目的 探讨卵巢癌化学治疗（化疗）耐药与焦孔素E（GSDME）基因的甲基化是否有关, 以及地西他滨是否可以通过去甲基化使GSDME蛋白表达水平升高从而逆转卵巢癌化疗耐药。方法 顺铂逆浓度梯度构建SKOV-3卵巢癌耐顺铂细胞株（SKOV-3/DDP）; CCK8法检测耐药前后细胞株的半抑制浓度（IC₅₀）; 实时荧光定量甲基化特异性PCR法检测两组细胞中GSDME基因的甲基化水平; Wetern Blot检测两组细胞中GSDME的表达水平。将耐药细胞株用不同质量浓度的地西他滨处理,重复上述实验, 检测地西他滨处理前后细胞的IC₅₀、GSDME基因的甲基化水平及GSDME蛋白的表达程度。结果 与SKOV-3细胞相比, SKOV-3/DDP中GSDME基因的甲基化水平升高（P<0.01）, 同时GSDME蛋白的表达水平降低（P<0.001）; 随着地西他滨作用浓度的升高, 耐药细胞中GSDME基因的甲基化程度逐渐降低, 蛋白的表达水平逐渐升高, 细胞的IC₅₀逐渐降低：在用0.5 μg/mL地西他滨处理耐药细胞后GSDME基因的甲基化水平虽然降低（P<0.01）, 但是此时蛋白的表达水平及耐药细胞的IC₅₀均无明显改变（P>0.05）; 当地西他滨的浓度增加到1.0 μg/mL时蛋白的表达水平才明显升高（P<0.05）, 而此时细胞的IC₅₀仍未见明显降低（P>0.05）; 待药物浓度达到1.5 μg/mL时, 细胞的IC₅₀才表现出明显的下降趋势（P<0.05）。结论 GSDME的表达与卵巢癌的化疗耐药密切相关, GSDME的高甲基化水平致使其低表达可促进卵巢癌的化疗耐药。但地西他滨可以通过去甲基化使卵巢癌耐药细胞中GSDME的表达水平升高, 从而增加卵巢癌细胞对化疗药物的敏感性, 进而逆转卵巢癌化疗耐药。

Objective To explore whether drug resistance in ovarian cancer is associated with gasdermin E（GSDME） methylation, and to explore whether decitabine can reverse ovarian cancer chemoresistance by increasing GSDME protein expression levels through demethylation．Methods The cisplatin-resistant cell line（SKOV-3/DDP）was constructed by inverse concentration gradient of cisplatin．Semi-inhibitory concentration（IC₅₀）of cell lines after drug resistance was detected using the CCK8 assay．Real-time fluorescence quantitative methylation-specific PCR was used to detect the methylation level of GSDME gene in the two groups of cells．Wetern Blot was used to detect the expression level of GSDME in the two groups of cells．Drug-resistant cell lines were treated with different concentrations of the demethylating drug decitabine．Experiments above were repeated to detect the methylation degree of IC₅₀ and GSDME genes and the expression level of GSDME protein in drug-resistant cells before and after decitabine treatment．Results Compared with SKOV-3 cells, the methylation level of GSDME gene in SKOV-3/DDP was significantly increased（P<0.01）, while the expression level of GSDME protein was significantly decreased（P<0.001）．With the increase of decitabine concentration, the methylation degree of GSDME gene in drug-resistant cells was gradually decreased, the expression level of protein was gradually increased, and the IC₅₀ of cells was gradually decreased：the methylation level of GSDME gene was decreased after 0.05 μg/mL decitabine treatment（P<0.01）, but there were no significant changes in protein expression level and IC₅₀ of drug-resistant cells（P>0.05）．The protein expression level was significantly increased when the concentration of local citabine was increased to 0.10 μg/mL（P<0.05）, while the IC50 of the cells was not significantly decreased（P>0.05）．When the drug concentration reached 0.15 μg/mL, he IC₅₀ of the cells showed a significant downward trend（P<0.05）．Conclusions The expression of GSDME is closely related to chemoresistance in ovarian cancer, and the low expression of GSDME due to its high methylation level can promote chemoresistance in ovarian cancer．However, decitabine can increase the expression level of GSDME in drug-resistant ovarian cancer cells through demethylation,thereby increasing the sensitivity of ovarian cancer cells to chemotherapeutic drugs, and then reversing the chemoresistance of ovarian cancer．

