BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.
Animals ; Rats ; Myocytes, Cardiac ; Kruppel-Like Factor 6 ; Connexin 43 ; Desmin ; Cell Differentiation ; Azacitidine/pharmacology* ; Mesenchymal Stem Cells ; RNA, Messenger ; MicroRNAs

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H₂O₂. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.
Animals ; Harmaline/metabolism* ; Harmine/metabolism* ; Heme ; Hydrogen Peroxide ; Rats ; Tandem Mass Spectrometry

Aim To investigate the effect of circRNA- 32011 on myocardial apoptosis induced by arsenic triox- ide (ATO).Methods Primary cardioniyocytes of suckling neonate mouse were treated with ATO ( final concentration 10 (xniol • L_1 ) for 24 h.Then cell via¬bility was measured by M IT assay.The mKNA expres¬sion levels of Bel-2/ Bax and circRNA-3201 I were de¬tected by KT-PCK.Bcl-2/Bax protein expression lev¬els were detected by Western blot.Overexpression and knock down circHNA-32011 respectively by plasmid and siHNA were used to verify its function in ATO-in- duced cardiomyocyte apoptosis.Results Myocardial cell viability decreased, Bel-2 expression significantly decreased while Bax expression increased in ATO group compared with the control group.CircKNA- 32011 was down-regulated in ATO ineuhated cardio¬niyocytes.Ovcrex press ion of circRNA-32011 in ATO- incubated cardioniyocytes increased myocardial cell vi¬ability and Bel-2 expression and decreased the expres¬sion of Bax.Knockdown of circRNA-32011 could fur¬ther reduce cardiomyoevte activity and Bel-2 expression and increase the experssion of Bax induced by ATO.Conclusions CircRNA-32011 protects cardiac myo¬cytes from apoptosis induced by arsenic trioxide, which may provide a new potential therapeutic strategy for ATO-induced myocardial injury.

Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg^-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.

Objective:Pin1 plays an important role in the pathogenesis of cardiovascular disease,our study aims to investigate the effects of Pin1 silencing by siRNA on H9c2 apoptosis induced by hypoxia/reoxygenation.Methods:H9c2 cells were cultured and subjected to a hypoxia/reoxygenation (H/R) condition in vitro,mimicking ischemic/reperfusion injury in vivo.The mRNA and protein expression of Pin1 were detected by RT-qPCR and Western blot.H9c2 cells were divided into control group,H/R group,H/R+Pin1 siRNA group,H/R+scramble siRNA group.MTT and flow cytometry with Annexin V-FITC/PI staining were respectively performed to detect cell viability and apoptosis.The expression of Bax and Bcl-2 were measured by Western blot.The activity of Caspase-3 was detected by automatic biochemistry analytic instrument.Results:The mRNA and protein levels of Pin1 were highly expressed in the cells of H/R group.Transfection with Pin1 siRNA strikingly inhibited the expression of Pin1.Compared with H/R group,Pin1 siRNA markedly increased cell viability,decreased the cell apoptosis and the Caspase-3 activity.Furthermore,the increased Bcl-2,decreased Bax and the ratio of Bcl-2 to Bax were observed in Pin1 siRNA group (P<0.05) compared with H/R group.Conclusion:Downregulation of Pin1 protects hypoxia/reoxygenation-injured H9c2 cells from apoptosis,which is possibly through the upregulation of Bcl-2 and downregulation of Bax and Caspase-3 activity.

Objective To propose time-effect standards and standard treatment measures for battlefield extremity injuries.Methods By conducting retrospective analysis of battlefield extremity injuries in the militariy in different countries using literature retrieval and comparative analysis,time-effect standards and standard technical measures of battlefield extremity injuries were outlined.Results In wars of conventional weapons,extremity injuries are the most prevalent.Such treatment should give top priority to the timing of rescue and be implemented in conjunction with the injury classification.Conclusion Time-effect standards and standard treatment measures for battlefield extremity injuries are proposed to strengthen the time-effect treatment capacity of battlefield extremity injuries.

