Although many long non-coding RNAs (lncRNAs) are modulators of biological events in hepatocellular carcinoma (HCC), the potential significance of most lncRNAs in HCC remains to be fully understood. The role of lncRNA ADAMTS9-AS1 in HCC was therefore determined. ADAMTS9-AS1 expression was higher in HCC cell lines compared to normal cells as determined by qPCR analyses. Furthermore, CCK-8, scratch wound healing, transwell migration, and invasion assays suggested that ADAMTS9-AS1 overexpression promoted the proliferation, migration, and invasion in MHCC97-H and HepG2 cells; ADAMTS9-AS1 knockdown showed the opposite results. Based on the results from GEO, the correlation between ADAMTS9-AS1 and PI3K/AKT/mTOR was identified. Thus, an association between ADAMTS9-AS1 and the PI3K/AKT/mTOR signaling pathway was further observed. To confirm the pathway protein levels, p-AKT, PIK3CB, and p-mTOR were selected. Western blot assays suggested that ADAMTS9-AS1 enhanced the expression levels of the three proteins. Because of their close relationship with PI3K/AKT/mTOR, apop tosisor autophagy-related proteins were further investigated. ADAMTS9-AS1 expression was negatively related with LC3-II, BECN1, and pro-apoptotic Bax, whereas it was positively correlated SQSTM1 and anti-apoptotic Bcl-2 expression. Western blot results suggested that ADAMTS9-AS1 decreased ADAMTS9 expression. Our data revealed that ADAMTS9-AS1 contributed to proliferation, migration, and invasion in HCC cells, likely due to the activation of the PI3K/AKT/mTOR signaling pathway, to influence autophagy and apoptosis. These findings suggest that ADAMTS9AS1 could serve as a molecular target in HCC treatment.
OBJECTIVE:To observe the effect of low-frequency electrical acupoint stimulation on gastrointestinal motility in patients undergoing radical gastrectomy, and its impact on regulation of inflammatory response, so as to evaluate its clinical value. METHODS:A total of 177 patients undergoing radical gastrectomy were randomly divided into conventional group (n=43), low-frequency electrical acupoint stimulation (LEAS) group (n=45), fast track surgery (FTS) group (n=46) and FTS+LEAS group (n=43). Patients of the conventional group received conventional treatment (pre-surgical mechanical bowel preparation, post-surgical fasting, and indwelling abdominal drainage tube, etc.). Patients in the LEAS group were treated by low-frequency electrical stimulation at bilateral Zusanli (ST36), Shangjuxu(ST37), Xiajuxu(ST39) and Sanyinjiao(SP6) for 30 min, once daily from 1 day after the operation to first postoperative flatus. FTS group was given fast track surgery treatment, such as preoperative education, preoperative nutritional support, early oral feeding, early removal of abdominal drainage tube, etc. The FTS+LEAS group was given low-frequency electrical acupoint stimulation on the basis of the FTS treatment. Levels of white blood cells (WBC), neutrophils (N), C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at 1, 3, and 6 d after the operation in the 4 groups were assayed. The first postoperative flatus and defecation time were recorded. RESULTS:After the treatment, the first postoperative flatus and defecation time in the LEAS, FTS and FTS+LEAS groups were significantly shorter than those of the conventional group (P<0.05), and the first flatus time of the FTS+LEAS group was even earlier than that of the FTS group (P<0.05). No significant differences were found among the 3 groups in the postoperative defecation time (P>0.05). The CRP levels in the 4 groups on 3 and 6 d after operation were higher than those on the 1st postoperative day, and the highest level was on 3 d after the operation. Compared with the conventional group, CRP level on 3 d and CRP and IL-6 levels on 3 and 6 d in the LEAS and FTS+LEAS groups were significantly lower (P<0.05). Compared with the LEAS group, the levels of N, CRP on 3 d and the levels of N, CRP, IL-6 on 6 d in the FTS group were significantly increased (P<0.05). Compared with the FTS group, the level of CRP on 3 d and the levels of N, CRP, IL-6 on 6 d in the FTS+LEAS group were significantly decreased (P<0.05). CONCLUSION:FTS combined with LEAS is superior to simple FTS or LEAS treatment in shortening the first flatus and defecation time and promoting the recovery of gastrointestinal motility function in patients undergoing radical gastrectomy, which may be associated with its effect in alleviating postoperative inflammatory responses.