目的 探究改良Miccoli手术治疗单侧甲状腺癌（TC）患者的效果及其对机体创伤应激反应的影响。方法 选取新密市中医院200例单侧TC患者（2021年3月—2023年3月）,按随机数字表法分两组。A组100例接受改良Miccoli手术治疗,B组100例接受开放根治术（OT）治疗。对比两组围术期指标、喉返神经损伤发生情况、美学效果、手术前后肿瘤指标[细胞角蛋白19片段抗原（Cyfra21.1）、半乳糖凝集素3（Gal-3）、可溶性白细胞介素-2受体（sIL-2R）]、创伤应激反应指标[去甲肾上腺素（NE）、肾上腺素（E）、皮质醇（Cor）]水平。结果 A组切口长度为（2.05±0.13）cm,短于B组的（7.11±0.49）cm,住院及手术用时分别为（3.12±0.44）d、（53.48±7.52）min,均短于B组的（5.22±0.81）d、（76.81±11.39）min,术中失血量、引流量分别为（19.24±2.66）mL、（21.47±3.41）mL,均少于B组的（45.08±5.75）mL、（64.82±7.24）mL,组间比较差异有统计学意义（P<0.05）;A组喉返神经损伤总发生率为2.00%（2/100）,低于B组的12.00%（12/100）,组间比较差异有统计学意义（P<0.05）;A组美容总满意度为97.00%（97/100）,高于B组的73.00%（73/100）,差异有统计学意义（P<0.05）;A组术后3个月血清Cyfra21.1、Gal-3水平分别为（1.78±0.26）ng/mL、（6.14±1.64）ng/mL,均高于B组的（1.55±0.21）ng/mL、（5.39±1.28）ng/mL,血清sIL-2R水平为（375.36±20.12）μg/mL,低于B组的（427.13±23.18）μg/mL,组间比较差异有统计学意义（P<0.05）;A组术后1 d血清NE、E、Cor水平分别为（0.73±0.17）mmol/L、（0.49±0.10）mmol/L、（185.46±22.95）μg/L,均低于B组的（0.96±0.19）mmol/L、（0.81±0.22）mmol/L、（272.53±32.41）μg/L,组间比较差异有统计学意义（P<0.05）。结论 相较于OT治疗单侧TC患者,经改良Miccoli手术治疗更有助于提升美学效果,减少喉返神经损伤,优化围术期指标,抑制肿瘤进展,且机体产生的创伤应激反应更轻微。

