“抗帕颗粒”对帕金森病小鼠结肠ICC细胞及线粒体自噬相关蛋白Beclin-l/LC3B表达的影响

目的探讨中药“抗帕颗粒”通过调控Cajal间质细胞(ICC)及线粒体自噬改善帕金森病(PD)肠道动力障碍的作用机制。方法PD小鼠模型制作采用MPTP腹腔注射法,随机法分组:空白组(A组)、PD对照组(B组)和PD干预组(“抗帕颗粒”)(C组),每组10只。A、B组予生理盐水灌胃(1ml·d^(-1)),C组“抗帕颗粒”灌胃(40mg·kg^(-1)·d^(-1))。4个月后每组中随机取5只小鼠结肠组织被用于免疫组化检测,每组余下5只小鼠结肠壁组织被用于提取蛋白Western blotting法检测,检测内容c-kit、Beclin l、LC3B的表达;透射电子显微镜观测结肠壁ICC细胞结构。结果(1)免疫组化结果显示:与A组相比,B组、C组C-kit、Beclin1、LC3B表达水平均显著升高(^(a)P<0.01),与B组相比,C组C-kit、LC3B表达水平显著降低(^(c)P<0.01),而Beclin1的表达水平无显著变化;(2)Western blot结果显示,与A组相比,B组、C组Beclin1、LC3B、C-kit表达水平均显著升高(^(a)P<0.01);与B组相比,C组的Beclin1、LC3B、C-kit表达水平均显著降低(^(c)P<0.01);(3)透射电子显微镜观察显示,PD模型小鼠的结肠ICC中出现自噬囊泡,“抗帕颗粒”干预后PD模型小鼠自噬囊泡减少。结论“抗帕颗粒”通过抑制肠道ICC过度自噬,保护细胞结构;并且抑制了由ICC过度自噬导致的细胞程序性死亡而出现的ICC数量反应性增加;其主要作用是改善了ICC结构的异常。这可能是“抗帕颗粒”改善PD小鼠肠道传输功能的机制之一。

“抗帕颗粒”通过PINK1/Parkin信号通路对帕金森小鼠结肠ICC线粒体自噬的影响

目的 探讨“抗帕颗粒”通过PINK1/Parkin信号通路对帕金森(PD)小鼠结肠Cajal间质细胞(ICC)线粒体自噬的影响。方法 MPTP腹腔注射技术用于制作PD小鼠模型,将其随机分为A组(空白对照组)、B组(PD对照组)和C组(PD “抗帕颗粒”组),每组10只。A组和B组接受生理盐水灌胃(1mL·d^(-1)),C组“抗帕颗粒”(40mg·kg^(-1)·d^(-1))的灌胃治疗。4个月后每组中随机取5只小鼠结肠组织被用于免疫组化检测,每组余下5只小鼠结肠壁组织被用于提取蛋白Western blotting法检测,检测项目为PINK1、Parkin的表达;透射电子显微镜观测结肠壁ICC细胞自噬情况。结果(1)经过免疫组化检测,B组和C组的PINK1和Parkin表达水平较A组显著上升(P <0.01);而C组的PINK1和Parkin表达水平较B组则显著下降(P<0.01);(2)经过Western blot检测,与A组相比,B组和C组的PINK1和Parkin表达水平均显著提高(P<0.01);最后,经过与B组对比分析,发现C组PINK1的表达水平没有明显变化,而Parkin的表达水平却有所下降(P<0.05);(3)透射电子显微镜观察发现,PD模型小鼠结肠ICC中存在自噬囊泡,“抗帕颗粒”干预后,这种囊泡的数量明显减少。结论 “抗帕颗粒”通过抑制PD小鼠肠道ICC过度自噬,保护细胞结构;PINK1/Parkin途径是实现这种神经保护作用的通路。

