致心律失常型右心室心肌病伴发心律失常性心肌病1例

致心律失常型右心室心肌病(arrhythmogenic right ventricular cardiomyopathy,ARVC)是一种遗传性心肌病,以右心室心肌被纤维和脂肪组织替代为病理特征,约50％的患者双心室受累[1].西方人群该病患病率约为1/5000 ～1/1000,临床比较少见.在该病发展的不同阶段,先后出现心律失常、右心室结构及功能异常以及全心衰竭等临床表现,是35岁以下人群心脏性猝死(sudden cardiac death,SCD)的重要原因之一[2].该病的心律失常以室性心律失常为特征,但房性心律失常同样很多见,长时间的快速性房性心律失常可以导致心功能进一步恶化.本文报告1例北京大学第三医院收治的ARVC伴发房性心动过速,并导致心律失常性心肌病的病例.     

88例重叠肌炎的临床及免疫学特征

目的探讨重叠肌炎(overlap myositis, OM) 患者的临床及免疫学特征。方法对2004年1月至2020年8月于北京大学人民医院住院的特发性炎性肌病(idiopathic inflammatory myopathies，IIMs) 患者资料进行回顾性分析，包括人口学特征、临床症状、实验室指标、免疫学指标(抗核抗体、类风湿因子、肌炎相关性抗体、肌炎特异性抗体)、生存情况，并比较OM和其他炎性肌病患者的临床和实验室特点及预后差别。结果共纳入368例IIMs患者，其中OM患者占23.9% (88/368)。OM患者女性占85.2% (75/88)，中位病程13.5个月，结缔组织病(connective tissue disease, CTD)合并皮肌炎(dermatomyositis, DM)、多肌炎(polymyositis, PM)、免疫介导坏死性肌病(immune-mediated necrotizing myopathy, IMNM)、抗合成酶综合征(anti-synthetase syndrome, ASS)分别为60. 2%、3. 4%、2.3%、34.1%。OM患者和非OM患者相比，女性比例高(85.2% vs. 72.1%, P=0.016)，病程长[13.5(4.5，48.0)月vs. 4.0(2.0，12.0)月，P < 0.001)]。在临床特点方面，OM患者比非OM患者V型疹(25.0% vs. 44.6%, P=0.001)、甲周红斑(8.0% vs. 19.6%, P=0.013)发生率低，雷诺现象(14.8% vs. 1.8%, P < 0.001)、间质性肺炎(88.6% vs. 72.1%, P=0.001)、肺动脉高压(22.7% vs. 7.5%, P < 0.001)、心脏受累(18.2% vs. 9.3%, P=0.033)发生率高。在免疫学特点方面，天门冬氨酸氨基转移酶升高比例低(31.8% vs. 45.0%, P=0.035)，C反应蛋白升高比例高(58.0% vs. 44.6%, P=0.037)，抗核抗体(85.1% vs. 63.4%, P=0.001)、类风湿因子(40.2% vs. 17.8%, P < 0.001)、抗Ro-52抗体(71.6% vs. 56.1%，P=0.038)阳性率高。OM患者和非OM患者的预后无明显差异。结论OM出现脏器受累多见，易合并肺动脉高压、心脏损害。     

秋水仙碱致慢性肾脏病患者肌肉病变1例

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.     

基于深度学习并行网络模型的心律失常分类方法

目的提出一种并行神经网络分类方法，以提高对正常搏动、室上性异位搏动、心室异位搏动、融合搏动4种心律失常的分类性能。方法首先进行心电信号去噪、小尺度心拍和大尺度心拍的分割、数据增强等预处理；然后基于深度学习理论，应用密集连接卷积神经网络改善人工提取波形特征的局限性，并结合双向长短时记忆网络和高效通道注意力网络，以增强提取波形时序特征和重要特征的功能；接着采用并行网络结构，同时输入小尺度心拍和大尺度心拍的的波形特征，以提高心律失常分类的准确性；最后使用Softmax函数实现对心律失常的4分类任务。结果利用MIT-BIH心律失常数据库和3组实验验证所提方法。多种并行网络模型分类性能对比实验和不同心拍输入方式下，各分类模型性能对比实验得出所提分类模型的总体准确率、平均灵敏度和平均特异性分别达到99.36%、96.08%、99.41%；并行网络分类模型收敛性能分析实验得出分类模型每次训练时间为41 s。结论并行多网络分类方法在保持较高总体准确率的同时，平均灵敏度、平均特异性以及训练时间均有改善，该方法有望为心律失常临床诊断提供新的技术方案。     

