Urantide对动脉粥样硬化大鼠胸主动脉组织中c-Jun氨基末端激酶表达的影响及其意义

目的：探讨Urantide对动脉粥样硬化（AS）大鼠胸主动脉组织中c-Jun氨基末端激酶（JNK）mRNA和蛋白表达的影响,阐明其防治AS的分子机制。方法：采用腹腔注射维生素D₃（VitD₃）联合高脂特制饲料饲养方法建立大鼠AS模型,同时设对照组。建模成功的150只AS模型大鼠随机分为模型组、辛伐他汀组、Urantide 3 d组、Urantide 7 d组和Urantide 14 d组,每组30只。辛伐他汀组大鼠灌胃给予辛伐他汀,连续14 d;Urantide 3、7和14 d组大鼠经尾静脉注射Urantide,分别连续3、7和14 d。采用全自动生化分析仪检测大鼠血清学指标,HE染色观察大鼠胸主动脉组织病理形态表现,免疫组织化学染色、qRT-PCR和Western blotting法检测大鼠胸主动脉组织中JNK mRNA和蛋白表达水平。结果：与对照组比较,AS模型组大鼠血清中甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白（LDL）水平均升高（P<0.05）,高密度脂蛋白（HDL）水平降低（P<0.05）。HE染色,模型组大鼠胸主动脉组织中泡沫细胞形成,中膜弹性纤维断裂以及钙化形成;与模型组比较,辛伐他汀组和Urantide组大鼠胸主动脉病理改变明显改善。免疫组织化学染色,对照组大鼠胸主动脉组织中JNK阳性颗粒微量表达;与对照组比较,模型组大鼠胸主动脉组织中JNK阳性表达强度明显增加（P<0.05）;与模型组比较,辛伐他汀组和不同时间Urantide组大鼠胸主动脉组织中JNK阳性表达强度明显降低（P<0.05）。qRT-PCR和Western blotting法检测,与对照组比较,模型组大鼠胸主动脉组织中JNK mRNA和蛋白表达水平明显升高（P<0.05）;与模型组比较,辛伐他汀组和不同时间Urantide组大鼠胸主动脉组织中JNK mRNA和蛋白表达水平明显降低（P<0.05）;与辛伐他汀组比较,不同时间Urantide组大鼠胸主动脉组织中JNK mRNA和蛋白表达水平进一步降低（P<0.05）。结论：Urantide可改善AS大鼠胸主动脉的病理损伤,其机制可能与抑制JNK信号通路的表达有关。     

基于雨课堂的混合式教学在生理学教学中的应用

为在课前高效督促学生预习,课中实施互动教学,课后精确分析教学效果,在生理学教学中,运用雨课堂构建了“课前-课堂-课后”高效、精准、互动、混合式教学和智慧课堂。问卷调查结果表明大部分学生喜欢或非常喜欢雨课堂支持的教学形式;有效促进了学生的平时学习,师生互动,精准掌握了学情,科学精准教学,提高了教学效率,改善了教学效果。     

Urantide对动脉粥样硬化大鼠心脏UⅡ和GPCR14基因与蛋白表达的影响*

目的 观察Urantide对动脉粥样硬化（AS）大鼠心脏UⅡ和GPCR14基因与蛋白表达的影响。方法 采用腹腔注射维生素D3及高脂饲料喂养复制大鼠AS模型,随机分为正常组、AS组、辛伐他汀组、Urantide组（3、7和14?d组）。应用免疫组织化学、实时荧光定量聚合酶链反应（qRT-PCR）、Western blotting检测大鼠心脏UⅡ、GPCR14基因和蛋白的表达水平。结果 与正常组比较,AS组大鼠心脏血管及病变部位UⅡ及GPCR14阳性表达增加（P?<0.05）,UⅡ及GPCR14基因与蛋白质的表达水平升高（P?<0.05）。与AS组比较,Urantide各给药组大鼠心脏血管及病变部位的UⅡ及GPCR14阳性表达减少（P?<0.05）,UⅡ及GPCR14基因与蛋白质的表达水平降低（P?<0.05）。结论 Urantide对AS大鼠的心脏具有保护作用。     

