伊立替康联合阿帕替尼治疗术后转移性胃癌患者临床疗效和安全性分析

摘要 目的：探讨伊立替康联合阿帕替尼治疗术后转移性胃癌患者临床疗效和安全性。方法：选取我院2017年5月-2018年10月期间收治的术后一线化疗失败转移性胃癌患者105例,根据随机数字表法分为研究组（53例）和对照组（52例）,对照组患者给予伊立替康静脉滴注治疗,研究组在此基础上使用阿帕替尼进行联合治疗,4周为一个周期,连续治疗两个周期。比较两组患者疾病控制率、生存情况,并对治疗前后两组患者肿瘤标志物[癌胚抗原（CEA）、糖类抗原125（CA125）和糖类抗原199（CA199）]水平、基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）水平进行比较,观察治疗过程中两组患者不良反应发生情况。结果：治疗后,研究组疾病控制率、中位生存时间和中位进展时间均优于对照组（P<0.05）。治疗后,两组肿瘤标志物、MMP-9和VEGF水平均降低,且研究组低于对照组（P<0.05）。研究组不良反应发生率低于对照组（P<0.05）。结论：伊立替康联合阿帕替尼治疗术后转移性胃癌患者临床疗效确切,可延长患者生存时间,延缓疾病进展,且安全性较好,其作用机制可能与降低肿瘤标志物及MMP-9、VEGF水平有关。     

免疫检查点抑制剂联合抗血管生成二线治疗晚期食管癌患者疗效及肿瘤标志物表达、预后生存期的影响

摘要 目的：研究信迪利单抗与阿帕替尼在晚期食管癌二线治疗中的应用效果。方法：根据随机数字表法将2019年1月～2022年1月本院收治的70例食管癌患者分为对照组与观察组,每组各35例,对照组给予阿帕替尼治疗,观察组给予信迪利单抗与阿帕替尼联合治疗,观察两组患者的客观缓解率（ORR）、疾病控制率（DCR）,并在治疗前后利用酶联免疫吸附法检测其糖类抗原50（CA-50）、糖类抗原199（CA199）、癌胚抗原（CEA）、鳞癌抗原（SCC）水平;随后通过随访记录两组患者的预后生存期,并建立多因素Logistic模型分析影响患者达到中位OS、PFS的独立危险因素。结果：与对照组比较,观察组ORR、DCR率较高（P＜0.05）。与对照组相比,治疗后观察组血清CA50、CA199、CEA、SCC水平较低（P＜0.05）。与对照组比较,观察组中位OS、PFS较长（P＜0.05）。多因素Logistic分析结果显示,治疗方法、CA50、CA199、CEA、SCC是影响食管癌预后生存期的独立危险因素（P＜0.05）。结论：利用免疫检查点抑制剂与抗血管生成药物对晚期食管癌患者开展二线治疗,不仅能降低血清中的肿瘤标志物浓度,还能延长患者的预后生存期,治疗效果较为显著。     

替吉奥联合阿帕替尼对晚期复发转移食管癌患者T细胞亚群和血清肿瘤标志物水平的影响

摘要 目的：观察晚期复发转移食管癌经阿帕替尼联合替吉奥治疗后的疗效及对患者T细胞亚群和血清肿瘤标志物水平的影响。方法：病例搜集时间为2015年3月至2018年3月,病例搜集范围为我院接收的晚期复发转移食管癌患者70例。采用信封抽签法将患者分为对照组和实验组,各为35例。对照组给予替吉奥治疗,实验组在对照组的基础上联合阿帕替尼治疗,两组均连续化疗2个周期。对比两组化疗2个周期后的客观缓解率、疾病控制率;对比两组化疗前、化疗2个周期后的T细胞亚群和血清肿瘤标志物水平;对比两组中位总生存期（mOS）、中位无进展生存期（mPFS）及生命质量评分,记录两组化疗期间毒副反应发生情况。结果：实验组的客观缓解率45.71%、疾病控制率68.57%高于对照组的22.86%、42.86%（P<0.05）。两组化疗2个周期后CD3⁺、CD4⁺、CD4⁺/ CD8⁺均较化疗前降低,但实验组高于对照组（P<0.05）;CD8⁺较化疗前升高,但实验组低于对照组（P<0.05）。两组化疗2个周期后肿瘤特异性生长因子（TSGF）、癌胚抗原（CEA）、糖类抗原199（CA199）较化疗前降低,且实验组低于对照组（P<0.05）。实验组的mOS、mPFS长于对照组（P<0.05）,两组化疗结束后3个月QLQ-OES24评分均升高,且实验组高于对照组（P<0.05）。两组不良反应发生率对比,差异无统计学意义（P>0.05）。结论：晚期复发转移食管癌经阿帕替尼联合替吉奥治疗后,病情得到有效控制,血清肿瘤标志物水平降低更为显著,同时还可减轻免疫抑制,延长mOS、mPFS,且不增加毒副反应,近期疗效可靠。     

