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论著

免疫联合化疗对晚期 NSCLC 患者淋巴细胞免疫及生活质量的影响

Effect of immunotherapy combined with chemotherapy on lymphocyte immunity and quality of life in patients with advanced NSCLC

:760-765
 
       目的   探讨免疫治疗联合化学治疗(化疗)对晚期非小细胞肺癌(NSCLC)患者淋巴免疫及生活质量的影响,为临床进一步治疗提供参考。  选择2021年6月—2023年6月天津市滨海新区大港医院收治的晚期NSCLC患者120例进行研究,按抽签法分为干预组及对照组,每组60例,对照组采取单纯化疗方案,干预组采取免疫联合化疗方案,对比两组临床疗效、药物不良反应,治疗前后免疫功能(CD3+ 、CD4+ 、CD8+ )、糖类抗原199(CA199)、糖类抗原 125(CA125)、血清癌胚抗原(CEA)水平及健康状态调查表(QOL)评分。结果  干预组患者治疗总有效率高于对照组(68.33%>41.67%,P<0.05);治疗后干预组患者CD3+ 、CD4+ 比例高于治疗前及对照组治疗后,CD8+ 比例低于治疗前及对照组治疗后(P<0.05);治疗后干预组血清CA199、CA125、CEA水平均低于治疗前及对照组治疗后(P<0.05);干预组药物不良反应发生率为16.67%,对照组为36.67%,干预组低于对照组(P<0.05);治疗后干预组QOL各维度评分高于对照组及治疗前(P<0.05)。结论  与单纯化疗相比,免疫联合化疗治疗晚期NSCLC患者,能有效降低肿瘤标志物水平,改善患者免疫指标,减轻药物不良反应,提高患者疗效及生活质量。
       Objective  To explore the effect of immunotherapy combined with chemotherapy on lymphatic immunity and quality of life of patients with advanced non-small cell lung cancer(NSCLC),and to provide reference for further clinical treatment.Methods  A total of 120 patients with NSCLC from June 2021 to June 2023 were selected and divided into observation group and control group evenly according to the method of drawing lots,control group was treated with chemotherapy,the observation group was treated with immunotherapy combined with chemotherapy,and the clinical efficacy and adverse drug reactions were compared between the two groups.Before and after treatment,immune function(CD3+ ,CD4+ ,CD8+ ),carbohydrate antigen 199(CA199),carbohydrate antigen 125(CA125),serum carcinoembryonic antigen(CEA)levels and health status questionnaire(QOL-RRB- scores)were measured.Results The total effective  rate in the observation group was significantly higher than that in the control group(68.33%>41.67%,P<0.05).After treatment,the ratios of CD3+  and CD4+  in the observation group were significantly higher than those before treatment and control group after treatment,and the ratio of CD8+  was significantly lower than that before and after treatment in the control group(P<0.05).After treatment,the serum levels of CA199,CA125 and CEA in the observation group were lower than those before and after treatment in the control group(P<0.05).The incidence of adverse drug  reactions was 16.67% in the observation group and 36.67% in the control group,which was significantly lower in the observation group than in the control group(P<0.05).After treatment,the QOL scores in the observation group were significantly higher than those in the control group and before treatment(P<0.05).Conclusions  Compared with chemotherapy alone,immunotherapy combined with chemotherapy can effectively reduce the levels of tumor markers,improve the immune indexes of patients,reduce the adverse drug reactions,and improve the efficacy and quality of life of patients with advanced NSCLC.
论著

单克隆免疫球蛋白血症患者 M 蛋白质量浓度检测的临床意义

Clinical significance of detecting M protein concentration in patients with monoclonal gammopathy

