维生素D受体在糖尿病肾病足细胞损伤及蛋白尿缓解中的作用

目的探讨维生素D受体(VDR)在糖尿病肾病(DKD)足细胞中的表达水平及在足细胞损伤及蛋白尿缓解中的作用。方法(1)本研究纳入了65例诊断患有2型糖尿病(伴或不伴蛋白尿)的患者,并纳入了25例年龄和性别相匹配的健康体检者为对照组。根据白蛋白/肌酐(ACR)的尿排泄比例对2型糖尿病患者进行分组,分别为无蛋白尿(ACR<30 mg/g,n=24)、微量白蛋白尿(ACR 30~300 mg/g,n=18)和临床蛋白尿(ACR>300 mg/g,n=23)。另选择25例经肾活检确诊的DKD患者作为DKD组。正常肾脏组织标本均取自泌尿外科同一时期肾脏肿瘤切除患者10例。将各组检测指标进行对比,同时采用实时定量PCR、ELISA法和免疫组化法检测VDR在各组患者的血液、尿液样本和肾脏组织中的表达情况,以及使用Pearson相关分析分析VDR与尿蛋白的相关性。(2)在2型糖尿病肾病小鼠模型中对上述结果进行验证,将遗传背景均为C57BLKs/J的雄性db/db小鼠及同窝出生的db/m小鼠,随机分为正常对照组(A组)、DKD对照组(B组)、DKD二甲基亚砜处理组(C组)、DKD帕立骨化醇(VDR激动剂)处理组(D组),C、D组连续腹腔注射处理8周,对照组不做任何处理。小鼠10周龄时开始连续干预8周,在小鼠22周龄(开始干预后12周)检测各组小鼠体重、血、尿生化指标对比;Western印迹法检测β⁃catenin、VDR的变化;免疫荧光观察足细胞标志蛋白podocin及足细胞损伤蛋白α⁃SMA的表达变化。结果(1)与正常健康对照组相比,无蛋白尿组、微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿组的糖尿病患者相比,微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05)。(2)与正常健康对照组相比,无蛋白尿糖尿病组和DKD组患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿糖尿病组患者相比,DKD组患者血浆中VDR的mRNA和蛋白水平亦较低(均P<0.05)。(3)免疫组化结果显示,DKD组肾组织中VDR的表达明显少于正常对照组。(4)DKD患者血浆中VDR mRNA相对水平与ACR呈负相关(r=-0.342,P<0.05)。(5)各组尿液上清液中VDR的水平与血浆中的水平呈相反趋势。(6)Western印迹结果显示,B组、C组肾小球足细胞β⁃catenin蛋白表达高于D组(均P<0.05),VDR蛋白的表达低于D组(均P<0.05);免疫荧光结果显示,B组、C组肾小球足细胞podocin的表达低于D组(均P<0.05),α⁃SMA的表达高于D组(均P<0.05)。结论VDR高表达缓解DKD足细胞损伤及蛋白尿。     

Anterior Interosseous Nerve Palsy After Shoulder Arthroscopy Treated With Surgical Decompression: A Case Series and Systematic Review of the Literature

Background: Anterior interosseous nerve (AIN) palsy is a very uncommon cause of upper extremity pain and weakness that comprises less than 1% of all upper extremity nerve palsies. Rarely reported but also mentioned in the literature is AIN palsy after shoulder arthroscopy. Methods: A systematic review of the literature to date using PubMed was conducted to identify patients who suffered AIN palsy after shoulder arthroscopy procedures. Articles included met the following criteria: (1) published in English; (2) primary presentation of the data; (3) patients had undergone shoulder arthroscopy before developing symptoms of AIN palsy; and (4) diagnosis was confirmed with clinical symptoms of AIN palsy. Measured outcomes included patient demographics, specific shoulder procedure, anesthesia procedure, intra-operative patient positioning, intra-operative compressive dressing, intra-operative traction, surgical versus conservative treatment, abnormal findings during decompression procedure, proposed mechanism of injury, and follow-up. Results: The search yielded 6 articles, of which 4 (13 cases) met inclusion criteria. An additional 2 cases were included in this report totaling 15 cases. The average patient age was 49 years (range: 31-64) with 73% males. At average follow-up of 24 months, 67% of patients experienced complete resolution of symptoms—more than half of which underwent surgical decompression. Patients who failed to progress experienced weakness of the flexor digitorum profundus and flexor pollicis longus muscles. Conclusions: Proposed injury mechanisms for AIN palsy after shoulder arthroscopy range from mechanical trauma, compressive hematoma, and direct anesthetic neurotoxicity. Management should be directed by clinical symptoms, imaging, and patient factors with majority of patients expected to have excellent clinical outcomes.     

