Abstract Background For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. Methods 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th–95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. Results 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. Conclusions Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Hypertension is a cardiovascular disease that seriously threat-ens public health worldwide.Early and effective control of blood pressure can prevent the occurrence of stroke,coronary heart dis-ease,kidney disease,etc.[1,2].The influence of genetic factors on hypertension has been confirmed multiple times,and targeted medication according to genetic testing remains a challenge for hypertension treatment at present[3].

Objective: Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, few large studies, and none in China, have described the outcomes of dysglycemia after resection, and the factors associated with the development and resolution of dysglycemia in patients with PPGLs. Design and method: We retrospectively analyzed the clinical data of consecutive patients with PPGLs admitted between January 2018 and June 2020. Clinical characteristics were compared between patients with and without dysglycemia. Multivariable logistic regression analysis was used to identify independent predictors and the receiver operating characteristic curves was used to evaluate the diagnostic performance of the variables. Results: Among 163 patients in this study, 47.9% had preoperative dysglycemia. Patients with dysglycemia were older at diagnosis and have a higher proportion of hypertension. The white blood cell count and 24-hour urinary epinephrine (24hU-E) concentration were higher in patients with dysglycemia. Multivariable logistic regression analysis showed that age [odds ratio (OR), 1.040; 95% confidence interval (CI), 1.011–1.070; p = 0.006], hypertension (OR, 3.318; 95% CI, 1.375 – 8.009; p = 0.008), and 24hU-E concentration (OR, 1.013; 95% CI, 1.005 –1.022; p = 0.016) were independent predictors of preoperative dysglycemia. Taking age, hypertension and 24hU-E into account in the same model, the area under the receiver operating characteristic curve of the model for predicting preoperative dysglycemia was 0.737. The proportion of patients with dysglycemia was significantly decreased after surgery (p < 0.001) and patients with postoperative dysglycemia in remission had larger preoperative tumor diameters (p = 0.005). Conclusions: Dysglycemia affects almost half of patients with PPGLs. Age, hypertension, and 24hU-E concentration are predictors of preoperative dysglycemia. Removal of PPGLs can improve dysglycemia in most patients, and the postoperative remission of dysglycemia is associated with the preoperative tumor diameter. These results are of great importance for risk assessment and selection of optimal therapy of dysglycemia in patients with PPGLs.

BackgroundAccurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC.PurposeTo design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC.MethodsUsing β-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system.ResultsGal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 μm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs.ConclusionWe designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.

Background: Mid-aortic syndrome (MAS), characterized by segmental stricture of the distal thoracic and abdominal aorta, is a heterogeneous clinical syndrome with multiple etiologies. Methods: We retrospectively analyzed 143 consecutive patients (99 females and 44 males, mean age 40.93 +/- 15.31 years) with MAS seen from January 1, 2010 to January 1, 2019. Results: Takayasu arteritis (76.9%, 110/143) and atherosclerosis (19.6%, 28/143) were the most-common causes. There were also one patient with Beh,cet's disease and one with congenital MAS in the cohort. Hypertension was the most -com-mon manifestation. Constitutional symptoms were mainly seen in Takayasu arteritis, and neurological, gastrointestinal and vascular symptoms were common in both Takayasu arteritis and atherosclerosis. The infrarenal segment was the most -commonly involved in atherosclerosis (89.3%, 25/28), whereas lesions were more distributed in Takayasu arteritis. The mean length of involved segments was longer (43.45 +/- 23.64 mm vs. 30.68 +/- 12.66 mm; P = 0.018) and the degree of ste-nosis was lower (80.20 +/- 13.36% vs. 87.50 +/- 13.95%, P = 0.004) in Takayasu arteritis than atherosclerosis. The most -common concurrently involved branch was the renal artery, followed by the celiac trunk and mesenteric arteries, in both Takayasu arteritis (51.8%, 32.7% and 27.3%, respectively) and atherosclerosis (53.6%, 25.0% and 17.9%, respectively). Concurrent artery involvement and coexisting lesions were absent in MAS caused by congenial coarctation of the abdomi-nal aorta and Beh,cet's disease. Conclusions: Takayasu arteritis and atherosclerosis were the most-common causes of MAS among these adults. Imaging tests provided evidence of involved segments and luminal and mural changes, aiding conclusive diagnoses and etiological dif-ferentiation of MAS. [Am J Med Sci 2023;365(5):420-428.]