Objective To investigate the effect of modified Miccoli surgery on patients with unilateral thyroid cancer（TC）and its impact on the body’s traumatic stress response．Methods The data of 200 patients with unilateral TC in Xinmi City Hospital of Traditional Chinese Medicine from March 2021 to March 2023 were retrospectively collected and divided into two groups according to different surgical protocols．A hundred patients treated with modified Miccoli surgery were classified as group A and 100 patients treated with open radical surgery（OT）were classified as group B．The perioperative indicators,incidence of recurrent laryngeal nerve injury,aesthetic effect,as well as tumor indicators [cytokeratin 19 fragment antigen（Cyfra21.1）,galectin-3（Gal-3）,soluble interleukin -2 receptor（sIL-2R）] and trauma stress response indicators [norepinephrine（NE）,epinephrine（E）,and cortisol（Cor）] before and after surgery were compared between the two groups．Results The incision length of group A was（2.05±0.13）cm,which was shorter than that of group B [（7.11±0.49）cm]．The duration of hospitalization and operation of group A were（3.12±0.44）d and（53.48±7.52）min,respectively,which were shorter than those of group B [（5.22±0.81）d and（76.81±11.39）min]．The intraoperative blood loss and drainage volume were（19.24±2.66）mL and（21.47±3.41）mL,respectively,which were lower than those in group B [（45.08±5.75）mL and（64.82±7.24）mL],and the difference was statistically significant（P<0.05）．The total incidence of recurrent laryngeal nerve injury in group A was 2.00%（2/100）,lower than that in group B [12.00%（12/100）],and the difference was statistically significant（P<0.05）．The total satisfaction of group A was 97.00%（97/100）,higher than that of group B [73.00%（73/100）],and the difference was statistically significant（P<0.05）．Serum Cyfra21.1 and Gal-3 levels in group A were（1.78±0.26）ng/mL and（6.14±1.64）ng/mL,respectively,higher than those in group B [（1.55±0.21）ng/mL and（5.39±1.28）ng/mL]．Serum sIL-2R level was（375.36±20.12）μg/mL,lower than that of group B [（427.13±23.18）μg/mL],and the difference was statistically significant（P<0.05）．The serum levels of NE,E and Cor in group A were（0.73±0.17）mmol/L,（0.49±0.10）mmol/L and（185.46±22.95）μg/L,respectively．They were lower than（0.96±0.19）mmol/L,（0.81±0.22）mmol/L and（272.53±32.41）μg/L in group B,and the differences were statistically significant（P<0.05）．Conclusions Compared to OT treatment for unilateral TC patients,the modified Miccoli surgery is more helpful in improving aesthetic effects,reducing damage to the recurrent laryngeal nerve,optimizing perioperative indicators,inhibiting tumor progression,and producing less traumatic stress response to the body．

目的 探讨导航护士主导的三级质控在胸腔镜肺癌切除术患者加速康复中的应用效果。方法 选取2020年6月—2023年6月周口市中心医院收治的106例肺癌患者,应用随机数字表法分为观察组（n=53）与对照组（n=53）。患者均采取胸腔镜肺癌切除术治疗,对照组实施常规的术前、术中及术后相关围术期护理,观察组在常规围术期护理基础上增加导航护士主导的三级质控护理。对比两组住院时间、术后并发症和护理前后世界卫生组织生活质量-100量表（WHOQOL-100）及癌因性疲乏程度（PFS）,最后对比两组的护理满意度。结果 观察组首次排气时间、首次下床时间、术后疼痛视觉模拟量表（VAS）评分、术后住院时间均优于对照组（P<0.05）;观察组并发症发生率低于对照组（P<0.05）;干预后两组WHOQOL-100评分升高、PFS评分降低,观察组均优于对照组（P<0.05）;观察组护理满意度高于对照组（P<0.05）。结论 对胸腔镜肺癌切除术患者,采取导航护士主导的三级质控管理的加速康复护理,可促进患者术后肠胃功能恢复,缩短住院时间,减轻术后疼痛感与减少并发症,在改善患者癌因性症状的同时,提升其生活质量,提高患者护理满意度。

Objective To explore the application effect of three-level quality control led by navigation nurses in accelerating rehabilitation of patients undergoing thoracoscopic lung cancer resection．Methods A total of 106 lung cancer patients admitted to our hospital from June 2020 to June 2023 were selected and randomly divided into an observation group（n=53）and a control group（n=53）using a random number table method．All patients were treated with thoracoscopic lung cancer resection,while the control group received routine preoperative,intraoperative and postoperative perioperative care,the observation group received a three-level quality control nursing led by navigation nurses in addition to routine perioperative care．The length of hospitalization,postoperative complications,WHOQOL-100 and PFS before and after care,and the nursing satisfaction of the two groups were compared．Results The observation group had significantly shorter first exhaust time,first time out of bed,postoperative visual analogue scale（VAS）score and postoperative hospital stay compared to the control group（P<0.05）．The incidence of complications in the observation group was lower than that in the control group（P<0.05）．After intervention,the WHOQOL-100 scores of both groups increased,and the observation group was higher than the control group．The PFS score decreased,and the observation group was lower than the control group（P<0.05）．The nursing satisfaction of the observation group was significantly higher than that of the control group（P<0.05）．Conclusions Adopting a three-level quality control management led by navigation nurses to accelerate rehabilitation care for patients undergoing thoracoscopic lung cancer resection can promote postoperative recovery of gastrointestinal function,reduce hospitalization time,reduce postoperative pain and complications,improve cancer related symptoms,improve their quality of life and increase patients nursing satisfaction．

