目的探讨CMTM6、PD-L1在子宫内膜异位症(endometriosis,EM)中的表达及意义。方法收集50例EM患者腹腔镜下手术切除的卵巢异位子宫内膜组织、刮除的在位子宫内膜组织(实验组)以及30例非EM患者刮除的在位子宫内膜组织(对照组),采用免疫组...目的探讨CMTM6、PD-L1在子宫内膜异位症(endometriosis,EM)中的表达及意义。方法收集50例EM患者腹腔镜下手术切除的卵巢异位子宫内膜组织、刮除的在位子宫内膜组织(实验组)以及30例非EM患者刮除的在位子宫内膜组织(对照组),采用免疫组化法检测CMTM6、PD-L1的表达水平。收集实验组相关临床病理资料,包括患者年龄、体重指数(body mass index,BMI)、病灶大小、血清CA-125浓度及rAFS评分等,采用Spearman系数法分析CMTM6、PD-L1的表达与上述病理参数的相关性。培养人EM上皮细胞系12Z,采用Western blot及免疫蛋白共沉淀法检测CMTM6、PD-L1的表达水平及相互作用。结果CMTM6、PD-L1在EM患者中高表达,EM患者异位、在位子宫内膜中的表达水平高于非EM患者在位子宫内膜组织(P<0.05),CMTM6、PD-L1表达共同定位于异位、在位子宫内膜组织上皮细胞质、细胞膜中,且两种蛋白表达呈正相关(P<0.05)。患者年龄、BMI、病灶大小、血清CA-125浓度及rAFS评分与CMTM6、PD-L1的表达呈正相关(P<0.01)。CMTM6、PD-L1蛋白在12Z中表达,且CMTM6和PD-L能够相互结合。结论CMTM6、PD-L1在EM患者中高表达,CMTM6、PDL1的表达水平与EM病变严重程度相关,CMTM6、PD-L1在EM中能相互结合共同参与EM的发生、发展,CMTM6、PD-L1或可成为EM的潜在生物学标志物,为EM的临床诊治提供新靶点。展开更多
目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)...目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)通路的影响。方法把MCF-7人乳腺癌细胞中NC组和AKR1C3组分别转染空质粒和AKR1C3质粒,采用MTT法检测转染后24 h、48 h、72 h细胞活力;采用流式细胞技术测定各组细胞的存活率以及早期、晚期凋亡比例;通过Transwell实验对各组细胞的迁移和侵袭能力进行检测;通过Western blot检测各组细胞PD-1、PD-L1、蛋白激酶B(protein kinase b,AKT)蛋白表达水平。使用C57BL/6小鼠构建荷瘤模型,将采用人乳腺癌MCF-7细胞转染NC质粒和AKR1C3质粒进行细胞荷瘤,每3 d测量瘤体积,持续21 d,绘制两组小鼠肿瘤生长曲线,并于实验终点测量肿瘤质量。结果相较于NC组,AKR1C3组细胞活力降低(P<0.05),并且具有时间依赖效应(P<0.05),迁移和侵袭能力降低(P<0.05),早期凋亡和晚期凋亡比例升高(P<0.05),PD-1、PD-L1、AKT蛋白表达水平降低(P<0.05)。动物实验表明,AKR1C3组小鼠肿瘤体积降低,肿瘤质量下降(P<0.05)。结论AKR1C3可以抑制人乳腺癌细胞恶性生物学行为,抑制PD-1/PDL1信号通路蛋白表达。展开更多
构建使用了PD-1抑制剂的肿瘤患者出现甲状腺功能障碍的风险预测模型,分析使用PD-1肿瘤抑制剂导致的甲状腺功能障碍的相关风险因素,设计监测预警系统。选取2020年—2023年广西医科大学附属肿瘤医院1225例使用PD-1抑制剂肿瘤患者的临床资...构建使用了PD-1抑制剂的肿瘤患者出现甲状腺功能障碍的风险预测模型,分析使用PD-1肿瘤抑制剂导致的甲状腺功能障碍的相关风险因素,设计监测预警系统。选取2020年—2023年广西医科大学附属肿瘤医院1225例使用PD-1抑制剂肿瘤患者的临床资料,包括人口学特征、既往史、实验室检测等63个变量。本文选取相关性前10/20/30/40/50/60个变量的4种传统机器学习模型进行性能比较。通过F1分数、灵敏度、准确率、精确率、特异性曲线下面积(Area Under the Curve,AUC)评估以上预测模型的性能,并利用Shapley加性解释(Shapley Additive Explanation,SHAP)可视化解释本文的机器学习模型。与促甲状腺激素相关性排名前10的变量依次为:羟丁酸脱氢酶、乳酸脱氢酶、淋巴细胞绝对值、天门冬氨酸转移酶、钙离子、碱性磷酸酶、谷氨酰转肽酶、单核细胞绝对值、红细胞分布宽度SD、胆碱酯酶。建立了使用PD-1抑制剂的肿瘤患者出现甲状腺功能障碍的风险预测模型,并在全局解释和局部解释的层面上分别作出模型预测结果影响的解释。展开更多
The bowel preparation is a crucial step to achieve an optimal quality in colonoscopy.The major clinical impact of an adequate colonic cleansing is to allow a more detailed and thorough inspection reducing the rates of...The bowel preparation is a crucial step to achieve an optimal quality in colonoscopy.The major clinical impact of an adequate colonic cleansing is to allow a more detailed and thorough inspection