从气机升降探讨胃癌的病机治则

胃癌是因外邪侵袭、情志内伤、饮食失调等,致气机升降失调,气血津液运化失常,气滞、血瘀、痰浊及癌毒内生,日久积聚于胃脘而成。脾胃为气机升降之枢纽,脾不升清,胃不降浊,则精微不能濡养,浊液不能排出,影响体内正常气机升降。肝主疏泄,调节全身气机的条达,肝之疏泄功能失常,气机升降失调,则影响气血运行。气机升降关系在胃癌形成中起关键作用,气机升降失调,气血津液不能正常输布运行,则气凝血滞,痰浊内停,甚则癌毒内生,发为癌瘤。故在临床治疗中注重恢复脾胃的升降功能,辛开苦降,调畅气机,恢复脾胃的正常升降功能,为胃癌的治疗提供临床指导。     

Management recommendations for patients with chronic kidney disease during the novel coronavirus disease 2019 (COVID-19) epidemic

COVID-19 has become a pandemic and it has already spread to at least 171 countries/regions. Chronic kidney disease (CKD) is a global public health problem with a total of approximately 850 million patients with CKD worldwide and 119.5 million in China. Severe COVID-19 infection may damage the kidney and cause acute tubular necrosis, leading to proteinuria, hematuria and elevated serum creatinine. Since the SARS-CoV-2 enters the cells by binding to the angiotensin-converting enzyme 2 receptor, some doctors question its ability to increase the risk and severity of developing COVID-19. Neither clinical data nor basic scientific evidence supports this assumption. Therefore, patients who take angiotensin-converting enzyme inhibitor or angiotensin receptor blocker are not advised to change their therapy. Patients with CKD are generally the elderly population suffering from multiple comorbidities. Moreover, some patients with CKD might need to take glucocorticoids and immunosuppressants. Dialysis patients are recurrently exposed to a possible contaminated environment because their routine treatment usually requires three dialysis sessions per week. Considering all the above reasons, patients with CKD are more vulnerable to COVID-19 than the general population. The development of COVID-19 may worsen the impaired kidney function and further lead to rapid deterioration of kidney function and even death. Strict comprehensive protocols should be followed to prevent the spread of COVID-19 among patients with CKD. In this review, we provide some practical management recommendations for health care providers, patients with CKD, dialysis patients and dialysis facilities.     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Epigenetically silenced PD-L1 confers drug resistance to anti-PD1 therapy in gastric cardia adenocarcinoma

ObjectivesThe anti-PD-1/PD-L1 therapy has been demonstrated safe and effective for cancer patients. However, our previous data showed that it had no obvious effects on gastric cardia adenocarcinoma (GCA). Thus, we investigated how the expression level of the PD-L1 was affected by the anti-PD-1 therapy, because it has been demonstrated that the PD-L1 level affects the therapeutic efficient of the anti-PD-1 therapy.Materials and methodsThe mRNA and protein levels of PD-L1 in the GCA tissues and corresponding normal tissues were determined by qPCR and ELISA. Promoter methylation was analyzed by bisulfite sequencing. Finally the methylation of PD-L1 promoter was confirmed in the mice.ResultsThe level of PD-L1 was up-regulated in the GCA tissues when compared to the adjacent non-tumor tissues. The anti-PD1 therapy could reduce the PD-L1 levels in patients with cancer recurrence. The promoter of PD-L1 was more hypermethylated in the secondary GCA after the anti-PD-1 therapy when compared with the adjacent non-tumor tissues or the primary GCA without the anti-PD-1 therapy. Furthermore, the promoter methylation of PD-L1 could be induced by the anti-PD-1 therapy in the mice model. Finally, the anti-PD-1 plus DNA hypomethylating agent azacytidine could significantly suppressed the tumor growth better than the anti-PD-1 therapy.ConclusionsHere we demonstrated that the unresponsiveness of GCA to the anti-PD-1 therapy might result from the promoter methylation and down-regulation of PD-L1. The anti-PD-1 plus azacytidine might be a more promising approach to treat GCA.     

