藤龙补中汤维持治疗对大肠癌转移抑制作用的临床研究

目的:观察藤龙补中汤对术后化疗后Ⅲ期大肠癌转移的抑制作用。方法:收集2014年1月—2019年12月上海中医药大学附属龙华医院和复旦大学附属肿瘤医院闵行分院术后化疗后Ⅲ期大肠癌患者101例,根据实际干预措施分为对照组和治疗组,分别予随访或藤龙补中汤治疗。观察患者肿瘤转移、临床证候、生活质量和免疫细胞变化。结果:对照组和治疗组肿瘤转移率分别为44.19%和20.69%(P<0.05)。藤龙补中汤同时可改善患者临床症状和生活质量,升高T细胞亚群、IL-12和NK细胞(P<0.05)。结论:藤龙补中汤维持治疗可抑制术后化疗后Ⅲ期大肠癌转移,同时可改善患者临床证候和生活质量,调节免疫功能。     

移植免疫中Th1/Th2的作用

1986年Ｍｏｓｍａｎｎ与Ｃｏｆｆｍａｎ根据分泌细胞因子的差别,将小鼠ＣＤ4 Ｔ细胞进一步分为Ｔｈ1与Ｔｈ2细胞亚群[1]。Ｔｈ1细胞亚群主要涉及细胞免疫,Ｔｈ2细胞亚群多与体液免疫有关。在一定条件下,Ｔｈ2型的细胞因子对Ｔｈ1细胞亚群的发育与功能起拮抗作用,而Ｔｈ1型的细胞因子亦可抑制Ｔｈ2反应。本文将对Ｔｈ1与Ｔｈ2之间的这种矛盾关系及其在移植免疫,免疫耐受中的作用综述如下。附图　Ｔｈ1与Ｔｈ2轴Ｔｈ0,Ｔｈ1,Ｔｈ2:Ｔ辅助细胞亚群;ＡＰＣ:抗原呈递细胞;ＮＫ:自然杀伤细胞;ＭΦ:巨噬细胞;Ｂ:Ｂ细胞;Ｂａ:嗜碱细胞/肥大细胞;Ｅ:…     

低分子量姬松茸多糖对树突细胞Th1型免疫反应的影响

目的探讨姬松茸多糖(LMPAB)对树突细胞(DCs)Th1型免疫反应的影响。方法体外培养ICR小鼠骨髓来源的DCs。应用WST检测LMPAB增强DCs对T淋巴细胞的增殖作用,应用酶联免疫吸附法(ELISA)检测LMPAB对DCs分泌的干扰素(IFN-)γ与白细胞介素(IL)-12的影响。结果与正常组(4.84±0.21)比较,LMPAB+卵白蛋白(OVA)组(6.59±0.19)可以增强DCs对T淋巴细胞的增殖作用(P<0.05);与正常组IL-12〔(32.31±2.45)pg/ml〕、IFN-γ〔(657.34±43.41)pg/ml〕比较,LMPAB+OVA组IL-12〔(45.89±1.03)pg/ml、IFN-γ(854.42±35.06)pg/ml〕明显升高(P<0.05)。结论 LMPAB可以增强DCs Th1型免疫反应,可能具有免疫佐剂的调节作用。     

甲型H1N1流感患者Th1和Th2型细胞因子的检测及其意义

目的探讨甲型H1N1流感患者外周血Th1和Th2细胞因子的表达水平,为临床诊断H1N1感染及判断疾病的严重程度提供一定的客观依据。方法采用流式细胞仪检测24例甲型H1N1流感患者和24名健康者外周静脉血Th1、Th2细胞因子,对结果进行统计学分析。结果 H1N1甲流患者与健康对照组相比,IL-6、IL-10水平差异有统计学意义(P<0.05),IL-2I、L-4、TNF-α和IFN-γ差异无统计学意义(P>0.05);重症组与一般患病组比较IL-6水平差异有统计学意义(P<0.05),IL-2I、L-4I、L-10、TNF-α、IFN-γ水平差异无统计学意义(P>0.05)。结论与健康者相比,甲型流感患者的Th2型细胞因子水平显著升高,IL-6、IL-10,特别是IL-6可能在流感发病中发挥作用。     