彩色多普勒超声对感染性休克患者急性肾损伤的预测价值

背景 感染性休克患者存在肾脏血液灌注异常,严重时可诱发急性肾损伤(AKI),严重威胁患者生命安全;彩色多普勒超声(CDU)可用于评估肾脏血流变化,但有关其在感染性休克患者AKI评估中价值的研究较少。目的 通过CDU评价感染性休克患者AKI的发生情况及其血流动力学改变。方法 选取2019年6月至2021年7月徐州市中心医院收治的105例确诊为感染性休克的患者并纳入感染组,选取同期健康体检者58例并纳入对照组,收集受试者一般资料。采用CDU检查受试者肾脏血流动力学指标[肾动脉管腔内径(D)、收缩期血流峰值速度(Vs)、舒张末期血流速度(Vd)、阻力指数(RI)、搏动指数(PI)],比较感染组与对照组的一般资料及肾脏血流动力学指标。根据感染组患者入院72 h内发生AKI与否将其分为AKI组及非AKI组,比较AKI组与非AKI组肾脏血流动力学指标。应用受试者工作特征(ROC)曲线分析肾脏血流动力学指标对感染性休克患者发生AKI的预测价值。应用单因素分析及多因素Logistic回归分析探讨感染性休克患者发生AKI的影响因素。以AKI由轻到重的程度将患者分为AKIⅠ组、AKIⅡ组、AKIⅢ组,比较...     

手术创伤后红细胞丙酮酸激酶活性改变与外科性糖代谢障碍的关系

探讨手术创伤后围术期红细胞丙酮酸激酶活性改变与糖代谢障碍 (或称“外科性糖尿病”)的关系。随机选择中等度手术创伤如上腹部胆囊切除或胃大部切除手术病人 17例 ,ASAⅠ～Ⅱ级 ,观察普鲁卡因静脉复合麻醉 (IPBA)下上腹部手术对围麻醉手术期红细胞(RBC)丙酮酸激酶 (PK)活性及其相关重要调理因子 ,如RBC内ATP、ADP、Pi、Mg2 + ,以及血浆葡萄糖、血清胰岛素的影响。结果显示 ,PK在手术结束后 10min较麻醉前明显下降 (P<0 0 1) ,术后 2 4h仍无回升趋势。RBC Pi的变化与PK无相关性 (r=- 0 0 4 1,P >0 0 5 ) ,ATP/ADP比值的变化与PK呈正相关趋势(r=0 6 80 ,P <0 0 1) ,RBC Mg2 + 的变化与PK呈明显负相关 (r=- 0 817,P <0 0 5 ) ,Glu/Ins的变化与PK呈负相关趋势 (r=- 0 6 97,P <0 1)。研究表明 ,IPBA和上腹部手术创伤可直接或(和 )间接引起细胞内PK活性下降和糖酵解通路的障碍 ,导致细胞对葡萄糖、Pi的利用和ATP的合成障碍 ;围术期糖酵解反应的抑制可能是应激性糖代谢障碍的重要机制之一 ,在手术后期和术后表现尤为明显     

Effects of Stamm gastrostomy on gastric emptying rate in rats

AIM: Although frequency of gastroesophageal reflux (GER) increases after gastrostomy, the role of gastric emptying in GER has not been evaluated. In this study, we examined the effects of Stamm gastrostomy on gastric emptying rate in rats and whether Stamm gastrostomy induces GER or not. METHODS: Sprague-Dawley rats were divided into three groups. Stamm gastrostomy was done in the first group (SG). Sham operation was carried out in group 2 and the 3rd group served as control. Gastric emptying was assessed using both liquid and solid meals in each group at postoperative 14th day. For solid meal emptying, after fasting of 16 h, the rats were fed for 3 h and gastric emptying rate was measured at the fifth hour. Methylcellulose was used for emptying of liquids and it was given after the animals were fasted for 16 h and gastric emptying rate was measured 30 min later. Histological evaluation for GER was performed in all groups. RESULTS: GER was observed pathophysiologically in 5 of the 7 rats in SG group. Gastric emptying rates of liquid and solid meals were found to be similar in control, SG or sham groups. CONCLUSION: Surgical gastrostomy does not affect the gastric emptying of solid and liquid meals in rats. Other mechanisms should be considered in the development of GER observed following gastrostomy.     

Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading

Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. This was accomplished by introducing a human SOST transgene driven by the 8 kb fragment of the DMP1 promoter that also provided osteocyte specificity of the transgene. Right ulnae were subjected to in vivo cyclic axial loading at equivalent strains for 1 min/day at 2 Hz; left ulnae served as internal controls. Endogenous murine Sost mRNA expression measured 24 h after 1 loading bout was decreased by about 50% in TG and wild type (WT) littermates. In contrast, human SOST, only expressed in TG mice, remained high after loading. Mice were loaded on 3 consecutive days and bone formation was quantified 16 days after initiation of loading. Periosteal bone formation in control ulnae was similar in WT and TG mice. Loading induced the expected strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed.     

