Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.

Candidate Vaccines against Tuberculosis and the Future of Novel TB Vaccine Research

Introduction: Tuberculosis (TB) continues to be a global health challenge and currently only one licensed vaccine is available. For nearly 100 years, the Bacillus Calmette-Guérin (BCG) vaccine has been in use. While it provides protection against disseminated TB in infants, its protection against adult and adolescent pulmonary tuberculosis (PTB) is variable. This literature review will provide an overview of the clinical status of candidate TB vaccines and discuss the challenges and future development trends of novel TB vaccine research, in combination with a general overview of the Tuberculosis (TB) disease and Mycobacterium tuberculosis itself. Methods: Bibliographic searches were carried out on medical journal databases, publishers, and aggregators. The most used databases were PubMed, NCBI and MDPI. Publications in English on these and other databases relating to novel TB vaccines were included in this review. Results: Currently, there are 12 main vaccine candidates in various phases of clinical trials, they include four protein or adjuvant vaccines, three viral-vectored vaccines, three mycobacterial whole cells or extract vaccines, and one each of the recombinant life and the attenuated Mycobacterium tuberculosis vaccine. Currently, the most likely candidate vaccines are the M72 + AS01E and Vaccae vaccines. M72 + AS01E is a recombinant fusion protein vaccine candidate, clinical trials showed that administering two doses of M72/AS01E was successful in reducing the development of active TB disease with 50% efficacy. Studies have also proven the efficacy of Vaccae (which is currently in phase III clinical trials) as an adjunctive therapy, with it being curative in conjunction with current therapy. Conclusion: Given the morbidity and mortality suffered globally by M. tuberculosis, it is time to realize the seriousness of the situation and accelerate our commitment and investment to the eradication of this infectious disease. With the number of vaccine candidates currently in clinical trials having promising results, it is imperative to continue these studies and accelerate towards phase III licensure trials if we are to achieve the milestone of “End TB Strategy” by 2035. Today, we are witnessing immense progress in both preclinical and clinical TB vaccine research despite disappointing results from some of the clinical efficacy trials like that of MVA85A. We can revisit the design of vaccines and learn from them. It is important not only to recognize and give credit to those that have tested well in human trials, such as M72 + AS01E, but to expedite and improve its efficacy through funding of its research.

A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG PSN) and thymopeptides on T lymphocytes of normal and immunosuppressed mice, CD4 + and CD8 + T lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG PSN and thymopeptides. Meanwhile, CD4 +/CD8 + ratio was also calculated. The results showed that both BCG PSN and thymopeptides could decrease the proportion of CD4 + CD8 + T lymphocyte subsets in the thymus, at the same time increase CD4 + T lymphocyte, CD8 +T lymphocyte proportion in the three tissues. The fluctuation in amplitude was greater in thymopeptides group than that in BCG PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG PSN, while BCG PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4 +T lymphocytes, and can maintain CD4 +/CD8 + ratio within normal range. So, BCG PSN is safer.

Protection of Citrullus colocynthis Fruit Extracts on Carbon Tetrachloride-induced and Bacillus Calmette-Guerin plus Lipopolysaccharide-induced Hepatotoxicity in Mice

Objective To investigate the hepatoprotective activities of the extracts from Citrullus colocynthis(ECC),a native plant used as traditional Uigur Medicine on acute liver injury in mice.Methods The activities of ECC of petroleum ether(ECCPE),chloroform(ECCC),ethyl acetate(ECCEA),n-butyl alcohol(ECCBA),and water(ECCW) were evaluated in vivo using two experimental models,carbon tetrachloride(CCl4)- and bacillus calmette-guerin(BCG) plus lipopolysaccharide(LPS)-induced acute hepatotoxicity in mice.The contents of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in serum were determined and the liver histological examination was carried out,respectively.Results The pretreatment with ECC for 7 d obviously reduced the impact of CCl4toxicity on the serum markers of liver damage,ECCEA and ECCC with a significant difference of AST(P < 0.01,0.05,respectively) and ALT(P < 0.05,0.01,respectively).The protective activity was reconfirmed against BCG + LPS-induced injury and the serum enzymatic levels were obviously elevated,for ECCEA and ECCC with a significant difference of AST(P < 0.05,0.01,respectively) and ALT(P < 0.01,0.05,respectively).Conclusion That ECCEA and ECCC are the potent hepatoprotective extracts that could protect liver against the acute injury,and this ability might be attributed to their hepatoprotective potentials.

