Alveolitis, Extrinsic Allergic ; chemically induced ; Humans ; Triazines ; adverse effects

Humans ; Lung ; immunology ; Pulmonary Fibrosis ; immunology ; T-Lymphocytes, Regulatory ; immunology

Objective To investigate the role of nicorandil pretreatment on protecting myocardium after coronary microembolization (CME) and on the PDCD4/NF-κB/TNF-α signaling pathway in miniature pigs. Methods Fifteen Bama miniature pigs were randomly(random number) divided into the sham operation group (sham group), microembolization group (CME group) and CME plus nicorandil group, with 5 pigs in each group. The CME model was constructed by injecting polyethylene microspheres via microcatheter into the left anterior descending artery, and pigs in the sham group were injected with the same amount of saline. Pigs in the CME plus nicorandil group were injected intravenously with nicorandil (150 μg/kg) via ear vein 30 min before CME. Cardiac function indexes were measured using cardiac ultrasonography. The expression of PDCD4 and TNF-α mRNA in myocardium were detected by fluorescence quantitative PCR, and the protein expression of PDCD4 and TNF-α in myocardium were detected by Western blotting. NF-κB activation was evaluated by electrophoretic mobility shift assay. Results (1) Cardiac function was significantly lower and the level of serum cTnI was significantly higher in the CME group compared with the sham group. CME reduced myocardial systolic dysfunction and left ventricular dilatation. The CME plus nicorandil group showed improved CME-induced cardiac function and reduced serum cTnI level when compared with the CME Group (P < 0.05). (2) Compared with the CME group, the CME plus nicorandil group showed lower PDCD4 and TNF-α expression and NF-κB activity as well as improved cardiac function (P < 0.05). Conclusions The pretreatment of nicorandil effectively reduced the myocardial damage caused by CME, mainly through inhibiting the PDCD4/NF-κB/TNF-α pathway in cardiomyocytes.

Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

BACKGROUNDCombined emphysema and pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), is a distinct disorder described with upper-lobe emphysema and lower-lobe fibrosis on chest computed tomography. Smoking appears to be the predominant risk factor for this disorder. We aimed to compare clinical features, smoking history, physiological and radiological findings between IPF with and without emphysema.

METHODSA sample of 125 IPF patients over a period of 48 months were evaluated. High resolution CT scans were reviewed blinded to clinical data. The IPF patients with or without emphysema were classified accordingly.

RESULTSThe prevalence of emphysema in this IPF sample was 70/125. IPF with emphysema was significantly associated with smoking status (OR 63; 95% CI 4.4 to 915; P = 0.002) and smoking pack year (OR 1.1; 95% CI 1.05 to 1.13; P = 0.000). The patients with IPF and emphysema had a higher decrease in carbon monoxide diffusing capacity adjusted for alveolar volume ((58±19)% pred vs. (66±21)% pred; P = 0.021) and a higher prevalence of pulmonary hypertension (24/70 vs. 7/55; P = 0.006). The two groups of patients had similar forced and residual volumes. No significant differences were found in cell differentials of bronchoalveolar lavage or the scores of fibrosis on chest CT. Survival of the patients with emphysema was significantly less than that of patients with IPF alone.

CONCLUSIONSCigarette smoking induces IPF combined with emphysema. Emphysema further impairs physiological function and increases the prevalence of pulmonary hypertension that leads to poor prognosis. The inclusion of the patients with combined pulmonary fibrosis and emphysema in IPF clinical trials may lead to under evaluation of the effect of treatment in patients.

Aged ; Female ; Humans ; Idiopathic Pulmonary Fibrosis ; etiology ; physiopathology ; Male ; Middle Aged ; Pulmonary Emphysema ; complications ; physiopathology ; Smoking ; adverse effects

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.
Adult ; Humans ; Cohort Studies ; Zinc ; Diet ; Hypertension/epidemiology* ; Eating ; China/epidemiology*