lncRNA-LINC00473在胃癌组织中的表达及临床意义

目的:分析LINC00473在胃癌中的表达情况、临床意义及对人胃癌细胞增殖水平的影响。方法:利用癌症基因组图谱(TCGA)数据库下载胃腺癌相关数据集，分析肿瘤组织与正常组织之间LINC00473的表达差异；利用 Kaplan-Meier 曲线进行患者生存分析；MTT方法检测胃癌细胞增殖水平、流式细胞术检测凋亡率的改变。结果:与癌旁组织比较，LINC00473在胃癌组织中的表达明显增加，差异具有统计学意义（P＜0.05）；生存分析发现，LINC00473表达与胃癌患者OS和DFS时间相关，LINC00473高表达的胃癌患者，OS和DFS时间明显缩短（P＜0.05）。转染LINC00473 siRNA至胃癌细胞后，结果发现与阴性质粒转染组比较:转染siRNA-LINC00473的胃癌细胞，LINC00473 表达明显降低；LINC00473表达下调后细胞增殖水平减慢，凋亡率增加。结论:LINC00473是一个新的胃癌生物标记物，可作为潜在的治疗新靶点。     

慢性鼻窦炎指南的评价与内容分析

背景　慢性鼻窦炎是耳鼻喉科高发疾病，对患者造成严重的影响和经济负担，但目前国内外慢性鼻窦炎诊疗指南推荐意见存在差异。目的　对慢性鼻窦炎诊疗指南进行质量评价并分析其治疗意见，为指南制定和推荐意见的采纳提供建议。方法　于2019年2月检索中英文数据库和各专业指南网站获取相关文献，同时追踪参考文献，筛选适用于青少年及成年人的推荐意见中包含对慢性鼻窦炎的治疗意见的指南。检索时间为建库至检索日期。使用临床指南研究与评估系统Ⅱ（AGREE Ⅱ）和卫生保健实践指南报告清单（RIGHT）对纳入指南的方法学质量和报告质量进行评价，并绘制气泡图和思维导图，对比分析关于慢性鼻窦炎治疗的推荐意见。结果　最终纳入8部指南，AGREE Ⅱ评价总分平均为48.76%（30.90%~73.09%），仅2部指南强烈推荐使用（得分>60%），其余6部需修订后推荐。RIGHT条目总体报告率为34.29%~65.71%，其中评审和质量控制方面报告率均为0。指南推荐一致的治疗方法包括皮质类固醇、鼻腔盐水冲洗和手术治疗，以及过敏者口服抗组胺药，可选用的措施包括细菌溶解物、黏痰溶解药、质子泵抑制剂、植物疗法、辣椒素、亮氨酸拮抗剂、鼻用呋塞米、木糖醇盐水冲洗液、次氯酸钠盐水冲洗液、含婴儿香波的盐水冲洗液，尚无统一观点的治疗措施包括抗生素、减充血剂、白三烯受体拮抗剂、IgE拮抗剂及阿司匹林加重呼吸系统疾病患者阿司匹林脱敏治疗。结论　现有慢性鼻窦炎诊疗指南制定方法及其报告质量需提高，建议纳入患者的偏好、使用统一的评价工具和考虑运用性。推荐意见有冲突时，建议参考制定方法更为严谨的指南。     

综合评估慢性阻塞性肺疾病稳定期中医证型与疾病程度及预后的相关性

目的:运用综合评估法分析慢性阻塞性肺疾病稳定期中医证型与病情程度及预后的相关性。方法:将符合纳入标准的200例患者分为肺气虚、肺脾气虚、肺肾气虚及肺肾气阴两虚四组,观察1年前后患者肺功能、mMRC分级、CAT评分,并进行数据整理及统计分析。结果:肺肾气虚证、肺肾气阴两虚证患者较肺气虚证、肺脾气虚证患者肺功能分级重且FEV1下降更明显、出现呼吸困难症状重且程度进展快、对生活质量影响较大且影响增加更显著,但肺气虚证与肺脾气虚证、肺肾气虚证与肺肾气阴两虚证之间无明显差异。结论:慢性阻塞性肺疾病稳定期中医证型与疾病程度及预后存在相关性。     

