iNOS regulates activation of the NLRP3 inflammasome through the sGC/cGMP/PKG/TACE/TNF-α axis in response to cigarette smoke resulting in aortic endothelial pyroptosis and vascular dysfunction.

BACKGROUND: Cigarette smoke (CS) is associated with vascular injury and dysfunction, which may be mediated by iNOS and NLRP3. However, the exact mechanism is unknown. METHODS: iNOS-knockout and NLRP3-knockout C57BL/6 mice were exposed to air or CS. The vascular structure was examined by hematoxylin-eosin staining. The vascular tension was measured by a vascular reactivity assay. The expression of iNOS, NLRP3, caspase-1p20, IL-1ß and eNOS were measured by western blotting. Human aortic endothelial cells (HAECs) were exposed to L-NIL (iNOS inhibitor), MCC950 (NLRP3 inhibitor), ODQ (sGC inhibitor), KT5823 (PKG inhibitor) or TAPI-1 (TACE/ADAM17 inhibitor) for 1 h prior to cigarette smoke extract (CSE) treatment. The cell viability and lactate dehydrogenase activity were assessed and pyroptosis was determined by scanning electron microscopy. The mRNA expression of TNF-α, and protein expression of iNOS, active-TACE, NLRP3, caspase-1p20, IL-1ß, and eNOS were measured. RESULTS: CS resulted in shrinkage of endothelial cells, impaired aorta relaxation, reduced eNOS expression, and induced expression of iNOS, NLRP3, caspase-1p20 and IL-1ß, which could be prevented by knockdown of iNOS and NLRP3. CSE reduced cell viability, induced LDH release and pyroptosis, and promoted iNOS, NLRP3, caspase-1p20, and IL-1ß expression and reduced eNOS reduction, which could be reversed by inhibition of iNOS or NLRP3 in HAECs. Altogether, activation of the NLRP3 inflammasome by iNOS in CS-exposed HAECs may be mediated by the sGC/cGMP/PKG/TACE/TNF- α pathway. CONCLUSION: These results link iNOS to NLRP3 in CSE-stimulated HAECs through the sGC/cGMP/PKG/TACE/TNF-α pathway. The findings identify a mechanism through which iNOS and NLRP3 contribute to the pathogenesis of CS-induced pyroptosis and impaired aorta relaxation in HAECs.

Characteristic analysis of clinical coronary heart disease and coronary artery disease concerning young and middle-aged male patients.

BACKGROUND: Coronary heart disease (CHD) is a type of coronary atherosclerotic heart disease. In recent years, the incidence of CHD has been increasing annually, with an increasing number of young patients. Severe CHD may cause severe myocardial ischemia or myocardial necrosis, which in turn may cause myocardial infarction and related complications that seriously affect the life and health of the patient. AIM: To examine the coronary arteries and clinical features of young and middle-aged male patients with CHD. METHODS: From February 2019 to January 2020, 110 male CHD patients admitted to our hospital were selected as research subjects and were divided into two groups by age: middle-aged group (n = 55) and young group (n = 55). The coronary arteries and clinical features of the patients were compared. RESULTS: There were no significant differences in dyslipidemia, stroke history, high-density lipoprotein cholesterol, or triacylglycerol (P > 0.05) between the two groups. In the young group, age, diabetes, hypertension, smoking history, body mass index, family history of CHD, drinking history, fibrinogen, low-density lipoprotein cholesterol, total cholesterol, and single-vessel disease were higher than those in the middle-aged group. Correspondingly, serum uric acid, hyperuricemia, myocardial infarction, Gensini score > 50, collateral circulation, multivessel disease, double vessel disease, involvement of the right coronary artery, and involvement of the left main coronary artery were lower in the young group than in the middle-aged group. The middle-aged group mainly suffered from a high Gensini score, implicating multiple arteries, whereas the young group was mainly affected by single-vessel disease. The between-group difference was significant (P < 0.05). CONCLUSION: In CHD attacks, multiple coronary arteries are implicated in middle-aged male patients and single-vessel disease in young male patients.

[Surgical treatment for intra-articular calcaneal fractures].

OBJECTIVE: To evaluate clinical result of surgical treatment for intra-articular calcaneal fractures using calcaneal anatomy plate. METHODS: From September 2004 to October 2009, 72 patients with intra-articular calcaneal fractures were reviewed. There were 61 males and 11 females, ranging in age from 19 to 54 years old,with an average of 39.7 years old. The course of the disease ranged from 1 to 17 days. All the patients performed X-ray and semi-coronal CT scan before and after operation. According to Sanders classification system, there were 40 cases of type III and 32 cases of type IV. All the patients were treated with lateral L-type incision and calcaneal anatomy plate. The therapeutic effects were evaluated according to the standard of calcaneal fracture of the American surgery association of foot and ankle. RESULTS: All the patients were followed up, and the duration ranged from 10 to 48 months, with a mean of 38 months. According to standard of calcaneal fracture of the American surgery association of foot and ankle, 14 patients got an excellent result, 38 good, 9 fair and 11 poor. Five patients got incision non-union. Arthritis of subtalar joint was found in 3 cases. CONCLUSION: Open reduction and internal fixation of plate is effective to get good reduction for subtalar joint, which is a good method to treat intra-articular calcaneal fracture.