G蛋白信号调节因子-13通过调控β-catenin抑制结直肠癌细胞增殖、迁移和侵袭

目的：探究G蛋白信号调节因子-13（RGS13）在结直肠癌（CRC）进展中的作用。方法：使用TCGA数据库和实时荧光定量聚合酶链反应（RT-qPCR）在mRNA水平分析CRC组织和细胞中RGS13 的表达量，使用免疫组织化学染色（IHC）和蛋白质印迹法（Western blot）在蛋白水平进一步分析。用ATP细胞活力检测实验、软琼脂克隆集落形成实验和细胞迁移侵袭实验检测RGS13对CRC细胞增殖、迁移和侵袭的影响，并通过Western blot、RT-qPCR等实验探究其下游分子机制。结果：RGS13在CRC组织与细胞系中低表达（P ＜0.01），RGS13 表达越低，患者的无病生存期越短（P =0.017）。RGS13 的下调可显著促进CRC细胞的增殖、迁移与侵袭（P ＜0.01），表明RGS13在CRC进展中发挥抑癌作用。机制上，RGS13通过下调Wnt/β-catenin信号通路中β-catenin的蛋白水平，进而降低癌基因c-Myc、MMP7 和CCND1等的表达水平（P ＜0.01），发挥对CRC的抑制作用。结论：RGS13可能通过下调β-catenin发挥抑制CRC进展的重要作用。     

ABCB1 C3435T、G2677AT基因形态与癌痛患者疼痛感知的相关性研究

目的:研究ABCB1 C3435T、G2677AT基因形态与癌痛患者疼痛感知的关系。方法:临床纳入2016年9月至2018年9月期间我院收治的185例恶性肿瘤患者组织病理学标本，将其中有癌痛的患者116例作为癌痛组，无癌痛的患者69例作为无痛组。应用三维聚丙烯酰胺凝胶DNA芯片技术检验患者ABCB1 C3435T、G2677AT基因分型情况，并分析ABCB1 C3435T、G2677AT基因形态与癌症患者癌痛的关系。结果:两组患者C3435T基因野生型、杂合子及突变型分布频率对比差异无统计学意义（P>0.05）。两组患者G2677AT基因野生型、杂合子及突变型分布频率对比差异无统计学意义（P>0.05）。疼痛程度不同的患者C3435T和G2677AT基因型分布频率无差异（P>0.05）。癌痛组患者C3435T与G2677AT不同基因型间组内对比NRS评分差异无统计学意义（P>0.05）；C3435T与G2677AT相同基因型对比NRS评分差异无统计学意义（P>0.05）。结论:ABCB1 C3435T与G2677AT基因形态与癌痛患者疼痛感知并无直接关联，尚需进一步进行深入研究。     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.     

Rapid diagnostic tests for determining dengue serostatus: a systematic review and key informant interviews

ObjectivesVaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue RDTs for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection.MethodsPubMed and EMBASE databases were searched from 2000 to 2018 to identify studies evaluating dengue RDTs in individuals with known or possible previous DENV infection. Study quality was evaluated using GRADE and QUADAS-2 criteria. Semi-structured interviews were also performed with available dengue RDT manufacturers.ResultsThe performance of four dengue IgG RDTs was determined in 3137 individuals across ten studies conducted in 13 countries, with serum used in most of the studies. No studies reported data for determining dengue serostatus, and limited data were available regarding cross-reactivity with other viruses. The majority of studies demonstrated sensitivities and specificities between 80% and 100% for dengue IgG detection in samples from secondary infection or convalescent time-points after recent infection.ConclusionsAlthough current dengue IgG RDTs have shown reasonable performance compared with laboratory-based tests in secondary infection, additional research is needed to determine how RDTs would perform in relevant populations targeted for vaccination. New RDTs or modifications to current RDTs are feasible and may optimize the performance of these tests for use in a pre-vaccination screening approach.     

Midterm Outcomes of the Dissected Aorta Repair Through Stent Implantation Trial

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Viral hepatitis: Past,present, and future

Each hepatitis virus—Hepatitis A, B, C, D, E, and G—poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.     

Prediction of the response to photodynamic therapy in patients with chronic central serous chorioretinopathy based on optical coherence tomography using deep learning

PurposeTo assess the prediction of the response to photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR) based on spectral-domain optical coherence tomography (SD-OCT) images using deep learning (DL).MethodsRetrospective study including 216 eyes of 175 patients with CSCR and persistent subretinal fluid (SRF) who underwent half-fluence PDT. SD-OCT macular examination was performed before (baseline) and 3 months after treatment. Patients were classified into groups by experts based on the response to PDT: Group 1, complete SRF resorption (n = 100); Group 2, partial SRF resorption (n = 66); and Group 3, absence of any SRF resorption (n = 50). This work proposes different computational approaches: 1st approach compares all groups; 2nd compares groups 1 vs. 2 and 3 together; 3rd compares groups 2 vs. 3.ResultsThe mean age was 55.6 ± 10.9 years and 70.3% were males. In the first approach, the algorithm showed a precision of up to 57% to detect the response to treatment in group 1 based on the initial scan, with a mean average accuracy of 0.529 ± 0.035. In the second model, the mean accuracy was higher (0.670 ± 0.046). In the third approach, the algorithm showed a precision of 0.74 ± 0.12 to detect the response to treatment in group 2 (partial SRF resolution) and 0.69 ± 0.15 in group 3 (absence of SRF resolution).ConclusionDespite the high clinical variability in the response of chronic CSCR to PDT, this DL algorithm offers an objective and promising tool to predict the response to PDT treatment in clinical practice.