A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control

BackgroundInhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders.ObjectiveThe primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.MethodsA comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies.ResultsResults of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.ConclusionBased on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.     

Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer’s Disease

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer''s disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

TACE对原发性肝癌患者的疗效及NLR、PLR的影响研究

目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月～2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。     

聪耳通窍汤联合耳针对老年神经性耳鸣近远期疗效观察

目的探讨聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效。方法选取耳鼻喉科门诊收治的老年神经性耳鸣患者136例,按随机数字表法分组,对照组68例予以耳针治疗,研究组68例在对照组基础上予以聪耳通窍汤治疗。检测比较两组间近、远期临床疗效、甲襞微循环指标、血液流变学指标以及不良反应发生率。结果治疗后,对照组总有效率为67.64%(46/68)低于研究组总有效率83.82%(57/68),具有统计学意义(P<0.05);随访6个月后,对照组总有效率64.71%(44/68)低于研究组总有效率89.71%(61/68),具有统计学意义(P<0.05);与对照组比较,研究组治疗后甲襞微循环襻周积分、管襻积分、流态积分及总积分较低,治疗后血浆黏度、高切全血黏度、低切全血黏度及红细胞压积较低,差异具有统计学意义(P<0.05);治疗中出现的不良反应为恶心、腹胀、针刺部位疼痛,两组间不良反应发生率无统计学差异(P>0.05)。结论聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效均较好,能明显改善患者微循环状态及血液流变学指标,减轻内耳循环障碍,具有较高安全性。     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach

In the Netherlands, safe and sufficient drinking water is provided to the general population by ten drinking water companies. To guarantee safe drinking water the World Health Organization (WHO) developed a Water Safety Plan (WSP), a Risk Assessment and a Risk Management (RA/RM) framework. The objective of the study was to identify legally required RA approaches, to document application of RA/RM activities at Dutch drinking water companies and to determine to what extent these RA/RM activities as a whole cover all the elements of the WHO WSP approach. This study could be of interest to both managers of large water utilities and decision makers.The assessment was performed by means of a policy review and interviews with two to four staff members involved in RA/RM from all ten Dutch drinking water companies combined with a joint workshop. The drinking water companies are well aware of the potential hazards and risks that can influence the drinking water quality. To guarantee the supply of safe and sufficient drinking water, the Dutch drinking water sector uses six different legally required RA/RM approaches. This study shows that by using the six legally required RA/RM approaches, all WSP steps are covered. WSP entails a generic risk assessment for identifying all hazards and hazardous events from source to tap, whereas the six legally required RA/RM each focus on specific risks at an advanced level. Each risk assessment provides information on specific hazards and hazardous events covering a part of the water supply chain. These legal requirements are complemented with additional RA/RM activities at sector and water company level such as codes of practices and standard operating procedures. The outcomes of all RA/RM approaches combined provide information from source to tap. When using multiple RA/RM approaches, it is crucial to share and combine information derived from the different activities.