不同尿钙水平的Gitelman综合征患者临床特点比较

目的观察不同尿钙水平Gitelman综合征(GS)患者的临床特点,探讨尿钙在GS疾病临床分型中的价值。方法收集2016—2018年来自中国国家罕见病注册系统(NRSC)、在北京协和医院行SLC12A3基因检测诊断为GS患者的临床资料,分析其尿钙特点,比较不同尿钙水平患者的临床和实验室检查指标。氢氯噻嗪试验按照标准操作流程进行,测定患者基线和用药后3 h内氯离子排泄分数改变量的最大值(ΔFECl)。结果共有83例GS患者被纳入研究,其中低尿钙患者53例(63.86%)。低尿钙组尿钙/肌酐比明显低于非低尿钙组[(0.085±0.058)mmol/mmol比(0.471±0.284)mmol/mmol,t=7.349,P<0.001]。两组患者在年龄、性别、估算肾小球滤过率、血压、血尿电解质水平、代谢性碱中毒方面差异均无统计学意义。低尿钙组患者乏力(χ2=4.595,P=0.032)及多尿(χ2=5.778,P=0.016)发生比例低于非低尿钙组,两组患者在其他临床症状方面差异无统计学意义。低尿钙和非低尿钙组各有16例患者行氢氯噻嗪试验,中位ΔFECl结果分别为0.539%(0.430%,1.283%)和0.829%(0.119%,1.298%),均提示对氢氯噻嗪无反应,组间差异无统计学意义(U=130.000,P=0.956)。结论GS患者中低尿钙比例为63.86%,尿钙水平与疾病临床表型、NCC功能损伤严重程度之间均无明确相关性。     

Role of Conventional and Diffusion-Weighted Magnetic Resonance Imaging of Spinal Treatment Protocol for Hydatid Disease

Objective:

To demonstrate the role of magnetic resonance imaging (MRI) in determining the treatment protocol for hydatid disease of the spine.

Design:

Case report; literature review.

Findings:

Diffusion-weighted MRI can help differentiate complicated infected hydatidosis from abscesses, epidermoid cysts from arachnoid cysts, and benign from malignant vertebral compression fractures. It is also helpful in differentiating between abscesses and necrotic tumors.

Conclusion:

Diffusion-weighted MRI can help differentiate between infections requiring immediate surgery and those that can be treated medically with antihelmintic treatment.     

Fibrinogen-thrombin collagen patch reinforcement of highrisk colonic anastomoses in rats

AIM To evaluate the effectiveness of human fibrinogenthrombin collagen patch(TachoSil~?) in the reinforcement of high-risk colon anastomoses.METHODS A quasi-experimental study was conducted in Wistar rats(n = 56) that all underwent high-risk anastomoses(anastomosis with only two sutures) after colectomies. The rats were divided into two randomized groups: Control group(24 rats) and treatment group(24 rats). In the treatment group, high-risk anastomosis was reinforced with TachoSil~? (a piece of Tacho Sil? was applied over this high-risk anastomosis, covering the gap). Leak incidence, overall survival, intra-abdominal adhesions, and histologic healing of anastomoses were analyzed. Survivors were divided into two subgroups and euthanized at 15 and 30 d after intervention in order to analyze the adhesions and histologic changes. RESULTS Overall survival was 71.4% and 57.14% in the TachoSil~? group and control group, respectively(P = 0.29); four rats died from other causes and six rats in the treatment group and 10 in the control group experienced colonic leakage(P 0.05). The intra-abdominal adhesion score was similar in both groups, with no differences between subgroups. We found non-significant differences in the healing process according to the histologic score used in both groups(P = 0.066).CONCLUSION In our study, the use of TachoSil~? was associated with a non-statistically significant reduction in the rate of leakage in high-risk anastomoses. TachoSil~? has been shown to be a safe product because it does not affect the histologic healing process or increase intra-abdominal adhesions.     

