Soil zinc deficiency and child stunting: Evidence from Nepal

We examine the negative child health impacts of soil zinc (Zn) deficiency in Nepal. Soil Zn deficiency limits both crop yields and the Zn concentration in food crops, leading many to speculate that it underlies human Zn deficiency and child stunting, globally and particularly in South Asia. We find strong evidence that soil Zn deficiency does have a causal impact on child stunting in Nepal’s Tarai region, the breadbasket of the country. Using causal bounds, we find that a 1 part per million increase in plant-available soil Zn – achievable with application of Zn-enriched fertilizer – decreases child stunting by between 1 and 7.5 percentage points. Multiple statistical sensitivity tests indicate that this relationship is unlikely to be manufactured by omitted, relevant variables.     

单孔胸腔镜下肺癌术后胸腔引流时间的影响因素分析北大核心

目的:探讨单孔胸腔镜下肺癌手术术后胸腔引流时间的影响因素。方法:本研究采用回顾性分析方法,回顾我院2018年01月至2019年12月原发性肺癌患者经单孔胸腔镜手术治疗的病例199例。按照术后胸腔引流时间分为两组,Ⅰ组(术后胸腔引流时间<5天)和Ⅱ组(术后胸腔引流时间≥5天)。对于影响术后胸腔引流时间的可能因素在两组间先采用单因素分析的方法筛选,再将筛选出来的对术后胸腔引流时间可能有意义的影响因素进行二项Logistic多因素回归分析。结果:经单因素分析及二项Logistic多因素回归分析结果显示:年龄≥60岁、手术部位、肺段切除术、胸膜粘连、手术时间≥180 min、术后早期下床活动是术后胸腔引流时间的独立影响因素(P<0.05)。结论:对于具有多个延长术后胸腔引流时间的独立影响因素的患者,应制定个体化管理方案,尽可能减少术后胸腔引流时间,减少住院天数,加快患者康复。     

伸筋易骨法调节兔膝关节周围软组织张力影响软骨形态的研究

[目的] 评价伸筋易骨法对膝关节周围软组织张力及软骨形态的影响，以探讨其对膝关节骨性关节炎（KOA）的治疗作用。[方法] 选择6~8月龄雌性健康新西兰大耳白兔50只，随机分为5组。其中模型组、推拿组、玻璃酸钠组采用Hulth造模法模拟KOA，正常组、假手术组不做干预。造模成功后，推拿组予伸筋易骨法治疗3周，玻璃酸钠组予局部关节内注射每周1次，共3周，模型组不予任何治疗。治疗结束后，测试股直肌、股二头肌张力，并取软骨组织进行HE染色后光镜下进行形态学观察，并进行Markin评分。分析推拿组与其余4组的异同。[结果] 模型组较正常组，股直肌FDD值和S值显著降低（P<0.05），股二头肌FDD值和S值显著升高（P<0.05）。推拿组和玻璃酸钠组相较于模型组的股直肌FDD值和S值均显著升高（P<0.05））；推拿组和玻璃酸钠组相较于模型组股二头肌的FDD值和S值均显著降低（P<0.05）。推拿组和玻璃酸钠组相较于模型组，Mankin’s评分比较有统计学意义（P<0.05）。[结论] 伸筋易骨法可以显著增加关节周围肌肉的肌力、调节组织张力、改善关节活动功能，对保护膝关节周围软组织功能具有重要意义。     

Time trend of exposure to the phthalate plasticizer substitute DINCH in Germany from 1999 to 2017: Biomonitoring data on young adults from the Environmental Specimen Bank (ESB)