目的 观察以药食两用中药为主的组成中药方健脾祛湿方对胃癌术后早期气虚寒湿证患者的影响.方法 纳入胃癌术后符合气虚寒湿证型且已排气患者68例,采用配对设计方法分为治疗组(健脾祛湿方+西药常规治疗组)和对照组(西药常规治疗组)两组,每组34例.观察服药后D1和D3患者的排气次数、排便次数、大便质地及服药2周后患者中医证候积分变化和疲乏评分、癌症疲乏量表积分.评价药食两用中药颗粒剂健脾祛湿方对胃癌术后早期气虚寒湿证的影响.结果 服药D3,治疗组患者的排气、排便次数少于对照组,大便质地评分优于对照组,差异有统计学意义(P<0.05).治疗后治疗组患者的气虚证积分低于对照组;治疗组气虚证治疗前后积分差、寒湿证治疗前后积分差均大于对照组,差异有统计学意义(P<0.05).治疗组患者的自觉治疗后症状改善率为73.5% (25/34)大于对照组38.2%(13/34),差异具有统计学意义(P<0.05).治疗后治疗组患者癌症疲乏总分、躯体疲乏积分均低于对照组,差异有统计学意义(P<0.05).结论 健脾祛湿方可加快胃癌术后早期患者的胃肠功能恢复,改善患者气虚寒湿证候,改善患者躯体疲乏,提高患者生存质量.
Objective To explore the influence of percutaneous coronary intervention (PCI) on the syndromes in patients with coronary heart disease (CHD) and blood stasis syndrome, and to investigate its improvement in blood stasis syndrome.Methods The influence of factors such as age, sex, number of coronary artery lesions and degree of lesion stenosis on blood stasis syndrome were observed before and after PCI.The relationship between electrocardiogram (ECG) changes and the blood stasis syndrome scores was analyzed.The difference of blood stasis syndrome scores were observed in patients with CHD and blood stasis syndrome before and after PCI.Results The syndrome score was positively correlated with age, the number of coronary artery lesions and the degree of stenosis.Patients with clinical symptoms or abnormal electrocardiogram had the higher the score of blood stasis syndrome.PCI could alleviate the patient's clinical symptoms, reduce the degree of stenosis, reduce the number of lesions, and improve the abnormal electrocardiogram.Conclusion PCI can improve the clinical symptoms and abnormal electrocardiogram in patients with CHD and blood stasis syndrome rapidly, and reduce the score of blood stasis syndrome.
Melittin (Mel), a major component of venom of honey bee (Apismellifera), has various biological effects. Recent researches have reported the anti-tumor activity of Mel in various human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to further discuss the role of Mel in HCC and investigate the correlation of autophagy with the effect of Mel in HCC cells. Methyl thiazolyl tetrazolium (MTT) assay and flow cytometry were used to detect the viability and apoptosis of HCC cells, respectively. To examine the changes of autophagy in HCC cells treated with Mel, transmission electronmicroscope (TEM) and immunofluorescence detection were adopted. Finally, we used western blot method to detect the changes of pivotal proteins in autophagy and mitochondrial apoptotic pathways. The results of MTT assay and flow cytometry revealed that Mel could suppress the cell viability and promote the apoptosis of HCC cells. Autophagy could be induced by the treatment with Mel in HCC cells. The inhibition of autophagy by chloroquine (CQ) contributed to the enhanced anti-tumor effect of Mel, but autophagy induction by RAPA decreased Mel effect in HCC cells. Mel was closely associated with the expression of proteins in mitochondrial apoptotic pathway. In summary, Mel could induce the autophagy of HCC cells, and the autophagy might offer protection against apoptosis in HCC. Mel might suppress the tumor through activating mitochondrial apoptotic pathway.
