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1.
A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system. 相似文献
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目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene,HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者,79例患者进行了血液标本HRR检测,53例患者进行了组织标本HRR检测,40例患者同时行血液和组织的HRR基因检测,收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例(12.6%)有临床意义HRR突变,在53例患者组织标本检测中发现9例(17.0%)有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例(10.0%)、ATM突变3例(7.5%)、BRCA1突变2例(5.0%)。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例(76.9%)、APC突变5例(38.5%)、PIK3CA突变4例(30.8%)。40例患者中13例患者血液和/或组织中有临床意义HRR突变,27例患者血液和组织中均无任何临床意义HRR突变且两组相比,有临床意义HRR突变组肿瘤突变负荷(tumor mutational burden,TMB)为6.17(2.24~11.52),而未携带HRR突变组TMB为0.4(0~3.75),差异有统计学意义(P<0.05)。40例患者组织检测中7例HRR有临床意义的突变,33例无HRR突变,血液检测中10例HRR有临床意义的突变,30例无HRR突变,一致性检验的Kappa值为0.333(P=0.031)。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高,血液和组织检测HRR突变有较好的一致性。 相似文献
4.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
5.
目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例,随机均分为3组:对照组(C组)、体温保护组(T组)和体温保护联合右美托咪定组(T-D组),每组30例。C组常规体温保护,T组和T-D组综合体温保护;T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时(T0)、手术开始30 min(T1)、60 min(T2)、90 min(T3)、120 min(T4)以及手术结束时(T5)的鼻咽温度;于T0、术后2 h(T6)、24 h(T7)和48 h(T8)时抽取静脉血标本,测定T淋巴细胞亚群(CD3+、CD4+和CD8+)和自然杀伤细胞(NK cell)水平;记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T0比较,C组T2~T5时点鼻咽温度均明显降低(P < 0.05);与C组比较,T组和T-D组T2~T5时点鼻咽温度明显升高(P < 0.05)。与T0时点比较,C组、T组和T-D组T6、T7和T8时点CD3+和NK cell活性均明显降低(P < 0.05);C组在T6、T7和T8时点,T组和T-D组在T6和T7时点,CD4+活性均明显降低(P < 0.05)。与C组比较,T组和T-D组T6和T7时点CD3+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6和T7时点,CD4+细胞活性均明显升高(P < 0.05);T组在T7时点,T-D组在T6、T7和T8时点,NK cell活性均明显升高(P < 0.05)。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定,减少围手术期意外低体温(IPH)的发生,并有效提高患者苏醒期质量,减轻免疫抑制程度,加速患者早期恢复。 相似文献
6.
The purpose of this study is to show a very rare complication of acute cocaine poisoning, namely heart rupture. In the present case report, acute cocaine intoxication caused massive myocardial infarction, resulting in heart rupture and cardiac tamponade. A crime scene investigation found a dead body on the street in a drug dealing district. Examination of the body showed no external injuries. A thorough autopsy was performed showing massive cardiac tamponade with 510 ml of blood within the pericardium and full-thickness tissue lesion at the posterior wall of the left ventricle of 3.5 × 3 cm. Histological examination in hematoxylin and eosin was performed and confirmed the interruption of the posterior wall of the left ventricle with the presence of blood. In fact, although the correlation between cocaine and myocardial damage is well established, the relationship between heart rupture and acute cocaine intoxication is an extremely rare event. Moreover, since there are, to date, few reports of similar deaths, our report provides useful information regarding sudden death in a cocaine abuser. It is, therefore, of crucial importance to report this case to the scientific community. 相似文献
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8.
Ludefu Su Yu Liu Yanhong Tang Mingmin Zhou Liang Xiong Congxin Huang 《International journal of clinical and experimental pathology》2021,14(4):408
Background and objective: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. Methods: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. Results: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). Conclusion: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive. 相似文献
9.
Her-Shyong Shiah Nai-Jung Chiang Chia-Chi Lin Chia-Jui Yen Hui-Jen Tsai Shang-Yin Wu Wu-Chou Su Kwang-Yu Chang Ching-Chiung Wang Jang-Yang Chang Li-Tzong Chen 《The oncologist》2021,26(4):e567-e579
Lessons Learned
- SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
- This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
- SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.
10.
Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy. 相似文献