Th1/Th2型细胞因子反应与肺纤维化

肺纤维化是多种原因引起肺部炎症和肺泡持续性损伤及细胞外基质的反复破坏、修复、重建和过度沉积从而导致正常的肺组织结构改变和功能丧失的一类疾病。肺纤维化疾病包括特发性肺纤维化(IPF)、结节病、尘肺、过敏性肺炎、药物和放射线导致的纤维化．以及与胶原血管疾病有关的致纤维化肺泡炎等。其确切的发病机制尚未阐明，缺乏特异有效的治疗方法，预     

补脾益气方药对哮喘大鼠Th1/Th2失衡的调节及机制

目的观察补脾益气方药对哮喘大鼠Th1/Th2失衡的免疫调节作用及机制。方法 SPF级雄性Wistar大鼠随机分为对照组、哮喘组、生理盐水治疗组、地塞米松组、补脾益气方药治疗组。检测支气管肺泡灌洗液(BALF)中嗜酸性细胞、巨噬细胞、淋巴细胞和中性粒细胞比例;采用ELASA方法检测BALF中IL-4和IFN-γ的含量;采用Western blot方法检测肺组织GATA-3和T-bet的表达。结果模型组和生理盐水治疗组与正常组比较,BALF中嗜酸性粒细胞、淋巴细胞和中性粒细胞的比例及IL-4含量均明显升高,IFN-γ含量显著下降;GATA-3表达增高,T-bet表达降低。经补脾益气方药与地塞米松治疗后,BALF中嗜酸性粒细胞、淋巴细胞和中性粒细胞的比例和IL-4含量均明显下降,IFN-γ含量显著升高;GATA-3表达下调,T-bet表达上调。上述结果均差异显著,具有统计学意义(P<0.01)。结论补脾益气方药对Th1/Th2失衡有调节作用,这种作用是通过调节GATA-3和T-bet的协调表达来实现。     

银杏内酯对老年哮喘患者外周血Th1/Th2型细胞因子的作用

目的探讨银杏内酯对老年哮喘患者外周血T淋巴细胞Th1/Th2型细胞因子的作用及其治疗哮喘的可能机制。方法采用流式细胞术检测25例健康体检者正常对照组和25例老年支气管哮喘急性发作期患者单个核细胞（PBMC）经银杏内酯干预后Th1型细胞因子（IFN-γ）和Th2型细胞因子（IL-4）水平及Th1/Th2比值变化。结果与正常组比较,哮喘组Th2型细胞因子（IL-4）水平显著增高（P〈0.01）,哮喘组Th1/Th2比值显著减低（P〈0.01）。哮喘组银杏内酯体外干预后Th2型细胞因子（IL-4）水平较干预前显著减低（P〈0.01）,Th1/Th2比值较较干预前显著增高（P〈0.01）。结论银杏内酯具有抑制哮喘Th2细胞亚群优势反应和调节免疫平衡的作用。     

趋化因子对Th1/Th2免疫平衡的影响

近年来 ,随着免疫学和分子生物学的发展 ,人们发现多种趋化因子及其受体是调节免疫应答的重要分子 ,它们的存在和变化对Th1 /Th2细胞的分化和极化具有重要作用。现就趋化因子对Th1 /Th2细胞免疫平衡的影响作一综述     

Clinical study on Yanghe decoction in improving neo-adjuvant chemotherapy efficacy and immune function of breast cancer patients