Background: Modern medicine has suggested exercise therapy is one of the main treatments for postoperative rehabilitation of tumors. It can influence the recovery of cancer patients by changing the body's material metabolism and energy metabolism. However, studies on metabolic changes of exercise therapy on hepatocellular carcinoma (HCC) patients after surgery are limited. The aim of this study was to explore the effect of aerobic exercise on mice after orthotopic HCC surgery by serum metabolomics test and explore the related mechanism. Material/Methods: A total of 60 C57Bl/6 mice were used to establish an orthotopic xenograft model of H22 mouse hepatoma cells. Mice were randomly divided into 6 groups and it was found that the metabolic products of the early postoperative exercise group and sedentary group mainly included L-tryptophan, citric acid, and other energy-related metabolites. Results: Energy metabolites, such as succinic acid of the high-intensity exercise group were increased after surgery, whereas phospholipid metabolites, including phosphatidylethanolamine (18: 0/0: 0), were decreased. In the moderate-intensity exercise group, the change tendency was consistent, and the level of various metabolites decreased. Conclusions: Thus, it is likely that aerobic exercise reduced the degree of postoperative stress responses and improved energy metabolism in mice. The underlying mechanism involves improving the tricarboxylic acid cycle, intervening in energy metabolism, reorganization caused by the tumor, reducing the abnormal increase of phospholipase activity caused by the stress of liver cancer, reducing the level of hemolytic phospholipids, thereby inhibiting mitochondrial pathway-initiated apoptosis.
目的 探讨中药方剂扶正消癥汤联合经典FOLFOX方案对胃癌患者生活质量的影响.方法 选取2017年6月至2018年6月本院收治的中晚期胃癌患者180例,随机分为研究组和对照组,每组90例.两组均给予经典FOLFOX6方案化疗,研究组加用中药方剂扶正消癥汤.治疗2个周期后比较两组患者的临床疗效、中医症候积分、生活质量评分.结果 研究组胃癌患者治疗总有效率(24.00%)明显高于对照组(13.00%),差异有统计学意义(P<0.05);其中部分缓解率、稳定率明显高于对照组,进展率明显低于对照组,差异均有统计学意义(均P<0.05).治疗2个周期后研究组胃脘胀痛、纳差食少、精神萎靡、气短乏力积分明显低于治疗前,对照组胃脘胀痛积分明显低于治疗前,差异均有统计学意义(均P<0.05);研究组治疗2个周期后胃脘胀痛、纳差食少、精神萎靡、气短乏力积分明显低于对照组,差异均有统计学意义(均P<0.05).与治疗前相比,治疗2个周期后研究组患者生活质量评分明显降低,差异有统计学意义(P<0.05).治疗前两组胃癌患者生活质量评分之间差异无统计学意义(P>0.05);治疗2个周期后与对照组相比,研究组患者生活质量评分明显降低,差异有统计学意义(P<0.05).结论 中药方剂扶正消癥汤联合经典FOLFOX6方案可有效缓解中晚期胃癌患者的临床症状,改善生活质量.
目的 探讨特定耳穴贴压法治疗胃癌患者术后疼痛的临床疗效.方法 选取2016年1月至2017年1月间第二军医大学长海医院收治的104例胃癌术后患者,采用随机数表法分为治疗组(51例)和对照组(53例).选定耳廓中的心、神门、交感、皮质下和胃5个穴位贴压,治疗组患者每日按压4次,对照组患者仅贴不按压.采用视觉模拟评分法评估两组患者术后疼痛程度,比较两组患者的γ-氨基丁酸(GABA)和β-内啡肽(β-EP)等血清学指标.结果 治疗组患者术后2~5d的疼痛评分均低于对照组,差异均有统计学意义(均P<0.05);治疗组患者治疗后的GABA和β-EP均高于对照组患者,差异均有统计学意义(均P<0.05).结论 特定耳穴贴压法可有效缓解胃癌患者的术后疼痛,机制可能与上调GABA和β-EP表达有关.