reducing the rates of missing lesions during the procedure and consequently reducing the incidence of interval colorectal carcinomas.Currently there are different colonoscopic preparation schemes,being the polyethylene glycol(PEG)based regimen one of the most used and recommended by the main international clinical guidelines.Nevertheless,PEG preparation requires the ingestion of considerably large volumes to achieve an optimal colonic cleansing,leading to poor tolerability in may patients,particularly in an elderly population.Other aspects that make accessibility to most colonoscopy preparation regimens difficult is their high cost and low availability.New options of colonoscopic preparation schemes based on oral lactulose are emerging with promising results,showing excellent efficacy-safety profiles and high tolerability indexes.Lactulose regimens present other benefits such as low cost and wide availability.The aim of this review is to analyze the scientific evidence to date and the current status of colonoscopy bowel preparation utilizing lactulose-based regimens,in order to consolidate this agent as a feasible“new player”in the field of colonoscopic preparation.展开更多
BACKGROUND Functional abdominal pain disorders(FAPDs)are common gut–brain interaction disorders with unclear pathophysiology.While impaired gastrointestinal motility is thought to play a key role,small intestinal dys...BACKGROUND Functional abdominal pain disorders(FAPDs)are common gut–brain interaction disorders with unclear pathophysiology.While impaired gastrointestinal motility is thought to play a key role,small intestinal dysmotility remains largely unexplored.Orocecal transit time(OCTT),an indirect indicator of small intestinal transit,offers an insight into its potential contribution to FAPD's pathophysiology.AIM To assess OCTT in children with FAPDs compared with healthy children using the lactulose breath hydrogen test.METHODS Thirty-four children(44.1%males,age 5–12 years,mean 7.2±2.4 years)with FAPDs attending North Colombo Teaching Hospital,Ragama,Sri Lanka,were included in the analysis.FAPDs were diagnosed using the Rome IV criteria.None had clinical or laboratory evidence of organic diseases.They were compared with 19 healthy controls(47.1%males,age 5-12 years,mean 7.8±2.7 years)from the same geographical area.OCTT was calculated after an 8-hour fast using a previously validated technique.Breath hydrogen levels were measured at baseline