近年来,甲状腺癌的发生率增长迅速,在一些地区,已成为发生率增长最快的恶性肿瘤.约30％的分化型甲状腺癌患者存在局部复发,且传统的治疗方法对持续、复发和转移患者效果有限,导致其预期生存率迅速下降.其中,放射性碘难治性甲状腺癌患者的10年生存率低至10％.甲状腺未分化癌侵袭性远高于分化型甲状腺癌,疾病特异性病死率接近100％,疾病进展十分迅速且治疗效果很差.纳米粒子已用于靶向诊断和治疗甲状腺癌,通过纳米载体给药减少治疗不良反应,同时改善治疗效果.另外,选择性地向甲状腺癌细胞输送药物还有望促进去分化甲状腺癌的再分化.本文对其应用现状及研究进展做一综述.

Background:BRAF has certain potential in distinguishing aggressive papillary thyroid microcarcinoma (PTMC). However, it is not recommended to conduct BRAF analysis for all suspicious thyroid nodules <1 cm. In order to investigate the ultrasound value indicating BRAF mutation among PTMC, which showed discrepancy in previous studies, we aimed to establish a predictive model based on conventional and contrast-enhanced ultrasonography. Methods:We consecutively and retrospectively enrolled patients with PTMC who underwent fine-needle aspiration biopsy (FNAB) at our hospital between January 2020 and January 2021. All PTMC patients received conventional and contrast-enhanced ultrasound prior to FNAB, samples gained went through cytological analysis and BRAF testing subsequently. The following conventional ultrasonography data were analyzed: maximum diameter, echogenicity, echo homogeneity, echogenic foci, location, shape, boundary, aspect ratio, and blood flow volume. Moreover, the following contrast-enhanced ultrasonography data were also analyzed: degree, homogeneity, completeness, and enhancement method. Time-intensity curves from contrast-enhanced ultrasonography were analyzed using VueBox software for different regions of interest, including the entire tumor, the area of strongest enhancement, and healthy thyroid glands. The independent risk factors for BRAF mutation in PTMC were identified using univariate and multivariate logistic regression. Their predictive value was tested through internal validation. Results:Of the 103 PTMC lesions analyzed, 72 involved BRAF mutations. Five independent ultrasonographic risk factors for BRAF mutation were identified: relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci. A predictive model based on these factors was able to diagnose BRAF mutations in PTMC, with an area under the curve (AUC) of 0.824. During internal validation, this model showed an AUC of 0.723. Conclusions:Conventional and contrast-enhanced ultrasound characteristics, including relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci, may be useful for predicting BRAF mutations in patients with PTMC.

Background: The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. Methods: Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medi-cal data from a-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. Results: Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symp-tomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a perma-nent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ven-tricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symp-toms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. Conclusions: FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertro-phy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.

目的 分析和总结以肥厚型梗阻性心肌病为表现的Fabry病患者的临床特征和预后.方法 连续收集2018年1月至2020年7月在阜外医院确诊为Fabry病的患者,通过来我院复诊和/或电话回访获得患者随访资料.结果 纳入Fabry病患者7例,发病年龄和确诊年龄分别为(40±7)岁和(50±5)岁;均因胸痛和/或中重度心力衰竭入院.其中3例合并先天性心脏病、2例累及主动脉瓣;7例患者均有双心室肥厚并表现为肥厚型梗阻性心肌病;6例有心脏传导系统疾病;2例升主动脉扩张.心脏磁共振检查提示下侧壁、室间隔及左心室前壁的肌壁内有延迟强化信号.组织病理电镜下心肌细胞及升主动脉平滑肌细胞内可见特征性的髓鞘样致密小体.3例应用法布赞或米格拉斯坦治疗.6例接受心肌部分切除术治疗;经(15±8)个月随访,左心室流出道压力阶差由(76±29)mmHg下降至(9±5)mmHg,纽约心功能稳定改善至Ⅰ级,Fabry稳定指数＜20％;其中1例行异体肾移植术、1例发生症状性窦性心动过缓.1例未手术患者因心力衰竭反复住院.结论 晚发双心室肥厚、心脏传导系统疾病、主动脉扩张和多系统受累为鉴别类似肥厚型梗阻性心肌病表型的Fabry病提供临床线索.心肌部分切除术可能是合并左心室流出道梗阻的Fabry病患者的有效治疗方式.

