基质金属蛋白酶12与肿瘤关系的研究进展

基质金属蛋白酶12(matrix metalloproteinase-12，MMP-12)是一类结构中含有锌离子和钙离子的蛋白水解酶类，可降解细胞外基质(extracellular matrix，ECM)成分。MMP-12 在多种肿瘤中呈现高表达，并与肿瘤的发生发展密切关联，参与了肿瘤的生成、转移、侵袭和免疫逃逸等多个过程。MMP-12与肿瘤的预后相关，其有希望成为肿瘤预后标志物和治疗的靶点。且近年来关于MMP的机制及其抑制剂的研究有了很大进展。本文将对近年来国内外的MMP-12与肿瘤的相关研究进展予以综述。     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

Higher vitamin B12 level at Parkinson's disease diagnosis is associated with lower risk of future dementia

IntroductionTo determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.MethodsWe utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.ResultsPD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44–0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60–0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05).ConclusionHigher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.     

Impact of Cinnamon Supplementation on cardiometabolic Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background & objectiveTo date, cinnamon supplementation has been investigated due to its antioxidant and anti-inflammatory properties. Several studies have confirmed the effects of cinnamon supplementation on several markers of cardiometabolic health. However, the effects of cinnamon supplementation on inflammation and oxidative stress levels warrant further investigation. Hence, the current meta-analysis was conducted to elucidate the impact of cinnamon supplementation on biomarkers of inflammation and oxidative stress.MethodsTo perform this systematic review and meta-analysis, we employed the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic search of available clinical trials was performed using the following databases: PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, and Google Scholar, up to January 2020.ResultsAfter removing the duplicates, 1145 studies were eligible for analysis and 12 of them were included in the meta-analysis. The dose of cinnamon powder investigated in the included trials ranged from 1.5 to 4 g/day. Cinnamon supplementation resulted in a significant reduction of C-reactive protein (CRP) (weight mean difference (WMD): −2.22 mg/L, 95 % CI: −3.74, −0.69, P = 0.004) and malondialdehyde (MDA) (WMD: −0.79 mmol/L, 95 % CI: −1.28, −0.29, P = 0.002), and marginally statistical significant decrease in interleukin-6 (IL-6) (WMD: −1.48 pg/mL, 95 % CI: −2.96, −0.01, P = 0.049). Moreover, it was associated with an increase in the total antioxidant capacity (TAC) (WMD: 0.34 mmol/L, 95 % CI: 0.04, 0.64, P = 0.026). However, the levels of intercellular adhesion molecule-1 (ICAM-1) (WMD: 1.53 ng/mL, 95 % CI: −12.03, 15.10, P = 0.82) did not change significantly following cinnamon supplementation.ConclusionsCinnamon supplementation may be an adjuvant for reducing inflammation and oxidative stress levels in humans.     

Unintended effects of reimbursement schedules in mental health care

We evaluate the introduction of a reimbursement schedule for self-employed mental health care providers in the Netherlands in 2008. The reimbursement schedule follows a discontinuous discrete step function—once the provider has passed a treatment duration threshold the fee is flat until a next threshold is reached. We use administrative mental health care data of the total Dutch population from 2008 to 2010. We find an “efficiency” effect: on the flat part of the fee schedule providers reduce treatment duration by 2 to 7% compared to a control group. However, we also find unintended effects: providers treat patients longer to reach a next threshold and obtain a higher fee. The data shows gaps and bunches in the distribution function of treatment durations, just before and after a threshold. About 11 to 13% of treatments are shifted over a next threshold, resulting in a cost increase of approximately 7 to 9%.     

Premature ventricular contractions of the right ventricular outflow tract: Upward displacement of the ECG unmasks ST elevation in V1 associated with the presence of low voltage areas

Introduction and Aims

Frequent premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT) are usually considered a benign entity and the ECG is typically normal. The aim of this study was to assess whether upward displacement of the ECG to the second intercostal space (ICS) would reveal any abnormal pattern.

Current thinking in management of the neck (including contralateral neck) in ipsilateral recurrent or second primary oral squamous cell carcinoma

Metastasis to the neck in patients with oral squamous cell carcinoma (SCC) has a huge impact on long-term survival and prognosis, and its incidence varies. Due consideration therefore should be given to management of the neck in each individual case. The pathways in patients with primary oral SCC are well-established, but there is a paucity of published papers on management of the neck in those with ipsilateral recurrent or second primary oral SCC whose necks have previously been operated on with or without radiotherapy or chemoradiotherapy, or treated with radiotherapy or chemoradiotherapy alone. These patients may be under treated because of failure to stage the most likely drainage site, and are likely to have a worse outcome if there is macroscopic recurrence in the neck after independent treatment of the recurrent or second primary tumour. Based on the current review, we think there is a need for a multicentre, collaborative, retrospective review of the outcomes of patients with ipsilateral second primaries or recurrent oral SCC in the previously treated neck. Our recommendations include consideration of positron emission tomography-computed tomography in all patients with recurrent or second primary oral SCC (if “hot” – neck dissection, if “cold” - sentinel node biopsy); consideration of sentinel node biopsy in all patients with recurrent or second primary oral SCC who have previously had treatment to the neck; and finally, consideration of definitive management of the sentinel biopsy zone or region if the node is invaded.