病例介绍患者,男,38岁,因“声嘶11个月,胸痛伴气紧7 d,加重伴心悸1 d”于2024年4月29日入四川大学华西医院。患者2023年6月因声嘶于外院就诊,诊断为甲状腺右侧结节:癌可能性大;右侧颈部淋巴结肿大:癌转移可能性大,并行全麻下甲状腺癌根...病例介绍患者,男,38岁,因“声嘶11个月,胸痛伴气紧7 d,加重伴心悸1 d”于2024年4月29日入四川大学华西医院。患者2023年6月因声嘶于外院就诊,诊断为甲状腺右侧结节:癌可能性大;右侧颈部淋巴结肿大:癌转移可能性大,并行全麻下甲状腺癌根治术,术后病理示左、右叶甲状腺髓样癌(medullary thyroid carcinoma,MTC),淋巴结见肿瘤转移。肿瘤基因检查示RET(rearranged during transfection)基因变异(外显子11:c.1901G>A:p.C634Y)。2023年11月患者行正电子发射断层成像(positron emission tomography,PET)/CT发现局部淋巴结、双肺、肾上腺转移,予以塞普替尼靶向药物治疗2个月,出现皮肤瘙痒、尿酸明显升高后停用靶向药物。2024年4月22日患者于外院行经皮穿刺左侧肾上腺病损冷冻消融+活检术(病理结果示肾上腺髓质增生,嗜铬细胞瘤不除外),术后随即出现全身疼痛,以胸、腹部疼痛明显,性质剧烈,伴气紧、心悸、恶心、双手麻木,伴有血压、心率大幅波动,心率由70次/min上升至170次/min,血压由140/70 mm Hg(1 mm Hg=0.133 kPa)上升至220/109 mm Hg。展开更多
目的:探究乳腺癌组织中RET(rearranged during transfection)基因、磷酸酶张力蛋白同源基因(phosphatase and tensin homolog,PTEN)表达水平与临床病理特征的相关性及其诊断乳腺癌的效能。方法:乳腺癌患者52例为观察组,良性乳腺肿瘤患...目的:探究乳腺癌组织中RET(rearranged during transfection)基因、磷酸酶张力蛋白同源基因(phosphatase and tensin homolog,PTEN)表达水平与临床病理特征的相关性及其诊断乳腺癌的效能。方法:乳腺癌患者52例为观察组,良性乳腺肿瘤患者52例为对照组。比较两组肿瘤组织中RET、PTEN表达阳性率,分析RET、PTEN表达与乳腺癌患者临床病理特征的关系,乳腺癌患者RET、PTEN表达水平与淋巴结转移、TNM分期的相关性,RET、PTEN表达水平联合诊断乳腺癌患者的效能。结果:观察组RET阳性率73.08%,高于对照组的9.62%,PTEN阳性率38.46%,低于对照组的71.15%(均P<0.05)。淋巴结转移患者RET阳性表达水平高于无淋巴结转移患者,Ⅲ~Ⅳ期患者RET阳性表达水平高于Ⅰ~Ⅱ期患者;淋巴结转移患者PTEN阳性表达水平低于无淋巴结转移患者,Ⅲ~Ⅳ期患者PTEN阳性表达水平低于Ⅰ~Ⅱ期患者(均P<0.05)。乳腺癌患者RET表达水平与淋巴结转移(r=0.609)、TNM分期(r=0.628)呈正相关,PTEN表达水平与淋巴结转移(r=-0.644)、TNM分期(r=-0.678)呈负相关(均P<0.05)。RET、PTEN联合诊断乳腺癌患者敏感度为80.77%,特异度为86.54%,准确度为83.65%,优于RET、PTEN单独诊断的效能(均P<0.05)。结论:RET、PTEN与乳腺癌淋巴结转移、TNM分期密切相关,两者联合检测可为乳腺癌的诊断提供有价值的参考。展开更多
Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism in...Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.展开更多
BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,fam...BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.展开更多
文摘病例介绍患者,男,38岁,因“声嘶11个月,胸痛伴气紧7 d,加重伴心悸1 d”于2024年4月29日入四川大学华西医院。患者2023年6月因声嘶于外院就诊,诊断为甲状腺右侧结节:癌可能性大;右侧颈部淋巴结肿大:癌转移可能性大,并行全麻下甲状腺癌根治术,术后病理示左、右叶甲状腺髓样癌(medullary thyroid carcinoma,MTC),淋巴结见肿瘤转移。肿瘤基因检查示RET(rearranged during transfection)基因变异(外显子11:c.1901G>A:p.C634Y)。2023年11月患者行正电子发射断层成像(positron emission tomography,PET)/CT发现局部淋巴结、双肺、肾上腺转移,予以塞普替尼靶向药物治疗2个月,出现皮肤瘙痒、尿酸明显升高后停用靶向药物。2024年4月22日患者于外院行经皮穿刺左侧肾上腺病损冷冻消融+活检术(病理结果示肾上腺髓质增生,嗜铬细胞瘤不除外),术后随即出现全身疼痛,以胸、腹部疼痛明显,性质剧烈,伴气紧、心悸、恶心、双手麻木,伴有血压、心率大幅波动,心率由70次/min上升至170次/min,血压由140/70 mm Hg(1 mm Hg=0.133 kPa)上升至220/109 mm Hg。
文摘目的:探究乳腺癌组织中RET(rearranged during transfection)基因、磷酸酶张力蛋白同源基因(phosphatase and tensin homolog,PTEN)表达水平与临床病理特征的相关性及其诊断乳腺癌的效能。方法:乳腺癌患者52例为观察组,良性乳腺肿瘤患者52例为对照组。比较两组肿瘤组织中RET、PTEN表达阳性率,分析RET、PTEN表达与乳腺癌患者临床病理特征的关系,乳腺癌患者RET、PTEN表达水平与淋巴结转移、TNM分期的相关性,RET、PTEN表达水平联合诊断乳腺癌患者的效能。结果:观察组RET阳性率73.08%,高于对照组的9.62%,PTEN阳性率38.46%,低于对照组的71.15%(均P<0.05)。淋巴结转移患者RET阳性表达水平高于无淋巴结转移患者,Ⅲ~Ⅳ期患者RET阳性表达水平高于Ⅰ~Ⅱ期患者;淋巴结转移患者PTEN阳性表达水平低于无淋巴结转移患者,Ⅲ~Ⅳ期患者PTEN阳性表达水平低于Ⅰ~Ⅱ期患者(均P<0.05)。乳腺癌患者RET表达水平与淋巴结转移(r=0.609)、TNM分期(r=0.628)呈正相关,PTEN表达水平与淋巴结转移(r=-0.644)、TNM分期(r=-0.678)呈负相关(均P<0.05)。RET、PTEN联合诊断乳腺癌患者敏感度为80.77%,特异度为86.54%,准确度为83.65%,优于RET、PTEN单独诊断的效能(均P<0.05)。结论:RET、PTEN与乳腺癌淋巴结转移、TNM分期密切相关,两者联合检测可为乳腺癌的诊断提供有价值的参考。
基金supported by the National Natural Science Foundation of China(No.81700471 and No.82270583)the National Key Research and Development Program of China(No.2022YFC2504005)。
文摘Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.
基金Supported by The Finance Bureau of Dongguan City,Guangdong Province.
文摘BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.
