目的:探讨直肠癌肺转移患者的一般临床特征,分析患者术前外周血中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)和血小板与淋巴细胞比值(platelet to lymphocyte ratio,PLR)对直肠癌肺转移患者预后的意义.方法:回顾性分析2016年1月—2018年12月在安徽医科大学附属省立医院就诊的104例直肠癌伴肺转移患者的临床病历资料,进行复发模式分析,并进一步对其中55例具有完整血液学参数的首诊直肠癌肺转移患者进行血液学分析.根据治疗前的血液学指标构建受试者工作特征(receiver operating characteristic,ROC)曲线以确定NLR、PLR、全身免疫炎症指数(systemic immune-inflammation index,SII)、平均血小板体积(mean platelet volume,MPV)、癌胚抗原(carcinoembryonic antigen,CEA)和糖类抗原199(carbohydrate antigen 19-9,CA19-9)水平预测直肠癌肺转移患者预后的最佳截断值.采用曲线下面积(area under the curve,AUC)评价其诊断价值.生存分析采用Kaplan-Meier法,差异分析采用log-rank检验,多因素分析采用COX回归分析.结果:直肠癌患者术后第1、2、3、4和5年的肺转移发生率分别为22.12％、28.85％、23.00％、10.58％和4.80％,提示肺转移主要发生在术后前3年.单因素分析显示,下段直肠癌(肿瘤下缘距离肛缘<7 cm)、低分化腺癌、远处淋巴结转移、T分期≥T3、N2患者的总生存(overall survival,OS)率曲线显著降低(P<0.05).多因素分析显示,下段直肠癌、低分化腺癌、术后T分期≥T3和N2是预后不良的独立影响因素(P<0.05),而下段直肠癌、术后T分期≥T3和低分化腺癌是至肺转移时间的独立影响因素(P<0.05).术前NLR升高、PLR升高以及高水平CEA和CA19-9患者的术后OS期和至肺转移时间均显著缩短(P<0.05),术前高水平MPV患者的术后OS期显著缩短(P<0.05).结论:直肠癌肺转移主要发生在术后3年内,原发肿瘤部位、肿瘤分化程度、术前NLR、PLR、CEA和CA19-9可能是直肠癌肺转移患者预后的独立影响因素.

目的 分析以肺转移为首发表现的结肠癌患者的预后的因素.方法 回顾性分析2011年10月～2020年4月安徽医科大学附属省立医院确诊的以肺转移为首发表现的47例结肠癌患者资料,采用Kaplan-Meier法分析临床病理特征(年龄、性别、原发灶位置、N分期、分化程度、有无肠梗阻、肺部病灶位置、有无肝转移、肿瘤标志物CEA及CA199)与无疾病生存期(DFS)的关系,并采用多因素Cox模型分析影响患者DFS的独立因素.结果 全组患者中位DFS为16.5个月.单因素分析显示,肺部病灶位置及有无肝转移与DFS有关(P<0.05);而年龄、性别、原发灶位置、N分期、分化程度、有无肠梗阻、肿瘤标志物CEA及CA199与DFS无相关性(P>0.05).多因素分析显示,肺部病灶位置、有无肝转移为影响DFS的独立因素.结论 在以肺转移为首发表现的结肠癌中肺部病灶位置、有无肝转移可能为影响疾病进展的独立预后因素.

目的 探讨胃癌术后外周血单核细胞、淋巴细胞水平变化对胃癌肝转移患者预后的影响.方法 回顾性分析63例胃癌术后发生肝转移患者的临床资料,分析不同临床特征与肝转移时间的关系、单核细胞与肝转移时间的关系及不同临床特征与生存时间的关系、淋巴细胞与生存时间的关系.结果 共纳入胃癌肝转移患者63例,其中单核细胞升高患者27例,降低患者36例,胃癌术后中位肝转移时间为8.47个月;术后单核细胞升高患者中位肝转移时间为11.97个月,单核细胞降低患者的肝转移时间为7.13个月,二者比较,差异有统计学意义(P<0.05);Cox单因素分析显示,病理分化程度、N分期、原发灶大小、单核细胞水平变化影响胃癌肝转移时间(P<0.05);Cox多因素分析显示,N分期、术后单核细胞变化是影响胃癌术后肝转移时间的独立预后因素;Kaplan-Meier生存分析显示,术后单核细胞升高患者发生肝转移的时间晚于术后单核细胞降低患者(P<0.05).术后淋巴细胞升高患者23例,降低患者40例,肝转移发生后中位生存时间为10.04个月;术后淋巴细胞升高患者中位生存期为11.33个月,术后降低患者生存期为6.93个月,二者比较,差异有统计学意义(P<0.05);Cox单因素分析显示,胃癌原发灶大小、术后淋巴细胞升高、肝转移灶数目、肝转移时ALB升高是胃癌肝转移预后的影响因素(P<0.05);Cox多因素分析显示,术后淋巴细胞变化和原发灶大小是影响肝转移后生存期的独立预后因素.Kaplan-Meier生存曲线显示,术后淋巴细胞升高患者生存期长于降低患者(P<0.05).结论 胃癌术后外周血单核细胞升高的患者发生肝转移时间较晚,淋巴细胞升高患者总生存期较长,而胃癌原发灶大小是肝转移后总生存期的独立危险因素.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

Objective To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. Methods In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. Results The percentage of CD19−CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19−CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. Conclusion B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

Tumor formation is a complex and dynamic process consisting of three phases: occurrence, development and metastasis. The tumor microenvironment is a complex local pathological environment that can induce neovascularization, and angiogenesis is an important condition for tumorigenesis, development and metastasis. Thus, antiangiogenic therapy becomes a new target for tumor therapy. Numer-ous studies have shown that clinical benefits have been achieved from antiangiogenic therapy for many tumors, such as non-small cell lung cancer, chondrosarcoma and the like. In addition, antiangiogenic therapy combined with PD-1/PD-L1 monoclonal antibody immunotherapy is also one of the current research hotspots. Some studies have shown that the combination of the two treatment strategies can enhance the efficacy. However, in recent years, it has been found in clinical practice that anti-angiogenesis drugs resistance, lack of predictive biomark-ers and other problems are still unavoidable. Yet the curative effect is not entirely satisfactory. Even some of short-term treatments might increase the invasiveness of tumors. The reasons for the above phenomena are closely related to the changes in the responsiveness of tumor microenvironment. This article provides a brief review of the current challenges of tumor microenvironment-mediated anti-angiogenic ther-apy to improve the clinical efficacy of anti-tumor angiogenesis therapy.