线粒体糖尿病患者三例及其家系的临床及基因检测分析

背景　线粒体糖尿病是一种特殊类型糖尿病，其早期临床表现不典型，易被误诊从而耽误治疗；基因检测是诊断线粒体糖尿病的主要手段，也是当前研究的热点。目的　对3例临床疑诊为线粒体糖尿病的患者及其家系成员进行线粒体基因测序，明确诊断，指导精准治疗。方法　选取2017-2019年在安徽医科大学第一附属医院及六安市人民医院内分泌科疑诊为线粒体糖尿病的3例患者，将3例先证者及7名家系成员纳入研究，分析其临床特征、实验室检查结果，并行线粒体基因测序。结果　3例疑诊患者及其部分家系成员基因测序结果显示存在线粒体tRNA 3243A→G点突变，明确诊断为线粒体糖尿病。对家系成员的分析显示部分成员存在该位点突变，已诊断为糖尿病，患者1家系成员基因检测显示其母亲、哥哥、女儿均为tRNA 3243A→G基因阳性者，其中1例虽有该基因突变，但目前尚未表现为糖尿病。结论　对于临床疑诊为线粒体糖尿病的患者应积极对患者及其家系成员进行基因检测，以求明确诊断及指导治疗。     

经泪前隐窝入路至翼腭窝和颞下窝的内镜解剖学研究

目的探讨经泪前隐窝入路至翼腭窝、颞下窝的方法及相关解剖结构,为临床手术提供解剖学数据。方法采用8具成人头颅标本,通过神经内镜下模拟经泪前隐窝入路至翼腭窝、颞下窝进行逐层解剖,并测量和采集相关数据或图片,对神经内镜解剖过程中的不确定结构和数据,通过显微镜下模拟耳前颞下-颞下窝开放入路证实。结果8具尸头标本(16侧)的膜性鼻泪管位于上颌窦内壁的骨性鼻泪管内,开口于下鼻道,其长度为(14.3±3.6)mm,直径为(5.3±1.8)mm。眶下神经和眶下动脉在眶下裂处形成神经血管束,走行于上颌窦顶壁的眶下管内;颊神经自下颌神经分出后从翼外肌上、下头之间穿出,在颞肌与翼外肌之间向前走行并支配颊肌。结论经泪前隐窝入路至翼腭窝、颞下窝的关键为膜性鼻泪管的显露和保护;进行神经内镜手术时,眶下神经血管束可作为识别翼腭窝内结构的标志,颊神经可作为识别颞下窝内各肌肉的标志。     

An evaluation of the efficacy of olmesartan medoxomil in Black patients with hypertension

Blacks appear to have a more modest blood pressure (BP) response to angiotensin receptor blocker (ARB) monotherapy than non-Blacks. This post-hoc analysis compared the BP-lowering efficacy of olmesartan medoxomil (OM), losartan potassium (LOS), and valsartan (VAL) in Black versus non-Black participants in a randomized, forced-titration study. Patients were randomized to OM 20, LOS 50, and VAL 80 mg/day or placebo for 4 weeks and uptitrated to 40, 100, and 320 mg/day doses, respectively, by study end. The primary end point was the mean change from baseline in diastolic BP (DBP) at week 8. All treatments produced significant reductions in mean DBP and systolic BP (SBP) in Blacks (n = 150; P < .001). BP <140/90 mm Hg was achieved in 35.0%, 15.6%, 29.7%, and 5.0% of Blacks receiving OM, LOS, VAL, and placebo, respectively, and in 41.0%, 21.1%, 28.8%, and 14.5% of non-Blacks receiving OM, LOS, VAL, and placebo, respectively, after 8 weeks. BP-lowering efficacy of the three agents was similar at 3 months. OM had the greatest early efficacy, with numerically greater mean reductions in DBP and SBP, and a higher proportion of Black and non-Black patients achieving goal BP of 140/90 mm Hg at week 8.     