Background: Mid-aortic syndrome (MAS) may induce changes in cardiac structure among patients with Takayasu arteritis (TA). Methods: Consecutive adult patients with TA (January 1, 2011 to January 1, 2018) were enrolled and their data was retrospectively analyzed. Results: Patients were divided into MAS group (100/457 patients, 21.8%) and non-MAS group (357, 78.1%). The left ventricular mass index (LVMI) was higher in the MAS group than the non-MAS (113.78 +/- 26.82 versus 100.74 +/- 23.66 g/m2, respectively; P<0.001). The MAS group showed higher prevalence than the non-MAS group of mild-to-severe mitral regurgitation (9.0% and 3.9%, respectively; P=0.040) and aortic regurgitation (26% and 14.8%, respectively; P=0.003). No difference was found in the rates of heart failure (27.0% and 19.9% for MAS and non-MAS, respectively; P=0.126). The MAS group also showed lower estimated glomerular filtration rates than the non-MAS group (89.93 +/- 18.89 versus 96.16 +/- 21.60 mL/min /1.73 m2, respectively; P=0.009) and higher prevalence of renal artery stenosis (57% versus 43.7%; P=0.018). MAS was independently related to greater LVMI in both unadjusted model [beta=12.60; 95% confidence interval (CI): 7.09-18.11; P<0.001] and the model adjusted for multiple indices (beta=9.91; 95% CI: 4.57- 15.25; P<0.001) in multivariate linear analysis. The LVMI significantly decreased from 111.49 +/- 25.65 to 100.36 +/- 22.91 g/m2 (P<0.001) among 55 patients who underwent successful revascularization treatment for MAS, while no significant difference (P=0.635) was observed among patients treated with medicine alone. Conclusions: TA-induced MAS is a potential independent risk factor for increased LVMI, and revascularization therapy for MAS is effective in reversing structural changes in the heart.

目的 比较利伐沙班与华法林在肺栓塞患者中应用的有效性与安全性.方法 选取2016年1月至2016年12月于阜外医院住院诊断为肺栓塞并且接受华法林或利伐沙班抗凝治疗的患者119例.根据患者口服抗凝药物的不同分为华法林组(60例)和利伐沙班组(59例).比较两组基线资料特征,随访观察并比较两组肺栓塞患者的治疗效果以及出血等安全性终点事件的发生率.结果 利伐沙班组慢性肾脏病的患病率高于华法林组(8.5％vs.0％,P=0.027);利伐沙班组既往静脉血栓栓塞史比例高于华法林组(33.9％vs.13.3％,P=0.008).除此以外,两组间年龄、既往卒中史、高血压、糖尿病、心力衰竭、心肌梗死等基线参数无显著差异.平均随访时间(24±9)个月,共7例(5.9％)患者死亡:华法林组5例(8.3％),利伐沙班组2例(3.4％),组间比较无显著差异(P=0.439).再住院患者共28例(23.5％),华法林组和利伐沙班组均为14例,组间比较无显著差异(P=0.959).有效性方面:华法林组5例(8.3％)肺栓塞复发,利伐沙班组3例(5.1％)复发,两组肺栓塞复发率无显著差异(P=0.717).安全性终点事件,华法林组大出血事件发生3例(5.0％),利伐沙班组4例(6.8％),两组间比较无显著差异(P=0.717).华法林组小出血事件发生2例(3.3％),利伐沙班组11例(18.6％),利伐沙班组高于华法林组(P=0.007).结论 与华法林相比,利伐沙班用于肺栓塞患者具有类似的有效性和更好的安全性.利伐沙班用药方便,不需要定期监测,可能成为肺栓塞患者更好的选择.

甲状腺结节是常见的临床问题.超声检查是其首选的影像学诊断工具,用于评估甲状腺结节患者的恶性风险,结合结节大小、局部侵犯情况、颈部淋巴结是否转移等推荐细针穿刺活检(fine-needle aspiration,FNA),并且在患者治疗后继续管理方案的决策中发挥不可或缺的作用.超声的正确高效使用,不仅可以减少不必要的FNA和(或)诊断性手术,还能减轻患者的焦虑及医疗保健系统的负担.近年来,以机器学习和深度学习为核心,基于人工智能的甲状腺结节计算机辅助诊断系统已取得巨大进步,在一定程度上克服了超声诊断中的操作者依赖性,但是受到数据源不同、算法不同等因素的影响,各中心的结果在跨中心运用时表现并不稳定.本文对其应用现状及研究进展进行综述.