and 15-minute intervals for 180 minutes post-lactulose ingestion(10 g in 10%solution).At each time point,3 breath samples were collected and analyzed.OCTT was quantified as the time taken to achieve a sustained breath hydrogen increase>10 parts per million above baseline.Symptoms were recorded using the Rome IV questionnaire,and symptom severity was graded on a 0-4 Likert scale.RESULTS Patients with FAPDs had increased OCTT(median,90 minutes;interquartile range,75-120 minutes)compared to controls(median,75 minutes;interquartile range,60-75 minutes)(P=0.0045,Mann-Whitney U-test).Children with functional dyspepsia had the longest mean OCTT(110.8±26.7 minutes).There was no significant correlation between abdominal pain severity and OCTT(r=0.18,P=0.35,Spearman correlation coefficient).OCTT did not differ between those exposed to stressful events and those not exposed to such events(P>0.05).CONCLUSION Children with FAPDs have longer OCTT than healthy controls.However,the lack of a significant correlation between OCTT and symptom severity suggests that delayed small intestinal transit alone is not a substantial contributor to FAPD pathophysiology.展开更多
目的:探究卵巢癌(ovarian cancer,OV)浸润性CD4^(+)调节性T细胞(regulatory T cell,Treg)的脂质摄取与积累情况,及其与CD4^(+)Treg中程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和细胞毒性T淋巴细胞相关蛋白-4(cytotoxi...目的:探究卵巢癌(ovarian cancer,OV)浸润性CD4^(+)调节性T细胞(regulatory T cell,Treg)的脂质摄取与积累情况,及其与CD4^(+)Treg中程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和细胞毒性T淋巴细胞相关蛋白-4(cytotoxic Tlymphocyte associated protein 4,CTLA-4)表达的相关性。方法:采用亲脂性荧光染料BODIPY^(TM)493/503和荧光脂肪酸探针BODIPY^(TM)500/510 C1 C12分别检测OV组织中的或与不同OV细胞系(ES-2、SKOV3、CAOV3)上清液共培养的人源CD4^(+)Treg的细胞内脂质含量和脂质摄取能力;使用脂肪酸氧化抑制剂(Etomoxir)、脂肪酸合成抑制剂(C75)和脂肪酸摄取抑制剂磺基-N-琥珀酰亚胺油酸酯(sulfo-N-succinimidyl oleate,SSO)干预脂质代谢;通过流式细胞术分析CD4^(+)Treg上免疫抑制分子PD-1和CTLA-4的表达。结果:OV组织CD4^(+)Treg相比传统CD4^(+)T细胞表现出更高的脂质含量和脂质摄取能力(P均<0.01)。在体外实验中,与基础培养基相比,OV细胞培养上清可显著提升CD4^(+)Treg的胞内脂质含量与脂质摄取能力(P均<0.05),其中CAOV3来源的上清作用最为显著。此外,CAOV3上清液还能提升CD4^(+)Treg中PD-1与CTLA-4的表达(P<0.05)。CD4^(+)Treg的脂质积累随CAOV3上清浓度增加呈剂量依赖性上升(P<0.05),且其对胞外荧光脂肪酸类似物的摄取能力具有浓度依赖性(P<0.05)。脂肪酸摄取抑制剂SSO可有效逆转CAOV3上清液诱导的CD4^(+)Treg脂质积累及PD-1、CTLA-4的高表达(P<0.05);而脂肪酸氧化抑制剂Etomoxir与合成抑制剂C75则无显著影响。结论:OV微环境通过促进CD4^(+)Treg的脂质摄取,提高细胞内脂质含量,促进其免疫抑制分子PD-1和CTLA-4表达。靶向脂肪酸摄取途径可能是逆转OV中Treg介导的免疫抑制的潜在策略。展开更多