目的 探讨超声弹性成像联合高频超声在甲状腺乳头状癌诊断中的应用价值。方法 2022年1月—2023年6月选择在中国人民解放军联勤保障部队第九九〇医院诊治的疑似甲状腺乳头状癌患者82例,所有患者均给予超声弹性成像联合高频超声检查,记录超声特征。所有患者均行病理检查,并以病理检查作为判断的金标准。结果 在82例患者中,病理诊断为甲状腺乳头状癌48例（癌性组）,占比58.54%;甲状腺良性结节34例（良性组）,占比41.46%。癌性组的形态异常、后方回声衰减、钙化、晕环征、边界不清晰、内部低回声等超声征象占比为81.25%、83.33%、83.33%、83.33%、81.25%、81.25%,高于良性组的52.94%、47.06%、47.06%、41.18%、47.06%、52.94%（P<0.05）。癌性组的收缩期最高流速低于良性组（P<0.05）,阻力指数、搏动指数与良性组相比有提高（P<0.05）。癌性组的弹性成像评分多为3~4分,良性组多为2分,两组比较差异有统计学意义（P<0.05）。超声弹性成像联合高频超声判断为甲状腺乳头状癌47例,诊断中的灵敏度与特异度分别为97.92%（47/48）和100.00%（34/34）。结论 甲状腺乳头状癌在超声上多表现为血流信号异常、钙化、后方回声衰减、晕环征等特征,超声弹性成像评分多为3~4分,超声弹性成像联合高频超声在其诊断中具有较高的应用价值。

Objective To explore the application value of ultrasound elastography combined with high-frequency ultrasound in the diagnosis of papillary thyroid cancer（PTC）．Methods From January 2022 to June 2023,82 patients with suspected PTC were treated at Chinese People’s Liberation Army Joint Logistics Force 990 Hospital．All patients were given ultrasound elastography combined with high-frequency ultrasound examination to record ultrasound features．All cases were given pathological examination,and the pathological examination were used as the gold standard for diagnosis．Results Among the 82 patients,48 were PTC（cancerous group）,accounting for 58.54%;and the other 34 were benign thyroid nodules（benign group）,accounting for 41.46%．The proportion of morphological abnormalities,posterior echo attenuation,calcification,halo ring signs,unclear boundary and internal hypoechoics in cancerous group were 81.25%,83.33%,83.33%,83.33%,81.25% and 81.25%,which were significantly higher than 52.94%,47.06%,47.06%,41.18%,47.06% and 52.94% in the benign group（P<0.05）．The highest systolic flow velocity in the cancerous group was significantly less than that in the benign group（P<0.05）,and the resistance index and pulse index were also significantly higher compared with the benign group（P<0.05）．The elastography score were mostly 3~4 in the cancerous group and 2 in the benign group,with a significant difference between the two groups（P<0.05）．Forty-seven cases of PTC were diagnosed by ultrasound elastography combined with high frequency ultrasonography,and the sensitivity and specificity in diagnosis were 97.92%（47/48）and 100.00%（34/34）,respectively．Conclusions PTC is often characterized by abnormal blood flow signals,calcification,posterior echo attenuation,halo sign and so on．The ultrasound elastography score is usually 3~4 points．Ultrasonic elastography combined with high frequency ultrasound has high value in diagnosis of PTC．

目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌（HNSCC）的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗（化疗）对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A（KLRC1）主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E（P<0.01）,与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关（P<0.01）。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平（P<0.01）;化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用（P=0.013）。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。

Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma（HNSCC）．Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases．The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry．Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel．Results NKG2A（KLRC1）was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes．The high expression of NKG2A/HLA-E in HNSCC tumors（P<0.01）were closely related to poor prognosis．NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints（P<0.01）．Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes（P<0.01）．Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC（P=0.013）．Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC．