DINCH (cyclohexane-1,2-dicarboxylic acid-diisononyl ester) is a phthalate plasticizer substitute introduced into the market in 2002. It is increasingly used especially in the production of toys, food contact materials and medical devices. In this measurement campaign on 24-h urine samples of young adults (20–29 years) from the German Environmental Specimen Bank (ESB) collected in 2010, 2011, 2013, 2015 and 2017 (in total 300 samples, 60 samples/year) we analyzed three specific, oxidized DINCH metabolites (OH-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester; cx-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(carboxy-isooctyl) ester, oxo-MINCH: cyclohexane-1,2-dicarboxylic acid-mono(oxo-isononyl) ester). We merged these data with earlier data of the ESB from the years 1999–2012 and are now able to report levels and time trends of internal DINCH exposure from 1999 to 2017.After first detections of the major oxidized DINCH metabolite OH-MINCH in 2006 (6.7%) detection rates rapidly increased to 43.3% in 2009, 80% in 2010 and 98.3% in 2011 and 2012. From the year 2013 on we could detect OH-MINCH in every urine sample analyzed. The median concentrations of OH-MINCH rapidly increased from 0.15 μg/L in 2010 to twice the concentration in 2011 (0.31 μg/L) with further increases in 2013 (0.37 μg/L), 2015 (0.59 μg/L) and 2017 (0.70 μg/L). Similar increases, albeit at lower detection rates and concentration levels, could be observed for cx-MINCH and oxo-MINCH. All metabolites strongly correlate with each other.For the ESB study population, DINCH exposures are still far below health based guidance values such as the German Human Biomonitoring Value (HBM-I; 4,500 μg/L for the sum of OH-MINCH and cx-MINCH) or the tolerable daily intake (TDI) of EFSA (1 mg/kg bw/d). The median daily DINCH intake (DI) calculated for 2017 was 0.23 μg/kg bw/d, thus 4,310-times lower than the TDI. The maximum DI calculated for one individual in 2012 (42.60 μg/kg bw/d) was a factor of more than 20 below the TDI.The ongoing increase in DINCH exposure needs to be closely monitored in the future, including populations with potentially higher exposures such as children. This close monitoring will enable timely exposure and risk reduction measures if exposures reached critical levels, or if new toxicological data lead to lower health based guidance values. DINCH belongs to the European Human Biomonitoring Initiative (HBM4EU) priority substances for which policy relevant questions still have to be answered.     

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide,Vincristine, Doxorubicin,Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study

BackgroundWe retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen.Patients and MethodsPatients received up to 6 mEPOCH cycles. Etoposide (50 mg/m²/day), doxorubicin (10 mg/m²/day), and vincristine (0.4 mg/m²/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m²/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert’s formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6.ResultsIn 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation.ConclusionThe mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.     

清热通利汤对宫颈炎并HPV感染患者生化指标与临床症状的影响研究

目的:观察清热通利汤对于宫颈炎合并人乳头瘤病毒(HPV)感染患者生化指标与临床症状的功效。方法:选取86例宫颈炎合并HPV感染患者作为观察资料,选取的患者按简单随机原则以数字表平均划分为对照组与治疗组,对照组给予常规治疗,治疗组给予清热通利汤外用; 治疗后3个月,对比临床疗效,统计临床症状的缓解时间; 评估治疗前、后患者生化指标、中医证候积分、血清炎性因子的变化情况。结果:治疗组显效率为53.49%、总有效率为95.35%,对照组依次为37.21%、72.09%,治疗组临床疗效优于对照组(P<0.05)。治疗后,治疗组患者HPV-DNA转阴率高于对照组,HPV-DNA转阴时间、HPV病毒载量均低于对照组,差异均有统计学意义(P<0.05); 治疗组患者宫颈柱状上皮异位、接触性出血、阴道清洁度异常、白带化验异常的消退时间均短于对照组(P<0.05); 治疗后两组患者各项中医证候积分、血清炎性因子与生化指标均较治疗前改善且治疗组均优于对照组(P<0.05)。结论:清热通利汤能够促进宫颈炎合并HPV感染患者HPV-DNA转阴,提高临床疗效,更有效的缓解临床症状、改善生化指标、减轻炎性反应程度。     

Inhibiting Pathways Predicted From a Steroid Hormone Gene Signature Yields Synergistic Antitumor Effects in NSCLC

