China has a heavy burden of hepatocellular carcinoma, which is a serious threat to people′s life and health. However, the available drugs for advanced hepatocellular carcinoma in the past are limited and the efficacy is not satisfactory. In recent years, immunotherapy has a significant effects in some tumors. The authors introduce the efficacy of restart immunotherapy on an advanced hepatocellular carcinoma patient undergoing interruption of treatment due to corona virus disease 2019, in order to provide references for the diagnosis and treatment of this kind of patients.

目的 观察白藜芦醇(Rec)对脓毒症大鼠急性肺损伤的保护作用,探讨其相关机制.方法 80只SD大鼠随机分为假手术组(20只)和造模组(60只),造模大鼠术后随机分为脓毒症模型组、低剂量Rec干预组(20mg/kg)和高剂量Rec干预组(40mg/kg),每组20只,干预组尾静脉注射无菌白藜芦醇,其余尾静脉注射等量0.9％NaCl注射液.ELISA法检测TNF-α和IL-6表达.取左肺下叶组织制作HE病理切片,显微镜下进行肺损伤评分.Western blot法检测肺组织细胞核P65的表达.结果 假手术组、脓毒症模型组和低剂量Rec干预组和高剂量Rec干预组的肺损伤评分为1.04±0.22分、12.25±2.14分、8.63±1.36分和5.18±1.13分,4组间比较差异有统计学意义(P<0.01).造模24h后低剂量和高剂量Rec干预组TNF-α和IL-6表达显著低于脓毒症模型组(P<0.01),高剂量Rec干预组TNF-α和IL-6表达显著低于低剂量Rec干预组(P<0.01).肺组织细胞核P65相对灰度值在假手术组、脓毒症模型组、低剂量Rec干预组和高剂量Rec干预组分别为0.14±0.03、0.82±0.15、0.56±0.09、0.25±0.06,各组间比较,差异有统计学意义(P<0.01).结论 白藜芦醇可以下调脓毒症大鼠肺组织细胞核P65蛋白的表达,抑制核因子κB(NF-κB)炎性通路,对肺损伤具有保护作用.

目的 探讨本地三甲医院急诊科人力资源管理强度对护士道德推脱倾向的影响.方法 便利抽样武汉市4家三甲医院2017年1月～2018年1月急诊科护士218例,调查其基本情况;采用人力资源管理量表调查急诊科人力资源管理强度,道德推脱倾向量表调查护士道德推脱倾向.结果 4家医院急诊科人力资源管理强度得分为(52.14±21.71)分,急诊科护士的道德推脱倾向得分为(71.52±27.83)分,急诊科人力资源管理强度与护士道德推脱倾向呈显著负相关(P＜0.01).多元线性回归分析显示,职称、学历、月收入、工作时间、人力资源管理强度均是急诊科护士道德推脱倾向显著影响因素(P＜0.05).结论 本地三甲医院急诊科人力资源管理强度能够降低护士道德推脱倾向,建议医院及急诊科应提高人力资源管理水平,提高急诊科护士职业道德水平,降低其道德推脱倾向.

目的:探讨微小RNA-30e(miR-30e)对胃癌细胞迁移和侵袭能力的影响及可能的作用机制.方法:利用Transwell实验和细胞划痕实验检测胃癌细胞系BGC823侵袭和迁移的能力;以脂质体包裹合成miR-30e转染至BGC823细胞,并设空白载体作为对照组;Real-time PCR分别检测实验组和对照组细胞中miR-30e的表达.RT-PCR检测过表达miR-30e后对上皮细胞间充质转化(EMT)相关标记分子Snail、Vimentin、N-cadherin和E-cadherin表达的影响.结果:miR-30e转染至胃癌细胞后,抑制EMT通路主要因子Snail,Vimentin和N-cadherin mRNA和蛋白质表达,而增加E-cadherin的mRNA和蛋白质表达;miR-30e通过TGF-β对BGC823细胞的侵袭和迁移能力有明显的抑制作用.结论:miR-30e可能是肿瘤细胞EMT过程的关键靶标靶点,阻断EMT过程,可以抑制胃癌细胞的侵袭和迁移能力.