目的 了解海军某部队训练伤发生的基本情况,及训练伤防治相关知识的知晓度,提出防治策略,为部队今后的训练伤防治工作提供合理依据和科学指导,同时为海军其他部队提供参考.方法 采用发放自制调查问卷的方式,对海军某部队训练伤的发生情况进行调查,并统计分析.结果 某部队训练伤发生率为38.40%,损伤类型以软组织损伤和骨关节损伤为主.56.12%的战士了解训练伤防治的方法,98.31%的战士认为有必要加强训练伤防治知识的学习.结论 军事训练伤高发的主要原因是训练伤防治意识不足,相关专业知识缺乏,应加强训练伤防治的教育力度,提高官兵防治意识,采用科学合理的训练方法.
Objective To investigate the evolution rule of traditional Chinese medicine (TCM) syndromes of patients with gastric cancer during perioperative period.Methods A total of 105 patients with gastric cancer,who received surgery in the Changhai Hospital of Second Military Medical University from June 2015 to January 2016,were selected and enrolled as the subjects.The TCM syndromes of gastric cancer patients after operation were investigated.Results Before surgery,the TCM syndromes of patients were mainly Qi stagnation syndrome and blood stasis syndrome (43.81%).In the early postoperative period,the TCM syndrome was mainly caused by deficiency syndrome (99.05%) especially Qi deficiency syndrome (91.89%).After the mid period the TCM syndromes were Qi deficiency syndrome in 97 cases (64.66%) and cold dampness syndrome in 35 cases (23.33%).After the late period the TCM syndrome was syndrome of intermingled deficiency and excess (51.43%),and among them 95 cases of Qi deficiency syndrome (59.01%) and 52 cases of cold dampness syndrome (32.30%).Conclusion TCM syndromes of gastric cancer patients during perioperation period are changed.In most common cases the TCM syndromes are Qi deficiency syndrome and the Qi deficiency plus cold dampness syndrome.
Objective Observe the influence of the resection of the tumor in situ liver on general state and the im-mune function in mice.Methods Do the resection of the tumor in situ liver in mice to observe the operation of sponta-neous activity of mice after different time node,ability of lymphocyte proliferation and the influence of CD4+/CD8+ ra-tio and other indexes.Results Compared with the normal mice,spontaneous activity in mice reduce on the first postop-erative day,with statistical significance(P <0.05);Compared with the normal mice,the reproductive capacity of lym-phocytes in mice reduce on the first and third day,with statistical significance(P <0.05);Compared with the first post-operative day mice,CD4+/CD8+ lymphocytes in mice increase on the seventh postoperative day and the normal mice, with?statistical significance(P <0.01).Conclusion Resection of the tumor in situ liver caused greater stress injury and immunosuppression in mice.Mice are similar to human perioperative after surgery,also need a certain amount of time gradually returned to normal state.
目的:检验构建的蜂毒素改造物是否达到减轻溶血副作用、保留或增强抗肿瘤活性的目的.方法:比较蜂毒素改造物与蜂毒素的体外溶血作用及急性毒性作用;MTT法检测其对H2肝癌细胞的增殖抑制作用;观察蜂毒素改造物瘤内注射对荷肝癌小鼠的抗肿瘤作用.结果:蜂毒素改造物致溶血浓度约为蜂毒素的2.2倍,LD50约为蜂毒素的4倍;蜂毒素改造物对H22肝癌细胞具有增殖抑制作用,呈浓度依赖性;蜂毒素改造物瘤内注射3d后,荷瘤鼠肿瘤增长速度减缓(P<0.05),中位生存时间长于蜂毒素及生理盐水组,但差异无统计学意义(P>0.05).结论:对蜂毒素分子一级结构进行适当修饰和改造,理论上和实践上均具有可行性,能达到降低蜂毒素溶血副作用、继续保留其抗肿瘤活性的目的.