Therapeutic effect of erythropoietin on brain injury in premature mice with intrauterine infection

ObjectiveThe objective of this study is to explore the protective effect of erythropoietin (EPO) on brain injury induced by intrauterine infection in premature infants and its related mechanism, so as to provide reference for clinical medication.MethodsIntrauterine infection model is established by injecting lipopolysaccharide into pregnant mice, and HE staining of mouse placenta is used to judge whether the model of intrauterine infection is successful or not. Fifteen female rats are successfully pregnant and divided into intrauterine infection group (10 rats) and control group (5 rats). The mice in the intrauterine infection group are intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 0.3 mg/kg. After delivery, 16 newborn mice in the control group are randomly selected as blank control group. 32 newborn mice in the intrauterine infection group are selected as model group, and then divided into infection group and EPO treatment group, 16 mice in each group. After birth, mice in the blank control group are intraperitoneally injected with 0.2 mL saline daily. The infected mice are intraperitoneally injected with 0.2 mL saline daily. The mice in the EPO treatment group are intraperitoneally injected with recombinant human erythropoietin (rhEPO) 5000 IU/kg daily. HE staining results, EPOR protein and NMDAR1 mRNA expression in brain tissue of three groups of neonatal mice were compared.ResultsFirstly, the blood vessels of the mice in the intrauterine infection group are markedly hyperemic and edematous, and the infiltration of neutrophils is increased. The white matter structure of the neonatal mice in the intrauterine infection group is loose and stained lightly. The nerve fibers in the brain are different in thickness and disordered in arrangement. The nucleus is small and dark stained. The number of glial cells in brain tissue increases significantly. Secondly, the EPOR protein expression and physiological level of neonatal mice in intrauterine infection group increase significantly at 3, 7 and 14 days after birth. Compared with the blank control group, the difference is statistically significant (P < 0.05). On the 3rd day after birth, the expression level of EPOR protein in the EPO treated group is significantly higher than that in the intrauterine infection group (P < 0.05). Thirdly, the expression level of NMDA R1mRNA in brain tissue of neonatal mice at birth, on the 3rd and 7th day after EPO treatment is significantly lower than that of intrauterine infection group (P < 0.05).ConclusionEPO can promote the proliferation and differentiation of brain endogenous neural stem cells, and has a certain therapeutic effect on brain injury of premature mice caused by intrauterine infection.     

Review: Prevention and management of gastric cancer

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.     

支气管肺泡灌洗联合局部注药治疗支气管扩张合并感染的临床观察

目的:观察支气管肺泡灌洗联合局部注药治疗治疗支气管扩张合并感染的的临床效果。方法:将所选取的114名支气管扩张合并感染的患者随机分为对照组(使用常规方法进行治疗)和实验组(在常规治疗的基础上,给予支气管肺泡灌洗联合局部注药方法进行治疗)。比较两组患者治疗后症状改善情况、血气指标、治疗时间、半年内再次就诊次数。结果:与治疗前相比,两组患者治疗后血气指标均有明显改善,差异均有统计学意义(P0.05);治疗后实验组血气指标相比对照组改善更明显,差异具有统计学意义(P0.05);实验组患者退热时间、咳嗽咳痰消失时间、湿罗音消失时间、平均住院时间、半年内再次就诊次数均短于对照组,差异均有统计学意义(P0.05);观察组患者总有效率为100%,高于对比组的89.5%,差异有统计学意义(P0.05)。结论:支气管肺泡灌洗联合局部注药治疗治疗支气管扩张合并感染能有效改善患者症状,显著提高治疗效果,降低疾病的复发率,值得临床推广。     

Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF,PI3K/Akt and Ki-67/CD31

This study aimed to investigate the anti-tumour effect of apatinib on extensive-stage small cell lung cancer (SCLC) and elucidate the associated mechanisms. NCI-H345 cells were selected as model cells because of high expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and phosphorylated-VEGFR2 (pVEGFR2). Cells were exposed to recombinant human VEGF (rhVEGF) and apatinib. Cells were then divided into eight groups, namely, control, rhVEGF, apatinib, rhVEGF+apatinib, serum-free medium (SM), SM+rhVEGF, SM+apatinib and SM+rhVEGF+apatinib. In comparison with the control group, cell proliferation in vitro in apatinib, SM, SM+apatinib and SM+rhVEGF+apatinib groups was inhibited, particularly in SM+apatinib group. The effect of apatinib on tumour growth in vivo was investigated using a mouse xenograft tumour model. In comparison with the control group, tumour sizes were reduced in apatinib-treated group on days 34 and 37. Immunohistochemical and immunofluorescence staining revealed that VEGF, pVEGFR2, PI3K, AKT, p-ERK1/2, Ki-67 and CD31 in the tumour cells of apatinib-treated group were downregulated compared with control group. Haematoxylin and eosin staining revealed that apatinib promoted the necrosis of SCLC cells in vivo. In conclusion, apatinib inhibited the growth of SCLC cells by downregulating the expression of VEGF, pVEGFR2, p-PI3K, p-AKT, p-ERK1/2, Ki-67 and CD31.     

肿瘤微环境中ROS介导IgG表达对膀胱癌细胞增殖和侵袭能力的影响

摘要 目的：探讨肿瘤微环境（TME）中活性氧（ROS）介导免疫球蛋白G（IgG）表达对膀胱癌EJ细胞增殖、迁移和侵袭能力的影响。方法：临床收集的18例膀胱癌患者样本,通过Western blot法检测膀胱癌和癌旁正常组织样本中IgG表达量。利用免疫荧光染色（IF）技术分别对膀胱癌组织和癌旁正常组织中ROS和IgG分子进行共定位和相对定量分析。将活性氧清除剂N-乙酰基-L-半胱氨酸（NAC）加入膀胱癌细胞EJ中,实验分为3组：空白组（EJ细胞）、阴性对照组（EJ+PBS）、实验组（EJ+PBS+NAC）,10 mM NAC药物处理48小时后,运用DHE-ROS荧光探针技术和Western blot实验检测药物NAC对ROS和IgG相对表达水平的影响;通过克隆集落形成实验、划痕实验、Transwell实验检测去除ROS后对膀胱癌细胞增殖、迁移和侵袭的影响。结果：人体膀胱癌组织中ROS和IgG分子表达水平显著高于癌旁正常组织（P<0.001）;荧光显微镜显示膀胱肿瘤组织中正常膀胱尿路上皮细胞组织被肿瘤细胞严重破坏,结构紊乱不规则,IgG和ROS表达水平均升高,而癌旁组织膀胱尿路上皮组织的结构均匀规则;NAC药物处理EJ细胞后,与空白组和阴性对照组相比ROS和IgG表达显著降低,同时实验组细胞的增殖、迁移和侵袭能力明显下降（P<0.01）。结论：ROS和IgG在临床膀胱癌组织和体外膀胱癌细胞株EJ中均显著高表达,在肿瘤微环境中ROS通过调控IgG表达,从而促进膀胱癌细胞的增殖、迁移、侵袭。ROS和IgG可能成为膀胱癌早期诊断和生物治疗的临床新靶点。     