Radiation cystitis is one of the major complications following radiotherapy for cervical cancer. However, spontaneous intraperitoneal bladder rupture as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare. Case presentation: We report a 52-year-old patient who received radiation therapy for cervical cancer 15 years prior to presentation. Eight years prior to presentation, she developed recurrent abdominal distension, oliguria, and ascites. Following ascites drainage and supportive treatment, all symptoms were relieved. However, all symptoms subsequently recurred every few months. The patient underwent exploratory laparotomy twice. The first exploratory laparotomy in July 2015 found no specific abnormalities. The second exploratory laparotomy in November 2016 found an intraperitoneal bladder rupture, and the patient underwent surgical repair. The ascites subsequently resolved. Conclusion: The occurrence of spontaneous intraperitoneal bladder rupture after radiation therapy for cervical cancer is rare. The prognosis is good when diagnosis and treatment are prompt.

目的 建立以信息-动机-行为技巧模型(IMB)为基础的心肌梗死急诊经皮冠状动脉介入(PCI)术后护理管理模式,探讨其对改善患者预后的价值.方法 将2016年3月-2017年3月成功接受急诊PCI的120例心肌梗死患者随机均分为观察组和对照组,各60例.对照组采用常规延续护理模式进行干预,观察组采用以IMB为基础的延续护理模式进行干预.出院12个月后,对比二组患者服药依从性、戒烟、血糖、血压及血脂达标情况、心脏不良事件再发情况.结果 观察组出院9个月、12个月时服药依从性明显好于对照组,观察组出院12个月时,血糖、血压及血脂达标率均明显高于对照组,观察组出院12个月内心绞痛、心肌梗死再发率明显低于对照组,上述差异均有统计学意义(P＜0.05).结论 以IMB为基础的延续护理模式应用于心肌梗死急症PCI术后患者,能够有效改善患者用药依从性,提升其血糖、血压及血脂控制效果,并改善其预后.

目的 探究多样化培训方式对新入职护士岗位胜任力的影响.方法 选取我院50名新入职护士作为研究对象,采取多样化培训方式对所有护士进行培训,培训上岗后抽取6名模拟病人纳入观察组实施护理干预,并选取既往采用常规培训方式进行岗前培训的50名新入职护士及6名模拟病人作为对照组,比较两组各方面考核指标.结果 观察组50名护士经培训后理论考核成绩、操作考核成绩及综合考核成绩均、岗位胜任能力优良率、护士培训满意率、护士中国护士核心能力量表评分均高于对照组(P均＜0.05);观察组新入职护士思维能力、病情观察能力、应变处理能力、护患沟通能力等临床护理能力评分均优于对照组(P均＜0.05).结论 多样化培训方式对新入职护士岗位胜任力有积极影响.

目的 分析急诊科规范化培训(规培)护士基础生命支持培训中应用站点式工作坊的效果.方法 选取我院2017年4月-2018年4月接受规培的急诊科护士80名,采用奇偶法分为研究组和参照组,每组各40名,参照组护士给予传统带教授课方式进行基础生命支持培训,研究组给予站点式工作坊的方式进行基础生命支持培训,对比两组护士培训前后实际操作能力、理论知识掌握、培训方式满意度等.结果 研究组护士对培训方式的满意度为97.50％,高于参照组的75.00％,组间对比差异有统计学意义(P＜0.05);研究组与参照组培训前实际操作能力、理论知识掌握评分对比差异无统计学意义(P＞0.05);培训后各项评分高于参照组,组间对比差异有统计学意义(P＜0.05).结论在急诊科规陪护士基础生命支持培训中应用站点式工作坊,能够全面提高护士专业技能及实际操作水平,从而全面提高总体急诊科护理质量.

