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Tuan Dinh Le,1,2,* Hoang Huy Duong,3,* Ly Thi Nguyen,4,5,* Nga Phi Thi Nguyen,2 Son Tien Nguyen,2 Manh Van Ngo6 1Center of Emergency, Critical Care Medicine and Clinical Toxicology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Rheumatology and Endocrinology,Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Neurology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam; 4Department of Internal Medicine, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam; 5Postgraduate Student, Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam; 6Postgraduate Training Management Department, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam*These authors contributed equally to this workCorrespondence: Tuan Dinh Le, Center of Emergency, Critical Care Medicine and Clinical Toxicology, Military Hospital 103, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La Ward, Ha Dong District, Hanoi City, Vietnam, Tel +840388166078, Email letuan985@gmail.com Hoang Huy Duong, Department of Neurology, Thai Binh University of Medicine and Pharmacy, 373 Ly Bon Street, Ky Ba Ward, Thai Binh, Vietnam, Tel +84 912675919, Email hoangdh@tbmc.edu.vnBackground: Depression is a common mental disorder in people with type 2 diabetes mellitus (T2DM). Depression and T2DM have a reciprocal interaction through many factors, of which the most important is the multifactorial control and microvascular complications of T2DM.Aim: This research aims to determine the rate of depression and the association between depression and multifactorial control and microvascular complications in patients with T2DM aged 30– 60 years in Vietnam.Methods: A cross-sectional and descriptive study was conducted on 231 outpatients with T2DM at Bach Mai hospital, Hanoi, Vietnam. Depression severity was measured with the Patient Health Questionnaire-9 (PHQ-9).Results: The rate of depression in patients with T2DM aged 30– 60 years was 16.9% (in which, the rate of mild depression was 15.2% and moderate depression was 1.7%; no serious depression). The prevalence of depression was higher in female patients than in male patients (p = 0.049). There is a statistically significant difference in the rate of depression by age, duration of diabetes, and treatment method for type 2 diabetes. Poor HbA1c control and microvascular complications increase the risk of depression (OR = 2.37; 95% CI 1.11– 5.02, p = 0.033 and OR = 2.62; 95% CI 1.15– 5.93, p = 0.027, respectively). When the multivariate analysis was performed, it was shown that sex, treatment for glycemic control, and microvascular complications had a statistically significant influence on PHQ-9 score.Conclusion: In Vietnam, there are 16.9% of patients with T2DM aged 30– 60 years suffer from depression. Poor HbA1c control, the presence of microvascular complications, and without antihyperglycemic treatment increase the risk of developing depression.Keywords: type 2 diabetes mellitus aged 30– 60 years, depression, multifactorial control, microvascular complications

Background: Granulosa cell tumor of the ovary is a rare disease and presents with two clinically and molecularly distinct subtypes: the juvenile and the adult type. GCT is considered as a malignant tumor with an indolent course and a tendency toward late recurrence. Purpose: To assess the clinical and paraclinical features, treatment findings, survival outcomes, and explored the prognostic factors in the granulosa cell tumor. Methods: The current study was conducted on 28 GCT patients who had surgical operations and adjuvant chemotherapy (stage IC-IV) by applying a retrospective cohort analysis. The clinical and paraclinical characteristics were recorded. Recurrent status was evaluated for analysis with clinical and paraclinical features and survival. All GCT patients’ survival were analyzed by using Kaplan-Meier and Log-Rank models. Results: 17.9% of patients experienced a relapse and two patients died due to disease. The mean time from initial diagnose to recurrence was 40.21 months. The 5-year OS and DFS of stage I-II were 100% and 80.8%, and of stage III were 50% and 25%, respectively. In survival analyses, using the log-rank test, age ≥50 years, irregular menstruation, stage I-II, and absence of residual lesion were all significant predictors for the improved DFS. Stage I-II and absence of residual lesion were associated significantly with better OS. Mean of age, FIGO stage, and residual lesion during surgery had significant differences to recurrent rate (p <

PurposeThe demand for clean vegetables has rapidly increased, many farmers gradually turn to vegetable cultivation to increase income; therefore, agricultural cooperative mobilized farmers group to facilitate them access to technical training and enhance compliance with the Vietnamese Good Agricultural Practices (VietGAP) standards. The purpose of this paper is to evaluate the impacts of the participation on farmer’s income as well as the major factors that affect the participation in cooperatives by the vegetable farmers in Vietnam.Design/methodology/approachThe study used primary data collected from vegetable farmers in Vietnam. This study utilized propensity score matching to avoid initial selection bias. The differences between participants and nonparticipants will be adjusted by matching each membership individual to a nonmember based on similar observable characteristics by summarizing the conditional probability of a member given pretreatment characteristics.FindingsThis study demonstrates that participation in cooperatives is significantly affected by ethnicity, age of household head, labor involving vegetable production and extension service access. The results of this study also confirm that agricultural cooperatives have positive effects on member farmers to enhance income and that participants – on average – have a higher income than nonparticipants.Research limitations/implicationsThe method cannot rule out the possibility of selection bias due to unobserved differences between participants and even an appropriate comparison group.Originality/valueThis study contributes to an improved understanding about impacts of cooperatives on farmers’ income in developing and emerging economies. Moreover, research also upgrades knowledge regarding the effectiveness of agricultural cooperatives in Vietnam, as well as guides policymakers in supporting the cooperatives in expanding the market and other necessary changes.

