Principles in the management of chronic kidney disease

Chronic kidney disease (CKD) is the term used to describe renal disease or impairment which has persisted for three months. This paper presents a brief overview of CKD, including classification, epidemiology, aetiology, clinical presentation, investigations and a discussion regarding the principles of management. The aims of management include: preservation of remaining renal function, avoiding further injury, correction of electrolyte disturbances, anaemia and fluid imbalance and also maintenance of good nutrition, bone health and growth. Some children will progress to end-stage disease and there is a brief discussion of renal replacement therapy. Prognosis depends largely on the cause of CKD. Where children should be followed-up is dictated primarily by their renal function and the likely clinical course.     

4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.     

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??Pediatrics fulminant hepatic failure is a result of massive necrosis of liver cells in a short time?? which is a serious acute illness with impaired liver function. In recent years?? blood purification play a very important role in terms of the treatment of the disease. But the disease is prone to serious bleeding complications. Therefore??it is very important to conduct coagulation monitoring during blood purification     

Cost-Effectiveness of Midazolam Versus Haloperidol Versus Olanzapine for the Management of Acute Agitation in the Accident and Emergency Department

ObjectivesA multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting.MethodsThis analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken.ResultsIn the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval ?770.89, 685.90).ConclusionsIM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them.     

雷帕霉素对去甲氧柔红霉素诱导急性髓系白血病THP-1细胞凋亡的影响

目的:探讨雷帕霉素（Rapa）对去甲氧柔红霉素（IDA）诱导急性髓系白血病THP-1细胞凋亡的影响及其分子机制。方法:分别用10、20、40、80 nmol/L Rapa处理THP-1细胞1 h，另设未经Rapa处理的细胞。采用蛋白质印迹法检测THP-1细胞自噬标志物LC3蛋白的转换情况（LC3Ⅱ/LC3Ⅰ），采用流式细胞术检测细胞凋亡，确定Rapa处理浓度。用不同浓度IDA作用THP-1细胞24 h，采用CCK-8法检测IDA对THP-1细胞的增殖抑制率，计算半数抑制浓度（ IC50）。以低于 IC50的IDA作用Rapa处理或未处理的THP-1细胞24 h，CCK-8法检测细胞增殖抑制率，流式细胞术检测细胞凋亡情况，实时荧光定量聚合酶链反应检测自噬相关基因Beclin-1、LC3和p62的表达变化，蛋白质印迹法检测自噬标志物LC3蛋白的转换情况。 结果:20 nmol/L Rapa处理的THP-1细胞LC3Ⅱ/LC3Ⅰ高于未处理的细胞（ P=0.002 4）；80 nmol/L Rapa处理的细胞凋亡率高于未处理的细胞（ P=0.007 3）。根据蛋白质印迹法和流式细胞术检测结果，选取20 nmol/L Rapa作为预处理浓度。IDA对THP-1细胞作用24 h的 IC50为59.874 nmol/L。50 nmol/L IDA作用24 h后，Rapa预处理的THP-1细胞增殖抑制率[（69.67±5.03）%比（41.67±3.51）%]和细胞凋亡率[（74.35±4.83）%比（41.25±5.24）%]均高于未预处理的细胞（均 P<0.05）；Rapa预处理的THP-1细胞Beclin-1、LC3 mRNA表达水平及LC3Ⅱ/LC3Ⅰ均高于未预处理的细胞，p62 mRNA表达水平低于未预处理的细胞（均 P<0.05）。 结论:Rapa能增强较低剂量IDA诱导的THP-1细胞凋亡，此效应可能是通过其引起THP-1细胞过度自噬实现的。     

中国云南基层医院远程卒中的有效性和安全性研究

目的远程卒中指导基层医院脑梗死静脉溶栓国外已经很成熟,但国内鲜有报道。该研究以上海九院中心与祥云中心建立7×24小时远程卒中合作,由九院中心指导祥云中心进行脑梗死静脉溶栓。方法利用远程卒中前瞻性收集1年内九院中心与祥云中心急性脑梗死病例,统计其静脉溶栓质控和随访情况,对比两中心静脉溶栓率、3小时静脉溶栓率、就诊到静脉溶栓时间(DTN)、发病到静脉溶栓时间(OTT)、3个月随访改良生活能力评分(mRS)及出血、死亡率。结果远程卒中后1年九院中心静脉溶栓率27. 04%,祥云中心静脉溶栓率7. 73%,差异有统计学意义(P=0. 000)。九院中心DTN为(62. 76±26. 41) min,祥云中心DTN为(70. 55±28. 51) min,差异无统计学意义(P 0. 05)。3个月随访两中心mRS评分、出血和死亡率,差异均无统计学意义(P 0. 05)。结论远程卒中指导下祥云中心静脉溶栓预后及安全性不差于九院中心,远程卒中是改善农村基层医院静脉溶栓的有效方法之一。     

灯盏细辛注射液联合丁苯酞治疗急性脑梗死的临床研究

目的探讨灯盏细辛注射液联合丁苯酞氯化钠注射液治疗急性脑梗死的临床疗效。方法选取2017年3月—2018年11月洛阳市第三人民医院收治的90例急性脑梗死患者为研究对象,按照随机数字表法将患者分为对照组和治疗组,每组各45例。对照组静脉滴注丁苯酞氯化钠注射液,25 mg/次,2次/d。治疗组在对照组治疗的基础上静脉滴注灯盏细辛注射液,30 mL加入到250 mL生理盐水中充分稀释,30 mL/次,1次/d。两组患者均连续治疗14 d。观察两组患者的临床疗效,同时比较两组治疗前后的神经功能缺损评分(NIHSS)、日常生活活动能力评定量表(ADL)评分和血管内皮功能指标。结果治疗后,对照组和治疗组的总有效率分别为75.56%、91.11%,两组比较差异具有统计学意义(P0.05)。治疗后,两组NIHSS评分显著降低,ADL评分显著升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组NIHSS评分显著低于对照组,ADL评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组的内皮素-1(ET-1)、血管生成素(Ang-1)、血管内皮生长因子(VEGF)水平明显降低,一氧化氮(NO)明显升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组血管内皮功能指标水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。结论灯盏细辛注射液联合丁苯酞氯化钠注射液治疗急性脑梗死具有较好的临床疗效,能改善患者的神经功能和血管内皮功能指标,具有一定的临床推广应用价值。     

Elucidation of demographic,clinical and trichoscopic features for early diagnosis of self-healing acute diffuse and total alopecia

The term “acute diffuse and total alopecia” (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as “self-healing ADTA” (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 ± 15.9 years. The progression of hair loss areas peaked at 3.6 ± 1.5 months, and complete hair regrowth was achieved in 7.9 ± 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.