OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

BACKGROUND: Abnormal autophagy in chondrocytes often leads to cartilage degeneration, thereby triggering osteoarthritis. Recent studies have found that microRNAs play an important role in chondrocyte autophagy; however, the molecular mechanism is yet unclear. OBJECTIVE: To investigate the role of microRNA-138-5p (miR-138-5p) in the regulation of chondrocyte proliferation and autophagy activities, and to reveal its mechanisms. METHODS: Chondrosarcoma cell line SW1353 were cultured in vitro and transfected with negative control miRNA or miR-138-5p mimic. Cell proliferation activity was measured by cell counting kit-8 assay, the expression of matrix metalloproteinases 1, 3, and 13 mRNA was measured by fluorogenic quantitative PCR. The endogenous LC3 subcellular location was detected by immunofluorescence staining. The miR-138-5p and SIRTI mRNA target sites were predicted using TargetScan 7.1 online tool. Autophagy-related proteins and AMPK signal proteins were detected by immunoblotting assay. RESULTS AND CONCLUSION: Cells transfected with miR-138-5p mimic, compared with those transfected with negative control miRNA, showed lower proliferation activity, less LC3 puncta, and reduced expression of SIRT1, LC3-II, p-AMPK, but increased protein expression of p62 and increased mRNA expression of matrix metalloproteinases 1, 3, 13. There was a conserved miR-138-5p binding site in the 3’UTR region of SIRT1 mRNA. To conclude, miR-138-5p regulates SW1353 cell autophagy and proliferation through the SIRT1/AMPK signaling pathway. The up-regulated expression of miR-138-5p promotes the secretion of matrix metalloproteinases from chondrocytes, indicating that miR-138-5p plays an important role in the progression of osteoarthritis.

Objective To establish a central serous chorioretinopathy (CSC) model on different strains of rabbits by intravenous injection of adrenaline,which may contribute to related researches of CSC.Methods This study was approved by Bioethics Committee of Fourth Military University and complied with Statement for the Use of Animals in Ophthalmic and Visual Research.Fundus fluorescein angiography (FFA) was initially performed on male New Zealand white rabbits (10),Belgium rabbits (5) and Chinchilla rabbits (10) to make sure that the retinas of subjects were normal.For the New Zealand white rabbits,adrenaline was injected via ear vein at a dose of 0.04 mg/kg once per day for the first 8 weeks and followed by a dose of 0.08 mg/kg for the next 4 weeks,while 0.04 mg/kg adrenaline was injected in the same way for 8 weeks in the Belgium rabbits and Chinchilla rabbits.FFA was performed every week after injection of adrenaline to evaluate the fluorescence leakage in ocular fundus.New Zealand white rabbits were sacrificed in 4 (3 rabbits),8 (3 rabbits) and 12 weeks (4 rabbits) after injection respectively,and Belgium rabbits and Chinchilla rabbits were sacrificed in the 8 weeks after injection.The eyeballs of the rabbits were enucleated to prepare the retinal sections for histopathological examination after hematoxylin-eosin staining.The results of FFA and retinal structure were compared among different strains of rabbits.Results No fluorescence leakage was found by FFA in ocular fundus,and the retinal structure was normal in all the 10 New Zealand white rabbits during the experiment.Fluorescence leakage was found by FFA in 2 Belgium rabbits at 1 week and 2 weeks after injection respectively,and retinal detachment and depigmentation of retinal pigment epithelium (RPE) with an enlarged intercellular space were shown by hematoxylin-eosin staining.For the Chinchilla rabbits,fluorescence leakages were found in 7 rabbits throughout the whole period of adrenaline administration.Circumscribed retinal detachment,depigmentation of RPE with enlarged intercellular space were also found in leakage lesions.Conclusions Repeated intravenous injection of adrenaline can induce CSC-like lesions in colored rabbits but not in albino rabbits.