Background and aim Cholangiocarcinoma has an unimproved prognosis. Interleukin 6 (IL-6) has an oncogenic potential in some cancer diseases. However, the role of IL-6 in cholangiocarcinoma carcinogenesis is not well understood. The current study investigated the role of IL-6 signaling in cholangiocarcinoma carcinogenesis and efficacy of siltuximab treatment on cholangiocarcinoma in vitro and in vivo. Methods The expression of IL-6 was analyzed on human cholangiocarcinoma cell lines and murine and human cholangiocarcinoma tissues, using reverse transcription real-time polymerase chain reaction and immunohistochemistry. In addition, the effect of anti-IL-6 chimeric monoclonal antibody, siltuximab, was investigated in vitro by proliferation, migration, and two-dimensional and three-dimensional invasion assays and in vivo by xenograft mouse model. Western blot was applied to study the molecular alteration. Results Our result shows high expression of IL-6 in human cholangiocarcinoma cells, and IL-6 stimulants enhance cholangiocarcinoma cell proliferation. In addition, murine and human cholangiocarcinoma tissues express significantly higher levels of IL-6, compared with adjacent non-tumor tissues. On the cholangiocarcinoma engineered mouse model, IL-6 level is associated with tumor volume. Taken together, our data indicate an oncogenic potential of IL-6 in cholangiocarcinoma carcinogenesis. Siltuximab sufficiently abrogates IL-6 signaling and inhibits cholangiocarcinoma progression in vitro and in vivo. The results additionally indicate a relative alteration of IL-6 signaling and its molecular targets, such as STAT3, Wnt/β-catenin, and mesenchymal markers. Conclusions Interleukin 6 plays an essential role in cholangiocarcinoma carcinogenesis, and siltuximab has the potential to be considered as a new treatment option for cholangiocarcinoma patients.

Background: Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. Objective: This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. Methods: Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. Results: CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. Conclusions: This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. CC treatment options are very limited especially for patients with distant metastasis. Kangai 1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in numerous cancers, but the role of KITENIN in CC remains unknown. Here, we have investigated for the first time the function of KITENIN in human CC cell lines (TFK-1, SZ-1), tissues and a CC mouse model (Alb-Cre/LSL-KRASG12D/p53L/L). KITENIN was expressed in 92.2% of human CC tissues, in murine CC samples and also in human CC cell lines. Knockdown of KITENIN by small interfering RNA (siRNA) effectively reduced proliferation, migration, invasion and colony formation in both intra- and extra-hepatic CC cells. The expression of epithelial-mesenchymal transition (EMT) markers like N-cadherin, Vimentin, Snail and Slug were suppressed in KITENIN knockdown CC cells. Our results indicate that KITENIN is crucial for cholangiocarcinogenesis and it might become a potential therapeutic target for human CC treatment.

Background: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxin against a panel of tumor cells in recent studies including HCC cells. The aims of this study are to evaluate the antitumor effect of haprolid in HCC and to understand its underlying molecular mechanisms. Methods: The efficacy of haprolid was evaluated in human HCC cell lines (Huh-7, Hep3B and HepG2) and xenograft tumors (NMRI-Foxn1nu mice with injection of Hep3B cells). Cytotoxic activity of haprolid was determined by the WST-1 and crystal violet assay. Wound healing, transwell and tumorsphere assays were performed to investigate migration and invasion of HCC cells. Apoptosis and cell-cycle distribution were measured by flow cytometry. The effects of haprolid on the Rb/E2F and Akt/mTOR pathway were examined by immunoblotting and immunohistochemistry. Results: haprolid treatment significantly inhibited cell proliferation, migration and invasion in vitro. The epithelial–mesenchymal transition (EMT) was impaired by haprolid treatment and the expression level of N-cadherin, vimentin and Snail was downregulated. Moreover, growth of HCC cells in vitro was suppressed by inhibition of G1/S transition, and partially by induction of apoptosis. The drug induced downregulation of cell cycle regulatory proteins cyclin A, cyclin B and CDK2 and induced upregulation of p21 and p27. Further evidence showed that these effects of haprolid were associated with Rb/E2F downregulation and Akt/mTOR inhibition. Finally, in vivo nude mice experiments demonstrated significant inhibition of tumor growth upon haprolid treatment. Conclusion: Our results show that haprolid inhibits the growth of HCC through dual inhibition of Rb/E2F and Akt/mTOR pathways. Therefore, haprolid might be considered as a new and promising candidate for the palliative therapy of HCC. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Aberrant activation of Sonic Hedgehog (SHH) pathway has been implicated in a variety of cancers including cholangiocarcinoma (CC); however, the influencing factors are still unknown. Additionally, intratumoral hypoxia is known to contribute towards therapeutic resistance through modulatory effects on various pathways. In this study, we investigated the relationship between hypoxia and SHH pathway activation and the effect of this interplay on cancer stemness and epithelial-to- mesenchymal transition (EMT) during cholangiocarcinogenesis. Hypoxia promoted SHH pathway activation, evidenced by upregulated SHH and SMO levels, and enhanced glioma-associated oncogene homolog 1 (GLI1) nuclear translocation; whereas silencing of HIF-1α impaired SHH upregulation. Hypoxia also enhanced the expression of cancer stem cell (CSC) transcription factors (NANOG, Oct4, SOX2), CD133 and EMT markers (N-cadherin, Vimentin), thereby supporting invasion. Cyclopamine treatment suppressed hypoxia induced SHH pathway activation, consequently reducing invasiveness by downregulating the expression of CSC transcription factors, CD133 and EMT. Cyclopamine induced apoptosis in CC cells under hypoxia, suggesting that hypoxia induced activation of SHH pathway has modulatory effects on CC progression. Therefore, SHH signaling is proposed as a target for CC treatment, which is refractory to standard chemotherapy.

