Effects of short-term continuous and pulse cadmium exposure on gut histology and microbiota of adult male frogs (Pelophylax nigromaculatus) during pre-hibernation

Cadmium (Cd) is an environmental endocrine-disrupting pollutant which mainly occurs in pulsed manner in natural waters, while traditional toxicology experiments have less examined the effects of pulsed exposure. Here, we studied the effects of short-term (7 days) continuous and pulse exposure to 100 μg/L Cd on gut morphology and microbiota of frogs (Pelophylax nigromaculatus) during pre-hibernation. Compared to continuous exposure, Cd pulse exposure significantly increased individual mortality and decreased the villi height and the ratio of villi height to crypt depth of the gut. Cd continuous and pulse exposure both changed the community structure and relative abundance of intestinal microbiota. Compared to continuous exposure, Cd pulse exposure significantly decreased the relative abundance of beneficial bacteria (e.g., Cetobacterium and Aeromonas genus), and significantly increased the relative abundance of harmful bacteria (e.g., Parabacteroides, Odoribacter, and Acinetobacter genus). This study shows that the gut histology and microbiota of amphibians during pre-hibernation are more susceptible to Cd pulse exposure than continuous exposure.     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

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.     

术前血清CA125、HE4和中性粒细胞与淋巴细胞比值联合检测在子宫内膜癌诊断中的作用

目的:探讨血清糖类抗原125（carbohydrate antigen 125，CA125）、人附睾蛋白4（human epididymis protein 4，HE4）、中性粒细胞与淋巴细胞比值（neutrophil-lymphocyte ratio，NLR）联合检测在子宫内膜癌诊断中的作用。方法:选取42例子宫内膜癌患者、50例子宫内膜良性疾病患者和50例健康体检人群。采用SYSMEX XN550全自动血液分析仪计数术前外周血中性粒细胞和淋巴细胞，计算NLR；采用Maglumi4000全自动化学发光仪检测术前血清CA125、HE4水平。采用ROC曲线分析CA125、HE4、NLR和三者联合指标在诊断子宫内膜癌中的作用。结果:外周血NLR在健康组、良性组和子宫内膜癌组中逐渐增高，且差异有统计学意义（P<0.05）；子宫内膜癌组HE4表达量显著高于良性组与健康组（P<0.05），而良性组与健康组之间差异无统计学意义（P>0.05）；CA125表达量在三组中差异无统计学意义（P>0.05）。CA125、HE4、NLR及三者联合标记物的AUC分别为0.530、0.733、0.795、0.823，当分别取它们的临界值时，特异性分别为70.8%、85.1%、61.7%、83.0%，敏感性分别为40.0%、63.3%、86.7%、73.3%。单项指标NLR的敏感性最高，HE4的特异性最高，联合指标的特异性和敏感性都很高。结论:术前血清CA125、HE4和NLR联合检测具有较高的特异性和敏感性，联合检测可以互为补充，提高子宫内膜癌的诊断准确率，对子宫内膜癌的诊断具有指导意义。     

The microbiome in pediatric oncology

The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.     

Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis

The gut microbiota and the bile acid pool play pivotal roles in maintaining intestinal homeostasis. Bile acids are produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. Gut dysbiosis has been reported to be associated with colorectal cancer. However, the interplay between bile acid metabolism and the gut microbiota during intestinal carcinogenesis remains unclear. In the present study, we investigated the potential roles of bile acids and the gut microbiota in the cholic acid (CA; a primary bile acid)‐induced intestinal adenoma‐adenocarcinoma sequence. Apc ^min/+ mice, which spontaneously develop intestinal adenomas, were fed a diet supplemented with 0.4% CA for 12 weeks. Mice that were fed a normal diet were regarded as untreated controls. In CA‐treated Apc ^min/+ mice, the composition of the gut microbiota was significantly altered, and CA was efficiently transformed into deoxycholic acid (a secondary bile acid) by the bacterial 7α‐dehydroxylation reaction. The intestinal adenoma‐adenocarcinoma sequence was observed in CA‐treated Apc ^min/+ mice and was accompanied by an impaired intestinal barrier function and IL‐6/STAT3‐related low‐grade inflammation. More importantly, microbiota depletion using an antibiotic cocktail globally compromised CA‐induced intestinal carcinogenesis, suggesting a leading role for the microbiota during this process. Overall, our data suggested that the crosstalk between bile acids and the gut microbiota mediated intestinal carcinogenesis, which might provide novel therapeutic strategies against intestinal tumor development.     

血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移

目的:探讨血清CEA、CA72-4及CA125联合诊断胃癌术后腹膜转移的价值，为临床诊治提供参考。方法:以我院于2015年11月至2016年11月因胃癌术后在本院复查且相关临床资料齐全患者120例作为研究对象并进行回顾性分析，按照有无腹膜转移分为转移组（38例）和无转移组（82例）。对比两组患者的血清CEA、CA72-4及CA125变化及单项诊断效能，并采用ROC曲线法对比三种肿瘤标志物的诊断效能。结果:转移组患者的血清CEA、CA72-4及CA125水平均高于无转移组，差异有统计学意义（P＜0.05）。三个单项指标比较，CA125灵敏度为73.3%，特异度为81.8%，均为三者最高，差异均有统计学意义（P＜0.05）。联合诊断比较，CEA+CA72-4+CA125联合检测的灵敏度最高（91.7%），但特异度最低（41.7%），差异均有统计学意义(P＜0.05)。结论:胃癌术后腹膜转移患者血清CEA、CA72-4及CA125均升高，且单项诊断CA125的灵敏度及特异度最高，而三项联合诊断的灵敏度最高，但特异度最低，值得临床参考。