阿帕替尼与白蛋白结合型紫杉醇在MDA-MB-231乳腺癌细胞系中的协同抗癌作用

目的阐明阿帕替尼 (apatinib)和白蛋白结合型紫杉醇 (nab-Paclitaxel)诱导MDA-MB-231乳腺癌细胞凋亡的分子机制。方法本研究以MDA-MB-231乳腺癌细胞为研究对象,并以apatinib和nab-Paclitaxel处理细胞后分组:0.1 %DMSO处理为阴性对照组;10 μmol/L apatinib处理组 (APA组);经5、10、15、20 nmol/L nab-Paclitaxel 处理组 (Nab-p 5组、Nab-p 10组、Nab-p 15组和Nab-p 20组);以及10 μmol/L apatinib分别与5、10、15、20 nmol/L nab-Paclitaxel 联合处理组 (APA+Nab-p 5组、APA+Nab-p 10组、APA+Nab-p 15组和APA+Nab-p 20组)。使用乳酸脱氢酶释放测定法测定apatinib和nab-Paclitaxel对MDA-MB-231细胞诱导的细胞毒活性,结合流式细胞术分析不同处理组细胞凋亡情况,通过JC-1染色法测定不同干预方式对MDA-MB-231细胞线粒体膜电位变化 (ΔΨ_m)的影响,借助FAM-FLICA荧光成像检测caspase-8和caspase-9 活性,通过彗星试验评估apatinib和nab-Paclitaxel对非致瘤上皮细胞株MCF-10A细胞DNA损伤的影响。两组之间独立样本t检验或单向ANOVA进行比较,多组之间使用Tukey事后检验。结果细胞毒性检测结果显示,与阴性对照组相比,Nab-p 20组MDA-MB-231细胞杀伤率在24 h时接近90 %;与单药处理组 (Nab-p 5组和Nab-p 10组)相比,APA+Nab-p 5组和APA+Nab-p 10组联合处理24 h和48 h后,分别检测到约85 %和95 %细胞死亡,差异均具有统计学意义 (P 均 < 0.001)。流式细胞术统计结果显示,与Nab-p5组和Nab-p10组相比,APA+Nab-p 5组和APA+Nab-p 10组24 h时MDA-MB-231细胞凋亡率(31.8 %±1.48 %、33.25 %±1.77 %比76.11 %±1.14 %、89.4 %±1.07%)升高 (P 均 < 0.05)。线粒体膜电位检测结果表明,与对照组相比,在单药处理组中,仅APA组和Nab-p 10组24 h时去极化细胞 (12.35 %±1.05%比78.33%±1.11%、46.74%±1.75%)增多;在联用处理组中,APA+Nab-p 5组和APA+Nab-p 10组24 h时去极化细胞 (68.47%±1.94%比90.03%±1.79%)增多,差异均有统计学意义 (P 均 < 0.05)。FAM-FLICA荧光成像结果显示,相较于单一处理组,apatinib和nab-Paclitaxel联用处理组的caspase-8和caspase-9蛋白高度活化。结合彗星试验分析,apatinib和nab-Paclitaxel 干预对MCF-10A非致瘤上皮细胞株DNA完整性没有显著影响。结论 apatinib/nab-Paclitaxel联用通过内源性的线粒体功能扰动和外源性的caspase激活诱导三阴性乳腺癌细胞MDA-MB-231凋亡,发挥协同抗癌作用。     