目的 评估多种气道湿化方法对喉癌患者术后气道湿化的效果。方法 检索PubMed、Cochrane、Embase、Web of Science、Ovid、中国知网、万方、CBM、Google Scholar等数据库和网站,检索时限为建库至2023年2月。搜集关于喉癌患者术后不同气道湿化方法的随机对照试验,采用JBI2016年随机对照试验RCT评价标准评价文献质量。使用ADDIS1.16.5软件进行网状Meta分析。结果 纳入18篇研究,共1 596例患者。结果显示,镇痛泵持续泵入与注射器间断滴入、喷雾瓶间断喷雾在痰痂形成方面比较差异有统计学意义[OR（95%CI）=537.70（4.18,124 511.88）、0（0,0.52）,P<0.05];湿化满意度方面,注射器间断滴入与喷雾瓶间断喷雾比较差异有统计学意义[OR（95%CI）=8.55（1.40,73.35）,P<0.05];其余比较差异无统计学意义（P>0.05）。概率排序显示,降低肺部感染、黏膜出血和痰痂形成、痰液黏稠度、咳嗽和湿化不满意的发生,最优方法分别为湿化泵持续泵入、镇痛泵持续泵入、MR400湿化器和输液器持续泵入。结论 综合网状Meta分析及概率排序结果,考虑到喉癌患者术后早期下床活动,推荐便携式持续湿化方法。

Objective To access the effects of multiple airway humidification methods for postoperative patients with laryngeal cancer．Methods PubMed,Cochrane Library,EMbase,Web of Science,Ovid,China National Knowledge Infrastructure,Wanfang database,CBM and Google Scholar were searched systematically from establishment to February 2023,respectively．Related randomized controlled trials on airway humidification for postoperative patients with laryngeal cancer was analyzed and the quality of the literature was assessed using the JBI 2016 RCT evaluation．The network Meta analysis was performed using ADDIS 1.16.5 softwares．Results A total of 18 articles and 1596 patients were inciuded．The results showed that the analgesia pump continued to pump into the airway compared with the syringe intermittently drip and the spray bottle intermittent spray was statistically different in the formation of sputum[OR（95%CI）=537.70（4.18,124 511.88）,0（0,0.52）,P<0.05]．In terms of satisfaction of wetness,the difference between the intermittent drop of the syringe and the intermittent spray of the spray bottle was statistically different[OR（95%CI）=8.55（1.40,73.35）,P<0.05],the others were not statistically different（P>0.05）．Probability ranking table shows that the optimal methods were the humidification pump continues to pump into the airway,the analgesia pump continued to pump into the airway,the MR400 humidifier and the infusion set continuously pumped into the airway,which were beneficial to the reduction in pulmonary infection,tracheal mucosal hemorrhage and formation of phlegm callus,the degree of sputum viscosity,cough and unsatisfactory wetness．Conclusions Based on the comprehensive mesh meta-analysis and probability ranking results,a portable continuous humidification method is recommended considering the early post-operative activities of laryngeal cancer patients．

目的 开发适合中国肾癌患者的生命质量测定量表的特异模块。方法 采用议题小组和核心小组的程序化决策方式,提出条目池,形成初步量表,采用医生及患者重要性评分法、相关系数法、变异度法、因子分析法和克朗巴赫系数α对20例肾癌患者和20名医护人员进行的数据进行统计分析。结果 经过上述方法进行筛检,结合专家小组的建议,最终得到含有11个条目的肾癌生命质量测定量表的特异模块。结论 肾癌的生命质量测定量表特异模块严格按照程序执行,具有较好的内容效度。