罗伊适应模式对腹股沟疝无张力疝修补术后恢复情况的影响

目的探讨罗伊适应模式对患者腹股沟疝无张力疝修补术后恢复情况的影响。 方法将2016年1月至2019年5月在秦皇岛市第二医院择期进行无张力修补术治疗的120例腹股沟疝患者，按照随机数字法分为对照组和观察组，每组各60例。对照组采用常规护理治疗，观察组在对照组的基础上采用罗伊适应模式。比较2组患者的术后临床指标、心理状态、围手术期并发症发生情况及满意度。 结果术后观察组患者的首次排气时间、恢复正常饮食时间、离床活动时间和术后住院时间均低于对照组（P<0.05）；术后观察组患者的抑郁自评量表（SDS）和焦虑自评量表（SAS）评分显著低于对照组（P<0.05）；术后2组患者均无切口感染发生，2组患者尿潴留、急性疼痛、认知功能障碍、发热、血肿等发生率相比无统计学差异（P>0.05）；术后观察组患者护理满意度为96.67%，显著高于对照组的83.33%（P<0.05）。 结论在常规护理的基础上，罗伊适应模式用于患者腹股沟疝无张力修补围手术期，能有效改善术后患者的焦虑/抑郁情绪，不增加围手术期并发症，促进术后患者的恢复及提高治疗满意度。     

Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers

BACKGROUND: Sugammadex rapidly reverses rocuronium- and vecuronium-induced neuromuscular block. To investigate the effect of combination of sugammadex and rocuronium or vecuronium on QT interval, it would be preferable to avoid the interference of anaesthesia. Therefore, this pilot study was performed to investigate the safety, tolerability, and plasma pharmacokinetics of single i.v. doses of sugammadex administered simultaneously with rocuronium or vecuronium to anaesthetized and non-anaesthetized healthy volunteers. METHODS: In this phase I study, 12 subjects were anaesthetized with propofol/remifentanil and received sugammadex 16, 20, or 32 mg kg(-1) combined with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1); four subjects were not anaesthetized and received sugammadex 32 mg kg(-1) with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) (n=2 per treatment). Neuromuscular function was assessed by TOF-Watch SX monitoring in anaesthetized subjects and by clinical tests in non-anaesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points. RESULTS: No serious adverse events (AEs) were reported. Fourteen subjects reported 23 AEs after study drug administration. Episodes of mild headache, tiredness, cold feeling (application site), dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma-glutamyltransferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium/vecuronium plasma concentrations declined faster than those of sugammadex. CONCLUSIONS: Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.     