BYL-719对结核杆菌诱导异常破骨细胞分化的作用及机制

背景:PI3K/AKT信号通路调控破骨激活在维持骨稳态中具有关键作用,而骨关节结核中的骨质破坏正是由于结核杆菌感染引起的异常破骨细胞生成所致,但是PI3K信号通路在结核杆菌诱导的异常破骨细胞生成中发挥的作用尚不明确。目的:探究PI3K/AKT信号通路抑制剂BYL-719对结核杆菌诱导的异常破骨细胞生成的影响及机制。方法:使用牛结核杆菌卡介苗(BCG)感染RAW264.7细胞,Ag85B进行细胞免疫荧光染色;CCK-8法确定BYL-719安全使用浓度。实验分为空白对照组、BYL-719组、卡介苗组、卡介苗+BYL-719组。各组细胞在RANKL诱导下,通过抗酒石酸酸性磷酸酶染色和鬼笔环肽染色,探究BYL-719对结核杆菌感染后破骨细胞分化、融合的影响;RT-PCR和Western Blot检测破骨细胞相关基因及蛋白表达情况,并进一步探索作用机制。结果与结论:①免疫荧光染色结果显示,RAW264.7细胞吞噬结核杆菌;②CCK-8数据显示,40 nmol/L浓度BYL-719没有细胞毒性;③抗酒石酸酸性磷酸酶染色和鬼笔环肽染色提示,BYL-719能抑制结核杆菌感染后的破骨细胞生成、融合能力;④RT-PCR和Western blot结果也提示,BYL-719抑制了结核杆菌感染诱导的破骨细胞特异性基因(包括c-Fos、NFATc1、基质金属蛋白酶9和CtsK)表达升高(P<0.05);⑤Western blot和免疫荧光染色结果揭示,BYL-719通过下调IκBα-p65来抑制结核杆菌诱导的破骨细胞过度分化;⑥结论:BYL-719通过下调IκBα/p65抑制结核杆菌诱导的异常破骨细胞生成,说明IκBα/p65信号通路是骨关节结核潜在治疗靶点,BYL-719有预防和改善骨关节结核中骨质破坏的潜在价值。

2018—2022年江苏省卡介苗疑似预防接种异常反应监测分析

目的掌握江苏省卡介苗(BCG)疑似预防接种异常反应(AEFI)流行病学特征,评价BCG接种安全性。方法通过中国疾病预防控制信息系统和江苏省预防接种综合服务管理信息系统收集2018—2022年江苏省BCG AEFI个案信息和接种数据,进行描述性流行病学分析。结果2018—2022年共报告BCG AEFI个案544例,报告发生率由53.86/10万剂降到12.42/10万剂,平均为27.18/10万剂,呈逐年下降趋势(χ2趋势=126.44,P<0.01)。一般反应、异常反应、偶合症分别为271例(13.54/10万剂)、258例(12.89/10万剂)、15例(0.75/10万剂)。异常反应中,局部脓肿和BCG淋巴结炎的报告发生率较高,分别为5.84/10万剂、4.00/10万剂;全身播散性BCG感染的报告发生率为0.15/10万剂。结论江苏省2018—2022年BCG AEFI报告发生率逐年下降,异常反应以局部脓肿为主,严重不良反应极为罕见,BCG安全性在预期范围内。

播散性卡介菌病1例

卡介苗是一种预防结核病的减毒活疫苗,健康新生儿出生时即予以接种。轻度不良反应为接种2~3 d后,接种部位皮肤发红,触之无硬结,数日后自行消退。播散性卡介菌病是最严重的不良反应,临床表现主要为接种部位红肿、破溃和溢脓,全身多发性淋巴结肿大、皮肤包块形成和肺部病变,也可累及肝脏、脾脏和骨骼。该病致死率高,早期诊断及治疗方法的选择仍是难题。现就我科诊治的1例临床诊断的播散性卡介菌病诊治过程及相关文献复习总结如下,以期为相应专业的临床医师提供一定帮助。

The Regulatory Effects of Polyporus Polysaccharide on the Nuclear Factor Kappa B Signal Pathway of Bladder Cancer Cells Stimulated by Bacillus Calmette-Guerin