IntroductionMounting evidence supports a role for estrogen signaling in NSCLC progression. We previously reported a seven-gene signature that predicts prognosis in estrogen receptor β positive (ERβ+) NSCLC. The signature defines a network comprised of ER and human EGFR-2/3 (HER2/HER3) signaling.MethodsWe tested the efficacy of combining the pan-HER inhibitor, dacomitinib, with the estrogen antagonist, fulvestrant, in ERβ+ NSCLC models with differing genotypes. We assessed the potency of this combination on xenograft growth and survival of host mice, and the ability to reverse the gene signature associated with poor outcome.ResultsSynergy was observed between dacomitinib and fulvestrant in three human ERβ+ NSCLC models: 201T (wild-type EGFR), A549 (KRAS mutant), and HCC827 (EGFR 19 deletion) with combination indices of 0.1-0.6. The combination, but not single agents, completely reversed the gene signature associated with poor prognosis in a mechanism that is largely mediated by activator protein 1 downregulation. In vivo, the combination also induced tumor regression and reversed the gene signature. In HCC827 xenografts treated with the combination, survival of mice was prolonged after therapy discontinuation, tumors that recurred were less aggressive, and two mechanisms of HER inhibitor resistance involving c-Met activation and PTEN loss were blocked.ConclusionsThe combination of an ER blocker and a pan-HER inhibitor provides synergistic efficacy in different models of ERβ+ NSCLC. Our data support the use of this combination clinically, considering its ability to induce potent antitumor effects and produce a gene signature that predicts better clinical outcomes.     

Human breast milk oligosaccharides attenuate necrotizing enterocolitis in rats by suppressing mast cell accumulation,DPPI activity and TLR4 expression in ileum tissue,and regulating mitochondrial damage of Caco-2 cells

Necrotizing enterocolitis (NEC), a devastating infant disease characterized by severe intestinal necrosis, its pathogenesis is poorly understood, but appears to be multifactorial and highly associated with immaturity of gastrointestinal tract and immature innate-immune system. Breast-milk is effective strategy to protect infants against NEC. This study is using a NEC rat model to investigate the pathological mechanism of NEC involved intestinal-damages, and the therapeutic mechanism of sialylated human milk oligosaccharides (SHMOs) on NEC rats; also using cell model to investigate the effects of SHMOs on colon-epithelial cells (Caco-2) in-vitro.Extraction and characterization of SHMOs from breast milk, establishment of a NEC rat model, histopathological analysis and mast cell accounting of the terminal ileum were taken; The levels of DPPI, TLR4, IL-6, TNF-α, MMP-2/9 and glutathione were measured using various methods. Caco-2 cells were pre-treated with SHMOs and cultured with LPS, histamine, chymase or DPPI, cell viabilities and mitochondrial membrane potential were examined; flow cytometry was used to detect cell cycle.The accumulation of mast cells was found in the ileum of NEC rats, but prohibited by SHMOs treatment; the increased levels of TLR4, DPPI, IL-6, TNF-α, MMP-2/9 in NEC ileum were suppressed by SHMOs in-vivo. SHMOs prevented Caco-2 cells from LPS, histamine, chymase induced damages by surviving cell viability, regulating G0/G1 and S phase in cell cycles, and increasing mitochondrial membrane potential. These findings provide a new insight into the pharmacological mechanism of SHMOs treatment for NEC and suggest that SHMOs needs well attention for therapeutic aims.     

乙酰紫草素通过PI3K/Akt信号通路诱导前列腺癌PC-3细胞凋亡的研究

目的：研究乙酰紫草素（ASK）对人前列腺癌PC-3细胞的诱导凋亡作用及相关的分子机制。方法：利用CCK-8实验检测ASK对体外培养PC-3细胞的杀伤作用；利用流式细胞术实验检测ASK处理后PC-3细胞凋亡情况；利用Western blotting检测凋亡蛋白和AKT信号通路蛋白的表达。结果：CCK-8实验证明ASK能够以时间和浓度依赖性抑制前列腺癌PC-3细胞的增殖；流式细胞术实验证明ASK能够诱导人前列腺癌PC-3细胞线粒体依赖性凋亡；Western blotting证明ASK能够有效抑制前列腺癌PC-3细胞中的AKT信号通路。结论：ASK能够有效抑制人前列腺癌PC-3细胞增殖，并能够有效诱导PC-3细胞发生线粒体依赖性凋亡，其机制可能是通过调控PI3K/Akt信号通路来实现，说明ASK具有一定的抗前列腺癌的潜力。