Objective To develop the specific module of the quality of life instruments for patients with renal cancer（QLICP-RE）．Methods With the structured group（nominal group and focus group）methods,the item pool was put forward and a preliminary instrument was formed．The data from 20 renal cancer patients and 20 doctors/nurses were analyzed by statistical procedures．Doctors and patients' importance rating procedure,correlation analysis,method of coefficient of variation,factor analysis,and Cronbach's α．Results By above statistical procedures and advises of expert panel,11-items of the specific module were formed finally．Conclusions The specific module of QLICP-RE developed on the strict procedures has good content validity and representativeness．

目的 探讨多梳蛋白SUZ12对肝细胞肝癌（HCC）细胞增殖、血管生成拟态形成和人脐静脉内皮细胞（HUVECs）血管生成的影响。方法 分别利用MTT比色法及体外血管生成实验检测SUZ12表达水平改变对HCC细胞SMMC-7721、Hep3B增殖、血管生成拟态形成和HUVECs血管生成的影响。结果 MTT结果显示,在HCC细胞中分别敲低或过表达SUZ12均对HCC细胞的增殖能力无明显影响。将SUZ12低表达HCC细胞与HUVECs共培养后,HCC细胞的血管生成拟态管样结构形成增多。此外,将SUZ12敲低组HCC细胞的培养上清用于培养HUVECs后,HUVECs的血管生成拟态管样结构形成也明显增多。结论 SUZ12对HCC细胞的增殖无影响,其在HCC中可抑制HCC细胞和HUVECs的血管生成拟态管样结构形成。上述结果提示SUZ12可能通过调控HCC细胞及HUVECs的血管生成发挥抑癌作用。

Objective To investigate the effects of SUZ12 on cell proliferation of hepatocellular carcinoma（HCC）,vasculogenic mimicry formation and human umbilical vein endothelial cells（HUVECs）angiogenesis．Methods MTT assay was performed to detect the proliferation of SMMC-7721 and Hep3B cells．The effects of SUZ12 on the angiogenesis of HCC cells and HUVECs cells were studied by in vitro angiogenesis experiment．Results The result of MTT assay showed that SUZ12 knockdown or overexpression in HCC cells had no significant effect on the proliferation of HCC cells．We found that when HCC cells with low SUZ12 expression were co-cultured with HUVECs cells,the formation of vasculogenic mimicry tubular structures in HCC cells increased．In addition,we also found that after the culture supernatant of HCC cells in the SUZ12 knockdown group was used to culture HUVECs cells,the formation of vasculogenic mimicry tubular structures in HUVECs cells also increased significantly．Conclusions SUZ12 has no effect on the proliferation of HCC cells,but it can inhibit the formation of vasculogenic mimicry tubular structures in HCC cells and HUVECs cells．These results suggest that SUZ12 plays a role in cancer inhibition by regulating the angiogenesis of HCC cells and HUVECs cells．

目的 探讨转录因子E盒结合锌指蛋白1（ZEB1）、溶酶体相关膜蛋白5（LAMP5）在结直肠癌组织中的表达水平分析及预后预测价值。方法 选取驻马店市中心医院2018年1月—2020年1月收治的120例结直肠癌患者,分别采取所有患者的结直肠癌组织及癌旁组织进行免疫组化染色,对比ZEB1、LAMP5阳性率。对比不同病理特征结直肠癌患者ZEB1、LAMP5表达水平差异。对所有患者进行4年随访,依照随访结果将患者分为2个亚组,即预后不良组（n=35）和预后良好组（n=85）,对比两组患者一般临床特征及ZEB1、LAMP5表达水平,应用Logistic回归分析ZEB1、LAMP5对结直肠癌预后的预测价值。结果 结直肠癌组织ZEB1、LAMP5相对表达量（38.26±5.49、26.77±3.85）与ZEB1、LAMP5阳性率（86.67%、72.22%）高于癌旁组织（15.46±2.54、8.04±1.59、23.33%、15.56%],对比差异有统计学意义（t=41.280,χ²=25.437;t=49.255,χ²=16.071;P<0.05）。不同TNM分期[Ⅰ~Ⅱ期（35.55±4.13）、Ⅲ~Ⅳ期（42.32±4.75）]、淋巴结转移患者[是（44.37±4.28）、否（35.84±3.77）]、肿瘤分化程度[低分化（35.27±4.57）、中高分化（41.34±4.60）]ZEB1相对表达量对比差异有统计学意义（t=-8.281,P<0.001;t=10.746,P<0.001;t=-7.253,P<0.001）;不同TNM分期[Ⅱ期（24.88±3.37）、Ⅲ~Ⅳ期（29.61±2.57）]、淋巴结转移[是（30.72±2.19）、否（25.21±3.19）]、肿瘤分化程度[低分化（24.57±3.62）、中高分化（29.04±2.55）]患者LAMP5相对表达量对比差异有统计学意义（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,<0.001）;预后良好组与预后不良组患者性别、年龄、大体类型、肿瘤大小对比差异无统计学意义（P>0.05）,预后良好组与预后不良组患者TNM分期、淋巴结转移、肿瘤分化程度、ZEB1、LAMP5阳性比例对比差异有统计学意义（P<0.05）;Logistic回归分析显示：淋巴结转移、ZEB1阳性、LAMP5阳性为结直肠癌预后不良独立预测因素（P<0.05）。结论 ZEB1、LAMP5在结直肠癌组织中呈现高表达状态,且与结直肠癌的发生有关,同时ZEB1、LAMP5是结直肠癌预后的独立预测因素,两者有希望成为结直肠癌的治疗靶点。