基于马尔可夫模型的社区人群糖尿病筛查预防心血管病的效果评价

目的在中国鄞州电子健康档案研究(Chinese electronic health records research in Yinzhou, CHERRY)的队列人群中，评估国内外不同指南最新推荐的2型糖尿病筛查策略在我国发达地区人群中预防心血管病的效果。方法采用马尔可夫(Markov)模型模拟并比较的系统性筛查策略包括：(1) 根据《中国2型糖尿病防治指南(2020年版)》的推荐，在40~70岁人群中筛查(策略1);(2) 根据2022年美国糖尿病学会《糖尿病医学诊疗标准》的推荐，在35~70岁人群中筛查(策略2);(3)根据美国预防服务工作组2021年更新的《2型糖尿病的筛查建议声明》的推荐，在35~70岁且超重或肥胖(体重指数24 kg/m²及以上)的人群中进行筛查(策略3)。根据指南推荐，对筛查阳性(空腹血糖7.0 mmol/L及以上)的人群强化控制血糖以达到目标值(糖化血红蛋白控制在7.0%以下)。马尔可夫模型循环周期设为1年，研究期限设为10年，模拟10个周期，计算的结局指标包括心血管病事件发病数和全因死亡数等结局事件数，以及每预防一例心血管病事件或全因死亡需筛查人数等效果评价指标。马尔可夫模型的参数主要来源于CHERRY队列人群和公开发表的文献。采用单因素敏感性分析探讨筛查方法的灵敏度变化对结果的影响，采用概率敏感性分析探讨糖尿病发病率、筛查方法的灵敏度、强化干预措施的效应强度等参数的不确定性。结果研究纳入的289 245名基线无心血管病且未诊断糖尿病的35~70岁人群中，与机会性筛查相比，在40~70岁人群中进行系统性筛查的策略1可预防的心血管病发病数为222[95%不确定性区间(uncertainty interval, UI)：180~264]例，在35~70岁人群中筛查的策略2为227(95%UI: 185~271)例，在35~70岁且超重或肥胖人群中筛查的策略3为131(95%UI: 98~164)例。每预防一例心血管病发病数的需筛查人数在策略1、2和3分别为1 184(95%UI: 994~1 456)人、1 274(95%UI: 1 067~1 564)人和814(95%UI: 649~1 091)人。策略2相比策略1每预防一例心血管病的需筛查人数增加90(95%UI: -197~381)人，但心血管病预防效果相似; 策略3相比策略2的需筛查人数减少460(95%UI: 185~724)人，筛查效率更高。单因素敏感性分析和概率敏感性分析的结果与主分析结果一致。结论在我国发达地区人群中，根据现有的最新指南开展糖尿病系统性筛查能够减少心血管病发病和全因死亡，但仅降低筛查起始年龄从40岁到35岁对预防心血管病效果的增益并不明显，如果降低筛查的起始年龄到35岁需要同时考虑超重或肥胖的危险因素以便提高筛查效率。     

北京城镇职工2型糖尿病患者缺血性脑卒中发病率及主要危险因素

目的通过对新发2型糖尿病患者进行前瞻性观察，探究2型糖尿病发病后缺血性脑卒中的发病特点，并进一步分析2型糖尿病患者缺血性脑卒中发病的危险因素。方法数据资料来源于北京市城镇职工基本医疗保险信息系统数据库。研究采用前瞻性设计，对2010年新诊断为2型糖尿病的患者在2010—2017年缺血性脑卒中的发病情况进行描述，采用Logistic回归模型分析2型糖尿病患者缺血性脑卒中发病的危险因素。结果共纳入185 813例新发2型糖尿病患者，平均年龄(58.5±13.2)岁，男性占49.0%。随访7年内出现新发缺血性脑卒中患者10 393例，累积发病率为5.6%，发病密度为8.1/1 000人年。2型糖尿病患者缺血性脑卒中在各个年龄段均有发生，不同年龄组累积发病率分别为：≤44岁组1.5%(95%CI：1.3%~1.6%)，45~54岁组3.6%(95%CI：3.4%~3.7%)，55~64岁组5.4%(95%CI：5.2%~5.5%)，≥65岁组9.2%(95%CI：9.0%~9.4%)，累积发病率随年龄升高而增加(P < 0.05)。男性累积发病率(6.8%，95%CI：6.7%~7.0%)高于女性(4.4%，95%CI：4.3%~4.6%)； < 80岁的患者中，男性在各年龄段累积发病率均高于女性；≥80岁的患者中，女性累积发病率(9.2%)高于男性(7.9%)。进一步分析2型糖尿病患者缺血性脑卒中发病的危险因素，发现患有冠心病(OR=3.18，95%CI：2.72~3.72)、心力衰竭(OR=1.53，95%CI：1.32~1.79)、肾衰竭(OR=1.45，95%CI：1.20~1.75)等合并症与2型糖尿病患者缺血性脑卒中的发病有关。结论2型糖尿病患者缺血性脑卒中发病率仍处于较高水平，应针对老年患者加强危险因素管理，尽早筛查2型糖尿病患者的合并症情况并采取针对性的预防控制措施。     

