On diabetic foot ulcer knowledge gaps,innovation, evaluation,prediction markers,and clinical needs

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and ‘multiomics’ arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.     

E-cadherin and calretinin as immunocytochemical markers to differentiate malignant from benign serous effusions

AIM: To investigate the expressions of E-cadherin and calretinin in exfoliated cells of serous effusions and evaluate their values in distinguishing malignant effusions from benign ones. METHODS: Fresh serous effusion specimens were centrifuged and exfoliated cells were collected. Cells were then processed with a standardized procedure, including paraformaldehyde fixation, BSA-PBS solution washing and smears preparation. E-cadherin and calretinin were detected by immunocytochemistry (ICC). RESULTS: In the exfoliated cells of serous effusions, most of carcinoma cells only expressed E-cadherin, and most of mesothelial cells only expressed calretinin, and benign cells (lymphocytes and granulocytes) did not express either of them. For E-cadherin, 85.7% (30/35) of malignant effusions and 8.1% (3/37) of benign fluids were ICC-positive (P<0.001). The sensitivity of E-cadherin ICC in the diagnosis of malignant effusions was 85.7%, specificity 91.9%, and diagnostic rate 88.9%. For calretinin, 94.6% (35/37) of benign effusions and 11.4% (4/35) of malignant effusions were ICC-positive (P<0.001). The sensitivity of calretinin ICC in the diagnosis of benign effusions was 94.6%, specificity 88.6%, and diagnostic rate 91.7%. For diagnosis of benign and malignant effusions by combining E-cadherin ICC and calretinin ICC, the specificities were up to 100% and 97.1%, respectively. CONCLUSION: E-cadherin ICC and calretinin ICC are sensitive and specific in differential diagnosis of benign and malignant serous effusion specimens and specificities are evidently improved when both markers are combined.     

江西农村社区蛔虫感染动态一年纵向研究

目的 :了解未加控制措施干预下农村社区蛔虫感染与传播动态。方法 :由 6次横断面调查组成的一年纵向研究。结果 :当地人群感染率常年稳定在 60 %以上 ,但年内社区感染率与感染度 ( EPG)有显著性波动。年龄分层分析进一步表明 ,感染的波动仅在部分儿童具显著性 ,而在几乎所有成人组波动不具显著性。蛔虫在土壤内的发育率变化与年内月平均温度的变化相一致。结论 :该地蛔虫感染呈相对稳定的地方性传播但存在明显季节波动 ,此种波动与季节对土壤中虫卵发育的影响有关 ,儿童是构成社区蛔虫感染波动的主要人群。     

Limitation standard of toxic aconitines in Aconitum proprietary Chinese medicines using on-line extraction electrospray ionization mass spectrometry

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional Chinese medicine. Herein, an on-line extraction electrospray ionization mass spectrometry (oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 Aconitum proprietary Chinese medicines (APCMs). Multi-type dosage forms (e.g., tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample (∼0.5 mg) and reagent (∼240 μL) consumption, and short analysis time for single sample (<15 min). The results were proved to be credible by high performance liquid chromatography−mass spectrometry (LC–MS) and electrospray ionization mass spectrometry, respectively. Moreover, the limitation standard for the toxic aconitines in 20 APCMs was established based on the holistic weight toxicity (HWT) evaluation and the Chinese Pharmacopoeia severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence, a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis, food safety control, public security, and many other disciplines.     

Inhibition of VTA neurons activates the centrally projecting Edinger–Westphal nucleus: Evidence of a stress–reward link?

The primary site of urocortin 1 (Ucn1) expression in the brain is the centrally projecting Edinger–Westphal nucleus. The EWcp is innervated by dopaminergic neurons of the ventral tegmental area (VTA). To investigate whether activity of EWcp is regulated by the VTA, we investigated the effects of local pharmacological inhibition of VTA activity on the induction of Fos immunoreactivity in the EWcp of male C57BL/6J mice. A unilateral intracranial administration of the GABA agonist muscimol aimed at the VTA resulted in increased number of Fos-positive cells in the EWcp. This induction was lower than that produced by an intraperitoneal injection of 2.5 g/kg of ethanol. To investigate whether inhibition of dopaminergic neurons was responsible for induction of Fos, a second experiment was performed where the dopamine agonist quinpirole was unilaterally injected targeting the VTA. Injections of quinpirole also significantly induced Fos in the EWcp neurons. The induction occurred only on the side of the EWcp ipsilateral to the VTA injection. These results indicate that activity of EWcp is inhibited by tonic activity of dopaminergic VTA neurons, and that unilateral projections of VTA onto Ucn1-containing EWcp neurons provide a link between systems regulating approach and avoidance behaviors.     