Apoptotic effects of curcumin on human osteosarcoma U2OS cells

Objective: Curcumin, an active ingredient derived from the rhizome of the plant, Curcuma longa, has antioxidant, anti‐inflammatory and anti‐cancer activities. The aims of this study were to examine whether curcumin can induce apoptosis in an osteosarcoma cell line. Methods: Curcumin‐induced apoptosis in human osteosarcoma U2OS cells was investigated using morphological analysis, marked nuclear condensation and fragmentation of chromatin, which were observed by Hoechst 33258 staining and DNA ladder formation. The U2OS cells were treated with or without curcumin. Cell viability was assessed by the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium (MTT) method. Cell‐cycle, apoptosis and apoptosis‐related proteins in U2OS cells were evaluated by flow cytometry and western blotting. Results: Curcumin showed growth inhibitory effects on U2OS cells in a dose‐and time‐dependent manner, inducing significant G1 arrest and apoptosis in U2OS cells. This curcumin‐induced apoptosis in U2OS cells was accompanied by up‐regulation of Bax, Bak, and p‐Bad and down‐regulation of Bcl‐2, but no effect on the levels of Bcl‐X_L or Bad proteins was noted. Moreover, curcumin treatment resulted in a significant reduction of mitochondrial membrane potential and increase in the concentrations of mitochondrial cytochrome C and caspase‐3. Conclusion: Multiple molecular pathways are involved in curcumin‐induced apoptosis of human U2OS cells. These include pro‐and anti‐apoptotic Bcl‐2 family proteins, mitochondrial membrane potential, mitochondrial cytochrome C and caspase‐3.     

皮肤恶性黑色素瘤患者预后的影响因素分析

目的分析皮肤恶性黑色素瘤(MM)患者预后的影响因素。方法选取74例接受手术联合免疫治疗的皮肤MM患者,采用Cox比例风险回归模型分析影响皮肤MM患者预后的危险因素。结果 74例皮肤MM患者中,死亡33例。单因素分析结果显示,不同TNM分期、肿瘤破溃情况、淋巴结转移情况、Clark分级皮肤MM患者的2年生存率比较,差异均有统计学意义(P<0.05);不同病理类型皮肤MM患者的2年生存率比较,差异无统计学意义(P>0.05)。Cox比例风险回归模型分析结果显示,TNM分期为Ⅲ～Ⅳ期、有淋巴结转移、有肿瘤破溃、Clark分级为Ⅲ～Ⅴ级是影响手术联合免疫治疗后皮肤MM患者预后的独立危险因素(P<0.01)。结论手术联合免疫治疗对皮肤MM具有较好的效果,临床上应重视患者的TNM分期、淋巴结转移情况、肿瘤破溃情况和Clark分级对皮肤MM患者预后的影响。     

全胰切除术治疗胰腺良恶性疾病11例

目的 探讨全胰切除术（total pancreatectomy,TP）治疗胰腺良恶性疾病的指征、安全性、可行性,总结临床经验。方法 回顾性分析2018年1月至2020年12月在中国科学技术大学附属第一医院胆胰外科行全胰切除术的11例胰腺良恶性疾病患者的临床资料。结果 11例中慢性胰腺炎3例,胰腺导管腺癌4例,胰腺黏液癌2例,胰腺导管内乳头状黏液肿瘤（intraductal papillary mucinous neoplasms,IPMN)）1例,神经内分泌肿瘤1例。11例均成功施行全胰切除术,其中腹腔镜下全胰切除术2例。术后并发胃十二指肠动脉残端出血1例。8例获得随访,平均随访20个月,术后每日胰岛素总量（31.22±4.79）U,血糖控制基本稳定。结论 全胰切除术在治疗胰腺良恶性疾病中是安全、可行的,但应严格掌握适应证,对于胰腺癌患者,可以提高R0切除率。     

Efficacy of trastuzumab deruxtecan in an advanced gastric cancer patient with brain metastasis