糖尿病足溃疡合并下肢动脉病变的临床特点及相关危险因素

目的研究糖尿病足溃疡（DFU）合并下肢动脉病变（LEAD）的临床特点，分析DFU合并LEAD相关危险因素。方法收集2017年1月~ 2019年12月南方医科大学南方医院内分泌代谢科住院治疗的650例DFU患者的临床资料，并进行随访。根据DFU是否合并LEAD分为LEAD组与非LEAD组，分析两组一般资料情况，使用Logistic回归分析DFU合并LEAD的相关危险因素。结果650例DFU患者中，72.4%的患者合并LEAD。平均随访时间约3.5个月，DFU平均愈合时间为2.55个月，其中愈合453例，截肢183例。两组年龄、住院费用、舒张压（DBP）、糖化血红蛋白（HbA1c）、血脂、病程、踝肱指数（ABI）、愈合时间、吸烟率、临床结局、Wagner分级、影像学结果其差异有统计学意义（P < 0.05）。多因素Logistic回归显示年龄（OR=1.070，95% CI 1.049-1.091）、吸烟史（OR=2.013，95% CI 1.268-3.195）、DBP下降（OR=0.980，95% CI 0.963-0.997）为DFU合并LEAD的独立危险因素，愈合时间长则为DFU合并LEAD的临床特点。结论DFU患者合并LEAD发病率高，易致残、死亡，具有高龄、高吸烟率、愈合时间更长的特点，特别发现舒张压的下降也是危险因素之一。     

失活剂烧伤致乳磨牙早失及恒牙胚丧失2例

Devitalization has been widely used in the root canal therapy of primary and permanent teeth in China more than ten years ago. With the development of local anesthetic drugs and injection technologies, this treatment method with high potential risks has been gradually abandoned. However, a questionnaire survey targeted all the participants at the 2018 China Pediatric Dentistry Conference showed that the devitalizer utilization proportion was still as high as 38.1% (383/1 005), even though the ratio was much lower than 75.5% (105/139) in 2003. These doctors had pay more attention to tissue burn caused by devitalizer marginal leakage or direct leakage, and know how to identify and handle with devitalizer burn. Devitalizers were usually made of arsenic trioxide, metal arsenic or paraformaldehyde, which have cytotoxicity, allergenicity, mutagenicity, carcinogenicity, and teratogenic effects on animals. Marginal leakage of devitalizers have high risks of causing soft and hard tissue necrosis. Most of the dentists have an understanding of the potential damages of arsenic containing devitalizers, so they will choose parafor maldehyde with relatively less toxicity. Paraformaldehyde has a certain self limitation, and there are few cases reported, so some dentists lack of vigilance. Paraformaldehyde can also causes tissue necrosis if leakage happens, and the treatment methods are similar to that of arsenic containing devitalizers. When handling with devitalizers burn, the necrosed soft and hard tissue, for example gingiva, alveolar bone or teeth that cannot keep, must be completely removed until fresh blood appears, then rinse with large amount of saline and seal with iodoform gauze. This paper described two cases of devitalizer burn during the root canal treatment of primary molars, both of the doctors failed to identify the devitalizer burn symptoms in the early stage, thus didn''t do proper treatments immediately after burning. Resulting in the necrosis of large area of gingiva and alveolar bone, loss of primary molars and permanent tooth germs 1-2 months after devitalizer burn. This paper reported these two cases in detail in order to warn dentists the high risks of using any kind of devitalizers, help them learn how to identify and treat devitalizer burn, and remind them to stop using devitalizers as soon as possible.     