目的:探讨癌因性疲乏的中医证候分布特点及规律.方法:参照《中药新药临床研究指导原则-中医证候指导原则》及《中医内科学》虚劳病中出现的疲乏证候,制定癌因性疲乏基本证候群,以消化道肿瘤的稳定期及无瘤幸存者为例,调查其证候分布及自述症状表现.结果:共调查142例患者,癌因性疲乏患者最常出现的疲乏伴随症状有出汗,睡眠差,脘腹胀,气短,食欲差,头晕,大便异常.证候分布依次为(阳)气虚,脾气虚,(阴)血虚,肺气虚,肾气虚,肝郁气滞,肾阳/阴虚,温(热)困脾,心气虚.结论:癌因性疲乏证候分布以虚证为主,虚证中以气虚类证为主,兼有湿阻及气滞证.
Hepatocellular carcinoma (HCC) is a highly malignant disease, and its outcome of routine therapies is poor. Comprehensive treatment including gene therapy is an important way to improve patients' prognosis and survival. In this study, we successfully constructed a triple-controlled cancer-selective oncolytic adenovirus, QG511-HA-Melittin, carrying melittin gene, in which the hybrid promoter, hypoxia-response element (HRE)-AFP promoter, was used to control viral E1a expression targeting AFP-positive cancer cells in hypoxia microenviroment, and the E1b-55 kDa gene was deleted in cancer cells with p53-deficiency. The cytological experiments found that the viral replication of QG511-HA-Melittin was increased to 12800-folds in Hep3B cells within 48 h, and 130-folds in SMMC-7721, but the virus did not replicate in L-02 cells. QG511-HA-Melittin had a strong inhibition effect on AFP-positive HCC cell proliferation, such as Hep3B and HepG2, whereas, there was low or no inhibition effect of QG511-HA-Melittin on AFP-negative cancer cells SMMC-7721 and normal cells L-02. In the in vivo experiment, compared with the blank control group, QG511-HA-Melittin can significantly inhibit the growth of HCC xenografts (P<0.05). The survival of mice in QG511-HA-Melittin group was much longer than that of the blank control group. Both in vitro and in vivo experiments manifested that QG511-HA-Melittin exerts an inhibitory effect on HCC cells, which may provide a new strategy for HCC biotherapy.
目的 合成具有抗肿瘤活性的二十六肽蜂毒素.方法 采用Fmoc固相逐步化学合成,确立了以Wang树脂为固相载体,HOBt/ DCC为缩合剂的合成工艺.结果 通过本法能够顺利合成得到二十六肽蜂毒素,收率达32%.结论 该合成方法具有可行性强、操作简便、总收率高等特点,适用于长链多肽的合成.