AJCC分期、术前PNI及不同淋巴结清扫方式与接受根治术治疗的ICC患者预后结局的关系

目的探讨第8版美国癌症联合委员会(AJCC)分期、术前预后营养指数(PNI)及不同淋巴结清扫方式与接受根治术治疗的肝内胆管细胞癌(ICC)患者预后结局的关系。方法选取本院2019年1月—2021年1月收治的105例ICC患者进行回顾性分析与病例对照研究相结合的方式进行研究,所有患者均接受肿瘤根治术治疗,其中59例患者术中采用整块融合清扫方式清扫淋巴结(A组)、另外46例患者术中采用传统常规的淋巴结清扫方式(B组),对两组患者随访1年观察生存率及生存时间进行比较;统计不同预后结局患者的AJCC分期、PNI及一般临床病理学参数,采用Logistic回归模型分析影响患者预后结局的关键因素。结果A组患者18个月随访后生存率为84.75%,B组为67.39%,A组显著高于B组,差异具有统计学意义(P<0.05);A组患者的生存时间长于B组患者,差异具有统计学意义(Log Rank(Mantel-Cox)=4.994,P=0.025)。死亡组患者T分期中≥T2期、N分期中N1分期、TNM分期中≥Ⅱ期、PNI指标<45.0的患者占比均显著高于生存组,差异具有统计学意义(P<0.05)。Logistic回归模型结果显示,TBIL≥20.0μmol/L、肿瘤数目多发、发生血管侵犯、手术中输血、N1分期、TNM分期≥Ⅱ期、PNI指标<45.0、常规淋巴结清扫方式是ICC患者不良预后结局的独立危险因素(P<0.05)。结论根据ICC患者的AJCC分期、术前PNI水平可以初步评估患者根治术后的预后结局,根治术中采取整块融合清扫方式清扫淋巴结有利于延长患者的生存时间。

拜拉姆ICC模型在英语教学中的应用

从态度、知识、技能和批判文化意识四个维度阐述拜拉姆ICC模型,并深入分析模型中四个关键维度的具体内涵。同时,进一步探讨将拜拉姆ICC模型应用于英语教学的方法和效果,并强调多样化课程内容和活动设计对促进学生语言能力发展、跨文化意识和态度培养、跨文化交际技能全面发展的重要性。阐述拜拉姆ICC模型在英语教学中的具体应用。

柴胡皂苷D调控CaMKKβ/AMPK信号通路介导ICCs细胞自噬的机制

目的探讨柴胡皂苷D调控CaMKKβ/AMPK信号通路,在功能性消化不良中对胃肠道Cajal间质细胞(Interstitial cells of Cajal,ICCs)细胞自噬的作用及机制。方法分离大鼠原代ICCs细胞,谷氨酸刺激构建ICCs自噬模型,免疫荧光检测Ca2+水平。将原代ICCs细胞分为对照组、模型组、模型+柴胡皂苷D组、模型+CaMKKβ抑制剂组、模型+柴胡皂苷D+CaMKKβ抑制剂组。透射电镜观察自噬体超微结构,ELISA检测Ghrelin和SP的水平,免疫荧光检测Ca2+和LC-3Ⅱ的表达,Western blot检测LC-3Ⅱ/Ⅰ、CaMKKβ、p-AMPK、Drp1、MFN2、IP3R和RyR的蛋白表达水平。结果谷氨酸诱导的模型组ICCs中LC-3Ⅱ荧光表达增强。柴胡皂苷D干预可降低Ca2+浓度,降低CaMKKβ、AMPK和MFN2水平(P<0.01),增加LC-3Ⅱ/Ⅰ、IP3R、RyR、Drp1、Ghrelin和SP水平(P<0.01)。柴胡皂苷D联合CaMKKβ抑制剂STO-609干预后效果更显著。结论柴胡皂苷D可通过CaMKKβ/AMPK信号通路介导Ca2+外流,影响ICCs细胞过度自噬及胃肠动力相关因子的表达。

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma

Hepatolithiasis(HL)poses a significant risk for cholangiocarcinoma(CCA)development,with reported incidences ranging from 5%-13%.Risk factors include older age,smoking,hepatitis B infection,and prolonged HL duration.Chronic inflammation and mechanical stress on the biliary epithelium contribute to CCA pathogenesis.Hepatectomy reduces CCA risk by removing stones and atrophic liver segments.However,residual stones and incomplete removal increase CCA risk.Kim et al identified carbohydrate antigen 19-9,carcinoembryonic antigen,and stone laterality as CCA risk factors,reaffirming the importance of complete stone removal.Nonetheless,challenges remain in preventing CCA recurrence post-surgery.Longer-term studies are needed to elucidate CCA risk factors further.

Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma

Primary biliary tract tumors are malignancies that originate in the liver,bile ducts,or gallbladder.These tumors often present with jaundice of unknown etiology,leading to delayed diagnosis and advanced disease.Currently,several palliative treatment options are available for primary biliary tract tumors.They include percutaneous transhepatic biliary drainage(PTBD),biliary stenting,and surgical interventions such as biliary diversion.Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors.It involves the administration of chemotherapy drugs,such as gemcitabine and cisplatin,which have shown promising results in improving overall survival in patients with advanced biliary tract tumors.PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction.Biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction.Surgical interventions,such as biliary diversion,have traditionally been used as palliative options for primary biliary tract tumors.However,biliary diversion only provides temporary relief and does not remove the tumor.Primary biliary tract tumors often present in advanced stages,making palliative treatment the primary option for improving the quality of life of patients.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Prognostic value of PEA3 subfamily gene expression in cholangiocarcinoma

BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.

感兴趣区范围对MRI影像组学模型预测ICC分化程度的影响

目的探讨不同感兴趣(ROI)范围对MRI影像组学模型预测肝内胆管细胞癌(ICC)病理分化程度的影响。方法回顾性收集经术后病理证实的ICC患者191例,按照7:3的比例随机分为训练组(n=133)和验证组(n=58)。两位医师在MRI平扫及增强序列上沿肿瘤边缘手动逐层勾画ROI,随后由软件自动外扩8、10、12mm并手动调整,得到ROItumor、ROI 8mm、ROI 10mm、ROI 12mm。分别提取以上4种ROI的组学特征,经过最小绝对收缩和选择算子(LASSO)筛选特征,利用逻辑回归建立模型,并用验证组进行验证。最后采用特征曲线下面积(AUC)、校准曲线及决策曲线对模型效能进行综合评估。结果验证组10mm模型AUC最高为0.754。Hosmer-Lemeshow检验所有模型校准曲线均表现良好(P>0.05)。决策曲线显示当阈值为0.24时,获益最高为10mm模型。结论ROI范围的选择对MRI影像组学模型预测ICC的分化程度有一定影响,10mm可能为最佳范围。

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Overexpression of proteasome 26S subunit non-ATPase 6 protein and its clinicopathological significance in intrahepatic cholangiocarcinoma

BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.

ICC理论模型指导下培养学生文化意识的高中英语阅读教学实践——以Unit 1 Food matters Reading Comfort food为例

阐述文化意识的内涵和ICC理论模型的相关研究。以译林版高中《英语》选择性必修一Unit 1 Food matters Reading Comfort food为例,探究ICC理论模型指导下培养学生文化意识的高中英语阅读教学过程。指出运用ICC理论模型,拓展文化知识,提高跨文化理解力,增强批判性文化意识,有助于逐步开展培养文化意识的高中英语阅读教学。阅读课进行文化意识教学应注意教学目标围绕主题意义探究,教学活动贯彻英语学习活动观,教学评价体现教、学、评一体化。

Vascular reconstruction provides short-term and long-term survival benefits for patients with hilar cholangiocarcinoma:A retrospective,multicenter study

