靶向测序诊断黑棘皮病1家系

【摘要】 报道临床症状不典型的家族性黑棘皮病1家系。先证者女，4岁，自1周岁时，颈部、腹部出现黑色斑片，近年来逐渐扩大至唇周、躯干前部。腹部皮肤全反式共聚焦显微镜检查可见乳头环下延扭曲及沟壑结构，乳头环内可见中高折光颗粒结构。先证者父亲及祖母既往有类似病史，但随着年龄增长色素沉着自发性消退，仅有局部皮纹增粗。采集先证者及父母、祖母外周血，对先证者外周血DNA行Panel靶向测序，结果显示，先证者存在FGFR3基因14号外显子c.1949A>C（p.Lys650Thr）错义突变，Sanger测序验证证实先证者及其父亲和祖母均存在此突变。诊断：家族性黑棘皮病。     

How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

BackgroundAbnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity.ResultsCompared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = ?0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites.ConclusionThis study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。     

Efficacy,effectiveness and side effects of medications used to prevent fractures

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long‐term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit–risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and ‘drug holidays’ should be considered at this time. Further studies are needed to guide clinical practice in this area.     

Importance of serum phosphate in elderly patients with diabetes mellitus

BACKGROUND Metabolic disturbances including changes in serum calcium,magnesium or phosphate(P) influence the prevalence of type 2 diabetes mellitus(DM).We assessed the importance of serum P in elderly patients with type 2 DM vs nondiabetes mellitus(non-DM) in relation to renal function.AIM To determine the association between serum P and serum glucose or insulin resistance in diabetic and non-diabetic patients.METHODS One hundred-ten subjects with a mean age of 69.02±14.3 years were enrolled.Twenty-nine of the participants had type 2 DM(26.4%).The incidence of hypertension,smoking and receiving vitamin D(vitD) derivates were recorded.The participants were classified by both estimated glomerular filtration rate(eGFR) and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria.RESULTS We divided the patients in two groups according to the P cut-off point related to DM value.A comparison between high and low P showed that body mass index30.2±6.3 vs 28.1±4.6(P=0.04),mean glucose 63.6 vs 50.2(P=0.03),uric acid 6.7±1.6 vs 6.09±1.7(P=0.05),mean intact-parathyroid hormone 68.06 vs 47.4(P=0.001),systolic blood pressure 147.4±16.7 vs 140..2±16.1(P=0.02),mean albuminuria 63.2 vs 50.6(P=0.04) and eGFR 45.6±22.1 vs 55.4±21.5(P=0.02)were significantly different.χ~2 tests showed a significant association between high P and DM,hypertension,receiving vitD,smoking and eGFR stage(χ~2=6.3,P=0.01,χ~2=3.9,P=0.03,χ~2=6.9,P=0.009,χ~2=7.04,P=0.01 and χ~2=7.36,P=0.04,respectively).The adjusted model showed that older age,female gender and increased body mass index were significant predictors of type 2 DM when entering the covariates.CONCLUSION High serum P contributes to vascular and metabolic disturbances in elderly patients with type 2 DM and renal impairment.     

Morphological imaging and CT histogram analysis to differentiate pancreatic neuroendocrine tumor grade 3 from neuroendocrine carcinoma

PurposeTo compare morphological imaging features and CT texture histogram parameters between grade 3 pancreatic neuroendocrine tumors (G3-NET) and neuroendocrine carcinomas (NEC).Materials and methodsPatients with pathologically proven G3-NET and NEC, according to the 2017 World Health Organization classification who had CT and MRI examinations between 2006-2017 were retrospectively included. CT and MRI examinations were reviewed by two radiologists in consensus and analyzed with respect to tumor size, enhancement patterns, hemorrhagic content, liver metastases and lymphadenopathies. Texture histogram analysis of tumors was performed on arterial and portal phase CT images. images. Morphological imaging features and CT texture histogram parameters of G3-NETs and NECs were compared.ResultsThirty-seven patients (21 men, 16 women; mean age, 56 ± 13 [SD] years [range: 28-82 years]) with 37 tumors (mean diameter, 60 ± 46 [SD] mm) were included (CT available for all, MRI for 16/37, 43%). Twenty-three patients (23/37; 62%) had NEC and 14 patients (14/37; 38%) had G3-NET. NECs were larger than G3-NETs (mean, 70 ± 51 [SD] mm [range: 18 - 196 mm] vs. 42 ± 24 [SD] mm [range: 8 - 94 mm], respectively; P = 0.039), with more tumor necrosis (75% vs. 33%, respectively; P = 0.030) and lower attenuation on precontrast (30 ± 4 [SD] HU [range: 25-39 HU] vs. 37 ± 6 [SD] [range: 25-45 HU], respectively; P = 0.002) and on portal venous phase CT images (75 ± 18 [SD] HU [range: 43 - 108 HU] vs. 92 ± 19 [SD] HU [range: 46 - 117 HU], respectively; P = 0.014). Hemorrhagic content on MRI was only observed in NEC (P = 0.007). The mean ADC value was lower in NEC ([1.1 ± 0.1 (SD)] × 10⁻³ mm²/s [range: (0.91 - 1.3) × 10⁻³ mm²/s] vs. [1.4 ± 0.2 (SD)] × 10⁻³ mm²/s [range: (1.1 - 1.6) × 10⁻³ mm²/s]; P = 0.005). CT histogram analysis showed that NEC were more heterogeneous on portal venous phase images (Entropy-0: 4.7 ± 0.2 [SD] [range: 4.2-5.1] vs. 4.5 ± 0.4 [SD] [range: 3.7-4.9]; P = 0.023).ConclusionPancreatic NECs are larger, more frequently hypoattenuating and more heterogeneous with hemorrhagic content than G3-NET on CT and MRI.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