长疗程利妥昔单抗治疗难治性幼年型特发性炎症性肌病3例

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.     

3例SUN5基因变异导致无头精子症的遗传学分析和助孕治疗结局

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.     

儿童川崎病合并轻微脑炎/脑病伴可逆性胼胝体压部病变综合征1例并文献复习

报道1例川崎病合并轻微脑炎/脑病伴可逆性胼胝体压部病变综合征(mild encephalitis/encephalopathy with a reversible splenial lesion，MERS)患儿的临床诊疗经过，并回顾相关文献报道，总结疾病特点，提高对该病的认识。本例患者为7岁余男孩，持续高热6 d，伴草莓舌、双眼球结膜充血、全身大片红斑样充血样皮疹和颈部淋巴结肿大，符合川崎病诊断标准。丙种球蛋白(2 g/kg)静脉滴注24 h后患儿仍有发热，且出现头痛、嗜睡表现，头颅磁共振成像(magnetic resonance imaging，MRI)显示胼胝体压部局限性梭形肿胀，T1稍低、T2稍高异常信号，扩散加权成像(diffusion-weighted images，DWI)呈明显高信号，表观扩散系数(apparent diffusion coefficient，ADC)图呈明显低信号，提示MERS，予甲泼尼龙2 mg/(kg·d)静脉滴注，数小时后患儿热退，头痛、嗜睡症状消失。1周后复查头颅MRI正常，出院时没有神经系统异常和冠状动脉扩张。共检索到符合条件的外文文献12篇，未检索到中文文献，共报道17例川崎病合并MERS患儿，中位年龄6.5岁(1~14岁)，其中5岁以上儿童11例，合并冠状动脉扩张者4例。所有患儿均有不同程度的意识障碍、幻视、惊厥等神经系统症状，头颅MRI符合MERS影像学改变，经积极治疗, 所有患儿的神经系统症状完全消失，其中13例患儿复查了头颅MRI，影像学改变均恢复正常，所有患儿均未遗留神经系统后遗症。川崎病合并MERS的病例报道非常少见，并发MERS的川崎病多发生在5岁以上年长儿童，头颅MRI检查有助于早期诊断，及时积极治疗可以使MERS病情短期内逆转，不留神经系统后遗症。     

2011—2020年宁波市鄞州区炎症性肠病发病的流行病学研究

目的描述宁波市鄞州区常住居民炎症性肠病发病的分布特征，了解该地区炎症性肠病的疾病负担和发展趋势。方法采用回顾性队列设计，收集2010—2020年鄞州区全民健康信息平台的居民健康档案中所有常住居民的登记信息，利用电子病历随访其炎症性肠病就诊情况，设置1年洗脱期，以登记1年后首次诊断且以炎症性肠病为首要诊断的患者为新发病例。采用泊松分布估算炎症性肠病的发病密度及其95%置信区间(confidence interval, CI)。结果2011—2020年累计纳入鄞州区常住居民1 496 427人，其中男性729 996人(48.78%)，总随访人年8 081 030.82，中位随访人年5.41 [四分位距(interquartile range, IQR): 5.29]。研究期间共有1 217例炎症性肠病新发病例，男性(624例，51.27%)多于女性(593例，48.73%)，总发病密度为15.06/10万人年(95%CI: 14.23, 15.93)，其中溃疡性结肠炎1 106例(90.88%)，发病密度为13.69/10万人年(95%CI: 12.89, 14.52)；克罗恩病70例(5.75%)，发病密度为0.87/10万人年(95%CI: 0.68, 1.09)；未定型结肠炎41例(3.37%)，发病密度为0.51/10万人年(95%CI: 0.36, 0.69)。溃疡性结肠炎的中位发病年龄为50.82岁(IQR: 18.77)，发病年龄在45~49岁组占比最高(15.01%)；发病密度随年龄增长逐渐上升，45~49岁年龄组达到较高水平，随后略有上升，65~69岁年龄组发病密度最高，为25.44/10万人年(95%CI: 20.85, 30.75)，至75~79岁组发病密度迅速下降；克罗恩病的中位发病年龄为44.34岁(IQR: 33.41)，发病年龄在25~29岁组占比最高(12.86%)，由于克罗恩病新发病例数较少，年龄分布波动较大，青年和老年各有峰值。2011—2020年间，鄞州区炎症性肠病的发病密度在2011—2013年处于较低水平，2014—2016年呈迅速上升趋势，2016年达到峰值[24.62/10万人年(95%CI: 21.31, 28.30)]，2017—2020年略有下降。结论2011—2020年鄞州区炎症性肠病发病密度呈较高水平，医疗机构和卫生部门需重视其所带来的疾病负担。     