血浆凝血因子VIII水平与IgA肾病患者临床病理改变及预后的关系

目的探讨血浆凝血因子VIII(factor VIII,FVIII)水平与IgA肾病(IgAN)患者临床参数及预后的关系。方法收集2016年1月至2016年12月中南大学湘雅二医院确诊的IgAN患者的临床资料。按照时间依赖的受试者工作特征曲线(ROC)得出的血浆FVIII预测IgAN预后的临界值,将患者分为高FVIII组(FVIII>140.50%)和低FVIII组(FVIII≤140.50%),比较两组患者肾活检时基线临床参数的差异。以估算肾小球滤过率(eGFR)下降≥30%或进入终末期肾脏病(ESRD)为终点事件,采用Kaplan-Meier生存曲线及Cox回归方程法分析血浆FVIII水平对IgAN患者预后的影响。结果共93例IgAN患者纳入本研究,中位随访时间为35.15(33.77,36.76)个月,12例(12.90%)患者发生终点事件。高FVIII组患者年龄、血肌酐、尿素氮、血三酰甘油、血总胆固醇、血浆纤维蛋白原、D-二聚体、24 h尿蛋白量、蛋白C、蛋白S和eGFR下降速率高于低FVIII组(均P<0.05);eGFR、血白蛋白、中位随访时间低于低FVIII组(均P<0.05)。Kaplan-Meier生存分析结果显示,与低FVIII组比较,高FVIII组患者肾脏累积生存率降低(χ2=5.635,P=0.018)。在校正收缩压、eGFR、尿蛋白、肾小管萎缩/间质纤维化程度等因素后,多因素Cox回归分析结果显示,高血浆FVIII水平是IgAN患者肾脏预后不良的独立危险因素(HR=4.147,95%CI 1.055~16.308,P=0.042)。结论血浆FVIII水平与IgAN患者临床指标及预后相关,高血浆FVIII水平是IgAN患者肾脏预后不良的独立危险因素。     

Factors Associated With Reoperation After Silicone Proximal Interphalangeal Joint Arthroplasty

Background: Silicone proximal interphalangeal (PIP) joint arthroplasty has a high revision rate. It has been suggested that persistent ulnar deviation and joint instability influence the durability of PIP silicone arthroplasties. The goal of this study was to evaluate what factors are associated with reoperation after silicone PIP arthroplasty. Methods: We retrospectively evaluated all adult patients who underwent PIP silicone arthroplasty between 2002 and 2016 at one institutional system for inflammatory-, posttraumatic-, and primary degenerative arthritis. After manual chart review, we included 91 patients who underwent 114 arthroplasties. Fingers operated included 14 index, 41 middle, 38 ring, and 21 small fingers. Results: The overall reoperation rate was 14% (n = 16). Non-Caucasian race (P = .040), smoking (P = .022) and PIP silicone arthroplasty for post-traumatic osteoarthritis (P = .021) were associated with reoperation. The 1-, 5- and 10-year implant survival rates were 87%, 85%, and 85%, respectively. Conclusion: Caution should be exercised when considering PIP silicone arthroplasty of the index finger or in patients with post-traumatic osteoarthritis. It may be worthwhile addressing smoking behavior before pursuing silicone PIP arthroplasty.     

Effect of the implementation of NICE guidelines for ultrasound guidance on the complication rates associated with central venous catheter placement in patients presenting for routine surgery in a tertiary referral centre

BACKGROUND: The National Institute for Clinical Excellence (NICE) guidelines of 2002 recommended the use of ultrasound (US) for central venous catheterization in order to minimize complications associated with central line placement. An ongoing audit of line placement by anaesthetists in the theatre complex of a tertiary referral centre looked at the associated complication rates. The objective of the study was to compare complication rates pre- and post-implementation of NICE guidelines. METHODS: This prospective, single centre audit looked at all patients in whom a central venous catheter was placed for surgery. Complication rates were assessed for procedures that were performed pre- and post-implementation of NICE guidelines. In total, 438 patients were identified for the study, and the procedures were performed either by trainee or by consultant anaesthetists. RESULTS: The pre- and post-implementation complication rates were 10.5% (16/152) and 4.6% (13/284), respectively, representing an absolute risk reduction of 5.9% (95% CI 0.5-11.3%). Comparison of those procedures in which US was used when compared with the landmark technique after implementation found a reduction of 6.9% in complications (95% CI 1.4-12.4%). The reduction in complication rates was larger for specialist registrars than for consultants (11.2% vs 1.6%). CONCLUSIONS: The implementation of NICE guidelines has been associated with a significant reduction in complication rates in our tertiary referral centre. In the light of the cross-speciality evidence of US superiority and our results, it is imperative that routine use of US guidance becomes more widespread.     

