Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To explore the role of ureteroacopy for acute upper urinary tract obstructive anuria.Methods Clinical data of 37 cases with acute upper urinary tract obstructive anuria were analyzed.Results Among 37 cases,34 cases were successfully performed ureteroseopy or ureteroseopic lithotripsy with double-J sent incubation (successful rate was 91.9%).Renal function were recovery in 32 cases.4 Cases returned to 180μmol/L,1 case need hemodialysis periodically.Conclusion Ureteroscopy could rapidly remove the obstruction and protect renal function in management of acute upper urinary tract obstruction anuria,which was contributed to the diagnosis.It was safe,effective and the preferred method.

Objective To analyze distribution of intracranial and extracranial arteriostenosis in patients with ischemic stroke. Methods 306 patients with ischemic stroke were collected during January 2002 to March 2005. All patients underwent color ultrasonography of carotid, TCD, MRA and DSA. According to NASCET, arteriostenosis was grouped into five grades: normal artery, mild stenosis(29%), moderate stenosis (30%—69%), severe stenosis(70%—90%) and occlusion(100%). Results (1) As for incidence of intracranial and extracranial arteriostenosis, 149 were of intracranial stenosis, 25 extracranial stenosis and 33 both. (2) As for incidence of single or dual stenosis, among 207 with arteriostenosis, single stenosis amounted to 129 and dual to 78. (3) Stenosis occurred in middle cerebral artery, distal vertebral artery, basilar artery, extracranial part of internal carotid artery, anterior cerebral artery, posterior cerebral artery, siphon part of internal carotid artery and onset part of vertebral artery in an order of decreased frequency. (4) DSA analysis revealed that, among 316 narrow blood vessels of 207 patients, 87 vessels were shown as severe stenosis or obstruction, accounting for 27.5%. (5) Among 164 cases, infarction occured in the corresponding stenostic vessel in 157 patients, accounting for 95.7%. ConclusionsIntracranial arteriostenosis is the most frequently encountered in those with ischemic stroke. Thereto, frequency of stenosis in middle cerebral artery is the highest, distal vertebral artery and basilar artery are next.