远端型遗传性运动神经病8例的临床、病理及遗传学特点

目的远端型遗传性运动神经病(distal hereditary motor neuropathy, dHMN)是一组选择性累及运动神经及其神经元的退行性病变，可引起肢体远端肌肉进行性萎缩无力。总结8例dHMN先证者的临床、电生理、病理及遗传学特点，丰富我国dHMN先证者的临床表型和基因型资料，提高临床工作者对dHMN的认识和诊治水平。方法选择2018年6月至2019年4月于北京大学人民医院神经内科就诊的8例dHMN先证者并进而追踪其家系，回顾性分析先证者的临床症状、神经电生理改变、病理特点及基因突变情况。运用基因靶向二代测序技术对所有先证者进行周围神经病相关基因检测，通过Sanger测序验证突变位点，并对可获得的家系成员进行遗传共分离分析。结果先证者发病年龄11~64岁，中位数39.5岁，均为慢性起病，进行性发展，主要表现为远端肢体无力，并逐渐出现肌肉萎缩。神经电生理结果示选择性运动神经损害，运动神经复合肌肉动作电位波幅下降伴神经传导速度减慢，感觉神经不受累，针刺肌电图符合神经源性损害表现。2例先证者肌肉活检显示神经源性骨骼肌损害，1例先证者腓肠神经活检提示感觉神经受累轻微。基因测序显示8例先证者携带了8种不同的已知dHMN致病基因，3例有已报道的致病突变位点，基因诊断率为37.5%，其余5例为临床意义未明的新发点突变，其中2例突变在家系内共分离。结论dHMN是一组临床和基因均具有显著异质性的遗传性周围神经病，二代测序技术广泛运用于dHMN先证者的致病基因搜寻，但仍有超过一半的先证者不能得到明确的基因诊断。     

龙杞方治疗糖尿病肾脏病的作用机制：基于网络药理学和大鼠验证实验

目的基于GEO数据库和网络药理学方法研究龙杞方治疗糖尿病肾脏病（DKD）的作用机制，并通过动物实验进一步验证龙杞方治疗DKD的信号通路。方法利用GEO、TCMSP、CNKI、ChemDraw、SwissTarget Prediction等数据库获得龙杞方和DKD靶点，VENNY获得龙杞方-DKD交集靶点，String进行蛋白互作分析，R包进行KEGG和GO富集分析，Cytoscape 3.7.2软件构建网络图。动物实验验证分析，40只健康雄性SD大鼠随机分为5组（8只/组），采用腹腔内注射链脲佐菌素（STZ）诱导的DKD大鼠模型，龙杞方低剂量组（1 g·kg^-1·d^-1），龙杞方中剂量组（2 g·kg^-1·d^-1），龙杞方高剂量组（2 g·kg^-1·d^-1），空白组和模型组采用等体积水灌胃；HE染色观察大鼠肾脏形态，检测肾功能情况；Western blot检测炎症指标NF-κB、p-NF-κB蛋白表达水平。结果龙杞方共760个主要靶点，通过GEO数据库获得差异基因共1026个，通过VENNY数据库获得龙杞方-DKD交集靶点共61个，通过PPI网络互作获得的核心靶点为MYC、EGF、CASP3、VEGFA、CCL2、SPP1、VCAM1、ICAM1。GO分析龙杞方主要与核受体活性、配体激活转录因子活性等有关，KEGG发现龙杞方主要通过干预NF-κB、TNF、PI3K-AKT等炎症信号通路有关。动物实验显示龙杞方高、中、低剂量干预后DKD大鼠的肾功能指标（Scr、BUN、UALB、UACR）与模型组比较有显著改善（P < 0.05）；HE染色观察出龙杞方高、中、低剂量干预DKD大鼠与模型组对照，肾小球和肾小管结构和排列改善明显，效应强度为：龙杞方高剂量组 > 中剂量组 > 低剂量组；Western blot结果显示龙杞方高、中、低剂量干预DKD大鼠，与模型组比较，可以使NF-κB、p-NF-κB表达显著下调，效应强度为：龙杞方高剂量组 > 中剂量组 > 低剂量组。结论龙杞方通过多成分、多靶点、多信号通路治疗DKD，龙杞方可能通过抑制炎症信号通路NF-κB起到保护肾功能的作用。     