患者,女性,60岁,于2019年9月以“间断胸闷痛12年,加重3d”为主诉入院.现病史:患者于12年前始出现活动时胸闷胸痛症状,经休息3～5 min可以缓解.11年前外院行冠状动脉造影:三支病变,建议行冠状动脉旁路移植(coronary artery bypass grafting,CABG),患者拒绝.10年前第1次于中国医学科学院阜外医院(我院)住院,行冠状动脉造影:左主干-前降支近段60％狭窄,远段60％狭窄,回旋支开口80％狭窄,中段50％狭窄,右冠状动脉近段弥漫80％～90％狭窄,后降支80％～90％狭窄,于右冠状动脉植入2枚支架,主动脉球囊反搏保护下于左主干-前降支及回旋支各植入1枚支架.

目的 分析肾动脉狭窄合并原发性醛固酮增多症患者的临床特点及预后.方法 回顾性分析10例确诊为肾动脉狭窄合并原发性醛固酮增多症的患者的临床基线资料、实验室检查结果、影像学检查特点、治疗情况以及随访资料.结果 所有患者均因3级高血压入院,70％的患者合并有低钾血症.50％的患者人院时原发性醛固酮增多症的筛查试验结果为阴性.4例患者同时进行了肾动脉支架植入术和经腹腔镜肾上腺切除术或肾上腺消融术.4例患者仅行肾动脉支架置人术.2例患者未接受任何手术或介入治疗.后续随访表明,同时针对两种疾病进行药物或手术治疗后,患者高血压情况均得到有效控制.结论 在合并肾动脉狭窄的患者中行原发性醛固酮增多症的筛查试验,应谨慎解读结果.建议对于在解除肾动脉狭窄后依然存在难治性高血压的患者复查筛查实验,以明确有无合并原发性醛固酮增多症.

目的 探讨基因检测在汉族肥厚型心肌病(hypertrophic cardiomyopathy,HCM)患者中Fabry病的基因突变情况及家系筛查中的应用,并分析基因型与表型的关系.方法 应用半导体靶向二代测序平台筛查在阜外医院诊断为HCM的217例患者,应用Sanger测序验证先证者和家系内成员的GLA基因突变位点,收集GLA突变携带者的临床资料并进行基因型与表型关联分析.结果 发现2例男性Fabry病先证者(在HCM中占比0.93％).1例携带GLA基因错义突变c.887T＞C(p.M296T),表现为迟发心脏型Fabry病;对其一家四代中的25个家庭成员进行家系突变筛查,结果发现有4个女性杂合突变携带者,其中1个确诊为HCM.另l例携带GLA基因错义突变c.758T＞C(p.I253T),表现为经典型Fabry病,累及肾和神经系统.对其一家四代中的32个家系成员进行家系调查,发现2个女性杂合突变携带者和2个男性早发心脏性猝死.两例先证者经室间隔心肌切除术后梗阻解除,后者应用分子伴侣药物Migalastat治疗后肾功能稳定于31 ml/min.结论 首次发现Fabry病在汉族HCM中并不少见,基因检测有助于早期鉴别诊断及筛查家系内突变携带者.GLA c.758T＞C为恶性基因型,男性突变携带者猝死风险高危,室间隔心肌切除术和Migalastat有助于改善预后.

Apparent mineralocorticoid excess (AME) is an ultrarare autosomal recessive disorder resulting from deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) caused by mutations in HSD11B2. The purpose of this study was to identify novel compound heterozygous HSD11B2 mutations in a Chinese pedigree with AME and conduct a systematic review evaluating the AME clinical features associated with HSD11B2 mutations. Next-generation sequencing was performed in the proband, and Sanger sequencing was used to identify candidate variants in family members, 100 hypertensives, and 100 healthy controls. A predicted structure of 11βHSD2 was constructed by in silico modeling. A systematic review was used to identify cases of HSD11B2-related AME. Data for genotyping and clinical characterizations and complications were extracted. Next-generation sequencing showed novel compound heterozygous mutations (c.343_348del and c.1099_1101del) in the proband with early-onset hypertension and hypokalemia. Sanger sequencing verified the monoallelic form of the same mutations in five other relatives but not in 100 hypertensives or 100 healthy subjects. In silico structural modeling showed that compound mutations may simultaneously perturb the substrate and coenzyme binding pocket. A systematic review of 101 AME patients with 54 HSD11B2 mutations revealed early-onset hypertension, hypokalemia and homozygous mutations as common features. The homozygous HSD11B2 mutations correlated with low birth weight (r = 0.285, P = 0.02). We report novel compound heterozygous HSD11B2 mutations in a Chinese teenager with early-onset hypertension, and enriched genotypic and phenotypic spectrums in AME. Genetic testing helps early diagnosis and treatment for AME patients, which may avoid target organ damage.