Objective：To detect the effects of Polyporus polysaccharide（PPS）,Bacillus Calmette-Guerin （BCG）,and their combination on the nuclear factor kappa B（NF-κB）signaling pathway associated-gene expression and investigate the molecular mechanisms of the toxic-reducing effect of PPS in coordination with BCG against bladder cancer.Methods：After T739 cells were treated with PPS,BCG and their combination, the changes in mRNA and protein expression of inhibitor of kappa B kinase beta（IKKβ）,NF-κB subunit p65 （NF-κB p65）,intracellular adhesion molecule 1（ICAM1）and chemokine（C-c motif）ligand 2（CCL2）in bladder cancer cell line T739 were determined by relative quantitative real-time PCR,Western blot,and flow cytometry （FCM）.NF-κB p65 DNA-binding activity in T739 cell was detected by biotinylated probe-ELISA,and NF-κB p65 nuclear expression in T739 cell was observed by immunohistochemistry.Results：Compared with the T739 control group,the mRNA expression of IKBKB（IKKβ）,Rel A（NF-κB p65）,ICAM1 and CCL2 in T739 cells treated with BCG were increased obviously（Ratio2.0）,as well as the expression of IKKβ,CCL2 and ICAM1 proteins.Meanwhile,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression in T739 cells treated with BCG were up-regulated significantly（P0.05）.Compared with the control,the increased expression in T739 cells were simultaneously down-regulated after PPS treatment,except for ICAM1 protein expression.With cells treated with a combination of BCG and PPS,the expression of genes associated with the NF-κB signaling pathway,such as IKBKB,ICAM1 and CCL2,were all down-regulated compared to the BCG group,as well as Rel A mRNA expression,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression.Conclusions： PPS could inhibit the over-activation of the NF-κB signaling pathway induced by BCG in bladder cancer cells and accordingly attenuate the adverse reactions to BCG therapy.

Cloning and expression of the fusion protein of interleukin-2 and ESAT6 in Mycobacterium bovis Bacillus Calmette Guérin strain

Tuberculosis (TB) is the most common cause of death in infectious diseases; it is estimated that approximately 2 million people per year die of TB. The present available TB vaccine is a live attenuated strain, Mycobacterium bovis Bacillus Calmette Guérin (BCG). However, it has been shown that BCG has variable protective efficacy, ranging from 0 to 85% in different clinical experiments. 1 Therefore, a new TB vaccine is urgently needed. Many trials have been done to develop the second-generation TB vaccines in recent years; candidates include avirulent, auxotrophic, subunit, DNA, and recombinant vaccines. 2 The outcomes of these vaccines disappointed investigators. Encouragingly, recombinant BCG, which overexpressed the mycobacterial antigen Ag85B, produced an excellent protective response, 3,4 suggesting that a vaccine based on recombinant BCG technique was a potential approach against TB.

Expression and immunogenicity of recombinant Mycobacterium bovis Bacillus Calmette-Guérin strains secreting the antigen ESAT-6 from Mycobacterium tuberculosis in mice

Background Tuberculosis remains the leading cause of human death. Currently, Bacillus Calmette-Guerin （BCG） is the only available vaccine against tuberculosis but its efficacy is highly variable. Thus, developing new tuberculosis vaccines becomes an urgent task. In this study, we evaluated in BALB/c mice the humoral and cellular immune responses of recombinant BCG expressing the antigen ESAT-6 from Mycobacterium tuberculosis.Methods Escherichia coli-BCG shuttle plasmid named pDE22-esat-6 was constructed by inserting the BamHI/EcoRI digested esat-6 gene PCR product into the similarly digested parental plasmid pDE22. BCG cells were transformed with pDE22-esat-6, which was named recombinant BCG （rBCG）. BALB/c mice were immunized subcutaneously on the back with 100 μl normal saline containing 106 CFU of BCG or rBCG. They were sacrificed after 4 weeks to detect their humoral and cellular responses. Results There was no any significant differences in the growth characteristics between the conventional BCG and rBCG. In immunized mice, the IgG antibody titres of rBCG group were as high as 1：8000, which was significantly higher than that in BCG group （1：1400, P〈0.05）. The elicited IFN-γ, level of rBCG group was （1993 ± 106） pg/ml, which was also significantly higher than that in BCG group （（1463 ± 105） pg/ml, P〈0.05）. The splenocyte proliferation index of rBCG group reached 4.34 ± 0.31, which was higher than that of BCG group （3.79 ±0.24, P〈0.05）. Conclusion rBCG secreted expressing antigen ESAT-6 stimulated stronger humoral and cellular immune responses than BCG did, and, therefore may be the better vaccine against mycobacterium tuberculosis.

Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with non-muscle invasive bladder cancer？ An update and cumulative meta-analysis

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer （NMIBC）. NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guerin （BCG） instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells

Objective:Our objective was to construct a recombinant bacillus Calmette-Guérin vaccine(rBCG) that secretes human interferon-alpha 2b(IFNα-2b) and to study its immunogenicity and in vitro antitumor activity against human bladder cancer cell lines T24 and T5637.Methods:The signal sequence BCG Ag85B and the gene IFNα-2b were amplified from the genome of BCG and human peripheral blood,respectively,by polymerase chain reaction(PCR).The two genes were cloned in Escherichia coli-BCG shuttle-vector pMV261 to obtain a new recombinant plasmid pMV261-Ag85B-IFNα-2b.BCG was transformed with the recombinant plasmid by electroporation and designated rBCG-IFNα-2b.Mononuclear cells were isolated from human peripheral blood(PBMCs) and stimulated with rBCG-IFNα-2b or wild type BCG for 3 d,and then cultured with human bladder cancer cell lines T24 and T5637.Their cytotoxicities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay.Results:BCG was successfully transformed with the recombinant plasmid pMV261-Ag85B-IFNα-2b by electroporation and the recombinant BCG(rBCG-IFNα-2b) was capable of synthesizing and secreting cytokine IFNα-2b.PBMC proliferation was enhanced significantly by rBCG-IFNα-2b,and the cytotoxicity of PBMCs stimulated by rBCG-IFNα-2b to T24 and T5627 was significantly stronger in comparison to wild type BCG.Conclusions:A recombinant BCG,secreting human IFNα-2b(rBCG-IFNα-2b),was constructed successfully and was superior to control wild type BCG in inducing immune responses and enhancing cytotoxicity to human bladder cancer cell lines T24 and T5637.This suggests that rBCG-IFNα-2b could be a promising agent for bladder cancer patients in terms of possible reductions in both clinical dosage and side effects of BCG immunotherapy.

Role of toll like-receptor 2 in inflammatory activity of macrophage infected with a recombinant BCG expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum

Objective: To investigate the role of toll-like receptor 2(TLR2) in inflammatory activity of macrophage infected with the recombinant Mycobacterium bovis bacillus Calmette-Guerin(rBCG). Methods: Mouse macrophage cell line J774 A.1 was infected with Mycobacterium bovis bacillus Calmette-Guerin(BCG) and rBCG cultures for 48 h in the presence or absence of 10 μg/mL of TLR2 inhibitor. Untreated macrophages were used as a negative control while lipopolysaccharide-stimulated macrophages were used as a positive control. The ability of the macrophage to engulf the BCG and rBCG in the absence or presence of TLR2 inhibitor was assessed using a phagocytic assay, while the production of inflammatory cytokines and nitric oxide by the infected macrophages was evaluated using ELISA and Griess reagent method, while the expression of the inducible nitric oxide synthase was determined using Western blot analysis. Results: The results showed that blocking TLR2 function reduced the phagocytic activity, nitric oxide production and proinflammatory cytokine secretion such as TNF-α, IL-1β and IL-12 p40 as well as inducible nitric oxide synthase expression in the infected macrophages. These data showed the importance of TLR2 in the activation of macrophages following BCG and r BCG infections. Conclusions: Through exploring the immunological mechanism which underlies the protection conferred by the candidate vaccine, this study will improve our understanding of the vaccine candidate's mechanism to protect the host from malaria infection.

Study of recombinant human IFN-α-2b bacilli Calmette–Guerin activated killer cells and against bladder cancer cell in vitro

Presently,one of the most potent immunothera-pies is the application of bacillus Calmette Guerin(BCG)to prevent recurrences of the superficial bladder cancer.Despite its successful use,nonresponders and certain side effects remain a major obstacle.Therefore,current studies aim at developing recombinant BCG(rBCG)strains secreting Th1-like cytokines to improve the effectiveness of the therapy.In this study,a new type of rBCG strain constructed by Tianjin institute of Urology was tested for its immunostimulatory capacity in vitro.Peripheral blood monocytes(PBMC)were stimulated by recombinant BCG and transformed into bacilli Calmette–Guerin activated killer(BAK)cells,and the effect of anticancer BAK cells was studied.Recombinant IFN-a-2b-BCG,wild-type BCG(wBCG),wild-type BCG and IFN-a-2b were coincubated with PBMCs respectively in vitro,and the proliferation of PBMC was detected with MTT in different time.BAK cells have the ability to kill bladder tumor cells,and the antitumor activity of effecter cells was determined by LDH release assay.The result of MTT showed that the proli-feration of PBMC in the recombinant BCG group was more powerful than in the other two groups(P<0.05).The result of LDH release assay showed that the antitumor activity of BAK cells stimulated by Recombinant BCG was the highest in all groups.We conclude that the recombinant BCG can activate more PBMCs to anti-bladder cancer in vitro than wild-type BCG does.