Objective To investigate the expression levels and prognostic value of transcription factor E-box binding to zinc finger protein 1（ZEB1）and lysosomal associated membrane protein 5（LAMP5）in colorectal cancer tissues. Methods A total of 120 colorectal cancer patients admitted to a hospital from January 2018 to January 2020 were selected．Immunohistochemical staining was performed on the colorectal cancer tissues and adjacent tissues of all patients,and the positivity rates of ZEB1 and LAMP5 were compared．The expression levels of ZEB1 and LAMP5 in colorectal cancer patients with different pathological characteristics were compared．All patients were followed up for 4 years and divided into two subgroups based on the follow-up results,namely the poor prognosis group（n=35）and the good prognosis group（n=85）．The general clinical characteristics and expression levels of ZEB1 and LAMP5 were compared between the two groups．Logistic regression analysis was used to evaluate the predictive value of ZEB1 and LAMP5 for the prognosis of colorectal cancer. Results The relative expression level of ZEB 1 and LAMP 5 in colorectal cancer tissues [（38.26±5.49）,（26.77±3.85）] and the positive rate of ZEB 1 and LAMP 5（86.67%,72.22%）were significantly higher than that of adjacent tissues [（15.46±2.54）,（8.04±1.59）,23.33%,15.56%],the contrast difference was statistically significant（t=41.280,χ²=25.437;t=49.255,χ²=16.071;P<0.05）．Relative ZEBI expression levels in different TNM stages [I-Ⅱstage（35.55±4.13）,Ⅲ-Ⅳstage（42.32±4.75）],lymph node metastasis[Yes（44.37±4.28）,No（35.84±3.77）],degree of tumor differentiation [hypodifferentiated（35.27±4.57）,and middle or high differentiated（29.04±2.55）],those differences were statistically significant（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001）．The relative expression of LAMP 5 between different TNM stages [I-Ⅱstage（24.88±3.37）,Ⅲ-Ⅳstage（29.61±2.57）],lymph node metastasis [yes（30.72±2.19）,no（25.21±3.19）],degree of tumor differentiation [hypodifferentiated（24.57±3.62）,and middle or high differentiated（29.04±2.55）],the contrast was statistically significant（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001）．There were no differences in gender,age,gross type,and tumor size between the good prognosis group and the poor prognosis group（P>0.05）,while there were differences in TNM stages,lymph node metastasis,tumor differentiation degrees,ratio of ZEB 1 and LAMP 5（P<0.05）．Logistic regression analysis showed that TNM stage,lymph node metastasis,ZEB 1 positive,and LAMP 5 positive were independent predictive factors of poor prognosis in colorectal cancer（P<0.05）. Conclusions ZEB1 and LAMP5 are highly expressed in colorectal cancer tissues and closely related to the occurrence and development of colorectal cancer．ZEB1 and LAMP5 are independent prognostic factors for colorectal cancer,and they have the potential to become therapeutic targets for colorectal cancer．