目的 比较应变力(strain elastography,SE)与剪切波(shear-wave elastography,SWE)弹性成像对甲状腺结节的诊断价值.方法 纳入北京协和医院2017年10月 ～2018年9月75例行甲状腺切除手术患者的116个结节(良性/恶性:34/82),术前进行常规超声、SE、SWE检查.常规超声利用2017版ACR-甲状腺影像报告和数据系统(Thyroid Imaging Reporting and Data System,TI-RADS)进行分类,SE利用改良5分法进行评分,SWE取Emean并获取cut-off值;TR5、SE评分≥4分,SWE Emean大于cut-off值诊断为恶性.以病理结果为金标准,获得SE、SWE及常规超声联合两者的敏感度、特异性、阳性预测值、阴性预测值、准确度、受试者工作特征曲线下面积,并进行比较.结果 SE的分值和SWE Emean值在良恶性组间比较,差异均有统计学意义.SE的敏感度显著高于SWE(87.80％vs 54.88％,P=0.000),受试者工作特征曲线下面积(0.748 vs 0.657,P=0.203)及准确度(80.17％vs 61.21％)高于SWE,而特异性低于SWE(61.76％vs 76.47％,P=0.359).联合两种弹性成像后,常规超声的敏感度均有提高,特异性及准确度均下降.结论 SE和SWE判断甲状腺结节性质均有一定价值,SE的诊断甲状腺结节敏感度、准确度高于SWE,而SWE的特异性高于SE,但两者单独诊断甲状腺结节价值有限.常规超声联合弹性成像能够提高诊断敏感度.

Progressive cardiac conduction defect (PCCD) is an inherited autosomal dominant cardiac disorder characterized by an age-dependent cardiac electrical conduction block. Several genes have been associated with the genetic pathogenesis of PCCD. The present study aimed to identify the causal mutation of PCCD and to investigate the association between genotype and phenotype in a Chinese family with PCCD. A total of 39 family members were included in the present study. All subjects participated in physical, biochemical, electrocardiography and echocardiography examinations. Whole-exome sequencing was performed for four individuals from the same generation, including three patients with PCCD and one normal control with no cardiovascular disease. Sanger sequencing and in silico analysis were used to identify the causal mutation. Whole-exome sequencing and variant identification revealed a candidate nonsense mutation (c.1443C>A, p.Tyr481*) in lamin A/C (LMNA). The mutation was identified in seven patients (including the proband) and two asymptomatic mutation carriers, but it was not detected in 100 control subjects of matched ancestry. Clinical examinations identified typical symptoms in patients with PCCD, including bradycardia and various types of conduction defect, and excluded other phenotypes related to the LMNA mutation. The genotype and phenotype were co-associated among all participants. In the present study, the c.1443C>A mutation in the LMNA gene was identified as a potential cause of PCCD. In silico analysis predicted that the identified mutation was damaging through its effect on the lamin tail domain of LMNA. From the present study, it could be suggested that genetic screening and family counseling, early pacemaker implantation or a sudden death in the family may be essential for risk stratification and treatment of patients with PCCD.

实体肿瘤是致死的最主要原因之一.随着基因编辑工具和生物信息学的快速发展,基因疗法在肿瘤治疗中发挥着重要作用,然而缺乏安全有效的基因传递技术成为了基因治疗最大的瓶颈.超声靶向微泡破坏技术(ultrasound-targeted microbubble destruction,UTMD)增强基因传递效率且侵袭性低、特异性强,是一种很有前景的基因递送策略.本文对UTMD在肿瘤基因治疗的应用现状及研究进展进行综述并提出展望.

Abstract BACKGROUND Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.