文摘目的探讨CMTM6、PD-L1在子宫内膜异位症(endometriosis,EM)中的表达及意义。方法收集50例EM患者腹腔镜下手术切除的卵巢异位子宫内膜组织、刮除的在位子宫内膜组织(实验组)以及30例非EM患者刮除的在位子宫内膜组织(对照组),采用免疫组化法检测CMTM6、PD-L1的表达水平。收集实验组相关临床病理资料,包括患者年龄、体重指数(body mass index,BMI)、病灶大小、血清CA-125浓度及rAFS评分等,采用Spearman系数法分析CMTM6、PD-L1的表达与上述病理参数的相关性。培养人EM上皮细胞系12Z,采用Western blot及免疫蛋白共沉淀法检测CMTM6、PD-L1的表达水平及相互作用。结果CMTM6、PD-L1在EM患者中高表达,EM患者异位、在位子宫内膜中的表达水平高于非EM患者在位子宫内膜组织(P<0.05),CMTM6、PD-L1表达共同定位于异位、在位子宫内膜组织上皮细胞质、细胞膜中,且两种蛋白表达呈正相关(P<0.05)。患者年龄、BMI、病灶大小、血清CA-125浓度及rAFS评分与CMTM6、PD-L1的表达呈正相关(P<0.01)。CMTM6、PD-L1蛋白在12Z中表达,且CMTM6和PD-L能够相互结合。结论CMTM6、PD-L1在EM患者中高表达,CMTM6、PDL1的表达水平与EM病变严重程度相关,CMTM6、PD-L1在EM中能相互结合共同参与EM的发生、发展,CMTM6、PD-L1或可成为EM的潜在生物学标志物,为EM的临床诊治提供新靶点。
文摘构建使用了PD-1抑制剂的肿瘤患者出现甲状腺功能障碍的风险预测模型,分析使用PD-1肿瘤抑制剂导致的甲状腺功能障碍的相关风险因素,设计监测预警系统。选取2020年—2023年广西医科大学附属肿瘤医院1225例使用PD-1抑制剂肿瘤患者的临床资料,包括人口学特征、既往史、实验室检测等63个变量。本文选取相关性前10/20/30/40/50/60个变量的4种传统机器学习模型进行性能比较。通过F1分数、灵敏度、准确率、精确率、特异性曲线下面积(Area Under the Curve,AUC)评估以上预测模型的性能,并利用Shapley加性解释(Shapley Additive Explanation,SHAP)可视化解释本文的机器学习模型。与促甲状腺激素相关性排名前10的变量依次为:羟丁酸脱氢酶、乳酸脱氢酶、淋巴细胞绝对值、天门冬氨酸转移酶、钙离子、碱性磷酸酶、谷氨酰转肽酶、单核细胞绝对值、红细胞分布宽度SD、胆碱酯酶。建立了使用PD-1抑制剂的肿瘤患者出现甲状腺功能障碍的风险预测模型,并在全局解释和局部解释的层面上分别作出模型预测结果影响的解释。
文摘The bowel preparation is a crucial step to achieve an optimal quality in colonoscopy.The major clinical impact of an adequate colonic cleansing is to allow a more detailed and thorough inspection reducing the rates of missing lesions during the procedure and consequently reducing the incidence of interval colorectal carcinomas.Currently there are different colonoscopic preparation schemes,being the polyethylene glycol(PEG)based regimen one of the most used and recommended by the main international clinical guidelines.Nevertheless,PEG preparation requires the ingestion of considerably large volumes to achieve an optimal colonic cleansing,leading to poor tolerability in may patients,particularly in an elderly population.Other aspects that make accessibility to most colonoscopy preparation regimens difficult is their high cost and low availability.New options of colonoscopic preparation schemes based on oral lactulose are emerging with promising results,showing excellent efficacy-safety profiles and high tolerability indexes.Lactulose regimens present other benefits such as low cost and wide availability.The aim of this review is to analyze the scientific evidence to date and the current status of colonoscopy bowel preparation utilizing lactulose-based regimens,in order to consolidate this agent as a feasible“new player”in the field of colonoscopic preparation.
基金Supported by The University of Kelaniya,No.RP/03/04/13/01/01.
