胃癌术后病人肠道菌群变化及其对围手术期恢复的影响

目的探讨胃癌术后病人肠道菌群的变化及其对病人术后围手术期恢复的影响。方法选择2018年6月至2019年6月南昌大学第二附属医院胃肠外科收治的行胃癌根治术的100例病人,对每位病人术前与术后的粪便进行菌群检测(双歧杆菌、嗜酸乳杆菌、大肠杆菌、链球菌),并根据病人术后有益菌相对丰度分为丰度高组和丰度低组,同时检测病人术后生化指标(白细胞计数、中性粒细胞百分比、C反应蛋白、淋巴细胞计数、淋巴细胞百分比、总蛋白、白蛋白和前白蛋白)。结果通过高通量测序检测胃癌病人手术前后菌群变化,发现胃癌术后病人双歧杆菌、嗜酸乳杆菌明显减少,大肠杆菌、链球菌明显增多,差异有统计学意义(P<0.05)。100例病人中双歧杆菌和嗜酸乳杆菌相对丰富的病人肠道功能恢复较早,炎症指标相对较低,免疫指数有所提高,同时提高总蛋白及白蛋白营养指标,差异有统计学意义(P<0.05)。结论胃癌术后病人肠道菌群发生改变,体内有益菌双歧杆菌、嗜乳酸杆菌减少,大肠杆菌、链球菌明显增加。同时体内有益菌减少会影响病人术后恢复,增加病人炎症反应,降低机体免疫能力,影响病人营养状态。     

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

关于改革完善重大疫情防控救治体系的建议

针对重大疫情防控救治，在系统梳理临床治疗、疾病控制和科学研究三者定位的基础上，结合本次新型冠状病毒肺炎疫情暴露出来的问题，提出了改革完善我国重大疫情防控救治体系的建议。临床治疗方面，要加强医务人员依法报告意识，强化症状检测能力，充分发挥传染病直报系统的作用，建立健全新发突发传染病的国家或地方监测平台。疾病控制方面，要从法律和体制机制上赋予疾控相关权限和保障，提升疾控队伍的数量和质量，加强防控与应急需求为导向的应用性研究和技术储备。科学研究方面，要加强以国家需求为导向的科研立项，建设重大疫情应对中“一锤定音”的科研机构，建立国家和区域传染病重点实验室，加强新发突发传染病防控救治的战略技术储备。     

胸腔镜肺小结节切除术前微弹簧圈定位的临床应用研究

目的:研究孤立性肺结节(SPN)胸腔镜术前CT引导下双弹簧圈精准标记定位的应用价值。方法:回顾分析43例SPN胸腔镜术前定位病例资料，包括双弹簧圈组22例，Hook-wire定位组21例。统计双弹簧圈定位的术中、术后并发症，衔接期时间以及作楔形切除所用时间，并将两组结果进行对比分析。结果:两组病例定位均取得成功；双弹簧圈组的气胸发生率(9.0%)，肺出血发生率(9.0%)，胸痛发生率(9.0%)均低于Hook-wire组，其中肺出血发生率与Hook-wire组比较，差异有统计学意义(P＜0.01)；衔接时间双弹簧圈组（15.38±8.32）h长于Hook-wire组（4.21±3.29）h，差异有统计学意义（P＜0.05）；作楔形切除所用时间双弹簧圈组(21.01±7.14)min与Hook-wire组(18.22±5.18)min差异无统计学意义(P＞0.05)。结论:采用双微弹簧圈进行SPN胸腔镜手术前精准标记定位安全可靠、效果良好，与Hook-wire定位比较并发症发生率更低，并可获得更长的衔接期，具有较高的应用价值。     

原肌球蛋白4在胃癌细胞迁移、侵袭和转移中的作用

目的:探索原肌球蛋白4（Tropomyosin4,TPM4）在胃癌细胞的迁移、侵袭和转移中的作用。方法:利用Real-time PCR、Western Blot及免疫荧光，检测原肌球蛋白4在不同胃癌细胞系及正常胃上皮细胞中的表达情况；利用免疫组化，检测原肌球蛋白4在胃癌组织及癌旁正常组织中的表达情况；利用慢病毒技术，在GC9811-P细胞中，分别转染LV-TPM4、shRNA-TPM4及对照空载体；通过Transwell和体内实验，检测胃癌细胞迁移、侵袭和转移。结果:Real-time PCR、Western Blot及免疫组化结果显示，原肌球蛋白4在胃癌细胞系及胃癌组织中的表达降低；上调原肌球蛋白4的表达后，抑制胃癌细胞的迁移、侵袭和转移；下调原肌球蛋白4的表达后，促进胃癌细胞的迁移、侵袭和转移（P<0.05）。结论:原肌球蛋白4抑制胃癌细胞的迁移、侵袭和转移。