Low TGFβ1 expression prevents and high expression exacerbates diabetic nephropathy in mice

Nephropathy develops in many but not all patients with long-standing type 1 diabetes. Substantial efforts to identify genotypic differences explaining this differential susceptibility have been made, with limited success. Here, we show that the expression of the transforming growth factor β1 gene (Tgfb1) affects the development of diabetic nephropathy in mice. To do this we genetically varied Tgfb1 expression in five steps, 10%, 60%, 100%, 150%, and 300% of normal, in mice with type 1 diabetes caused by the Akita mutation in the insulin gene (Ins2^Akita). Although plasma glucose levels were not affected by Tgfb1 genotype, many features of diabetic nephropathy (mesangial expansion, elevated plasma creatinine and urea, decreased creatinine clearance and albuminuria) were progressively ameliorated as Tgfb1 expression decreased and were progressively exacerbated when expression was increased. The diabetic 10% hypomorphs had comparable creatinine clearance and albumin excretion to wild-type mice and no harmful changes in renal morphology. The diabetic 300% hypermorphs had ∼1/3 the creatinine clearance of wild-type mice, >20× their albumin excretion, ∼3× thicker glomerular basement membranes and severe podocyte effacement, matching human diabetic nephropathy. Switching Tgfb1 expression from low to high in the tubules of the hypomorphs increased their albumin excretion more than 10-fold but creatinine clearance remained high. Switching Tgfb1 expression from low to high in the podocytes markedly decreased creatinine clearance, but minimally increased albumin excretion. Decreasing expression of Tgfb1 could be a promising option for preventing loss of renal function in diabetes.Diabetes is the number one cause of end-stage renal disease in the United States and many other developed countries. However, despite having similar levels of blood glucose only 20–40% of all diabetic patients develop diabetic nephropathy. In diabetic nephropathy, increased expression of transforming growth factor β1 (TGFβ1) has been demonstrated to promote accumulation of extracellular matrix components (1), apoptosis (2), dedifferentiation of podocytes (3), and epithelial–mesenchymal transition of proximal tubules (4), all of which are thought to facilitate a decline in nephron number and renal function.Tgfb1-null mice on a mixed genetic background show severe multiorgan inflammation with massive infiltration of lymphocytes and macrophages that culminates in death by 3–4 wk of age (5, 6). Their death effectively prevents determining whether absence of TGFβ1 influences the development of nephropathy. To overcome this problem and also to allow the study of the effects of above-normal TGFβ1, we have generated mice with five genetically graded levels of TGFβ1, and have made them diabetic with the Ins2^Akita mutation, which causes pancreatic beta-cell dysfunction and type 1 diabetes.Here we show that the features characteristic of diabetic nephropathy are progressively minimized as Tgfb1 expression is decreased below normal and are progressively exacerbated when expression is increased above normal.     

农村地区女性自评抑郁量表中文版的信度效度分析

目的:对中文版自评抑郁量表SDS的信度和效度进行评价。方法:采用中文版抑郁量表对嘉定区某农村社区501名20～74岁女性进行问卷调查,用Cronbach α系数、因子分析、Pearson相关系数和t检验等方法考察量表的信度和效度。结果:量表的总Cronbach α系数为0.784,量表各维度的Cronbach α系数在0.350~0.737之间;分半信度的Cronbach α系数分别为0.662和0.819;因子分析的分析结果和量表的理论结构基本相符,各维度得分之间的相关系数在0.057～0.322之间,除精神性-情感症状维度和精神运动性障碍的相关性外,其余维度间的相关性均有统计学意义;抑郁组和非抑郁组在各维度得分的差异均有统计学意义。结论:中文版自评抑郁量表SDS除内容效度需做部分修订外,信度和效度较好,可以应用于中国文化背景下的女性抑郁情况等心理学状况评价。     

胸椎管狭窄症术后脊髓缺血再灌注损伤的临床分析

目的 探讨胸椎管狭窄症患者手术后出现脊髓功能受损的原因,总结脊髓手术后缺血再灌注损伤(spinal cord ischemic reperfusion injury,SCII)[1]的预处理和早期治疗方法.方法 回顾性分析我科2年内收治的32例胸椎管狭窄症患者术后脊髓恢复情况,出现脊髓损伤患者的临床资料及处理方法,并对其预后进行客观评估.结果 2年内在收治并手术的胸椎管狭窄症患者中,手术减压前给予1克甲基强的松龙预防.5例患者于手术后出现不同程度的脊髓功能受损,即刻给予大剂量甲基强的松龙冲击治疗、脱水药及神经营养药,1例患者症状改善不理想,2例患者症状部分改善,生活可自理,2例患者基本恢复正常.结论 胸椎管狭窄症患者手术后出现的脊髓功能受损可能是脊髓缺血再灌注损伤引起,再灌注损伤在胸椎管狭窄症患者中较多见,但出现严重监床症状的少见,诊断有一定的困难.妥善的处理可望改善患者的生存质量.     