胃癌患者根治术后腹腔灌洗液中CEA mRNA表达的临床意义

目的：探讨胃癌患者根治术后腹腔冲洗液中CEA mRNA表达情况及其临床意义。方法: 回顾性分析了2013 年1 月至2017 年12 月在南京大学医学院附属鼓楼医院接受胃癌根治切除术后进行腹腔灌洗液CEA mRNA检测的139 名患者的病历资料，并进行术后常规随访。用RT-PCR检测139 胃癌患者根治术后腹腔灌洗液中CEA mRNA表达情况。卡方检验分析腹腔灌洗液中CEA mRNA表达与临床基本特征、组织病理学资料、血液学指标及复发方式之间的关系。采用Logistic 单因素及多因素回归分析筛查影响CEA mRNA表达水平的因素。结果：139 名患者中44 名（31.7%）患者腹腔灌洗液CEA mRNA阳性。分析显示，胃癌患者腹腔灌洗液CEA mRNA阳性表达与性别、年龄、病理分级、Lauren 分型和HER2、EGFR、VEGFR等标记物间均没有明显的关联（均P>0.05），与病理类型、脉管是否侵犯、局部浸润深度、淋巴结转移程度和临床AJCC 分期有明显的关联（均P<0.05）。CEA mRNA阳性患者腹膜复发率明显高于阴性患者（P=0.012）。Logistic 单因素回归分析显示，印戒细胞癌（P=0.04，HR=2.810，95% CI: 1.050~7.520）、T 分期（P=0.016，HR=6.329，95% CI: 1.417~28.264）、N 分期（P=0.022，HR=3.068，95% CI: 1.172~8.027）、AJCC分期（P=0.016 ，HR=3.971 ，95% CI: 1.295~12.173 ）、神经侵犯（P=0.002 ，HR=6.738，95% CI: 1.995~22.757）、脉管侵犯（P<0.001，HR=16.36，95% CI: 3.85~69.512）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的危险因素。Logistic 多因素回归分析显示，经过对其他因素的校正，脉管侵犯（P<0.001，HR=21.314，95% CI: 4.21~107.907）为胃癌患者腹腔灌洗液CEA mRNA阳性表达的独立危险因素。结论：胃癌腹腔灌洗CEA mRNA阳性的患者腹膜复发转移风险高且预后不良，应考虑包括腹腔局部治疗在内的更加积极的抗肿瘤治疗。     

儿童慢性腹泻高营养风险情况及对预后的影响

目的 探讨儿童慢性腹泻高营养风险情况及对预后的影响。方法 选择2019年1～12月在我院诊断治疗的慢性腹泻患儿100例为研究对象,进行营养风险筛查,分析高营养风险患儿与非高营养风险患儿临床特征以及预后情况,分析性别、年龄、病因对慢性腹泻患儿高营养风险的影响。结果 (1)100例患儿24例患儿STAMP评分≥4分,为高营养风险组,占24.0%。(2)7～14岁患儿高营养风险发生率显著高于其他年龄段患儿(P0.05);炎症性肠病患儿高营养风险发生率显著其他病因的患儿(P0.05)。(3)炎症性肠病是慢性腹泻患儿发生高营养风险的独立危险因素(P0.05)。(4)高营养风险组白蛋白、前白蛋白水平显著低于非高营养风险组,差异有统计学意义(P0.05)。两组Hb水平比较差异无统计学意义(P0.05)。(5)非高营养风险组痊愈率显著高于高营养风险组,医院感染率显著低于高营养风险组,住院时间显著短于高营养风险组,差异均有统计学意义(P0.05)。结论 儿童慢性腹泻高营养风险发生率相对较高,病因会影响患儿高营养风险的发生,而高营养风险影响患儿的预后,延长住院时间。