目的 研究在急诊规培生临床带教中应用现场急救情景教学的临床作用.方法 此次数据统计参考带教方式的不同,将2017年3月—2018年3月在本医院实习的80名急诊科规培生平均分成参照组(n=40)与实验组(n=40).将我院传统的教学法带教纳入参照组,将我院现场急救情景教学纳入实验组,分析对比实验组和参照组经不同带教之后急诊科规培生优良率,操作技能、理论知识、临床案例分析得分.结果 实验组急诊科规培生优良率,操作技能、理论知识、临床案例分析得分,与参照组各项指标比较,差异具有统计学意义(P＜0.05).结论 将现场急救情景教学应用在急诊规培生临床带教中的作用比较突出.

Objective The aim of the study was to evaluate the role of postoperative sequential chemotherapy and radiotherapy in patients with locally advanced gastric cancer.Methods From January 2003 to December 2010, 146 gastric cancer patients at our institution（Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China） received postoperative sequential chemotherapy and radiotherapy after radical surgery. Radiotherapy was administered as a dose of 4500 cGy in 25 fractions. For patients with positive margins, the dose was raised to 5040 cGy in 28 fractions. Three cycles of m FOLFOX or PF（cisplatin, 5-fluorouracil） chemotherapy regimen were applied before and after radiotherapy. Three-and 5-year survival rates were analyzed; any adverse effects with respect to hematology, hepatic and renal function, or the gastrointestinal tract that occurred during the treatment were evaluated.Results This cohort consisted of non-metastatic patients: 104 men and 42 women with a median age of 51.0 years. The full course of sequential chemotherapy and radiotherapy（4500–5040 cGy） was completed by 129 patients（88.4%）. Seventeen regional relapses（9.8%） and 46 distant relapses（23.8%） were recorded. Fifty patients（34.2%） died during follow-up. The 3-and 5-year overall survival rates（OS） were 60% and 54%, and disease-free survival rates（DFS） were 53% and 47%, respectively. There were no significant differences in survival rate with respect to age, sex, histopathology, N stage, site of the tumor, or margin status. Multivariate analysis showed that only the depth of tumor invasion（T stage） was an independent prognostic factor for OS（P = 0.009） and DFS（P = 0.006）. The rates of grades 3 and 4 neutropenia and vomiting were 9.6% and 3.4%, respectively, during the treatment.Conclusion Postoperative sequential chemotherapy with an m FOLFOX or PF regimen and radiotherapy were found to be an effective means of treating advanced gastric cancer patients with T3–T4 disease. The adverse effects of this treatment were tolerable.

ARID1A, a component of the chromatin remodeling complex SWI/SNF, is an evolutionarily conserved complex that uses the energy of adenosine triphosphate hydrolysis to remodel chromatin structure and functions as a master regulator of gene transcription. Recent genomic studies have revealed that ARID1A is one of the most frequently mutated genes in human cancers. However, therapeutic approaches that selectively target ARID1A-mutant tumors are not yet clinically available. Our previous study showed that ARID1A facilitates chromatin response and cell cycle checkpoint activation after DNA damage. Therefore, an ARID1A deficiency may result in therapeutic vulnerabilities in cell cycle modulators. The goals of our study were to develop a novel screening approach, based on fluorescent ubiquitination-based cell cycle indicators (FUCCI), and to identify chemical agents that can selectively modulate the cell cycle transition in ARID1A-deficient cancer cells. Using this high-throughput assay, we screened 2643 compounds and identified six potential chemical modulators that can selectively modulate the cell cycle in ARID1A-deficient cells; these agents may be useful for developing new therapeutics for ARID1A-mutant tumors. In summary, our study demonstrates that FUCCI cell-based high-content screening is a powerful and effective approach for identifying cell cycle modulators and can be applied to multigenotypic screening for targeted cancer therapeutics.