百日咳毒素联合卡介苗诱导CD-1小鼠抑郁症模型研究

为了构建具备良好的治疗性干预时间窗的新型抑郁症动物模型,本研究基于抑郁症发病的炎症假说,选用血脑屏障通透剂——百日咳毒素,联合低剂量免疫激活剂——卡介苗(牛结核分枝杆菌)对CD-1小鼠造模。实验发现,与单独低剂量卡介苗诱导相比,百日咳毒素联合低剂量卡介苗诱导可以增强小鼠的抑郁样行为,如行为绝望状态增加(悬尾实验中一动不动时间)、探索性行为降低(开场实验中的区域穿梭次数和抬头直立次数)、自发运动状态降低(开场实验总运动距离)等,促进小鼠中枢神经炎症和外周炎症(IL-1β、IL-6、IFN-γ等);同时,加剧脑中色氨酸-犬尿氨酸通路的激活,表现为其关键酶——吲哚胺2,3-双加氧酶1(IDO1)进一步显著升高。经口给予抗抑郁药丙咪嗪,可缓解百日咳毒素联合低剂量卡介苗诱导的小鼠抑郁样症状、炎症反应和激活的色氨酸-犬尿氨酸通路。另外,发现百日咳毒素联合低剂量卡介苗诱导的小鼠抑郁样症状可以从第7天至少持续到第28天。综上,本研究基于百日咳毒素和低剂量卡介苗构建的小鼠抑郁模型具有较好的表面效度、结构效度和预测效度,其长期持续性的抑郁表型可为抗抑郁疗法研究提供宝贵的治疗性干预时间窗。

结核病疫苗研究进展及挑战

卡介苗是目前唯一应用于预防人类结核病的疫苗,但其保护效果备受争议,研究新型高效的结核病疫苗尤为重要。从安全性、经济成本及保护效果等方面考虑,多阶段抗原亚单位疫苗或多表位疫苗具有较好的应用前景。随着对结核分枝杆菌致病机制的深入了解以及疫苗研发技术的不断更新,结核病疫苗会有重大突破。本文论述结核病疫苗的类型及其特性,并针对结核病新型疫苗研究中抗原选择、动物模型选择、疫苗效果评价指标及人群特异性存在的问题和挑战进行讨论,旨在为新型结核病疫苗的研究提供参考。

单中心非肌层浸润性膀胱癌患者行卡介苗灌注治疗的疗效分析

目的探讨非肌层浸润性膀胱癌(NMIBC)患者行卡介苗(BCG)灌注治疗的疗效、不良反应及其独立危险因素。方法回顾2015年9月~2021年9月于中山大学肿瘤防治中心术后BCG灌注的患者资料。采用无复发生存率(RFS)、无进展生存率(PFS)和疾病特异生存率(DSS)评估BCG灌注患者的预后。不良反应事件评价标准5.0版评估灌注后不良反应。采用Kaplan-Meier生存分析,单因素、多因素COX回归分析BCG灌注的独立预测因子。结果共纳入患者421名,患者平均年龄为61.79±11.51岁,中位随访时间为17月。BCG灌注后88名患者发现复发(20.9%),中位复发时间为13个月;40名患者出现进展(9.5%),中位时间为18个月;14名患者死亡(3.3%),中位时间为30个月。201名患者出现相关不良反应,1级不良反应的患者有69名;2级不良反应有110名;3级不良反应23名。生存分析提示当患者年龄小于67.5岁(P=0.013),肿瘤为初发(P<0.001)、单发(P=0.010)、超过1年复发(P=0.042),且患者中性粒细胞较低(P=0.005),单核细胞较低(P=0.001),NLR(中性粒细胞/淋巴细胞)(P=0.014)较低,细胞角蛋白19片段(CyFra21-1)(P=0.002)较低时无复发生存率明显升高,当患者年龄小于67.5岁(P=0.042),肿瘤为初发(P<0.001),CyFra21-1较低(P=0.042)时患者无进展生存率更高。多因素COX分析提示:肿瘤复发时间(P=0.007,HR=2.669,95%CI 1.316-5.414)、单核细胞数(P=0.015,HR=0.376,95%CI 0.171-0.829)和CyFra21-1值(P=0.002,HR=0.312,95%CI 0.151-0.647)是NMIBC患者BCG灌注RFS的独立预测因素;肿瘤初发或复发(P=0.003,HR=0.301,95%CI 0.138-0.660)、中性粒细胞数(P=0.028,HR=0.302,95%CI 0.103-0.882)和CyFra21-1值(P=0.029,HR=0.358,95%CI 0.142-0.903)是PFS的独立预测因素。结论对于中、高危的NMIBC患者术后的BCG灌注治疗效果显著,且大部分的不良反应患者可耐受。肿瘤的复发时间、单核细胞计数和CyFra21-1为RFS的独立预测因素,肿瘤的初发或复发、中性粒细胞计数以及CyFra21-1为PFS的独立预测因素。