蜂毒素(melittin)是一种具有抗菌、抗病毒、抗炎镇痛、抗肿瘤等广泛生物活性的天然生物活性物质,但强烈的溶血副作用制约了其走向临床,本文就近年来对降低Melittin溶血等毒副作用,并能保持抗肿瘤活性做的各种改进方式做一综述。
BACKGROUND: The CONSORT Statement is a reporting guideline for authors when reporting randomized controlled trials (RCTs). It offers a standard way for authors to prepare RCT reports. It has been endorsed by many high-impact medical journals and by international editorial groups. This study was conducted to assess the endorsement of the CONSORT Statement by high-impact medical journals in China by reviewing their instructions for authors. METHODOLOGY/PRINCIPAL FINDINGS: A total of 200 medical journals were selected according to the Chinese Science and Technology Journal Citation Reports, 195 of which publish clinical research papers. Their instructions for authors were reviewed and all texts mentioning the CONSORT Statement or CONSORT extension papers were extracted. Any mention of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM) developed by the International Committee of Medical Journal Editors (ICMJE) or 'clinical trial registration' was also extracted. For journals endorsing the CONSORT Statement, their most recently published RCT reports were retrieved and evaluated to assess whether the journals have followed what the CONSORT Statement required. Out of the 195 medical journals publishing clinical research papers, only six (6/195, 3.08%) mentioned 'CONSORT' in their instructions for authors; out of the 200 medical journals surveyed, only 14 (14/200, 7.00%) mentioned 'ICMJE' or 'URM' in their instructions for authors, and another five journals stated in their instructions for authors that clinical trials should have trial registration numbers and that priority would be given to clinical trials which had been registered. Among the 62 RCT reports published in the six journals endorsing the CONSORT Statement, 20 (20/62, 32.26%) contained flow diagrams and only three (3/62, 4.84%) provided trial registration information. CONCLUSIONS/SIGNIFICANCE: Medical journals in China endorsing either the CONSORT Statement or the ICMJE's URM constituted a small percentage of the total; all of these journals used ambiguous language regarding what was expected of authors.
目的:通过实验探讨斛芪浸膏是否具有减轻电离辐射所致胸腺淋巴细胞氧化损伤的作用.方法:取4~6 周健康雄性昆明小鼠,分离胸腺淋巴细胞作原代培养,并分为对照组、辐照组和辐照加低、中、高剂量斛芪浸膏组,除对照组外,其余各组均采用60CO γ射线5Gy 单次辐照.辐照后30min 内分别用流式细胞仪及超氧化物检测试剂盒检测各组细胞内活性氧荧光强度及超氧化物含量.结果:与辐照组比较,辐照加低、中、高剂量斛芪浸膏各组细胞内活性氧强度及超氧化物水平有不同程度下降,差异有统计学意义.结论:斛芪浸膏能在一定程度上降低电离辐射后早期小鼠胸腺淋巴细胞内活性氧水平,具有减轻电离辐射所致的氧化损伤的作用.
OBJECTIVE:To explore the effects of Huqi Extractum (HQE) on the viability and apoptosis in mouse thymic lymphocytes against 60Co radiation.METHODS:Thymic lymphocytes were isolated from 4 -8 weeks healthy male Kunming mice and primarily cultured. Then they were divided into the control group, the irradiation group, the low dose HQE group, the medium dose HQE group, and the high dose HQE group. Equal volume of serum free RPMI-1640 culture solution was added in the control group and the irradiation group, while equal volume of HQE solution (at the daily dose of 25, 50, and 100 mg/mL) was respectively added in the low, medium, and high dose HQE groups. Except the control group, those in the rest groups were exposed radiation at a single dose of 5 Gy gamma-ray. Changes of the thymic lymphocytes' viability were measured by MTT colorimetric assay at 12, 24, 36, and 48 h after radiation. The early apoptosis rate was detected using flow cytometry (FCM) after 10-h radiation. The apoptosis was detected using agarose gel electrophoresis to observe the DNA injury after 24-h radiation.RESULTS:The viability level decreased more obviously in the irradiation group than in the control group at 24 -48 h after radiation (P < 0.01, P < 0.05). The average viability level was obviously higher in the low, medium, and high dose HQE groups than in the irradiation group (P < 0.05) in a dose dependent manner. The early apoptosis rate was obviously lower in the low, medium, and high dose HQE groups than in the irradiation group, with statistical difference shown in the high dose HQE group (P < 0.01). Typical DNA ladder fragments were found in the electrophoresis in all groups except the control group. But the DNA injury was comparatively milder in the low, medium, and high dose HQE groups, with more obvious effects shown in the high dose HQE group.CONCLUSION:HQE showed protection for the viability of early thymic lymphocytes exposed to the 60CO radiation, and could lower the early apoptosis level.