Investigation of natural products is an attractive strategy to identify novel compounds for cancer prevention and treatment. Numerous studies have shown the efficacy and safety of natural products, and they have been widely used as alternative treatments for a wide range of illnesses, including cancers. However, it remains unknown whether natural products affect homologous recombination (HR)-mediated DNA repair and whether these compounds can be used as sensitizers with minimal toxicity to improve patients' responses to radiation therapy, a mainstay of treatment for many human cancers. In this study, in order to systematically identify natural products with an inhibitory effect on HR repair, we developed a high-throughput image-based HR repair screening assay and screened a chemical library containing natural products. Among the most interesting of the candidate compounds identified from the screen was β-thujaplicin, a bioactive compound isolated from the heart wood of plants in the Cupressaceae family, can significantly inhibit HR repair. We further demonstrated that β-thujaplicin inhibits HR repair by reducing the recruitment of a key HR repair protein, Rad51, to DNA double-strand breaks. More importantly, our results showed that β-thujaplicin can radiosensitize cancer cells. Additionally, β-thujaplicin sensitizes cancer cells to PARP inhibitor in different cancer cell lines. Collectively, our findings for the first time identify natural compound β-thujaplicin, which has a good biosafety profile, as a novel HR repair inhibitor with great potential to be translated into clinical applications as a sensitizer to DNA-damage-inducing treatment such as radiation and PARP inhibitor. In addition, our study provides proof of the principle that our robust high-throughput functional HR repair assay can be used for a large-scale screening system to identify novel natural products that regulate DNA repair and cellular responses to DNA damage-inducing treatments such as radiation therapy.

Globally, gastric cancer is the second leading cause of cancer deaths because of the lack of effective treatments for patients with advanced tumors when curative surgery is not possible. Thus, there is an urgent need to identify molecular targets in gastric cancer that can be used for developing novel therapies and prolonging patient survival. Checkpoint kinase 1 (Chk1) is a crucial regulator of cell cycle transition in DNA damage response (DDR). In our study, we report that Chk1 plays an important role in promoting gastric cancer cell survival and growth, which serves as an effective therapeutic target in gastric cancer. First, Chk1 ablation by small interfering RNA could significantly inhibit cell proliferation and sensitize the effects of ionizing radiation (IR) treatment in both p53 wild type gastric cancer cell line AGS, and p53 mutant cell line MKN1. Secondly, we tested the anticancer effects of Chk1 chemical inhibitor LY2606368, which is a novel Chk1/2 targeted drug undergoing clinical trials in many malignant diseases. We found that LY2606368 can induce DNA damage, and remarkably suppress cancer proliferation and induce apoptosis in AGS and MKN1 cells. Moreover, we identified that LY2606368 can significantly inhibit homologous recombination (HR) mediated DNA repair and thus showed marked synergistic anticancer effect in combination with poly (ADP- ribose) polymerase 1 (PARP1) inhibitor BMN673 in both in vitro studies and in vivo experiments using a gastric cancer PDx model. The synergy between LY2606368 and PARP1 was likely caused by impaired the G2M checkpoint due to LY2606368 treatment, which forced mitotic entry and cell death in the presence of BMN673. In conclusion, we propose that Chk1 is a valued target for gastric cancer treatment, especially Chk1 inhibitor combined with PARP inhibitor may be a more effective therapeutic strategy in gastric cancer.

Globally, gastric cancer is the second leading cause of cancer deaths because of the lack of effective treatments for patients with advanced tumors when curative surgery is not possible. Thus, there is an urgent need to identify molecular targets in gastric cancer that can be used for developing novel therapies and prolonging patient survival. Checkpoint kinase 1 (Chk1) is a crucial regulator of cell cycle transition in DNA damage response (DDR). In our study, we report that Chk1 plays an important role in promoting gastric cancer cell survival and growth, which serves as an effective therapeutic target in gastric cancer. First, Chk1 ablation by small interfering RNA could significantly inhibit cell proliferation and sensitize the effects of ionizing radiation (IR) treatment in both p53 wild type gastric cancer cell line AGS, and p53 mutant cell line MKN1. Secondly, we tested the anticancer effects of Chk1 chemical inhibitor LY2606368, which is a novel Chk1/2 targeted drug undergoing clinical trials in many malignant diseases. We found that LY2606368 can induce DNA damage, and remarkably suppress cancer proliferation and induce apoptosis in AGS and MKN1 cells. Moreover, we identified that LY2606368 can significantly inhibit homologous recombination (HR) mediated DNA repair and thus showed marked synergistic anticancer effect in combination with poly (ADP-ribose) polymerase 1 (PARP1) inhibitor BMN673 in both in vitro studies and in vivo experiments using a gastric cancer PDx model. The synergy between LY2606368 and PARP1 was likely caused by impaired the G2M checkpoint due to LY2606368 treatment, which forced mitotic entry and cell death in the presence of BMN673. In conclusion, we propose that Chk1 is a valued target for gastric cancer treatment, especially Chk1 inhibitor combined with PARP inhibitor may be a more effective therapeutic strategy in gastric cancer.

