%) had esophageal varices. A univariate analysis revealed a significant difference in age and type Ⅳ collagen levels between patients with and without esophageal varices. A logistic regression analysis identified type Ⅳ collagen as the only independent variable predictive for esophageal varices (P = 0.017). The area under the curve (AUC) for type Ⅳ collagen as determined by the receiver operating characteristic (ROC) for predicting esophageal varices was 0.78. CONCLUSION: This study suggests that the level of type Ⅳ collagen has a high diagnostic accuracy for the detection of esophageal varices in SAD.
基金Supported by National Natural Science Foundation of China,No.31771284National Natural Science Foundation of China Youth Project,No.31702024+1 种基金Major Basic Research Project of Shandong Provincial Natural Science Foundation,No.ZR2019ZD27Shandong Province Higher Educational Science and Technology Plan Project,No.J17KA258。
文摘BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.
文摘The regenerating islet-derived members (Reg ),a group of small secretory proteins,which are involved in cell proliferation or differentiation in digestive organs,are upregulated in several gastrointestinal cancers,functioning as trophic or antiapoptotic factors.Regenerating islet-derived type Ⅳ (RegⅣ ),a member of the Reg gene family,has been reported to be overexpressed in gastroenterological cancers.RegIV overexpression in tumor cells has been associated with carcinogenesis,cell growth,survival and resistance to apoptosis.Cancer tissue expressing RegⅣ is generally associated with more malignant characteristics than that without such expression,and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers.We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorectal cancer.The biologic functions of RegⅣ protein in cancer tissue,associated with carcinogenesis,antiapoptosis and invasiveness,are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegⅣ,and the feasibility of antibody therapy targeting RegⅣ is being assessed.These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegⅣ .This review article summarizes the current information related to biological functions as well as clinical importance of RegⅣ gene to clarify the significance of RegⅣ expression in gastroenterological cancers.
文摘BACKGROUND Liver resection is an effective treatment for benign and malignant liver tumors.However,a method for preoperative evaluation of hepatic reserve has not yet been established.Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve.When determining eligibility for hepatectomy,the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy.AIM To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery.METHODS This study was a retrospective cohort study.We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016.Early post-hepatectomy liver failure(PHLF)was defined using the International Study Group of Liver Surgery’s definition of PHLF.Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of<2 mg/dL and>2.8 g/dL,respectively,and the time taken for Child-Pugh score to return to Child-Pugh class A.RESULTS Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function.Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S≤6 ng/mL than in those with type IV collagen 7S>6 ng/mL.In additional analyses,similar results were observed in patients without chronic viral hepatitis associated with fibrosis.CONCLUSION Preoperative type IV collagen 7S is a preoperative predictor of PHLF and longterm postoperative liver function recovery.It can also be used in patients without chronic hepatitis virus.
基金Project supported by the National High-Tech Research and Development Program of China (Grant Nos. 2006AA01Z440,2009AA012441 and 2009AA012437)National Basic Research Program of China (Grant No. 2007CB311100)+4 种基金the National Natural Science Foundation of China (Grant Nos. 60873191 and 60821001)the Scientific Research Common Program of Beijing Municipal Commission of Education (Grant No. KM200810005004)Beijing Natural Science Foundation (Grant Nos. 1093015 and 1102004)the ISN Open FoundationSpecialized Research Fund for the Doctoral Programm of Higher Education (Grant No. 20091103120014)
文摘Based on x-type entangled states and the two-step protocol [Deng F G, Long G L and Liu X S 2003 Phys. Rev. A 68 042317], a quantum secret sharing protocol of secure direct communication based on x-type entangled states |X00〉3214 is proposed. Using some interesting entanglement properties of this state, the agent entirety can directly obtain the secret message from the message sender only if they collaborate together. The security of the scheme is also discussed.