左西替利嗪、孟鲁司特联合卡介菌素对慢性荨麻疹的治疗效果及价值分析

目的研究左西替利嗪、孟鲁司特联合卡介菌素对评慢分性荨麻疹的治疗效果及价值。方法200例慢性荨麻疹患者,随机分为观察组和对照组,每组100例。对照组实施孟鲁司特联合卡介菌素治疗,观察组在对照组的基础上采用左西替利嗪治疗。比较两组患者症状消失时间、治疗效果、不良反应发生情况(轻度皮肤刺激、恶心、呕吐)及治疗前后生活质量评分、实验室指标[白三烯B4(LTB4)、白细胞介素(IL-)4、IL-6]。结果观察组患者烦躁消失时间(16.25±1.12)d、瘙痒消失时间(14.21±1.22)d、风团消失时间(15.25±1.45)d均短于对照组的(24.52±1.78)、(21.52±1.02)、(27.52±1.85)d,差异均具有统计学意义(P<0.05)。观察组治疗总有效率95.00%高于对照组的80.00%,差异具有统计学意义(P<0.05)。治疗后,观察组患者躯体功能评分(95.25±1.20)分、心理功能评分(94.56±1.45)分、社会功能评分(95.25±1.45)分、物质生活评分(95.75±1.45)分均高于对照组的(79.25±1.58)、(79.25±1.52)、(78.25±1.14)、(81.25±1.45)分,差异均具有统计学意义(P<0.05)。观察组不良反应发生率3.00%低于对照组的32.00%,差异具有统计学意义(P<0.05)。治疗后,观察组患者LTB4(14.33±1.54)pg/ml、IL-4(39.65±1.24)pg/ml、IL-6(166.98±1.54)pg/ml均低于对照组的(30.61±1.68)、(50.65±1.22)、(186.82±1.37)pg/ml,差异均具有统计学意义(P<0.05)。结论左西替利嗪、孟鲁司特联合卡介菌素对慢性荨麻疹的治疗效果十分显著,且安全性高。

福建叶下珠抗小鼠免疫性肝损伤的实验研究

目的评价福建叶下珠对小鼠免疫性肝损伤的保护作用。方法48只NIH小鼠随机分为叶下珠高、低剂量组、联苯双酯组、正常对照组及模型组。于造模之日起,叶下珠高、低剂量组分别以20 g/kg、10 g/kg叶下珠药液灌胃,联苯双酯组以0.15 g/kg联苯双酯药液灌胃,正常对照组及模型组每天给予等量生理盐水。每天灌胃1次,连用12 d。检测血清谷丙转氨酶(ALT)和肝、脾脏器指数,并做肝脏病理学检查。结果联苯双酯组、叶下珠高、低剂量组小鼠血清ALT、肝指数、脾指数值较模型组有不同程度的改善(P<0.05,P<0.01)。炎症坏死程度:5组间比较,差异有非常显著性意义(P<0.005);模型组与正常组、联苯双酯组、福建叶下珠高、低剂量组与模型组间两两比较,差异有显著性意义(P值均<0.05);联苯双酯组与福建叶下珠大、小剂量组间比较,差异无显著性意义(P>0.05)。结论福建叶下珠能显著降低血清转氨酶活力和肝脾脏器指数,对肝细胞坏死有一定的改善作用,具有较好的抗小鼠免疫性肝损伤作用。