目的 探讨中文版患者神经毒性自评(PNQ)量表在评价化疗药物草酸铂周围神经毒性中的信度和效度.方法 采用中文版PNQ和医师评估量表(NCI-CTC),分别对接受草酸铂化疗的105例结直肠癌患者进行问卷调查和医师评估;分析PNQ量表的信度、效度及与NCI-CTC量表条目的相关性.结果 PNQ量表具有良好的重测信度(相关系数为0.512 ～0.650,P＜0.01)和良好的内部一致性(Crocnbach α系数为0.82);PNQ量表各条目与总分的相关系数为0.524 ～0.609(P＜0.01),PNQ量表各条目与NCI-CTC量表各条目的相关系数为0.435 ～0.568,(P＜0.05或P＜0.01),具有良好内容效度和效标效度;因子分析结果示PNQ量表存在2个公因子,累积方差贡献率为86.474％.结论 中文版PNQ量表具有良好信度和效度,可用于临床评估化疗药物草酸铂周围神经毒性。

Objective To evaluate the clinical efficacy and adverse effects of sorafenib plus chemotherapy in the first-line treatment of non-small cell lung cancer (NSCLC).Methods The stage Ⅳ NSCLC patients were divided into two groups in a random ,controlled and double-blinded manner :sorafenib plus gemcitabine + cis-platinum (GP ) group and placebo plus GP group.The efficacy and safety of sorafenib plus GP chemotherapy were analyzed.Results The median overall survival (OS) was 12.8 months and 12.7 months in the sorafenib plus GP group and placebo plus GP group ,respectively (P=0.369).The median progression-free survival (PFS) was 7.4 months and 4.3 months in the sorafenib plus GP group and placebo plus GP group ,respectively (P= 0.070).The 1-year ,2-year ,5-year OS rates were 58.3% vs.52.9% ,41.7% vs.29.4% ,and 8.3%vs.0% in the sorafenib plus GP group and placebo plus GP group ,respectively (P=0.537 ,P=0.385 ,P=0.414).The 6-month PFS rate and 1-year PFS rate were 58.3% vs. 41.2% and 16.7% vs .0% in the sorafenib plus GP group and placebo plus GP group ,respectively (P=0.297 ,P=0.163).The occurrence of adverse effects was similar in the two groups.Patient tolerability was good in the sorafenib plus GP group.The incidence of hand-foot syndrome was increased in the sorafenib plus GP group compared with the placebo plus GP group (P=0.007).Conclusion No survival benefits were observed in first-line treatment of NSCLC with sorafenib in combination with GP chemotherapy.

The aim of our study was to investigate if common toxicities are correlated to objective response rate (ORR) in metastatic colorectal cancer (mCRC) patients treated by irinotecan based regimens.