MiR-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用分析

目的:研究Mi R-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用及机制。方法:采集从2017年1月～2019年1月,于我院确诊为正常宫颈、宫颈上皮内瘤变(CIN)、宫颈癌患者的病变组织各90例。采用逆转录多聚酶联反应(RT-PCR)法分别检测正常宫颈组织、CIN组织、宫颈癌组织中的Mi R-23a表达水平。此外,通过■转染试剂将Mi R-23a模拟物、Mi R-23a抑制物以及空白对照片段转染至宫颈癌细胞Siha中,检测转染后0 h、48 h、72 h时三组Siha细胞的增殖能力情况。另外,以RT-PCR法检测正常宫颈组织、CIN组织、宫颈癌组织中的HOXC8表达水平。结果:宫颈癌组织中Mi R-23a的相对表达量显著高于CIN组织与正常组织,且CIN组织中Mi R-23a的相对表达量显著高于正常组织(均P0.05)。Mi R-23a模拟物组Siha细胞的增殖能力显著优于Mi R-23a抑制物组与空白对照组,且空白对照组Siha细胞的增殖能力明显优于Mi R-23a抑制物组(均P0.05)。宫颈癌组织中HOXC8的相对表达量显著高于CIN组织与正常组织,且CIN组织中HOXC8的相对表达量显著高于正常组织(均P0.05)。结论:Mi R-23a可能是通过靶向下调HOXC8基因的表达,进一步促进了宫颈癌的发生、发展,这为临床宫颈癌的防治提供了新的靶点,值得临床重点关注。     

The Multifaceted Role of Long Non-Coding RNA in Gastric Cancer: Current Status and Future Perspectives

Gastric cancer (GC) is one of the major public health concerns. Long non-coding RNAs (lncRNAs) have been increasingly demonstrated to possess a strong correlation with GC and play a critical role in GC occurrence, progression, metastasis and drug resistance. Many studies have shed light on the understanding of the underlying mechanisms of lncRNAs in GC. In this review, we summarized the updated research about lncRNAs in GC, focusing on their roles in Helicobacter pylori infection, GC metastasis, tumor microenvironment regulation, drug resistance and associated signaling pathways. LncRNAs may serve as novel biomarkers for diagnosis and prognosis of GC and potential therapeutic targets. The research gaps and future directions were also discussed.     

Apatinib inhibits tumour progression and promotes antitumour efficacy of cytotoxic drugs in oesophageal squamous cell carcinoma

Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor‐2 (VEGFR‐2), inhibits the angiogenesis of tumours. The function and mechanism of apatinib in oesophageal squamous cell carcinoma (ESCC) remain unknown. In present study, we found that the development of ESCC in patients was controlled by treatment of combination of apatinib and a chemotherapeutic drug. Moreover, apatinib efficiently promotes cell apoptosis, inhibits cell proliferation, invasion, epithelial‐mesenchymal transition (EMT) and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that apatinib significantly increased vimentin protein levels, decreased Bcl2, matrix metalloproteinase 9 (MMP9), E‐cadherin, p‐Akt and p‐mTOR protein levels in ESCC cells. Furthermore, apatinib enhanced chemosensitivity of cytotoxic drugs paclitaxel (TAX), 5‐fluorouracil (5‐FU) and cisplatin (DDP) by upregulating expression of vimentin protein, and downregulating expression of Bcl2, MMP9 and E‐cadherin protein in vitro. Compared with single‐agent groups, the combination of apatinib with each chemotherapeutic drug significantly repressed tumour growth and angiogenesis through blocking the expression of Ki67 and VEGFR‐2 in vivo. Taken together, apatinib efficiently inhibits cell growth through blocking Bcl2 and Akt/mTOR pathway, and suppresses metastasis via inhibiting MMP9 and EMT in ESCC cells. Apatinib promoted antitumour effect of chemotherapeutic agents through promoting cell apoptosis and inhibiting EMT and angiogenesis in ESCC.     

