Association of DYNC1H1 gene SNP/CNV with disease susceptibility,GCs efficacy,HRQOL, anxiety,and depression in Chinese SLE patients

BackgroundSystemic lupus erythematosus is a heterogeneous autoimmune disease characterized by multi‐system injuries and overproduction of autoantibodies. There are many genetic studies on SLE, but no report has considered the relationship between cytoplasmic dynein and SLE susceptibility.ObjectivesOur study intends to investigate whether DYNC1H1 gene SNP/CNV is related to SLE susceptibility, GCs efficacy, HRQOL, anxiety, and depression in Chinese SLE patients.MethodsA total of 502 cases and 544 healthy controls were recruited into the case‐control study, and 472 subjects from the case group were followed up for 12 weeks to evaluate GCs efficacy, HRQOL, anxiety, and depression. Multiplex SNaPshot technique was applied to genotype the seven SNPs of DYNC1H1, and AccuCopy^TM method was conducted to quantify the copy number of DYNC1H1. Anxiety and depression were evaluated using HAMA and HAMD‐24 scales, respectively. The SF‐36 scale was used to assess HRQOL.ResultsThe significant association between SNP rs1190606 and SLE susceptibility was displayed in the dominant model (P_BH = 0.004) as well as its allele model (P_BH = 0.004). We also found that SNP rs2273440 was related to photosensitization symptom in SLE patients (P_BH = 0.032). In the follow‐up study, SNP rs11160668 was connected with the improvement of BP in male patients (P_BH = 0.011). However, no association of DYNC1H1 gene with GCs efficacy, anxiety, and depression was found. No CNV in DYNC1H1 was detected.ConclusionsThe study suggests that DYNC1H1 gene polymorphisms may have an effect on SLE susceptibility and BP improvement of HRQOL in Chinese SLE patients.     

Analysis of COMT Val158Met polymorphisms and methylation in Chinese male schizophrenia patients with homicidal behavior

International Journal of Legal Medicine - Schizophrenia is a severe mental disorder, and its mechanisms have not been fully elucidated. A functional single nucleotide polymorphism (SNP) present in...     

川黄柏及其活性成分治疗痛风病作用研究进展

痛风病是与高尿酸血症、尿酸盐沉积密切相关的代谢性疾病。因其致病机制复杂，高发病率、多并发症和患病年轻化而备受关注。目前西医主要通过降尿酸及抗炎等方式治疗痛风病，但存在严重不良反应和使用禁忌。川黄柏为芸香科植物黄皮树的干燥树皮，具有清热燥湿、泻火除蒸、解毒疗疮等功效。众多研究表明黄柏及其活性成分具有抗炎、镇痛、降尿酸、抗痛风等多种药理活性，具有来源广，安全性高的特点。机制研究发现，黄柏及其活性成分可通过多靶点、多途径防治痛风病，但是缺乏系统、全面的总结与分析。故该文针对川黄柏及其活性成分抗痛风作用机制的相关文献进行分析归纳。分析结果表明，黄柏及其活性成分主要通过降低尿酸水平、抑制炎症反应、改善氧化应激，调节肠道菌群及缓解肾脏损伤等作用机制发挥治疗痛风病的作用，其中以生物碱类成分为代表的活性成分效果尤为显著。该研究在此基础上分析当前研究存在的问题及未来发展趋势，以期为川黄柏抗痛风的物质基础及新药研发提供理论支持与科学依据。     

交锁髓内钉治疗胫骨骨折术后再骨折的效果

目的观察交锁髓内钉治疗胫骨骨折术后再骨折的临床疗效。方法将到本院就治的22例胫骨骨折术后再骨折患者随机分为两组,对照组10例采用钢板内固定,观察组12例采用交锁髓内钉固定,观察两组治疗效果。结果观察组手术操作时间、骨质愈合时间均短于对照组;观察组患者均获得Ⅰ期骨性愈合,对照组2例患者超过28周骨折未愈合,需要手术植入髂骨后才获得骨性愈合。结论交锁髓内钉治疗胫骨骨折术后再骨折,手术操作简便,骨折骨性愈合快,固定牢靠,值得临床广泛推广。     

肿瘤坏死因子受体相关因子家族成员间相互作用的初步研究

目的 探讨肿瘤坏死因子受体相关因子 (TRAFs)各成员间的相互作用及各成员间的关系.方法 利用PCR技术扩增出TRAFs;构建到pDBLeu、pPC86载体上,分别形成诱饵、猎物质粒;转化,扩增酵母菌;将诱饵、猎物菌液结合酵母双杂交阵列组合(Mating)技术筛选相互作用.最后用免疫共沉淀技术进行验证.结果 成功构建...     

Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators

Cilia are critical mediators of paracrine signaling; however, it is unknown whether proteins that contribute to ciliopathies converge on multiple paracrine pathways through a common mechanism. Here, we show that loss of cilopathy-associated proteins Bardet-Biedl syndrome 4 (BBS4) or oral-facial-digital syndrome 1 (OFD1) results in the accumulation of signaling mediators normally targeted for proteasomal degradation. In WT cells, several BBS proteins and OFD1 interacted with proteasomal subunits, and loss of either BBS4 or OFD1 led to depletion of multiple subunits from the centrosomal proteasome. Furthermore, overexpression of proteasomal regulatory components or treatment with proteasomal activators sulforaphane (SFN) and mevalonolactone (MVA) ameliorated signaling defects in cells lacking BBS1, BBS4, and OFD1, in morphant zebrafish embryos, and in induced neurons from Ofd1-deficient mice. Finally, we tested the hypothesis that other proteasome-dependent pathways not known to be associated with ciliopathies are defective in the absence of ciliopathy proteins. We found that loss of BBS1, BBS4, or OFD1 led to decreased NF-κB activity and concomitant IκBβ accumulation and that these defects were ameliorated with SFN treatment. Taken together, our data indicate that basal body proteasomal regulation governs paracrine signaling pathways and suggest that augmenting proteasomal function might benefit ciliopathy patients.     

Phakomatosis Pigmentovascularis Associated With Sturge–Weber Syndrome,Ota Nevus,and Congenital Glaucoma

Phakomatosis pigmentovascularis (PPV) is a rare congenital malformation syndrome that is characterized by a combination of capillary abnormalities and dermal melanocytosis.We describe 3 cases of PPV combined with bilateral Sturge–Weber syndrome (SWS), Ota nevus, and congenital glaucoma.Case 1 was a 2-year-old boy. Facial port-wine stains distributed along the 3 branches of his trigeminal nerves, which suggested the existence of SWS. Gray-blue patches were spread over the frontal and temporal areas of bilateral face, waist, buttocks, and thigh. Bilateral triangular alopecia was found on the temporal scalp. The diagnosis of Ota nevus was made by the bilateral scleral malanocystosis. Increased intraocular pressure, enlarged cornea, and pathologic optic disc cupping supported the diagnoses of infantile bilateral glaucoma. Case 2 was a 4-year-old boy. Port-wine stains were found on the face along the 3 branches of the trigeminal nerve and distributed along the trunk, arms, and legs. Mongolian spots spread over his frontal and temporal areas of the bilateral face, waist, buttocks, thigh, abdomen, and back. Infantile glaucoma was found in both eyes. Ota nevus were found in the both eyes. Optic coherent tomography (OCT) scans revealed increased thickness of choroid. Case 3 was a 5-year-old boy. Besides Ota nevus and infantile glaucoma in both eyes, color Doppler ultrasonography showed choroidal hemagioma. OCT scan showed increased choroidal thickness. The bilateral triangular alopecia on the child''s temporal scalp was similar to that of Case 1. Cases 1 and 2 presented with port-wine stain patches that were consistent with the characteristic manifestation of PPV type IIb. However, the CMTC of Case 3 met the diagnostic criteria for PPV type Vb.Case 1 was treated with trabeculotomies in both eyes. For Cases 2 and 3, surgical interventions were not considered due to the high risks of antiglaucomatous operation complications. We prescribed them antiglaucoma indications.The simultaneously coexistence of PPV with SWS, Ota nevus, and congenital glaucoma is rare. In the clinic, additional detailed examinations and tests of PPV patients to exclude other ocular abnormalities or extraocular involvements are necessary.     

研精覃思,见微知著——人工智能开启精准病理诊断新时代

精准医疗时代,病理学作为基础医学与临床医学的桥梁学科,担负着为疾病个体化治疗提供关键信息的重要任务.精准病理诊断为病理医师的工作带来巨大挑战,人工智能"赋能"病理诊断,通过整合患者临床信息、组织病理学影像、多组学信息,有效辅助精准病理诊断、预测患者预后、分子改变等,有望在精准病理诊断的新时代发挥至关重要的作用,开启精准...