Scale‐up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model

To realize the therapeutic potential of mesenchymal stem cells (MSCs), we aimed to develop a method for isolating and expanding New Zealand rabbit MSCs in a great scale. Rabbit MSCs expanded under hypoxic and normoxic conditions were compared in terms of replication capacity, differentiation potential, and the capacity for allogeneic transplantation in a calvarial defect model. The cells from all tested rabbits were expanded more rapidly when plated at low‐density under hypoxic conditions compared to under normoxic conditions. Moreover, cells expanded under hypoxic conditions increased in the potential of osteoblastic, adipocytic, and chondrocytic differentiation. More importantly, radiographic analysis and micro‐CT measurement of bone volume revealed the hypoxic cells when transplanted in the calvarial defects of another rabbit increased in the ability to repair bone defect compared to the normoxic cells. Six weeks after allogeneic transplantation of hypoxic MSCs, histological analysis revealed a callus spanned the length of the defect, and several bone tissues spotted in the implant. At 12 weeks, new bone had formed throughout the implant. Using BrdU labeling to track the transplanted cells, the hypoxic cells were more detected in the newly formed bone compared to the normoxic cells. For defects treated with allogeneic MSCs, no adverse host response could be detected at any time‐point. In conclusion, we have developed a robust method for isolation and expansion of rabbit MSCs by combining low‐density with hypoxic culture, which can be applied for the design of clinical trials in allogeneic transplantation of MSCs for bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1213–1220, 2012     

成都地区健康人群髋部骨密度及几何参数 变化的初步研究

目的观察成都地区健康人群股骨近端骨密度及几何参数的变化。方法用美国GELUNAR 公司生产的Prodig advance测定成都地区健康人群4121例,其中男例2271例,女1850例,年龄20 ~ 96岁。测量部位包括左股骨颈（Neck),大转子（Troch )、Wards区、股骨干（Shaft)、全髋（Total)骨密 度,并计算几何参数：髋轴长度（HAL)、横断面转动惯量（CSMI)、横截面积（CSA)、颈干角（NSA)、髋 部强度指数（FSI)。按年龄、性别分别输人数据,以10岁为一年龄组,分别计算各组骨密度及几何参 数值;结果用spss14. 0统计软件处理。结果1.男性髋部骨密度峰值出现在20-219岁,女性骨密度 峰值出现在30 -39岁。同年龄组女性骨密度累积丢失率明显高于男性。2.男性CSMI峰值在30 ~ 39岁,CSA峰值在20-29岁,随年龄增加逐渐降低。女性CSMI、CSA、SI峰值在20 -四岁,随着年龄 增加逐渐降低。3.男、女HAL与年龄、BMI、股骨各部位骨密度呈弱相关性,与身高、体重呈正相关。 男、女CSMI、CSA与身高、体重、股骨骨密度呈正相关。男、女NSA、SI与骨密度呈正相关。结论 1. 本组健康人群股骨骨密度、几何参数为成都地区骨质疏松防治提供参考依据;2.随年龄增长伴随骨 密度丢失和几何参数变化,以女性更为明显;3.女性更应注意骨质疏松的防治。     

Multilevel Arthroplasty for Cervical Spondylosis: More Heterotopic Ossification at 3 Years of Follow-up

STUDY DESIGN.: Retrospective cohort study. OBJECTIVE.: To investigate the differences between single- and multilevel degenerative disc diseases (DDDs) treated with cervical arthroplasty. SUMMARY OF BACKGROUND DATA.: The US Food and Drug Administration clinical trials compared arthroplasty with anterior cervical discectomy and fusion for single-level DDD. However, cervical arthroplasty for multilevel DDD is rarely addressed in the literature. METHODS.: A total of 102 consecutive patients who underwent Bryan arthroplasty were divided into either a single- or multilevel group. Clinical outcomes were measured by the visual analogue scale (VAS) of neck and arm, and by the neck disability index with a minimum follow-up of 25 months. Every patient had radiographical evaluations, and computed tomography. RESULTS.: Eighty-six patients (84.3%) completed the follow-up with a mean time of 38.3 ± 8.7 months. Postoperatively, there were significant improvements in clinical outcomes (i.e., VAS neck, VAS arm, and neck disability index) at each time point of evaluation (i.e., 3-, 6-, 12-, and 24 mo postoperation). The sex composition and clinical outcome improvements between the single- and multilevel groups were not significantly different. The multilevel group was older (51.3 ± 8.6 vs. 46.3 ± 11.2 yr; P = 0.02), had more intraoperative blood loss (218.0 ± 182.4 vs. 102.8 ± 79.2 mL; P = 0.001), and demonstrated a higher rate of heterotopic ossification (HO) than the single-level group (66.0% vs. 25.0%; P < 0.001). The majority (97.7%) of the artificial discs in this series remained mobile despite HO. CONCLUSION.: Clinical outcomes of cervical arthroplasty in multilevel spondylosis are similar to single-level outcomes. However, the significantly higher rate of HO found in multilevel arthroplasty and its long-term effect warrant further investigation.