阿帕替尼联合多西他赛对多线治疗晚期非小细胞肺癌患者血清肿瘤标志物、免疫功能及生活质量的影响

目的:分析阿帕替尼联合多西他赛用于多线治疗晚期非小细胞肺癌患者的临床效果。方法:选择我院2017年1月到2019年8月共86例晚期非小细胞肺癌患者为研究对象,按照随机抽签法分为对照组、观察组各43例,地塞米松预处理后,对照组仅应用多西他赛治疗,观察组联合应用阿帕替尼与多西他赛治疗,3周为1个治疗周期,均治疗4个周期。比较两组治疗前、治疗4周期后血清肿瘤标志物水平、免疫功能及生活质量及不良反应发生情况。结果:观察组治疗4周期后总缓解率为44.19%(19/43),高于对照组总缓解率23.26%(10/43)(P<0.05);治疗4周期后两组患者细胞角蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原(CEA)、糖蛋白抗原125(CA125)、鳞状上皮细胞癌抗原(SCC)水平、CD8⁺、生命质量测定量表EORTC QLQ-C30(QLQ-C30)中的功能及症状总得分均较治疗前降低,且观察组低于对照组(P<0.05);CD3⁺、CD4⁺、CD4⁺/CD8⁺水平及QLQ-C30的总体健康状况及生活质量总得分均高于治疗前,且观察组高于对照组(P<0.05),两组患者治疗期间的不良反应发生率无差异(P>0.05)。结论:阿帕替尼联合多西他赛用于多线治疗晚期非小细胞肺癌患者,可在一定程度上提高缓解率,其改善血清肿瘤标志物水平的效果更优,有助于提高患者机体免疫功能和生活质量,且短期内不会增加不良反应。     

索拉非尼与重组腺病毒H101对肝癌细胞株HepG2的作用及机制研究

目的:研究索拉非尼与重组腺病毒H101对肝癌细胞株HepG2的作用并分析其具体机制。方法:选择索拉非尼、重组腺病毒H101分别组成重组腺病毒H101组、索拉非尼组、两药联合组以及空白对照组,并分别作用于购自中国科学院上海细胞生物研究所细胞库的肝癌细胞株HepG2。采用流式细胞技术检测HepG2细胞的凋亡情况;采用Western blot法检测细胞外信号调节激酶1/2(ERK1/2)、磷酸化ERK1/2(p-ERK1/2)以及髓样细胞白血病-1(Mcl-1)蛋白相对表达量;采用酶联免疫吸附法检测不同组别细胞培养上清液中的血管内皮生长因子(VEGF)水平。结果:重组腺病毒H101组、索拉非尼组、两药联合组的G0-G1期与G2-M期细胞均明显低于空白对照组,S期细胞均明显高于空白对照组,且两药联合组较重组腺病毒H101组与索拉非尼组更明显,差异均有统计学意义(均P0.05);重组腺病毒H101组、索拉非尼组、两药联合组的HepG2细胞凋亡率明显高于空白对照组,而两药联合组又明显高于重组腺病毒H101组与索拉非尼组,差异均有统计学意义(均P0.05)。重组腺病毒H101组、索拉非尼组、两药联合组的p-ERK1/2、Mcl-1蛋白相对表达量和VEGF表达均明显低于空白对照组,而两药联合组又明显低于重组腺病毒H101组与索拉非尼组,差异均有统计学意义(均P0.05)。结论:索拉非尼、重组腺病毒H101均可抑制肝癌细胞株HepG2的增殖,并诱导其凋亡,控制VEGF表达,联合应用具有更明显的效果,其主要机制可能与二者协同作用有效抑制p-ERK1/2、Mcl-1蛋白表达有关。     

