Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM).MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively.ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: ?0.494 to ?0.054; P = 0.015) and gait speed (95 % CI: ?0.039 to ?0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001).ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.     

Gender difference in association between diabetes mellitus and all-cause mortality in atrial fibrillation patients

ObjectiveThere may be gender difference in correlation of diabetes mellitus (DM) and cardiovascular events. We attempt to investigate whether there is gender-heterogeneity in one-year outcomes of atrial fibrillation (AF) patients with DM or not.MethodsPatients who were diagnosed with AF admitted to the emergency departments in the Chinese AF Multicenter Registry study were enrolled. Basic demographics information, initial Blood Pressure and heart rate, medical histories, and treatments of each patient were collected. Follow-up was carried out with a mean duration of one year. The primary endpoint was all-cause mortality and systemic embolism.ResultsA total of 2016 patients were selected from September 2008 and April 2011. All-cause mortality was significantly higher in male AF patients with DM than those without (21.8 % & 13.6 %, P = 0.014). Cox regression analysis showed that there was an interaction between gender and DM for one-year all-cause mortality (P = 0.049). DM was significantly associated with one-year all-cause mortality regardless of univariate analysis (HR = 1.436, 95%CI:1.079–1.911, P = 0.013) or multivariate analysis (HR = 1.418, 95%CI: 1.059–1.899, P = 0.019). For male patients with AF, DM was significantly associated with one-year all-cause mortality (P = 0.048), but not for female patients with AF (P = 0.362).ConclusionDM was independently associated with one-year all-cause mortality in the entire cohort of AF patients. This association was found mainly in male patients with AF, but not in female patients. DM management programs may need to reflect gender difference.     

Positive correlation between miR-570 and prognosis of colon cancer: inhibition of cell proliferation and invasion

Clinical and Experimental Medicine - Colon cancer is one of most common cancers. The progression of various cancers is driven by miRNA-570. The role of miRNA-570 in the progression of colon cancer...     

Challenges and limitation of MTAP immunohistochemistry in diagnosing desmoplastic mesothelioma/sarcomatoid pleural mesothelioma with desmoplastic features

AimGenomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear.Methods and resultsWe evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity.ConclusionsMTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.     

Risk factors and a simple scoring system for predicting bowel resection in infants with NEC

Background and aimsWe intended to investigate the predictors for bowel resection in infants with necrotizing enterocolitis (NEC). We further developed a scoring system for better predicting bowel resection.MethodsA total of 207 infants who underwent surgical management at Children's Hospital, Chongqing Medical University between April 2008 and December 2020 were identified for the following investigation. Bowel resection was reviewed among the infants who underwent the procedure. Potential parameters related to bowel resection were explored using a multiple logistic regression method, and then a scoring system was developed.ResultsAmong the 207 patients who underwent operative intervention that were reviewed, 109 infants underwent bowel resection. Multivariate logistic regression analysis showed that birth weight, hypotension, neutropenia, pneumoperitoneum, acidosis, and intestinal wall thickness were predictors related to the occurrence of bowel resection. A 6-point scoring system was further developed based on the obtained total coefficient, and the infants could be divided into low-, moderate- and high-risk groups according to cut values of 7 and 13.ConclusionThe results of this study demonstrated that severe NEC features and low birth weight were associated with bowel resection. The risk scoring system could accurately separate infants that were suspected to have bowel loss during surgery.     

Plectin ensures intestinal epithelial integrity and protects colon against colitis

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; Ple^ΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the Ple^ΔIEC colon.     

Efficacy and safety of cold snare polypectomy for sessile serrated polyps ≥ 10 mm: A systematic review and meta-analysis

BackgroundCold snare polypectomy (CSP) is a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. However, the efficacy and safety of this technique remain undetermined.AimsWe aimed to comprehensively evaluate the efficacy and safety of CSP for SSPs ≥ 10 mm.MethodsPubMed, EMBASE, Web of Science and Cochrane Library were searched up to January 2021.ResultsA total of 10 studies consisting of 1727 SSPs (range, 10–40 mm) from 1021 patients were included. The overall rates of technical success, adverse events (AEs) and residual SSPs were 100%, 0.7% and 2.9%, respectively. Subgroup analysis showed that the rates of technical success and AEs were comparable between CSP and cold endoscopic mucosal resection (EMR) (99.9% vs. 100% and 1.3% vs. 0.5%, respectively), between the proximal and distal colon (100% vs. 99.9% and 0.3% vs. 0, respectively), and between polyps of 10–19 mm and ≥20 mm (99.8% vs. 100% and 0.9% vs. 0, respectively). However, subgroup analysis showed that the rate of residual SSPs was slightly lower in CSP compared with cold EMR (1.3% vs. 3.9%), as well as in polyps of 10–19 mm compared with those ≥20 mm (3.1% vs. 4.7%).ConclusionCSP was an effective and safe technique for removing SSPs ≥ 10 mm.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.