Workflow and Outcomes of Endovascular Thrombectomy for In-Hospital Stroke a Systematic Review and Meta-Analysis

Background and PurposeAcute strokes due to large vessel occlusion in hospitalized patients is not uncommon. We performed a systematic review and meta-analysis to investigate the timing and outcome of endovascular thrombectomy (EVT) for in-hospital stroke.MethodsWe conducted a meta-analysis of clinical studies published in English until September 2020 in the MEDLINE and Cochrane databases. Studies reporting original data on the characteristics and outcomes of in-hospital stroke patients treated with EVT were included. We extracted data on the time-metrics from last known well (LKW) until reperfusion was achieved. We also collected data on procedural and functional outcomes.ResultsOut of 5093 retrieved studies, 8 were included (2,622 patients). The median age was 71.4 years and median NIHSS score on admission was 16. Patients were mostly admitted to the cardiology service (27.3%). The pooled time from LKW to recognition by staff was 72.9 min (95% CI: 40.7 to 105 min). 25.6% received IV tPA. The mean time from stroke recognition to arterial puncture was 134.5 min (95% CI: 94.9 to 174.1). Successful reperfusion occurred in 82.8.% with a pooled mean time from detection to reperfusion of 193.1 min (95% CI: 139.5 to 246.7). The 90-day independent functional outcome was reported in 42% of patients (95% CI 29 to 55%).ConclusionEVT can be performed safely and successfully for in-hospital strokes. Noticeable delays from LKW to detection and then to puncture are noted. This calls for better stroke pathways to identify and treat these patients.BackgroundStroke in hospitalized patients, referred to as in-hospital stroke (IHS), accounts for 2.2–17% of all strokes.¹ The majority of these are ischemic while intracranial hemorrhage represents 2–11% of all IHS.¹ These patients are expected to have a rapid diagnosis and treatment given the ongoing medical supervision, and therefore favorable outcomes.^1–3 However, existing studies report poor outcomes in patients with IHS with a mortality risk that exceeds that of community-onset stroke (COS): 24.7% vs 9.6%.⁴ Surviving IHS patients are also less likely to be discharged home compared to COS (27.7% vs 49.9%) and to be functionally independent at 3 months (31.0% vs 50.4%).^1–4     

Neferine Inhibits the Upregulation of CCL5 and CCR5 in Vascular Endothelial Cells During Chronic High Glucose Treatment

We investigated whether the expressions of CCL5 and CCR5 participate in dysfunctional changes in human umbilical vein endothelial cells (HUVECs) induced by chronic high glucose treatment and examined whether neferine exerts its therapeutic effects by blocking the development of dysfunctional vascular endothelium. HUVECs were cultured with control or high concentrations of glucose in the absence or presence of neferine for 5 days. Nitric acid reductase method was used to detect the concentration of nitric oxide (NO) released into culture media. The level of intracellular reactive oxygen species (ROS) was measured by fluorescent DCFH-DA probe. The expressions of 84 genes related to endothelial cell biology were assessed by Human Endothelial Cell Biology RT² Profiler PCR Array. The expressions of the chemokine CCL5 and its receptor CCR5 were further determined by real-time RT-PCR and western blotting. PCR array indicated that CCL5 was the most significantly upregulated when HUVECs were exposed to chronic high glucose; the intracellular ROS level and the expressions of CCL5 and CCR5 at both mRNA and protein levels were significantly increased, whereas NO production was decreased simultaneously. The increased level of ROS and elevated expressions of CCL5 and CCR5 at high glucose were significantly inhibited by neferine; meanwhile the decreased NO production upon chronic high glucose treatment was relieved. An antioxidant (vitamin E) exerted similar beneficial effects. These data indicate that neferine can reduce the upregulation of CCL5 and CCR5 of vascular endothelium exposure to chronic high glucose and prevent or inhibit subsequent occurrence of inflammation in blood vessels possibly through antioxidation.