The SCIRehab project: treatment time spent in SCI rehabilitation. Inpatient treatment time across disciplines in spinal cord injury rehabilitation

Background/objective

Length of stay (LOS) for rehabilitation treatment after spinal cord injury (SCI) has been documented extensively. However, there is almost no published research on the nature, extent, or intensity of the various treatments patients receive during their stay. This study aims at providing such information on a large sample of patients treated by specialty rehabilitation inpatient programs.

Methods

Six hundred patients with traumatic SCI admitted to six rehabilitation centers were enrolled. Time spent on various therapeutic activities was documented by each rehabilitation clinician after each patient encounter. Patients were grouped by neurologic level and completeness of injury. Total time spent by each rehabilitation discipline over a patient''s stay and total minutes of treatment per week were calculated. Ordinary least squares stepwise regression models were used to identify patient and injury characteristics associated with time spent in rehabilitation treatment overall and within each discipline.

Results

Average LOS was 55 days (standard deviation 37), during which 180 (106) hours of treatment were received, or 24 (5) hours per week. Extensive variation was found in the amount of treatment received, between and within neurologic groups. Total hours of treatment provided throughout a patient''s stay were primarily determined by LOS, which in turn was primarily predicted by medical acuity. Variation in minutes per week of treatment delivered by individual disciplines was predicted poorly by patient and injury characteristics.

Conclusions

Variations between and within SCI rehabilitation patient groups in LOS, minutes of treatment per week overall, and for each rehabilitation discipline are large. Variation in treatment intensity was not well explained by patient and injury characteristics. In accordance with practice-based evidence methodology, the next step in the SCIRehab study will be to determine which treatment interventions are related with positive outcomes (at 1 year post injury), after controlling for patient and injury differences.     

Comparison of University of Wisconsin and University of Pittsburgh solutions for heart transplantation

The effectiveness of University of Wisconsin (UW) and University of Pittsburgh (UP) solutions for the preservation of rat hearts was compared. Lewis rat hearts were preserved with UW (group A, n=45) or UP (group B, n=45) solution for 0 or 24 h and then transplanted heterotopically into the recipients' abdomen. Ten recipients in each group were observed to obtain 1-week graft survival rates. Tissue water content and tissue content of adenine nucleotides were measured 2 h after transplantation in six grafts from each group. Six hearts preserved for 0 h and seven hearts preserved for 24 h were taken from each group 24 h after grafting for histopathology. The 1-week graft survival rates of groups A24 and B24 were 60% and 10%, respectively. In the 24-h preserved grafts, adenosine triphosphate (ATP) and energy charge [(ATP+adenosine diphosphate/2)/(ATP+adenosine diphosphate+adenosine monophosphate)] of groups A and B were 0.972±0.165 and 0.200±0.123 mg/g wet tissue (P<0.05) and 74.4% and 61.1% (P<0.05), respectively. The tissue water content of group A24 was 71.7%, whereas that of group B24 was 74.1% (P<0.05). Histopathology revealed more severe muscle edema and necrosis and infiltration of polymorphonuclear cells in group B24 than in group A24. We conclude that UW solution is more appropriate for rat heart preservation than UP solution.     

Protective effect of a prostaglandin oligomer on liver mitochondria in situ: time-shared measurements of fluorescence and reflectance in the cold-preserved rat liver