:669-674
 
       目的   探讨单克隆免疫球蛋白血症患者M蛋白质量浓度检测的临床意义。方法   选取2018年6月—2023年6月龙岩人民医院收治的88例单克隆免疫球蛋白血症患者为研究对象,其中意义未明单克隆免疫球蛋白血症(MGUS)21例,具有肾脏意义单克隆免疫球蛋白血症(MGRS)50例,血液系统恶性肿瘤17例。对比其M蛋白质量浓度及临床实验室相关指标表达水平,采用Spearman相关分析法分析临床实验室相关指标的与M蛋白的相关性,对所有患者进行半年随访,以预后情况作为因变量,纳入Logistics回归模型分析M蛋白质量浓度对单克隆免疫球蛋白血症预后的预测价值。结果   不同病种M蛋白水平分别为(2.42±0.55)(2.57±0.64)(4.36±0.64)g/L、24 h尿蛋白分别为(1.45±0.16)(2.98±0.68)(2.43±0.44)g/24 h、血清白蛋白质量浓度分别为(31.01±3.06)(35.03±5.04)(39.05±7.08)g/L、总胆固醇水平分别为(3.42±1.25)(3.87±0.64)、(4.16±0.64)mmol/L、血肌酐水平分别为(114.35±23.23)(81.18±12.12)(146.36±21.12)μmol/L、血红蛋白质量浓度分别为(148.12±15.26)(141.69±12.15)(133.34±15.31)g/L,组间对比差异均有统计学意义(F分别为23.890,19.700,12.044,25.767,36.572,10.267,P<0.05)。MGUS患者24h尿蛋白与M蛋白有相关性(r=-0.384,P=0.033),24 h尿蛋白、血清白蛋白、总胆固醇、血肌酐与MGRS患者M蛋白有相关性(r=-0.586,P=0.006;r=0.431,P=0.018;r=-0.457,P=0.020;r=0.523,P=0.009),血清白蛋白、总胆固醇、血红蛋白与血液系统恶性肿瘤患者M蛋白有相关性(r=0.374,P=0.029;r=-0.617,P=0.001;r=-0.414,P=0.024);年龄、M蛋白为单克隆免疫球蛋白血症患者预后的影响因素(P<0.05)。结论   不同单克隆免疫球蛋白血症患者M蛋白水平存在差异,其中血液系统恶性肿瘤患者的M蛋白水平最高,且M蛋白为单克隆免疫球蛋白血症预后的独立影响因素。  
       Objective  To explore the clinical significance of detecting M protein concentration in patients with monoclonal gammopathy.Methods  From June 2018 to June 2023,88 patients with monoclonal gammopathy admitted to the hospital were selected as the study subjects.Among them,21 cases of monoclonal gammopathy with undetermined  significance(MGUS),50 cases of monoclonal gammopathy with renal significance(MGRS),and 17 cases of hematological malignancies were selected.Concentration of M protein and the expression levels of clinical laboratory related indicators were compared,Spearman correlation analysis was used to analyze the correlation between clinical laboratory related indicators and M protein.All patients were followed up for six months,with prognosis as the dependent variable,included in the logistic regression model to analyze the predictive value of M protein concentration on the prognosis of monoclonal gammopathy.Results  There were significant differences in the expression levels of M protein([2.42±0.55],[2.57±0.64],[4.36±0.64])g/L,24-hour urine protein([1.45±0.16],[2.98±0.68],[2.43±0.44])g/24 h,serum albumin([31.01±3.06],[35.03±5.04],[39.05±7.08])g/L,total cholesterol([3.42±1.25],[3.87±0.64],[4.16±0.64])mmol/L,blood creatinine([114.35±23.23],[81.18±12.12],[146.36±21.12])μmol/L,and hemoglobin([148.12±15.26],[141.69±12.15],[133.34±15.31])g/L among different diseases(F=23.890,19.700,12.044,25.767,36.572,10.267;P<0.05).There was a significant correlation between 24 h urinary protein and M protein in MGUS patients(r=-0.384,P=0.033).Urinary protein,serum albumin,serum cholesterol and blood creatinine were significantly associated with M protein in MGRS patients(r=-0.586,P=0.006;r=0.431,P=0.018;r=-0.457,P=0.020;r=0.523,P=0.009),Serum albumin,total cholesterol,and hemoglobin were significantly associated with M protein in patients with hematological malignancies(r=0.374,P=0.029;r=-0.617,P=0.001;r=-0.414,P=0.024;P<0.05).Age and M protein were independent  risk factors for the prognosis of patients with monoclonal gammopathy(P<0.05).Conclusions  There are significant differences in the concentration of M protein among patients with different levels of monoclonal gammopathy,with the highest level observed in patients with hematological malignancies.M protein is an independent prognostic factor for monoclonal gammopathy.
论著

