Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.     

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

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What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari’s Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study

PurposeTo compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC).Materials and MethodsFoam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope.ResultsMedian foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50–300 s; POL entropy: at 0–60 s; EO SD: at 0–600 s; EO entropy: at 0–460 s; POL energy: at 0–40 s; POL GLCM homogeneity: at 0–250 s; EO energy: at 0–360 s; EO GLCM homogeneity: at 0–480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 μm (P < .01), respectively, in the POL foam; and 36 and 36 μm (P = .45), respectively, in the EO foam.ConclusionsPOL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.     

补肾活血方对血管性痴呆大鼠海马神经细胞自噬的影响＊

目的 探究补肾活血方对血管性痴呆（Vascular Dementia， VD）大鼠模型自噬的影响。方法 52周龄SD雄性大鼠50只，随机分为假手术组（Sham组）、模型组（VD组）、模型+补肾活血方组（BSHX组）、模型+雷帕霉素组（Rap组）和模型+3-甲基腺嘌呤组（3-MA组），每组10只大鼠。除Sham组外其余各组采用两血管阻断法（2-VO）建立VD模型。BSHX组中药灌胃治疗28天；自噬干预组于造模前30 min侧脑室给药。运用Morris水迷宫测试各组大鼠的学习记忆能力；通过尼氏染色和透射电子显微镜（Transmission electron microscope，TEM）观察大鼠海马区病理形态及自噬变化；采用蛋白免疫印迹（Western blot）法和反转录实时荧光定量PCR（RT-qPCR）检测大鼠海马Beclin-1、P62以及微管相关蛋白1轻链3（LC3）蛋白及mRNA表达情况。结果 与VD组比较，BSHX组大鼠学习记忆能力显著提升（P<0.05），镜下观察BSHX组和3-MA组的细胞形态及数量均有改善，自噬小体鲜见，Beclin-1以及LC3蛋白和mRNA表达水平显著降低（P<0.05），P62蛋白和mRNA表达水平明显升高（P<0.05）结论 补肾活血方可以降低VD大鼠海马区Beclin-1和LC3蛋白及mRNA的表达，提高P62的表达，通过抑制自噬的发生，减轻对神经细胞的损伤，改善学习记忆能力。