褐藻素通过调控Nrf2/Keap1通路缓解糖尿病大鼠心肌肥大

目的探索褐藻素（FX）对糖尿病心肌病的保护效应和作用机制。方法腹腔注射链脲佐菌素建立糖尿病大鼠模型，进行分组：糖尿病组（DM）、褐藻素干预糖尿病组（DM+FX）和二甲双胍干预糖尿病组（DM+Met），另取正常大鼠给予正常喂养作为正常组（Con）。造模成功后连续12周每日灌胃给药，褐藻素组每日给予200 mg/kg褐藻素灌胃，二甲双胍组每日给予230 mg/kg灌胃，糖尿病组同步灌胃生理盐水。HE染色观察各组大鼠心脏细胞肥大情况；Western blot法检测大鼠心脏中纤维化蛋白TGF-β1和FN蛋白表达水平。H9C2细胞分为3组：正常糖组（NG，5.5 mmol/L葡萄糖）、高糖组（HG，45 mmol/L葡萄糖）和褐藻素干预高糖组（HG+1 μmol/L FX）。FITC标记的鬼笔环肽检测大鼠心肌细胞H9C2表面积变化；qRT-PCR法测定各组细胞肥大因子ANP、BNP和β-MHC基因表达变化；Western blot法检测各组大鼠心脏组织和H9C2细胞中Nrf2、Keap1、HO-1、SOD1蛋白表达水平；DCFH-DA探针检测细胞内活性氧水平变化。结果褐藻素改善糖尿病大鼠心肌纤维化和心肌细胞肥大，同时上调心脏组织中Nrf2和HO-1蛋白表达，抑制Keap1蛋白表达（P < 0.05）。褐藻素可抑制高糖诱导H9C2心肌细胞表面积增加，降低ANP、BNP和β-MHC的mRNA表达水平（P < 0.05）。褐藻素可促进高糖诱导的H9C2细胞中Nrf2入核，上调下游靶蛋白SOD1和HO-1蛋白表达（P < 0.05）来增强细胞抗氧化能力，降低细胞内活性氧的水平。结论褐藻素具有良好的抗糖尿病心肌纤维化和心肌细胞肥大作用，同时上调Nrf2信号通路并促进下游抗氧化蛋白SOD1和HO-1的表达，降低活性氧水平。     

单中心就诊2~18岁儿童胆固醇水平异常发生率及病因分析

目的探讨单中心就诊患儿血浆胆固醇水平异常情况及分布规律。方法回顾性分析2016年6月至2019年6月在北京大学第一医院有胆固醇检测结果的2~18岁儿童血浆胆固醇水平。总胆固醇(total cholesterol, TC)采用胆固醇氧化酶法，低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)采用清除法检测，计数资料比较应用卡方检验。结果调查有效数据11 829例，其中男性7 087例, 女性4 742例。TC升高儿童1 822例(15.4%)，LDL-C升高儿童1 371例(11.6%)，HDL-C降低儿童2 798例(23.7%)，胆固醇水平异常儿童总和4 427例(37.4%)。非常见继发性高脂血症病因就诊儿童7 835人，其中TC升高儿童731例(9.3%)，LDL-C升高儿童561例(7.2%)，HDL-C降低儿童1 886例(24.1%)，胆固醇水平异常儿童总和2 576例(32.9%)。不同疾病就诊儿童中，胆固醇异常发生率差异有统计学意义(P < 0.05)。TC升高及LDL-C升高发生率的前三位主要就诊原因均分别为“血脂异常”“泌尿系统疾病”“营养性疾病”。除小儿内科外，其他科室送检的1 257例患儿血脂检测样本中，300例存在胆固醇水平异常(23.8%)，其中高胆固醇血症患儿70例(5.6%)，高低密度脂蛋白血症患儿44例(3.5%)，低高密度脂蛋白血症患儿224例(17.8%)。在非常见继发性高脂血症病因就诊儿童中，因LDL-C≥140 mg/dL (3.6 mmol/L) 需要进一步排除家族性高胆固醇血症的患儿共365例，占该部分患儿的4.6%。结论就诊儿童胆固醇异常发生率高，在原发病诊治的同时加强胆固醇管理不仅有助于控制继发性高胆固醇血症，也为及时发现家族性高胆固醇血症提供可能。     