In Vietnam, especially central Vietnam, patients with fascioliasis are increasingly being reported. Since the fascioliasis is zoonotic, survey on the cattle fascioliasis should be informative for the control of human fascioliasis. In this study, the prevalence of cattle fascioliasis as well as the density of the intermediate host snails, Lymnaea swinhoei and L. viridis, were studied in Thua Thien Hue (TTH) province during 2014–2015. A total of 572 cattle feces were examined from 27 communes in 9 districts. Fasciola eggs were detected in cattle from 24 communes with an average prevalence of 23.4% (134/ 572). The highest prevalence was detected in cattle in the coastal plain terrain (31.0%) followed by plain (25.5%), mountain (21.7%), and low hilly (16.2%) terrains. The highest proportion of heavy infection (>200 EPG) was observed in the coastal plain terrain (36.1%), followed by mountains (20.0%), low hills (13.0%), and plains (8.9%). Low number of heavy infection, as well as relatively low prevalence in low hills and plains were associated with the extensive use of anti-fluke treatments. High number of intermediate host snails in low hilly and plain terrains also indicate high risk of fascioliasis. In this study, the density of Lymnaea snails in the coastal plain terrain was found to be very high (17.3 snails/m2) compared to that in previous studies. This is the first report indicating the recent expansion of cattle fascioliasis in the coastal region in Vietnam.

Proliferation of the number of vehicles is one of the main causes of traffic congestion, accidents, energy waste and environmental pollution. Recently, several intelligent applications are equipped in modern vehicles such as advanced driver assistance systems (ADAS), especially an adaptive cruise control (ACC) system which was successfully implemented on some luxury cars and still remains to be an interesting topic of research. An adaptive neuro-fuzzy predictive control (ANFPC) is proposed in designing of ACC system in this paper. By controlling the ACC vehicle through the throttle force or brakes, the ACC vehicle follows its predecessor and maintains the safe distance with the minimized tracking error. In the ANFPC scheme, a Takagi-Sugeno (T-S) fuzzy model is utilized to approximate the preceding vehicle model and then the predicted state sequence of the preceding vehicle is obtained. More importantly, the predictive control law is derived by a fuzzy neural networks (FNNs) approach. Simulation results demonstrate that the proposed ANFPC can achieve better performance than other methods in terms of safety, comfort and fuel consumption, simultaneously.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.

323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRASG12D/p53L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.

Rapid growth in economies and a sharp increase in the present quantity of vehicles have contributed to congested cities, traffic accidents, energy crises and air pollution, which not only cause serious economic damage but also affect human life and safety. According to the Kyoto Protocol international standards and consensus, the trend in the automotive industry is to develop more ecological vehicles in order to reduce fuel consumption and air pollution. Recently, a number of modern premium cars have been equipped with advanced driver assistance systems (ADAS), especially an adaptive cruise control (ACC) system, which was found to be one of the most widely and successful ADAS systems to date. However, the road topography on highways affects fuel consumption of vehicles. Rapid acceleration, rapid deceleration, and unreasonable gear use can all result in increasing fuel consumption. Therefore, an eco-cruise control (ECC) system on roads with up-down slopes is critical for improving vehicle fuel economy in coordination with the Global Positioning System (GPS) and Geographic Information System (GIS). This proposed approach combines the road elevation profile of digital road maps with nonlinear optimal predictive control (NOPC) algorithms to handle the vehicle velocity control; it is aimed at providing the most economical speed according to road grade. The developed algorithms not only provide ecological driving guidance for the driver, but also contribute to driving safety. Finally, extensive simulations demonstrate that the proposed controller can significantly reduce fuel consumption of a vehicle while ensuring driving comfort and safety.