阻塞性睡眠呼吸暂停低通气综合征患者CYP3A4基因多态性的检测

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)CYP3A4基因的多态性,了解其对芬太尼类药物的敏感性及不同基因型的人群分布特征,指导临床个体化用药。方法对50例OSAHS患者进行CYP3A4基因的多态性检测,采静脉血,通过DNA抽提-PCR扩增-焦磷酸测序方法检测CYP3A4基因。结果野生纯合型型34例(68%),突变杂合型15例(30%),突变纯合型型1例(2%)。结论OSAHS患者中约2%为AA型,该型对芬太尼类药物极其敏感,术后有易发生窒息的风险,应高度警惕芬太尼类药物呼吸抑制的潜在风险。     

中日友好医院分型股骨头坏死腓骨植入治疗的三维有限元分析

文题释义：股骨头坏死中日友好医院分型的有限元分析：根据李子荣等提出的中日友好医院分型，建立股骨头坏死三维模型，分为 M型(内侧型)、C型(中央型)和 L型(外侧型)，其中 L型包括L1型(次外侧型)、L2型(极外侧型)和 L3型(全头型)。通过对建立的模型进行有限元分析，为该分型的保髋治疗提供了一定力学依据，显示外侧柱的存留是精准预防塌陷的重要因素，为进一步实现个体化治疗提供力学基础。 腓骨支撑坏死股骨头保髋手术：是对于早中期股骨头坏死需要保留股骨头患者进行的一种手术方式。首先需对股骨头进行髓芯减压，清除一定坏死骨，空腔填塞松质骨(髂骨为主)，打压结实后植入腓骨(异体或自体)支撑，给坏死区的提供力学支撑及生物学修复，预防股骨头进一步坏死及塌陷。 背景：研究报道股骨头坏死的保髋疗效与外侧柱存留密切相关，中日友好医院分型是根据三柱结构确立的，对股骨头塌陷的预测准确性高。 目的：建立股骨头坏死中日友好医院分型各分型仿真的三维有限元模型，通过有限元分析各分型腓骨植入的力学变化，探讨外侧柱存留对保髋疗效的意义，为该分型的塌陷精准预测提供基础。 方法：建立正常股骨头、中日友好医院分型(M型、C型、L1型、L2型、L3型)股骨头坏死及其腓骨植入3组11种三维有限元模型，运用ANSYS软件进行有限元分析计算，观察各组模型的最大应力值、最大位移值及股骨头内部载荷传递模式。 结果与结论：①坏死组位移最大，应变最大，且因坏死分型不同而位移不同，位移变化如下：M型相似文献   

丹红注射液对急性心肌梗死PCI围手术期心功能和TIMI血流影响的Meta分析

目的:系统评价丹红注射液对急性心肌梗死(AMI)经皮冠状动脉介入治疗(PCI)围手术期心功能和心肌梗塞溶栓治疗(TIMI)血流分级的影响。方法:计算机检索CNKI,万方数据库,维普数据库,Pub Med,CBM,Web of Science,The Cochrane Library共7个数据库,全面采集在PCI围手术期应用丹红注射液治疗急性心梗的临床试验,采用Cochrane风险评价表进行文献质量评价,运用Revman 5.3软件进行Meta分析。结果:共纳入12个临床试验,包含1131例患者,其中丹红治疗组569例,对照组562例,结果显示在常规治疗的基础上加入丹红注射液治疗,患者的左室射血分数明显增高[均数差(MD)=6.62,95%可信区间(CI)(4.91,8.34),P<0.00001],TIMI分级3级患者明显增多[相对危险度(RR)=0.22,95%CI(0.12,0.41),P<0.00001],脑利钠肽水平明显降低[MD=-151.86,95%CI(-247.00,-56.72),P=0.002]。结论:丹红注射液可以提高急性心梗PCI围手术期心功能和增加TIMI血流的分级。