认知行为干预对乳腺癌外科手术患者认知水平、自护能力及心理状态的影响

目的 探讨认知行为干预对乳腺癌外科手术患者认知水平、自护能力及心理状态的影响.方法 选择2018年6月至2020年6月我院进行乳腺癌外科手术的50例患者作为研究对象,按照护理模式将其分为对照组和观察组,各25例.对照组给予常规护理干预,观察组在对照组的基础上采用认知行为干预.比较两组的干预效果.结果 干预后,观察组的认...     

Intrapartum Rupture of the Uterus Diagnosed by Ultrasound

Background

Spontaneous uterine rupture is a life threatening obstetrical emergency encountered infrequently in the emergency department. Its diagnosis is often missed or delayed, leading to maternal and fetal mortality.

Method

We present a case of ruptured uterus diagnosed by ultrasound in a 33-year-old gravid female with two previous cesarean sections.

Objective

To show the role of ultrasound in uterine rupture

Result

Ultrasound demonstrates uterine laceration and intra-abdominal dislocation of placenta and foetus

Conclusion

Because of the severity of the complication and the great variation of symptoms in connection with it, the authors encourage the use of ultrasound screening in the detection of this rare, but often catastrophic complication.     

The efficacy of local anaesthesia for percutaneous epididymal sperm aspiration and testicular sperm aspiration

A total of 37 percutaneous epididymal sperm aspiration (PESA) and/or testicular sperm aspiration (TESA) procedures were performed under local anaesthesia (LA) on 34 men between June and November 1996. Local anaesthesia was achieved by injecting 10 ml of 1% lignocaine solution along the sides of the vas deferens near the external inguinal ring (spermatic cord block). Sperm retrieval was successful in 92% of the procedures. Of the 37 procedures, in 29 the patients felt either no pain or mild discomfort while in six they experienced moderate but tolerable pain. Analgesia was incomplete in two procedures and was supplemented with i.v. sedation. Vasovagal reflex in two procedures was reversed by i.v. atropine. In 24 procedures patients felt relaxed, whilst in 13 they felt anxious. In 32 procedures the patients expressed overall satisfaction. If the procedure was to be repeated, after 29 procedures the patients requested LA again, while after four procedures they preferred i.v. sedation and after four were undecided. LA is adequate for PESA and TESA in a large proportion of patients. Prior discussion of LA technique with the patient is necessary. Back-up facilities for i.v. sedation and atropine should be available.      

Changing prevalence of gastroesophageal reflux with changing time: longitudinal study in an Asian population

BACKGROUND: The purpose of the present paper was to study previously obtained population-based data on the prevalence of reflux symptoms in a random sample of community adults in Singapore. This sample was re-investigated 5 years later to determine changes in the prevalence of reflux symptoms. METHODS: In 1999, 237 (34%) of the original cohort of 696 persons who were interviewed in 1994, were re-interviewed using a validated Gastrointestinal Symptoms Questionnaire. The original cohort was a race-stratified random sample of residents in a Singaporean town. Reflux was defined as heartburn and/or acid regurgitation occurring at least once a month. RESULTS: Among the 237 respondents (aged 25-89 years; male : female, 49:51; Chinese n = 106, 45%; Malay n = 69, 29%; Indian n = 60, 25%), reflux was reported by 25 respondents, giving a prevalence of 10.5 +/- 2.0%. This compared with the prevalence of 5.5 +/- 1.5% (odds ratio [OR], 2.2; 95% confidence interval [CI]: 1.0-5.2; P = 0.05) among the same 237 respondents in the 1994 survey. Of the 25 subjects who reported reflux in the current survey, 22 (88.0%) did not complain of reflux symptoms in the 1994 survey. The ethnic-adjusted prevalence of reflux in 1999 was estimated to be 9.9 +/- 1.9%. This was an increase above the prevalence in 1994 of 1.6 +/- 1.0% (P = 0.051). The upward trend in the prevalence of reflux was not related to age, smoking, alcohol consumption, or increase in bodyweight. CONCLUSIONS: There is a rising trend of reflux symptoms frequency in the general population of Singapore over a 5-year period.     

Risk factors for sensorineural hearing loss in extremely premature infants

Objective: To identify potentially preventable risk factors for sensorineural hearing loss (SNHL) in extremely premature infants.
Methodology A case control study of survivors with gestational age (GA) <28 weeks or birthweight (BW) <1000 g using data collected prospectively in our Neonatal Intensive Care Unit database. Each subject with bilateral SNHL >40dB was matched according to GA, BW and sex with two controls who had neither sensorineural nor conductive hearing loss.
Results Infants with SNHL had increased mean (±s.d.) days ventilated (53 ± 21 vs 37±23 days, P = 0.006) and in oxygen (107±44 vs 69±28 days, P = 0.02) compared with controls. The risk for SNHL was increased for infants who spent >90 days in oxygen (OR 4.0 [95% Cl 1.1-15.6]), had maximum FiO₂ >0.90 (5.6 [1.2-26.9]), minimum plasma Na <125mmol/L (5.6 [1.1-27.8] or maximum pH >7.60 (5.6 [1.1-89.0]). Neither maximum serum bilirubin nor exposure to ototoxic drugs was associated with SNHL.
Conclusions: Avoidance of severe hyponatraemia and extreme alkalosis, as well as use of surfactant to minimize the severity of hyaline membrane disease, may result in a decreased incidence of SNHL in extremely premature infants.