Background:In patients with hilar cholangiocarcinoma(HCCA),radical resection can be achieved by resection and reconstruction of the vasculature.However,whether vascular reconstruction(VR)improves long-term and short-term prognosis has not been demonstrated comprehensively.Methods:This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR.Variables associated with overall survival(OS)and recurrence-free survival(RFS)were identified based on Cox regression.Kaplan-Meier curves were used to explore the impact of VR.Restricted mean survival time(RMST)was used for comparisons of short-term survival between the groups.Patients’intraoperative and postoperative characteristics were compared.Results:Totally 447 patients were enrolled.We divided these patients into 3 groups:VR with radical resections(n=84);non-VR radical resections(n=309)and non-radical resection(we pooled VRnonradical and non-VR nonradical together,n=54).Cox regression revealed that carbohydrate antigen 242(CA242),vascular invasion,lymph node metastasis and poor differentiation were independent risk factors for OS and RFS.There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery(10.18 vs.10.76 mon,P=0.179),although the 5-year OS(P<0.001)and RFS(P<0.001)were worse in the VR radical group.The incidences of most complications were not significantly different,but those of bile leakage(P<0.001)and postoperative infection(P=0.009)were higher in the VR radical group than in the non-VR radical group.Additionally,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)up to 7 days after surgery tended to decrease in all groups.There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups.Conclusions:Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR.After adequate assessment of the patient’s general condition,VR can be considered in the resection.

Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc

Background: Cholangiocarcinoma(CCA), a malignancy that arises from biliary epithelial cells, has a dismal prognosis, and few targeted therapies are available. Aurora B, a key mitotic regulator, has been reported to be involved in the progression of various tumors, yet its role in CCA is still unclarified.Methods: Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA. A loss-of-function model was constructed in CCA cells to determine the role of Aurora B in CCA progression. Subcutaneous and liver orthotopic xenograft models were used to assess the therapeutic potential of Aurora B inhibitors in CCA.Results: In murine spontaneous CCA models, Aurora B was significantly upregulated. Elevated Aurora B expression was also observed in 62.3% of human specimens in our validation cohort(143 CCA specimens), and high Aurora B expression was positively correlated with pathological parameters of tumors and poor survival. Knockdown of Aurora B by siRNA and heteroduplex oligonucleotide(HDO)or an Aurora B kinase inhibitor(AZD1152) significantly suppressed CCA progression via G2/M arrest induction. An interaction between Aurora B and c-Myc was found in CCA cells. Targeting Aurora B significantly reduced this interaction and accelerated the proteasomal degradation of c-Myc, suggesting that Aurora B promoted the malignant properties of CCA by stabilizing c-Myc. Furthermore, sequential application of AZD1152 or Aurora B HDO drastically improved the efficacy of gemcitabine in CCA.Conclusions: Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA.

ICC跨文化交际能力教学模式下军事英语教学策略探究

全球化背景下,世界各国国防力量已聚焦国际舞台。各国军事行动和军事合作交流日益频繁,这对军事人员的外语能力提出了更高的要求。因此,跨文化能力已成为衡量国际化环境下新型军事人才综合素质的重要尺度。作为开展军事英语教学的院校,培养和提高学员的跨文化能力成为亟待探究的重要课题。本研究基于英国语言学家Byram提出的ICC (Intercultural Communicative Competence) 文化教学模式,从军事英语跨文化教学出发,探索培养和提高学员的跨文化交际能力的相关策略,充分发挥军事英语在对外交往中的桥梁纽带作用,为培养军事国际化人才提供有效借鉴。

Glucagon-like peptide 1 receptor agonist:A potential game changer for cholangiocarcinoma

Glucagon-like peptide-1 receptor(GLP-1R)agonist,a subgroup of incretin-based anti-diabetic therapies,is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection.Contrarily,concerns have been raised about GLP-1R agonists increasing the risk of particular cancers.Recently,several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma(CCA).The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA.Later studies,however,showed a null effect of incretinbased therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist.Mechanistically,glucagon-like peptide 1 receptor is multifunctional,including promoting cell growth.High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro.Unexpectedly,the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms.Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo,leading to the inhibition of CCA tumor growth.This editorial reviews recent evidence,discusses the potential effects of GLP-1R agonists in CCA patients,and proposes underlying mechanisms that would benefit from further basic and clinical investigation.