BACKGROUND: Three recent genome-wide association studies (GWASs) have reported that three SNPs (rs4072037, rs13361707 and rs2274223) located on genes related to host inflammatory response are significantly associated with susceptibility to gastric cancer (GC) in Chinese populations. Helicobacter pylori infection is also an important risk factor for GC through causing inflammatory response in the gastric mucosa. However, no study has established whether there are potential gene-environment interactions between these genetic variants and H. pylori infection to the risk of GC. METHODS: We genotyped three polymorphisms (rs4072037 at 1q22, rs13361707 at 5p13, and rs2274223 at 10q23) in 335 Chinese gastric adenocarcinoma patients and 334 controls. H. pylori serology was examined by enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to evaluate the association between the variables and GC risk. RESULTS: We confirmed that the three SNPs (rs4072037, rs13361707 and rs2274223) were significantly associated with GC susceptibility. H. pylori infection also significantly increased the risk of GC. Furthermore, there were joint effects between H. pylori infection and the three SNPs on the risk of GC. The most elevated risk of GC was found in subjects with H. pylori seropositivity and AA genotypes for rs4072037 [odds ratio (OR), 3.95; 95% confidence interval (CI), 2.29-6.79], H. pylori seropositivity and CT/CC genotypes for rs13361707 (OR, 2.68; 95% CI, 1.62-4.43), H. pylori seropositivity and AG/GG genotypes for rs2274223 (OR, 2.45; 95% CI, 1.55-3.88) compared with those with H. pylori seronegativity and other genotypes of each SNP. Significant interactions were observed between H. pylori seropositivity and the three SNPs (all P(G× E) <0.05) to the risk of GC. CONCLUSION: These findings indicate that the three SNPs (rs4072037, rs13361707 and rs2274223) identified in the GWASs may interact with H. pylori infection to increase the risk of GC.

Objective To identify the mutations in Cu/Zn superoxide dismutase ( SOD1 ) gene in three Chinese kindreds with amyotrophic lateral sclerosis ( ALS), compare the genotypes with those found in other ethnic groups and to analyze the clinical characteristics.Methods The diagnosis of ALS met El Escorial ALS diagnostic criteria.Genomic DNA was extracted from peripheral blood in ALS patients using standard procedure.PCR amplifications of five exons of SOD1 were performed using primers as described in the previous publication.The PCR products were directly sequenced.Results A heterozygous mutation H46R was found in four affected members in a family with middle age onset and slowly progressive ALS.A heterozygous mutation of G72C was identified in a 20-year-old male who died of respiratory failure after two years of ALS.His father carried the same mutation without clinical phenotype.In the third family with 20affected members with middle age onset and rapidly progress, a mutation of E13V was identified in 5 affected subjects.Conclusions This study is the first large screening of SOD1 mutation in Chinese familiar ALS patients.H46R has previously been found only in Japanese and Pakistanis; this is the first report in Chinese, suggesting H46R may be specific to Asians.The family with mutation G72C presented decreased penetrance, therefore screening SOD1 mutation in sporadic cases and unaffected family members is necessary.E133V is the first reported mutation and needs more study to investigate its effect on the disease.

BACKGROUND:Treatments to brain metastases in patients of NSCLC include operation, chemotherapy and radiotherapy, while the disease control rate of brain lesions is not so good, the media survival time is 4-6 months. Tyrosine kinase inhibitor erlotinib can get into blood-brain barrier as reported, and it is used as a effetive method to control brain metastases. The aim of this clinical observation was to evaluate the efficacy and adverse reactions after concomitant therapy of erlotinib and whole brain radiotherapy (WBRT) in patients of NSCLC with brain metastasis.METHODS:This was a retrospective study. From 2006 to 2009, There were 12 cases of NSCLC with brain metastases. They were accepted the concomitant therapy of erlotinib and WBRT. The dose of erlotinib was 150 mg/d and the radiotherapy dose was (3 000-3 600) cGy/(10-12) F. After 2 months of radiotherapy the early efficacy was evaluabed.RESULTS:The control rate of brain metastases was 91.7% with PR 66.7%, SD 25%. The major adverse reactions were skin rash (75%) and fatigue (91.7%).CONCLUSIONS:The effect of the concomitant of erlotinib and WBRT in patients of NSCLC with brain metastases is better than WBRT alone, and the concomitant therapy is well tolerated.