RIP1/RIP3-MLKL信号通路与慢性心力衰竭的发生、发展及预后相关

目的通过检测正常人与慢性心力衰竭（HF）患者血浆中受体相互作用的蛋白激酶RIP1、RIP3和混合谱系激酶结构域样蛋白MLKL的表达水平，探讨程序性坏死信号通路RIP1/RIP3-MLKL在HF过程中的表达规律及临床意义。方法入选2020年2月~2020年10月在我院接受治疗的慢性HF患者（NYHA Ⅱ~Ⅳ级）。正常对照组（n=21），Ⅱ级（n=20），Ⅲ级（n=33），Ⅳ级（n= 43）。采集所有患者的空腹静脉血，ELISA法和Western blotting分别检测RIP1/RIP3-MLKL表达水平和通路蛋白表达情况，同时对心功能Ⅳ级患者进行为期5个月的临床随访，评估临床预后指标。结果与正常对照组相比，心功能Ⅱ、Ⅲ、Ⅳ级组RIP1、RIP3、MLKL表达量均增加（P＜0.01）；与Ⅱ级组相比，心功能Ⅲ、Ⅳ级组RIP1、RIP3、MLKL表达量均增加（P＜0.01）；与Ⅲ级组相比，心功能Ⅳ级组RIP1、MLKL表达量增加（P＜0.05）。WB检测RIP1/RIP3-MLKL通路中各蛋白表达量，均存在上调趋势。经pearson相关性分析，HF患者RIP1/RIP3-MLKL表达量与Scr、AST、LVEDD、NT-ProBNP呈正相关（r=0.375、0.231、0.238、0.339、0.299、0.373、0.228、0.256、0.253、0.184、0.189、0.187，P＜0.05），与LVEF呈负相关（r=-0.268、-0.234、-0.322，P＜0.05）。此外对临床随访结果运用独立样本t检验分析，发现在心功能Ⅳ级患者中RIP1/RIP3-MLKL表达量更高组临床预后指标更差。结论RIP1-RIP3-MLKL信号通路在HF患者中表达明显增加，与HF严重程度呈正相关；慢性HF的发生、发展及预后可能与RIP1/RIP3-MLKL信号通路的激活与表达有关。     

泌尿肿瘤免疫检查点抑制剂相关性肌炎的临床特征

目的分析泌尿肿瘤免疫检查点抑制剂(immune checkpoint inhibitor, ICI)相关性肌炎的临床特征及治疗转归。方法选择2018年3月—2022年3月北京大学第一医院泌尿外科诊治的8例泌尿肿瘤ICI治疗后免疫相关性肌炎患者的临床资料进行回顾性分析，对人口学特征、用药方案、临床症状、实验室指标、肌电图检查、病理表现、治疗转归等信息进行分析。结果8例患者包含女性2例、男性6例，中位年龄68岁，均因泌尿肿瘤接受ICI治疗，包括2例上尿路尿路上皮癌(upper tract urothelial carcinoma，UTUC)、3例肾细胞癌(renal cell carcinoma，RCC)和3例膀胱癌(bladder cancer, BCa)。首次ICI治疗至发现免疫相关性肌炎的中位时间为39.5 d，中位疗程为2个疗程。主要症状为肌肉酸痛乏力，5例伴眼睑下垂，3例继发横纹肌溶解，5例合并心肌炎，1例合并重症肌无力，1例合并肠炎。发现合并免疫相关性心肌炎的患者首次接受ICI治疗至肌炎起病的间隔时间更短(P=0.042)。8例患者均有转氨酶及肌酶谱指标显著升高，5例患者出现自身抗体阳性。3例患者完善了肌肉活检，表现出典型的骨骼肌炎性肌病样病理改变，伴CD3⁺、CD4⁺、CD8⁺、CD20⁺淋巴细胞和CD68⁺巨噬细胞浸润。诊断免疫相关性肌炎后8例患者均立即停用ICI治疗，使用甲泼尼龙单独或合并丙种球蛋白静脉注射后病情均好转。结论ICI治疗后免疫相关性肌炎是具有独特临床及病理特征的免疫相关不良反应(immune-related adverse events, irAEs)，常见合并心血管不良反应，立即停用ICI并开始糖皮质激素治疗可以及时改善患者病情。