Introduction:Neoadjuvant chemotherapy (NAC) plays an important role in downgrading preoperative tumor size, providing information on regimen activity, and increases treatment efficacy in breast cancer patients. An increasing number of patients have sought Traditional Chinese Medicine (TCM) during NAC to relieve discomfort, regulate immune function, and improve survival. However, limited evidence is available on how concurrent TCM treatment combined with NAC affects tumor response. This study aims to assess the efficacy of Yanghe decoction, a classical warming Yang formula, on pathological complete response (pCR) and explore its mechanism via the phosphatidylinositol-3-kinase/ protein kinase B/nuclear factor kappa-B (PI3K/Akt/NF-κB) pathway-mediated immune-inflammation microenvironment.Methods:A single-center, randomized, placebo-controlled, double-blinded randomized control trial (RCT) was designed. This trial aims to recruit 128 participants with breast cancer scheduled to receive NAC in China. All participants will be randomly assigned (1:1) to the Neo-Yanghe group (Yanghe decoction plus NAC) or the control group (placebo plus NAC). The primary outcome will be evaluated by the proportion of participants achieving pCR. The secondary outcomes include the expression level of PI3K/Akt/NF-κB pathway-related proteins, the objective response rate, the time to response, serum level of immune-inflammatory indicators, quality of life, disease-free survival, and overall survival.Discussion:This study will be the first RCT to evaluate the efficacy of Yanghe decoction combined with NAC in treating breast cancer patients, and elucidate the antitumor mechanism via the PI3K/Akt/NF-κB pathway-mediated immune-inflammation microenvironment. If possible, Neo-Yanghe treatment pattern will be a better pharmacological intervention to manage breast cancer than chemotherapy alone. The results of the trial will provide research-based evidence for the development of integrated Chinese and Western medicine guidelines and expert consensus.Trial registration: Chinese Clinical Trial Registry ChiCTR-INR-2000036943. Registered on September 28, 2020 (https://www.chictr.org.cn/hvshowproject.aspx?id=57141).     

芪玉三龙汤对荷肺癌小鼠免疫功能的影响

目的研究芪玉三龙汤对荷肺癌小鼠皮下移植瘤生长,以及对荷瘤小鼠免疫功能的影响。方法采用LLC细胞株培养移植法构建荷肺癌小鼠模型,随机分成模型组、化疗组、中药高、中、低剂量组、联合组,每组8只,另设8只正常小鼠为空白组;观察各组小鼠的生存状态,称取瘤质量,计算抑瘤率;透射电镜观察肿瘤组织内癌细胞超微结构的变化;流式细胞术检测小鼠外周血T细胞亚群(CD4~+、CD8~+、CD4~+/CD8~+)的变化;酶联免疫吸附试验(ELISA)法检测小鼠脾脏IL-2、IL-10浓度。结果芪玉三龙汤高剂量组、联合组的生存状态优于化疗组;芪玉三龙汤具有温和的抑制肺癌移植瘤的作用,但与顺铂联用无明显增效作用;电镜下观察肿瘤细胞超微结构可见中药组肿瘤细胞有凋亡发生,以高剂量组凋亡坏死最明显,化疗组可见多个凋亡小体,联合组肿瘤细胞严重坏死;芪玉三龙汤能明显增加CD4~+水平,升高IL-2浓度,降低CD8~+的水平和IL-10含量,提高CD4~+/CD8~+比值,联合组与化疗组比较有显著差异(P0.01)。结论芪玉三龙汤能改善行化疗的荷瘤小鼠生存状态,可温和抑制肺癌移植瘤生长,诱导肺癌细胞凋亡,并具有改善荷瘤小鼠以及化疗药导致免疫功能低下的作用。     

调节性T细胞抑制约氏疟原虫感染小鼠早期Th1应答的建立

目的探讨调节性T细胞(Tregs)参与约氏疟原虫感染早期调控Th1型免疫应答的相关机制。方法用约氏疟原虫(致死型)感染对照组和anti-CD25 mAb注射组BALB/c小鼠,计数红细胞感染率;感染后第0、3和5d制备脾细胞悬液,磁珠分选、纯化树突状细胞(DCs)并体外培养;ELISA方法检测脾细胞培养上清中IFN-γ和DCs培养上清中IL-12的水平,Griess方法检测脾细胞培养上清中NO含量。结果两组小鼠脾细胞培养上清中IFN-γ和NO水平在感染后第3～5d均明显升高,但对照组小鼠IFN-γ和NO水平明显低于anti-CD25 mAb注射组小鼠。anti-CD25 mAb注射组小鼠DCs培养上清中IL-12的水平于感染后第3d达峰值,并于感染后第5d仍维持较高水平。相比,对照组小鼠DCs培养上清中IL-12的水平仅于感染后第3d出现有意义的升高。结论Tregs在致死型约氏疟原虫感染BALB/c小鼠早期可能通过抑制DCs分泌细胞因子IL-12来抑制Th1型免疫应答的有效建立。     