免疫及靶向药物联合肝动脉灌注化疗治疗晚期肝癌的临床分析

Clinical analysis of immune and targeted drugs combined with hepatic artery infusion chemotherapy in the treatment of advanced liver cancer

:662-668
 
       目的   探讨免疫及靶向药物联合肝动脉灌注化学治疗(化疗)治疗晚期肝癌的临床疗效。方法   选取甘肃省武威市人民医院2021年1月—2024年1月收治的78例晚期肝癌患者进行回顾性分析,其中20例患者采取单纯肝动脉灌注化疗(HAIC)治疗为单化疗组,30例患者采取HAIC联合程序性细胞死亡受体-1(PD-1)抗体治疗为免疫组,28例患者采取HAIC联合PD-1抗体免疫治疗与甲磺酸仑伐替尼胶囊靶向治疗为联合组。对比三组临床疗效、治疗前后胚抗原(CEA)、糖类抗原125(CA125)、甲胎蛋白(AFP)表达水平,不良反应发生率,并采用Piper疲乏修正量表(PFS-R)、世界卫生组织生存质量量表简表(WHOQOL-BREF)对两组癌因性疲乏程度及生存质量进行评价。结果   单纯化疗组、免疫组、联合组客观缓解率分别为15.00%、40.00%、64.29%,疾病控制率为30.00%、66.67%、82.14%,联合组高于单纯化疗组与免疫组(χ 2 =11.720,P=0.003;χ 2 =13.890,P<0.001);治疗后三组患者CEA、CA125、AFP水平均降低,且联合组[CEA:(13.62±4.24)ng/mL、CA125:(31.62±13.66)U/mL、AFP:(35.21±5.93)ng/mL]低于免疫组[(17.85±3.32)ng/mL、(59.26±9.35)U/mL、(42.12±4.12)ng/mL]及单纯化疗组[(23.73±4.79)ng/mL、(64.57±5.23)U/mL、(47.46±5.32)ng/mL],对比差异有统计学意义(F=7.698,P<0.001;F=11.480,P<0.001;F=14.952,P<0.001;P<0.05);所有患者均无5级不良反应及严重肝功能损害出现,且三组血小板减少、白细胞减少、腹痛、呕吐、消化道出血、厌食等不良反应发生率对比差异无统计学意义(P>0.05);治疗后三组患者PFS-R评分均降低,联合组(3.85±1.13)分低于免疫组(5.39±1.25)分及单纯化疗组(6.33±1.26)分,WHOQOL-BREF评分均升高,联合组(348.58±66.12)分高于免疫组(297.24±72.21)分及单纯化疗组(256.35±41.67)分,对比差异有统计学意义F=2.526,P=0.014;F=2.167,P=0.033)。结论   免疫及靶向药物联合肝动脉灌注化疗治疗晚期肝癌疗效显著,可有效控制疾病进展的同时,降低机体肿瘤标志物水平,安全性可控,同时可改善患者生存质量,减轻癌因性疲乏程度。
       Objective  To explore the clinical efficacy of immune and targeted drugs combined with hepatic artery infusion chemotherapy(HAIC)in the treatment of advanced liver cancer.Methods  A retrospective analysis was conducted on 78 patients with advanced liver cancer admitted to our hospital from January 2021 to January 2024.Among them,20 patients were treated with simple HAIC and divided into a single chemotherapy group.Thirty patients were treated with HAIC combined with PD-1 antibody,and divided into an immune group.Twenty-eight patients were treated with HAIC combined with PD-1 antibody immunotherapy and lenvatinib mesylate capsule targeted therapy,and divided into a combination group.The clinical efficacy of three groups,the expressionlevels of CEA,CA125,AFP,and incidence of adverse reactions before and after treatment were compared.Piper Fatigue Correction Scale(PFS-R)and the WHO QOL-BREF were used to assess cancer-related fatigue in both groups.The degree of fatigue and quality of life were assessed.Results  The objective response rates of the simple chemotherapy group,the immune group,and the combination group were 15.00%,40.00% and 64.29%,respectively.The disease control  rates were 30.00%,66.67% and 82.14%,respectively.The indicators above of the combination group was significantly higher than those in the simple chemotherapy group and the immune group(χ 2 =11.720,P=0.003;χ 2 =13.890,P<0.001;P<0.05).After treatment,the levels of CEA,CA125 and AFP were all decreased in the three groups,and those in the combined group (CEA[13.62±4.24]ng/mL,CA125[31.62±13.66]U/mL,AFP:Ng/mL[35.21±5.93])were lower than those in the immune group(17.85±3.32 ng/mL,59.26±9.35 U/mL,/ 42.12±4.12 ng/mL)and single chemotherapy group(23.73±4.79 ng/mL,64.57±5.23 U/mL47.46±5.32]ng/mL),the differences were statistically significant(F=7.698,P<0.001;F=11.480,P<0.001;F=14.952,P<0.001;P<0.05).All patients had no grade 5 adverse reactions or severe liver function damage,and there was no statistically significant difference in the incidence adverse reactions such as thrombocytopenia,leukopenia,abdominal pain,vomiting,gastrointestinal bleeding,and anorexia among the three groups(P>0.05).After treatment,the PFS-R score of the three groups was decreased,and the combined group(3.85±1.13)score was lower than that of the immune group(5.39±1.25)and the chemotherapy group(6.33±1.26).While the WHOQOL-BREF score was increased,the score of combination group(348.58±66.12)was higher than that of immune group(297.24±72.21)and chemotherapy group(256.35±41.67),and the difference was statistically significant(F=2.526,P=0.014;F=2.167,P=0.033;P<0.05).Conclusions  The combination of immune and targeted drugs with hepatic artery infusion chemotherapy has a significant therapeutic effect on advanced liver cancer.It can effectively control disease progression,reduce tumor marker levels in the body,improve patient quality of life,and alleviate cancer-related fatigue,with controllable safety
学术前沿