Background: There is no clinical evidence supporting the effectiveness of trastuzumab deruxtecan (T-DXd) for treating advanced gastric cancer (AGC) with brain metastasis. Case report: This is a case of a 65-year-old man with human epidermal growth factor-2 (HER2)-positive AGC. He was initially treated with capecitabine, cisplatin, and trastuzumab, followed by paclitaxel and ramucirumab, nivolumab, trifluridine and tipiracil, and irinotecan regimens in addition to radiation therapy for brain metastasis. The patient exhibited refractoriness to the standard regimen used for AGC and developed relapse of the brain metastasis after radiation accompanied by headache, nausea, and dizziness. In August 2020, following the approval of T-DXd for HER2-positive AGC, he received T-DXd therapy. After 5 cycles of T-DXd, contrast-enhanced computed tomography and magnetic resonance imaging demonstrated significant tumor shrinkage and improvement of symptoms. Conclusion: T-DXd demonstrated effectiveness for the treatment of brain metastasis arising from HER2-positive AGC.     

Risk and survival of second primary malignancies following diagnosis of gastric mucosa-associated lymphoid tissue lymphomas: A population-based study

Whether gastric mucosa-associated lymphoid tissue lymphoma (GML) is associated with a higher risk of second primary malignancy (SPM) remains controversial. This study aimed to evaluate the detailed risk of SPM and its prognosis in patients with GML based on a large population-based cohort. The Surveillance, Epidemiology, and End Results database was searched to identify patients who were diagnosed with GML during 2000–2014. The standardized incidence ratio was used to estimate the relative risk of developing SPM. Overall survival was evaluated using the Kaplan-Meier method with the log-rank test, as well as Cox regression analysis. Among 3,379 patients with GML, 416 patients (12.31%) developed SPMs. Compared to the general US population, GML patients had a significantly increased risk of developing SPM (standardized incidence ratio: 1.46, 95% CI: 1.33–1.61). The SPM sites were stomach, lung and bronchus, small intestine, thyroid, mouth, and non-Hodgkin's lymphoma. The risk of developing SPM in GML patients varied according to clinical and demographic characteristics. Patients with younger age (<50 year), chemotherapy use and radiotherapy use had the higher risk of developing SPMs. Relative to patients with only GML, GML patients who developed the SPMs had significantly poorer overall survival (P < 0.001). Among GML patients with SPMs, poor overall survival was independently associated with non-localized SPM disease, shorter latency period (<60 months), chemotherapy use and older age (≥70 year). Patients with GML had an elevated risk of developing SPM, which was associated with a poor prognosis. These findings may be useful for improving follow-up surveillance for patients with GML.     

微创经皮钢板内固定技术结合前外侧单一切口入路治疗开放性胫腓骨远端骨折

目的:探讨经皮微创钢板内固定(minimally invasive percutaneous plate osteosynthesis,MIPPO)技术结合前外侧单一切口入路Ⅰ期治疗胫腓骨远端开放性骨折的临床疗效。方法:自2015年3月至2019年2月对10例开放性胫腓骨远端骨折患者行单一前外侧切口结合MIPPO技术治疗,其中男8例,女2例;年龄31～68岁。开放性骨折根据Gustilo分型,Ⅰ型6例,Ⅱ型3例,ⅢA1例。观察患者的手术时间、术中出血量、骨折愈合情况,采用Mazur踝关节功能评分进行临床疗效评价。结果:10例患者均获得随访,时间9～24个月。手术时间85～120 min,术中出血量80～200 ml,骨折愈合时间18～30周。9例Gustilo分型为Ⅰ、Ⅱ型患者伤口均取得满意愈合,1例GustiloⅢA期患者原创口愈合差,给予Ⅱ期皮瓣移植取得愈合,所有患者无钢板外露及感染发生。末次随访时根据Mazur踝关节评分,总分61～97分,其中优8例,良1例,差1例。结论:MIPPO技术结合小腿前方单一前外侧切口治疗胫腓骨远端开放性骨折,术中保护原内侧切口,通过前外侧伸肌群覆盖内固定物避免钢板外露,MIPPO技术微创操作保护骨折端血供提高骨折端愈合率,是一种可选择的手术方式。