The protective effect of a new oligomeric derivative of prostaglandin B₂, known as OC-5186, was evaluated using time-sharing spectrofluorometry in the coldpreserved rat liver. Experiments were divided into three groups: in group A, a 5000 ng dose of OC-5186 was administered via the peripheral vein, 1000 ng via the portal vein, and 200 ng/ml in University of Wisconsin (UW) solution; in group B, the OC-5186 dosage was ten times greater than that in group A; in group C (control group), liver procurement and storage were performed without OC-5186. At 0, 12, and 24 h after cold preservation at 4°C, the liver was perfused for 30 min at 12°C with oxygenized Krebs-Henseleit solution, after which the perfusate was switched to deoxygenized Krebs-Henseleit solution. Time sharing spectrofluorometry was used to follow NADH fluorescence at 450 nm with a 360-nm excitation wavelength, as well as the reflectance of cytochrome aa ₃ with 605 minus 620 nm from oxidation to reduction. Rate constants of NADH fluorescence and cytochrome aa ₃ reflectance were used as indices of integrity of the mitochondrial respiratory chain. In group C, the rate constant of NADH fluorescence decreased significantly (P<0.05) from the control value of 8.31±0.21×10^-3 (sec^-1) to 4.97±0.15×10^-3 and 5.58±0.16×10^-3 (mean±SEM) at 12 and 24 h after cold preservation, respectively. By contrast, in groups A and B, the rate constant of NADH fluorescence was maintained at significantly (P<0.05) higher levels of 6.57±0.54×10^-3 and 7.29±0.48×10^-3, and 6.94±0.44×10^-3 and 6.86±0.44×10^-3 at 12 and 24 h, respectively. The rate constant of cytochrome aa ₃ reflectance between the OC-5186 groups and the control group was not significant. It is concluded that OC-5186 has a protective effect on the mitochondrial respiratory chain against cold-preservation and/or reperfusion injury.     

Magnetic resonance imaging for the evaluation of rejection of a kindney allograft in the rat

Orthotopic DA (RT1^a) into Lewis (RT1¹) rat kidney allografts and control Lewis-into-Lewis grafts were assessed by magnetic resonance imaging (MRI) and perfusion measurement after intravenous injection of a superparamagnetic contrast agent. MRI anatomical scores (range 1–6) and perfusion rates were compared with graft histology (rank of rejection score 1–6). Not only acute rejection, but also chronic events were monitored after acute rejection was prevented by daily cyclosporine (Sandimmune) treatment during the first 2 weeks after transplantation. In acute allograft rejection (n=11), MRI scores reached the maximum value of 6 and perfusion rates were severely reduced within 5 days after transplantation; histology showed severe acute rejection (histologic score 5–6). In the chronic phase (100–130 days after transplantation), allografts (n=5) manifested rejection (in histology cellular rejection and vessel changes), accompanied by MRI scores of around 2–3 and reduced perfusion rates. Both in the acute and chronic phases, the MRI anatomical score correlated significantly with the histological score (Spearman rank correlation coefficient r _s 0.89, n=30, P<0.01), and perfusion rates correlated significantly with the MRI score or histological score (r _s values between-0.60 and -0.87, n=23, P<0.01). It is concluded that MRI represents an interesting tool for assessing the anatomical and hemodynamical status of a kidney allograft in the acute and chronic phases after transplantation.     

Renal allograft rejection: the temporal relationship and predictive value of plasma TNF (alpha and beta), IFN-gamma and soluble ICAM-1

Recently, close interactions have been described between the tumour necrosis factors alpha and beta (TNF-alpha and beta), interferon-gamma (INF-gamma) and intercellular adhesion molecule-1 (ICAM-1) in T-cell mediated immune activation. During the process of renal graft rejection, the properties of these cytokines to act as powerful stimulators of macrophages, to upregulate class II MHC expression and to stabilise cell-to-cell binding make them of great potential interest. The aim of the present study was to determine the plasma levels of each cytokine and soluble ICAM-1 in 16 renal allograft recipients. We examined plasmas of patients for the first 2 weeks after transplantation and correlated results with the clinical pattern of rejection. Our data suggest an immunopathologic involvement of TNF-alpha, TNF-beta and slCAM-1 in renal allograft rejection and showed that there was a significant elevation in plasma concentrations of these parameters 2 or 3 days prior to the diagnosis of clinical rejection. Rises in INF-gamma did not appear to be significant with regard to rejection as very high levels were found in patients showing no evidence of clinical rejection.     