萝卜硫素通过Nrf2信号通路对大鼠草酸钙肾结石形成的作用和机制研究

摘要 目的：探究萝卜硫素通过Nrf2信号通路对大鼠草酸钙肾结石形成的作用和机制。方法：选取7~8周龄Wistar健康雄性大鼠30只,随机分为空白对照组、模型组和药物干预组。空白对照组给予正常饮用水,标准饲料;模型组给予1%乙二醇饮用水+2%氯化铵2 mL/d灌胃,标准饲料;药物干预组给予1%乙二醇饮用水+2%氯化铵2 mL/d灌胃+0.2 mg萝卜硫素腹腔注射,标准饲料。灌胃给药均连续28天。于第29天收分别集各组大鼠24 h尿液及肾脏标本,使用全自动生化分析仪检测尿液中K⁺、Na⁺、Cl⁺、Ca²⁺、Mg²⁺、P⁵⁺、Fe²⁺含量,使用ELISA法测定尿液中丙二醛( malondialdehyde,MDA)与草酸水平,使用HE染色分析大鼠肾脏标本病理损伤情况,Von Kossa染色比较各组大鼠钙盐沉积情况,免疫组化法测定谷胱甘肽(glutathione,GSH)、核因子E₂相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)、8-羟基脱氧鸟苷(8-hydroxy-2 deoxyguanosine,8-OHDG)蛋白表达水平。结果：模型组大鼠尿液P⁵⁺、Ca²⁺、草酸、MDA含量显著高于空白对照组,HE染色示模型组肾小管较空白对照组变性严重,Von Kossa染色结果显示模型组钙盐沉积较空白对照组明显增多,模型组GSH、Nrf2免疫组化评分显著低于空白对照组,8-OHdG显著高于空白对照组,差异均有统计学意义（P＜0.05）;药物干预组大鼠尿液P⁵⁺、Ca²⁺、草酸、MDA含量显著低于模型组,HE染色、Von Kossa染色显示肾小管较模型组损伤减轻,钙盐沉积较模型组减轻,免疫组化显示GSH、Nrf2蛋白表达显著高于模型组,8-OHdG显著低于空白对照组,差异均有统计学意义（P＜0.05）。结论：萝卜硫素对大鼠肾小管具有抗氧化损伤作用,可降低草酸钙晶体的释放,抑制草酸钙结石的形成,该作用可能是通过激活Nrf2蛋白及其下游信号通路实现的。     

川芎嗪联合缬沙坦治疗糖尿病肾病肾衰竭的临床疗效观察

目的:探讨川芎嗪联合缬沙坦治疗糖尿病肾病肾衰竭的临床疗效。方法:选择我院2011年1月至2013年1月收治的糖尿病肾病肾衰竭患者96例,并将其随机分为实验组和对照组,每组48例。两组患者均根据病情给予对症支持治疗,并严格控制血糖。在常规治疗基础上,实验组患者给予川芎嗪注射液240 mg,静脉滴注,1次/d,同时给予缬沙坦80 mg,口服,1次/d,21天为1个疗程;对照组患者给予缬沙坦80 mg,口服,1次/d,21天为1个疗程。1个疗程后观察两组患者的临床疗效、血液学指标、尿检指标等实验室检查。结果:治疗21天后,实验组的临床有效率达83.3%,显著高于对照组(60.4%),差异具有统计学意义(P0.05);两组空腹血糖、尿蛋白、尿素氮、血肌酐水平均较治疗前显著改善,且实验组以上指标及胆固醇水平的改善程度明显优于对照组,差异有统计学意义(P0.05)。治疗过程中,两组均无严重不良反应发生。结论:川芎嗪联合缬沙坦可以更有效地改善糖尿病肾病肾衰竭患者的临床疗效,有一定的临床应用价值。     

Long noncoding RNA DGCR5 suppresses gastric cancer progression by acting as a competing endogenous RNA of PTEN and BTG1

Long noncoding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) has been reported to correlate with a variety of cancers, with its expression pattern and potential mechanism not clarified in gastric cancer (GC). In this study, we demonstrated that DGCR5 was downregulated in cancerous tissues and plasma samples from patients with GC, and its downregulation was associated with advanced TNM stage and positive lymphatic metastasis. Plasma DGCR5 had an area under the receiver operating characteristic curve (AUC) of 0.722 for diagnosis of GC. Gain- and loss-of-function of DGCR5 revealed that DGCR5 functioned as a competing endogenous RNA for miR-23b to suppress GC cell proliferation, invasion and migration, and facilitate apoptosis by regulating PTEN and BTG1 in vitro. Furthermore, the overexpression of DGCR5 suppressed tumor growth, and inhibited the expression of miR-23b and proliferation antigen Ki-67, but increased the expression of PTEN and BTG1 in vivo. In conclusion, our results show that DGCR5 is a tumor-suppressive lncRNA that regulates PTEN and BTG1 expression through directly binding to miR-23b. This mechanism may contribute to a better understanding of GC pathogenesis and provide a potential therapeutic strategy for GC.     

