Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

基于雨课堂的临床流行病学教学改革与实践

目的探讨雨课堂在临床流行病学教学中的作用和效果。方法采用随机对照法在本科阶段无流行病学学习经历的临床专业硕士研究生中,使用雨课堂线上课前预习及课后随堂练习的功能,用于评价雨课堂线上功能的辅助教学效果。结果应用雨课堂线上功能干预组与对照组在基线、阶段小测和末考卷面成绩均无统计学差异;但对于主动学习,雨课堂参与度较高的学生成绩提高明显。结论雨课堂有利于理论性较强课程的学习,但是仍不能忽略课堂教学师生互动过程。     

Investigation of Bimetallic Nickel Catalysts in Catalyst‐Transfer Polymerization of π‐Conjugated Polymers

A comparative study involving bimetallic nickel catalysts designed from disubstituted N,N,N′,N′‐tetra(diphenylphosphanylmethyl)benzene diamine bridging ligands is reported. Catalyst behavior is explored in the Kumada catalyst‐transfer polymerization (KCTP) using poly(3‐hexylthiophene) (P3HT) as the model system. The success of a controlled polymerization is monitored by analyzing monomer conversion, degree of polymerization, end‐group identity, and molecular weight distribution. The characterization of P3HT obtained from KCTP initiated with the bimetallic catalysts shows chain‐growth behavior; however, the presence of Br/Br end‐groups and broader molecular weight distribution reveals a reduced controlled polymerization compared to the commonly employed Ni(dppp)Cl₂. The observed increase in intermolecular chain transfer and termination processes in KCTP initiation with the bimetallic catalysts can be attributed to a weaker Ni(0)‐π‐aryl complex interaction, which is caused by increased steric crowding of the coordination sphere.     

1例抗中性粒细胞胞浆抗体相关性血管炎的临床表现

选取明确诊断抗中性粒细胞胞浆抗体(ANCA)相关性血管炎患者1例作为研究对象,描述病程中的临床表现、诊疗思路及相应的检查结果。患者明确诊断后,调整治疗方案最终好转出院。ANCA相关性血管炎表现多样化,临床诊疗中应时刻警惕。     

Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer

Gastric cancer, one of the most common disease, has become a major public health problem worldwide. Cisplatin (DDP) has been a widely used drug for the treatment of cancer, also usually applied in gastric cancer in clinic. However, the side effects including toxicity and drug-resistance restricted the usage of DDP in clinic, so we prepared a DDP-complexed hydrogel (DDP-Gel) and investigated its efficacy in gastric cancer. For in vivo studies, MKN45-Luc cells were injected into BLAB/C node mice subcutaneously to establish gastric cancer with orthotopically grown tumors. Mice bearing tumors were treated with normal saline, DDP and DDP-Gel. Body weight and survival condition were observed and recorded. The treatment efficacy in vivo was detected by luciferase imaging and histological evaluation was performed by H&E staining of different organs. Additionally, normal ICR mice were treated with different doses of DDP/DDP-Gel to calculate their LD₅₀ in vivo. The results showed that DDP-Gel prolonged survival time and ameliorated body weight changes of mice bearing tumors. DDP-Gel exhibited higher efficacy to inhibit tumor growth and metastasis, compared to DDP. Besides, LD₅₀ of DDP-Gel was 166.0?mg/kg, 13.2 folds higher than DDP. As a conclusion, DDP-Gel showed a more effective and safer function than DDP in gastric cancer, which indicating that DDP-Gel might be a novel strategy for gastric cancer therapy.     

丙戊酸钠联合利培酮对癫痫性精神障碍患者精神功能及认知功能的影响

目的:探讨丙戊酸钠联合利培酮对癫痫性精神障碍患者精神功能及认知功能的影响。方法:纳入2018年12月~2020年12月期间某院收治80例癫痫性精神障碍患者为研究样本,以随机对照原则,经数字表法分为观察组和对照组各40例,对照组采用利培酮治疗,观察组采用利培酮+丙戊酸钠治疗,对比两组患者治疗后各症状缓解时间,治疗前后精神功能评价量表(GAF)、简明精神病评定量表(BPRS)、认知功能障碍评估量表(MoCA)、简易智力状态检查量表(MMSE)的评分结果及用药后不良反应发生情况。结果:观察组治疗后知觉、记忆、思维、情感障碍等症状缓解时间均低于对照组,差异具有统计学意义(P<0.05);治疗前两组患者的以上评分无明显差异(P>0.05),治疗后观察组的GAF高于对照组、BPRS低于对照组,MoCA、MMSE高于对照组,差异均具有统计学意义(P<0.05);观察组治疗后不良反应发生率12.50%(5/40)略高于对照组7.50%(3/40),差异无统计学意义(P>0.05)。结论:丙戊酸钠联合利培酮治疗癫痫性精神病对改善患者的精神、认知功能具有积极影响,二者合用不会增加药物不良反应发生风险,此用药方案有效性及安全性均较高。     

A novel surgical technique to prevent post-enucleation conjunctival cyst:conjunctival staining with methylthioninium

Dear Editor,Conjunctival cyst of the orbit acquired from enucleation is an infrequent but serious complication;which can occur in 3%-7%of patients,more commonly after a secondary procedure;.The most common manifestations are the inability to retain the external prosthesis.     

Cardiac Denervation for Arrhythmia Treatment with Transesophageal Ultrasonic Strategy in Canine Models

Stellate ganglion (SG) modification has been investigated for arrhythmia treatment. In this study, transesophageal SG imaging and intervention were explored using a homemade 30F integrated focused ultrasonic catheter in healthy mongrel canines in vivo. Anatomic details of SGs were ultrasonically imaged and evaluated. SG had a heterogeneous echoic structure and characteristic profiles sketched by hyper-echoic outlines in an ultrasonogram. Left SGs in the experimental group were successfully ablated through the esophagus under ultrasonic guidance provided by the catheter itself. Two weeks after the ablation, the QT and QTc of the experimental group decreased compared with those of the sham group and at baseline (both p values < 0.001). Histologic examination revealed that left SGs were destroyed. No major complications were observed. This approach may be further explored as a method for ganglia remodeling evaluation and as a strategy of ganglia modification for arrhythmia and for other diseases.