梦醒汤治疗老年脑卒中后抑郁症的临床研究

目的观察梦醒汤在老年脑卒中后抑郁症治疗中的临床疗效。方法82例卒中后抑郁症患者随机分为治疗组和对照组（各41例）,对照组接受常规西药治疗,治疗组在常规西药治疗的同时加用中药梦醒汤方。治疗2周、8周后分别观察疗效。结果治疗后治疗组汉密尔顿抑郁量表评分、神经功能缺损评分均明显优于对照组（P〈0.01）。结论梦醒汤具有较好的抗抑郁作用,并能有效促进脑卒中后神经功能的康复,值得临床推广。     

扶正补虚方对原发性肝癌患者细胞免疫功能及生活质量的影响

[目的]探讨扶正补虚方治疗原发性肝癌的疗效及应用价值.[方法]选择我院治疗的原发性肝癌患者58例,随机分为观察组和对照组.对照组采用常规治疗,观察组在对照组基础上联合使用扶正补虚方剂治疗,观察2组的治疗情况.[结果]观察组治疗总有效率为55.17％,对照组的总有效率为27.59％,组间比较差异有统计学意义（P＜0.05）.观察组治疗后中医症状评分（3.15±0.56）分,生活质量评分（78.26±6.84）分,改善幅度同对照组治疗后比较差异有统计学意义（t=19.2497、4.7436,P＜0.05）.观察组治疗后CD3＋ （64.02±7.65）,CD4＋ （40.71士7.17）,CD8＋ （23.74±3.97）,CD4＋/CD8＋（1.56士0.66）,改善幅度优于对照组,同对照组治疗后比较差异有统计学意义（t=5.1410、5.3073、6.2669、3.0764,P＜0.05）.[结论]在常规治疗基础上给予患者扶正补虚方剂治疗能够提高治疗效果,改善患者生存质量,提高患者免疫功能,值得临床推广使用.     

Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

AIM： To investigate the efficacy and safety of cape- citabine plus irinotecan ＋ bevacizumab in advanced or metastatic colorectal cancer patients. METHODS： Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer （mCRC） were recruited between 2001-2006 in a pro- spective open-label phase Ⅱ trial, in German commu- nity-based outpatient clinics. Patients received a stan- dard capecitabine plus irinotecan （CAPIRI） or CAPIRI plus bevacizumab （CAPIRI-BEV） regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of 〉 grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were response and toxicity and sec- ondary endpoints included progression-free survival and overall survival. RESULTS： In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients （47% vs 24%）, and more patients had colon as the primary tumor site （58.8% vs 48.2%） with fewer patients having sigmoid colon as primary tumor site （5.9% vs 20.7%）. Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev： 82% vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates were 70.6% and 75.9%, respectively. No complete re- sponses were observed. The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CA- PIRI-Bev, respectively. The median overall survival for CAPIRI was 15 mo （458 d） and for CAPIRI-Bev 24 mo （733 d）. These differences were not statistically different. In the CAPIRI-Bev, group, two patients under- went a full secondary tumor resection after treatment, whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION： Both regimens were well tolerated and offered effective tumor growth control in this out- patient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.     

中药治疗对老年晚期肺癌患者生存质量的研究

目的观察中药（含中草药和中成药）治疗对老年肺癌晚期患者生存质量的影响。方法将90例老年肺癌晚期患者分为汤药治疗组、艾迪注射液组及对照组,应用肺癌患者生存质量测定量表（QLQ-LC43）及卡氏评分（Karnofsky评分）评估中药治疗对老年肺癌晚期患者生命状态的影响。结果汤药治疗组和艾迪注射液组中生理功能、情感功能、认知功能、总健康状况评分较治疗前升高,疲倦、恶心呕吐、丧失食欲、失眠、腹泻、肺癌子模块评分均较治疗前降低,经统计学检验有显著性差异。在生理功能、情感功能、认知功能、总健康状况、疲倦、恶心呕吐、失眠、丧失食欲、腹泻及肺癌子模块10个指标中汤药治疗组和艾迪注射液组与对照组比较有显著性差异。结论口服汤药及静脉艾迪注射液治疗可以提高老年肺癌晚期患者的生存质量。     

Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials

Background: Elderly patients are underrepresented in chemotherapy trials for advanced colorectal cancer (CRC) and non‐small‐cell lung cancer (NSCLC). However, the change in underrepresentation over time has not been documented. Aims: This study aimed to quantify (i) the change in the median age of patients enrolled in clinical trials for metastatic CRC and NSCLC between 1982–1991 and 1992–2001 compared with the general colorectal and lung cancer population, and (ii) the proportion of trials with an upper age limit for eligibility. Methods: A retrospective review of data from the Victorian Cancer Registry and all large published randomized chemotherapy trials for advanced CRC and NSCLC between 1982 and 2001 was conducted. Results: The median age of patients with CRC enrolled in clinical trials remained constant between the two decades (62.0 and 62.2 years), whereas the median age of the CRC population increased from 68.4 to 70.2 years, increasing the median age difference from 6.4 to 8.0 years. The median age of patients with lung cancer in clinical trials increased from 59.8 to 61.8 years, whereas the median age of the lung cancer population increased from 67.4 to 70.4 years, widening the age difference from 7.6 to 8.6 years. More trials set an upper age limit for eligibility in the first decade than in the second decade for both CRC (51 vs 29%, P = 0.04) and NSCLC (68 vs 41%, P = 0.03). Conclusion: International clinical trials for CRC and NSCLC are becoming increasingly unsuitable for application to Australian patients because of the increasing age discrepancy, despite fewer trials restricting eligibility by age.     

Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer

PURPOSE: The present study was designed to determine the frequency of germline mutations in the hMLH1 and hMSH2 genes in 31 families suspected of having hereditary nonpolyposis colorectal cancer who do not fulfill the criteria of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer but in whom a genetic basis for colon cancer is strongly suspected and 45 patients with sporadic early-onset colorectal cancer who developed colorectal cancer before the age of 40 years without any family history of colorectal cancer. METHODS: Genomic DNAs were prepared from peripheral blood samples of patients who were tested. All coding exons and exon-intron borders of these two genes were screened, first with the polymerase chain reaction-single-strand conformation polymorphism method, followed by sequencing of the DNA fragments displaying an abnormal single-strand conformation polymorphism pattern. RESULTS: In 31 families with suspected hereditary nonpolyposis colorectal cancer, we found six different germline mutations in seven unrelated families, including one missense mutation and three frame-shift mutations in the hMLH1 gene and one missense mutation and one frame-shift mutation in the hMSH2 gene. Totally, frequency of mutation was 23 percent, 16 percent and 7 percent in the hMLH1 and hMSH2, respectively. Only one missense mutation of the hMSH2 gene was identified in 45 patients (2 percent) with sporadic early-onset colorectal cancer. The mutation detection rate in families with suspected hereditary nonpolyposis colorectal cancer was significantly higher than that of patients with sporadic early-onset colorectal cancer (P<0.05). CONCLUSION: Our definition of suspected hereditary nonpolyposis colorectal cancer is useful in the diagnosis of hereditary nonpolyposis colorectal cancer and for identifying those families who need genetic presymptomatic diagnosis. Our results indicate that it may be important to perform DNA testing in families suspected of having hereditary nonpolyposis colorectal cancer. On the other hand, we only detected a low mutation rate (2 percent) in 45 patients with sporadic early-onset colorectal cancer.Supported, in part, by the 1997 Good Health R & D Project, the Ministry of Health and Welfare of the Republic of Korea, and the Korea Science and Engineering Foundation (KOSEF-CRC-94K2-0402-04-00-3) through the Cancer Research Center at Seoul National University.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997. Winner of the Southern California Society of Colon and Rectal Surgeons Award.