MDSCs 在肿瘤免疫治疗中的研究进展

Research progress of MDSCs in tumor immunotherapy

:151-159
 
       实体瘤对免疫治疗应答非常有限,因此,如何有效提升肿瘤免疫治疗的疗效,已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞(MDSCs)的趋化募集及其所介导的肿瘤免疫逃逸机制,是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制,以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外,文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战,并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应,为癌症患者提供更为个性化、高效的治疗方案,从而开启肿瘤免疫治疗领域的新纪元,为癌症治疗策略的创新与发展贡献力量。
  Solid tumors exhibit a very limited response to immunotherapy.Consequently,effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy.The chemotaxis and recruitment of myeloid-derived suppressor cells(MDSCs)and the tumor immune evasionmechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors.In this review,we discuss the origins and phenotypic characteristics of MDSCs,the specific mechanisms by which they mediate tumor immune evasion,as well as current targeted therapeuticstrategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy.Furthermore,we  have  systematically analyzed the  key challenges faced by the combination of MDSC-targeted and immunotherapy strategies,and accordingly proposed a precise targeting strategyfor MDSCs.This strategy aims to precisely activate anti-tumor immune responses,providing more personalized and efficienttreatment options for cancer patients,thereby opening a new era in tumor immunotherapy and contributing to the innovation anddevelopment of cancer treatment strategies.
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