Objective To evaluate the cognitive function and its correlative factors in centenarians.Methods Forty-nine subjects in Zhongxiang city were included in this mass screening.Questionnaire was utilized to collect basic data,including age,gender,ability of daily life,depression,life habits,body mass index,and history of chronic diseases on all the subjects.And the mini-mental state examination(MMSE)was adopted to evaluate cognitive function of old people.T test and chi-square test were used to compare the difference in effectiveness of multiple different factors on cognitive function,while binary logistic regression analysis was used to assess the effects of multiple different factors on cognitive function.Results The mean score of the ability of different dimensions of cognitive function was (7.10 ± 2.71) in direction,(1.94 ±± 0.80) in memory,(0.61 ± 1.07) in attention and computation,(1.92 ± 0.86) in recall,and (4.73 ± 2.14) in speech,respectively,with total score of cognitive function of(16.30±6.02) in forty-nine centenarians.Normal cognitive function was found in 25 cases,and decreased cognitive function was found in 24 cases.Single factor logistic analysis indicated that body mass index(t=-3.399,P=0.001)and self-rating depression scale(t=-5.731,P＜0.001) were lower in patients with normal cognitive function than in patients with declined cognitive function.And smoking patients were associated with higher rates of normal cognitive function than the non-smoking patients(87.5％ vs.43.9％,x2 =5.091,P=0.028),and patients with normal hearing were associated with higher rate of normal cognitive function than patients with hearing loss(70.3 ％ vs.27.3 ％,x2 =9.01,P=0.030).Multivariate logistic analysis indicated that depression index(β=-14.40,P=0.001) and body mass index(β=-0.424,P=0.015) were independent effective factors for cognitive function.Conclusions Improvement of the condition of depression and controlling the body mass index are hopeful for recovering or postponing their cognitive impairment in centenarians.

INTRODUCTIONLiver cirrhosis is a common cause of morbidity and mortality and an important burden on the healthcare system. There is limited literature on liver cirrhosis in Singapore. We aimed to describe the epidemiology and clinical characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary referral centre.

MATERIALS AND METHODSThis is a retrospective observational cohort study of cirrhotic patients attending the ambulatory clinic of Singapore's largest tertiary hospital over 5 years. Cirrhosis was diagnosed on characteristic radiological features and/or histology. Aetiology of cirrhosis was determined by history, serology, biochemistry and/or histology. Data on decompensation events and death were retrieved from computerised hospital records.

RESULTSThe study included 564 patients with median follow-up of 85 months. Mean age was 60.9 ± 12.5 years with 63.8% males. Main aetiologies of cirrhosis were chronic hepatitis B (CHB) (63.3%), alcohol (11.2%), cryptogenic (9%) and chronic hepatitis C (CHC) (6.9%). CHB was the predominant aetiology in Chinese and Malays whereas alcohol was the main aetiology in Indians. CHC cirrhosis was more common in Malays than other races. Majority had compensated cirrhosis with 76.8%/18.3%/5%; Child-Pugh A/B/C respectively. Decompensation events occurred in 155 patients (27.5%) and 106 of them (18.8%) died. Diagnosis of cirrhosis via surveillance ultrasound was associated with improved 10-year survival. Age at diagnosis, portal vein thrombosis, Child-Pugh class and decompensation within 1 year of diagnosis were independent predictors of mortality.

CONCLUSIONCHB is the primary cause of liver cirrhosis in Singapore. The major aetiologies of cirrhosis vary amongst the different ethnic groups. Cirrhotics with advanced age, portal vein thrombosis, poorer liver function and early decompensation have a higher mortality risk.

Adult ; Aged ; Ambulatory Care ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis ; diagnosis ; epidemiology ; etiology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Singapore ; epidemiology