Objective To evaluate the feasibility and efficacy of Guidezilla TM guide extension catheter in retrograde technique for chronic total occlusion (CTO) recanalization. Methods We retrospectively collected 119 CTO cases from the 2nd Cardiology Department of Guangdong General Hospital who had received retrograde percutaneous coronary intervention( PCI). The Guidezilla TMguide extension catheters were applied in 39 cases from October 2015 to November 2016. 80 CTO cases without using the Guidezilla TMguide extension catheter during PCI admitted between January 2015 and October 2015 were collected as the control. Results The overal success rate of the 2 group was 84.0%. The group using the Guidezilla TMguide extension catheter had a higher success rate(100% vs.76.2%,P<0.05).The baseline clinical characteristics of the two groups showed no statistical diff erence. In terms of CTO crossing diffi culty by J-CTO score, patient in the Guidezilla TMguide extension catheter group had higher percentage of diffi cult lesions(35.9% vs.15.0%,P<0.001)and very difficult lesions(61.5% vs.32.5%,P<0.001).Patients in the Guidezilla TMguide extension catheter group had more longer lesions(89.7% vs.72.5%,P=0.035),blunt proximal occlusion(53.8% vs.32.5%,P=0.030)and tortuosity lesions(84.6% vs.63.8%,P=0.020). More cases in the control group needed a second operation(63.8% vs.25.6%,P<0.001)and more ostial/bifurcation lesions(62.5% vs.30.8%,P=0.002).All cases had no target vessel revascularization or in-hospital death. Conclusions Guidezilla TMguide extension catheter is convenient and safe for complicated CTO retrograde PCI.

Objective To evaluate the clinical safety and efficacy of GuidezillaTM guide extension catheter during complex coronary percutaneous coronary intervention(PCI). Methods A total of 13 patients were included in the studywho presented with complex coronary lesions during PCI. Stents or balloons could not be delivered to these complex lesions with conventional approach and GuidezillaTM guide extension catheters were used. Results Among these 13 patients,there were 7 CTO lesions,7 calcified lesions, 6 tortuous lesions,8 diffuse lesions,8 distal lesions and 8 lesions with pre-existing stents. PCI success rate was 100% .In one patient,GuidezillaTM guide extension catheter was obstructed which were relieved after stent implantation. There was no major adverse cardiac event(MACE) during follow-up.Conclusions The GuidezillaTM guide extension catheter was safe and effective for PCI of complex coronary artery lesions.

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Adolescent ; Adult ; Anesthesia, General ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Septal Occluder Device ; Treatment Outcome ; Young Adult

Objective To investigate the effect of curcumin (Cur)on AngⅡ-induced proliferation and oxidative stress of vascular smooth muscle cells (VSMCs).Methods Primary rat VSMCs were cultured and divided into control group,AngⅡ group,AngⅡ+Cur 5μmol/L group,AngⅡ+Cur 10μmol/L group,AngⅡ+Cur 20μmol/L group,and Cur 20μmol/L group.The proliferation of AngⅡ-induced VSMCs was measured by MTT assay.The mRNA and protein expressions of inducible nitric oxide synthase (iNOS)and p47phox were detected by real-time PCR and Western blot.Nitric oxide (NO)production was measured by Griess reaction.Production of intracellular reactive oxygen species (ROS)was measured by DCFH-DA staining,and the activities of superoxide dismutase (SOD)and glutathione peroxidase (Gpx)were detected by xanthine oxidase assay and visible spectrophotometer. small interfering RNA (siRNA)was used to silence the expression of p47phox to further explore the mechanism for Cur inhibiting the proliferation of AngⅡ-induced VSMCs and oxidative stress.Results VSMCs activities were not significantly affected by Cur at the concentration between 0 and 80μmol/L.Cur (5,10 and 20μmol/L)significantly inhibited AngⅡ-induced proliferation of VSMCs.Cur had an inhibitory effect on the overexpression of NO,iNOS, p47phox and ROS in VSMCs and upregulated the activities of SOD and Gpx in a concentration-dependent manner. AngⅡ-induced ROS production in VSMCs was significantly attenuated by pretreatment with p47phox specific siRNA.Conclusion Cur can inhibit the proliferation and oxidative stress of AngⅡ-induced VSMCs.