Resveratrol activates Notch signalling pathway via Sirtuin 1 in podocytes

Objective To explore the relationship between resveratrol and Notch 1 signalling pathway in podocytes. Methods Interference RNA (RNAi) and doxycycline (Dox) were used to inhibit the Sirtuin (SIRT) 1 expression in the wild - type and inducible SIRT1 shRNA (CAGGS) podocytes respectively. Recombinant mouse delta - like ligand 4 (DLL4) was used to activate Notch1 signalling. The message RNA of SIRT1, Notch1 downstream gene Hes1 and Hey2, as well as the key enzymes of Notch1 signalling pathway were detected by using real - time PCR. Western blotting was used to detect intracellular domain of Notch 1 (ICD1), SIRT1, and metalloprotease (ADAM) 10 and components of γ-secretase complex protein expression. Results In WT murine podoytes, resveratrol up-regulated ICD1 protein production, as well as the mRNA of Hes1 and Hey2 in a dose-dependent manner. Treatment with resveratrol resulted Nicastrin mRNA and protein increase in podocytes (P＜0.05), as well as inhibit ADAM10 expression (P＜0.05), but all these changes were prevented after the use of SIRT1 RNAi(P＜0.05). DLL4 up-regulated the expression of mRNA of Hes1 and Hey2, as well as ICD1 protein production in a dose-dependent manner. Treatment with doxycycline resulted decrease of SIRT1 gene and protein expression in CAGGS podocytes after 24 h and 48 h respectively(P＜0.05),which weakend the role of DLL4 significantly(P＜0.05). Conclusion Resveratrol induces Nicastrin expression, as well as activation of Notch1 signalling pathway in a SIRT1-dependent manner.     

地塞米松预防腹腔镜胆囊切除术后恶心呕吐的临床观察

目的 :总结地塞米松预防腹腔镜胆囊手术全麻后恶心、呕吐的效果。方法 :腹腔镜胆囊切除术2 0 0例ASAⅠ～Ⅱ级 ,2 2～ 79岁。随机分为研究组和对照组各 10 0例。研究组静注地塞米松 10mg ,对照组未用地塞米松。两组麻醉给药一样 ,观察 2 4h心率、血压、呼吸频率及恶心、呕吐发生率。结果 :地塞米松组发生恶心 11例 ,呕吐 6例。未用地塞米松组发生恶心 38例、呕吐 33例 ,两组恶心呕吐总发生率分别为 17%和71% (P <0 0 1)。结论 :地塞米松 10mg能减少腹腔镜胆囊切除术后恶心、呕吐的发生率 ,无副作用     

Ligand Gated Ion channels: crucial targets for anaesthetics?

Anaesthetic agents range from simple inert gases to complex synthetic compounds. It is difficult to envisage a unifying mechanism by which all of these agents induce anaesthesia. This review is focused on ligand-gated ion channels. We introduce the molecular classification (plus the concept of superfamilies and receptor isomerism) and nomenclature of the pore-forming proteins, then overview the large body of recent data suggesting they may be selective anaesthetic targets. A wide variety of anaesthetics (volatiles, propofol, etomidate, neurosteroids and barbiturates) have been shown to interact with GABA_A receptors. Point mutations in membrane spanning subunits comprising circa 450 amino acids can ablate the sensitivity of recombinant channels suggesting that the site of action is not in bulk membrane or interfacial lipids. Such drugs act stereoselectively to enhance the amplitude and or duration of inhibitory synaptic currents. In contrast, ketamine, nitrous oxide and xenon produce their anaesthetic effects (and untoward side effects) by depressing activity in the glutamatergic NMDA receptor. A minority of energetic researchers suggest that NMDA receptor activity is crucial for arousal (plays a more pivotal role in anaesthesia) and others suggest that voltage-gated channels are equally important in depressant drug action. Molecular biology and electrophysiology have been crucial for our understanding of channel function, but no concensus mechanism for anaesthetic action has yet emerged.