文摘BACKGROUND Functional abdominal pain disorders(FAPDs)are common gut–brain interaction disorders with unclear pathophysiology.While impaired gastrointestinal motility is thought to play a key role,small intestinal dysmotility remains largely unexplored.Orocecal transit time(OCTT),an indirect indicator of small intestinal transit,offers an insight into its potential contribution to FAPD's pathophysiology.AIM To assess OCTT in children with FAPDs compared with healthy children using the lactulose breath hydrogen test.METHODS Thirty-four children(44.1%males,age 5–12 years,mean 7.2±2.4 years)with FAPDs attending North Colombo Teaching Hospital,Ragama,Sri Lanka,were included in the analysis.FAPDs were diagnosed using the Rome IV criteria.None had clinical or laboratory evidence of organic diseases.They were compared with 19 healthy controls(47.1%males,age 5-12 years,mean 7.8±2.7 years)from the same geographical area.OCTT was calculated after an 8-hour fast using a previously validated technique.Breath hydrogen levels were measured at baseline and 15-minute intervals for 180 minutes post-lactulose ingestion(10 g in 10%solution).At each time point,3 breath samples were collected and analyzed.OCTT was quantified as the time taken to achieve a sustained breath hydrogen increase>10 parts per million above baseline.Symptoms were recorded using the Rome IV questionnaire,and symptom severity was graded on a 0-4 Likert scale.RESULTS Patients with FAPDs had increased OCTT(median,90 minutes;interquartile range,75-120 minutes)compared to controls(median,75 minutes;interquartile range,60-75 minutes)(P=0.0045,Mann-Whitney U-test).Children with functional dyspepsia had the longest mean OCTT(110.8±26.7 minutes).There was no significant correlation between abdominal pain severity and OCTT(r=0.18,P=0.35,Spearman correlation coefficient).OCTT did not differ between those exposed to stressful events and those not exposed to such events(P>0.05).CONCLUSION Children with FAPDs have longer OCTT than healthy controls.However,the lack of a significant correlation between OCTT and symptom severity suggests that delayed small intestinal transit alone is not a substantial contributor to FAPD pathophysiology.
文摘目的:探究卵巢癌(ovarian cancer,OV)浸润性CD4^(+)调节性T细胞(regulatory T cell,Treg)的脂质摄取与积累情况,及其与CD4^(+)Treg中程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)和细胞毒性T淋巴细胞相关蛋白-4(cytotoxic Tlymphocyte associated protein 4,CTLA-4)表达的相关性。方法:采用亲脂性荧光染料BODIPY^(TM)493/503和荧光脂肪酸探针BODIPY^(TM)500/510 C1 C12分别检测OV组织中的或与不同OV细胞系(ES-2、SKOV3、CAOV3)上清液共培养的人源CD4^(+)Treg的细胞内脂质含量和脂质摄取能力;使用脂肪酸氧化抑制剂(Etomoxir)、脂肪酸合成抑制剂(C75)和脂肪酸摄取抑制剂磺基-N-琥珀酰亚胺油酸酯(sulfo-N-succinimidyl oleate,SSO)干预脂质代谢;通过流式细胞术分析CD4^(+)Treg上免疫抑制分子PD-1和CTLA-4的表达。结果:OV组织CD4^(+)Treg相比传统CD4^(+)T细胞表现出更高的脂质含量和脂质摄取能力(P均<0.01)。在体外实验中,与基础培养基相比,OV细胞培养上清可显著提升CD4^(+)Treg的胞内脂质含量与脂质摄取能力(P均<0.05),其中CAOV3来源的上清作用最为显著。此外,CAOV3上清液还能提升CD4^(+)Treg中PD-1与CTLA-4的表达(P<0.05)。CD4^(+)Treg的脂质积累随CAOV3上清浓度增加呈剂量依赖性上升(P<0.05),且其对胞外荧光脂肪酸类似物的摄取能力具有浓度依赖性(P<0.05)。脂肪酸摄取抑制剂SSO可有效逆转CAOV3上清液诱导的CD4^(+)Treg脂质积累及PD-1、CTLA-4的高表达(P<0.05);而脂肪酸氧化抑制剂Etomoxir与合成抑制剂C75则无显著影响。结论:OV微环境通过促进CD4^(+)Treg的脂质摄取,提高细胞内脂质含量,促进其免疫抑制分子PD-1和CTLA-4表达。靶向脂肪酸摄取途径可能是逆转OV中Treg介导的免疫抑制的潜在策略。