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.MethodsFrom September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).ResultsTwenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34–4.66]. The median OS was 4.5 months (95%CI: 3.49–5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).ConclusionApatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.Trial registrationAHEAD-G202 ({"type":"clinical-trial","attrs":{"text":"NCT02668380","term_id":"NCT02668380"}}NCT02668380).     

Analysis of metabolome changes in the HepG2 cells of apatinib treatment by using the NMR-based metabolomics

Neovascularization is required for the growth of tumors, vascular endothelial growth factor (VEGF) and related signal pathways are important in tumor angiogenesis. Apatinib is a highly selective and potent antiangiogenesis drug targeting the receptor of VEGFR2, blocking downstream signal transduction and inhibiting angiogenesis of tumor tissue. Apatinib has a wide range of antitumor activities in vitro and in vivo, but its effect on metabolic changes has not deeply research at present. Nowadays, our research first systematically studied the metabolic changes affected by apatinib in the HepG2 cells at the half-maximal inhibitory concentration value. We used the metabolomics by using ¹H nuclear magnetic resonance (¹H-NMR) to analyze the HepG2 cell culture media. Multivariable Statistics was applied to analyze the ¹H-NMR spectra of the cell media, including principal component analysis, partial least squares discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA). Compared with the uncultured and cultured media (negative/positive control), the metabolic phenotypes were changed in the apatinib treatment with a continuous effect over time. The metabolic pathway analysis is shown that the mainly disturbed metabolic pathways pyruvate metabolism, alanine, aspartate, and glutamate metabolism and amino acid metabolism associated with them in the apatinib treatment. The differential metabolites which were identified from the reconstructed OPLS-DA loading plots also reflected in these disturbed metabolic pathways. Our works could allow us to well understand the therapeutic effect of apatinib, especially in metabolism.     

Targeting cellular microtubule by phytochemical apocynin exhibits autophagy-mediated apoptosis to inhibit lung carcinoma progression and tumorigenesis

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. Several targets have been identified for lung cancer therapy, amongst which ‘Microtubule’ and its dynamics are the most widely studied and used in therapy. Tubulin–microtubule polymer dynamics are highly sought after targets in the field of anti-cancer drug designing. Natural compounds are important sources for developing anticancer therapeutics owing to their efficacy and lower cytotoxicity. Evidence suggested that therapeutic targeting of microtubule by natural compounds is amongst the most widely used interventions in numerous cancer therapies including lung cancer.PurposeTo determine the efficacy of apocynin (a natural compound) in suppressing the progression of lung carcinoma both in vitro and in vivo, along with the identification of targets and the underlying mechanism for developing a novel therapeutic approach.MethodsWe have demonstrated themicrotubule depolymerizing role of apocynin by established protocols in cellular and cell-free system. The efficacy of apocynin to inhibit lung carcinoma progression was studied on A549 cells.The tumoricidal ability of apocynin was studied in BALB/c mice model as well.Mice were classified into 4 groups namely-group II mice as tumor control; group III-IV mice asalso tumor-induced but treated with differential apocynin doses whereas group I mice were kept as normal.ResultsApocynin, showed selective cytotoxicity towards lung cancer cells rather than normal lung fibroblast cells. Apocynin inhibited oncogenic properties including growth, proliferation (p < 0.05), colony formation (p < 0.05), invasion (p < 0.05) and spheroid formation (p < 0.05) in lung cancer cells. Apart from other established properties, apocynin was found to be a novel and potent component to bind with tubulin and depolymerize cellular microtubule network. Apocynin mediated cellular microtubule depolymerization was the driving mechanism to trigger autophagy-mediated apoptotic cell death (p < 0.05) which in turn retarded lung cancer progression. Furthermore, apocynin showed tumoricidal characteristics to inhibit lung tumorigenesis in mice as well.ConclusionTargeting tubulin-microtubule equilibrium with apocynin could be the key regulator to catastrophe cellular catabolic processes to mitigate lung carcinoma. Thus, apocynin could be a potential therapeutic agent for lung cancer treatment.