目的 评价不同间变性淋巴瘤激酶（ALK）抑制剂联合安罗替尼治疗非小细胞肺癌（NSCLC）的疗效。方法 收集ALK突变阳性NSCLC患者的临床资料,筛选服用ALK抑制剂疗效不佳再加用安罗替尼的病例。根据不同的用药方案分为阿来替尼+安罗替尼,塞瑞替尼+安罗替尼和克唑替尼+安罗替尼三个组别。记录患者联合用药前最近一次的影像学检查结果,并以此为基线按Recist1.1评价疗效,以病情进展、患者死亡、停药、改变治疗方案为终点计算各组患者的无事件生存期（EFS）,收集肿瘤标志物、血常规和肝功、心功能、肾功能生化检测等指标数据,统计分析患者联合用药前后各项指标的变化。结果 经筛选,共纳入49例患者的临床数据。阿来替尼+安罗替尼组有23例,疾病控制率（DCR）为86.96%;平均EFS为（10.8±3.6）个月,中位EFS为8.3个月;塞瑞替尼+安罗替尼组有14例,DCR为71.43%;平均EFS为（6.5±2.9）个月,中位EFS为5.6个月;克唑替尼+安罗替尼组有12列,DCR为66.67%;平均EFS为（7.7±3.2）个月,中位EFS为7.2个月。阿来替尼+安罗替尼组的平均EFS长于另外两组（P<0.05）。各研究组肿瘤标志物仅有CyFra21-1在克唑替尼+安罗替尼组在联合用药后升高（P<0.05）,生化检测和血常规指标在用药前后差异无统计学意义（P>0.05）。结论 ALK抑制剂与安罗替尼联用,疗效最好为阿来替尼,其次为塞瑞替尼,最后为克唑替尼。三种ALK抑制剂与安罗替尼联用后,均未导致心、肝、肾功能和血细胞损害。

Objective To evaluate the efficacy of different anaplastic lymphoma kinase（ALK）inhibitors combined with anlotinib in the treatment of non-small cell lung cancer（NSCLC）. Methods Clinical data of drug resistant NSCLC patients with ALK positive mutation was collected who were treated with ALK inhibitors and anlotinib synchronously．According to different regimens,three groups were set,alectinib+anlotinib,ceritinib+anlotinib,and crizotinib+anlotinib．The latest imageological examination results of the patient before the synchronous therapy was set as the baseline to evaluate the therapeutic effect according to Recist1.1．The event free survival（EFS）of each group was calculated with disease progression,patient death,treatment discontinuation and changing regimen as endpoints．Data of tumor markers,hematology test,liver function,cardiac function,renal function biochemical examination was collected and analyzed statistically before and after the combination therapy,with P<0.05 as the statistically significant difference. Results After screening,clinical data of 49 patients were collected．Twenty-three patients in the alectinib+anlotinib group,with a disease control rate（DCR） of 86.96%;mean EFS was（10.8±3.6）months,median EFS of 8.3 months;14 patients in the ceritinib+anlotinib group,with a DCR of 71.43%,mean EFS was（6.5±2.9）months,median EFS was 5.6 months;12 patients in the crizotinib+anlotinib group,with a DCR of 66.67%,mean EFS was（7.7±3.2）months,median EFS was 7.2 months．EFS of alectinib+anlotinib group was longer significantly than the other two groups（P<0.05）．Only CyFra21-1,increased significantly after the combination of crizotinib and anlotinib（P<0.05）．No statistically significant difference in biochemical test and hematology test before and after the treatment（P>0.05）． Conclusions The therapeutic effect of ALK inhibitors with anlotinib was ordered,alectinib being the most effective,followed by ceritinib and finally crizotinib．The combination of ALK inhibitors with anlotinib did not cause any abnormal results in the examination of heart,liver,kidney and blood cells．