Objective:To investigate the status of allostatic load (AL) in patients with polycystic ovary syndrome (PCOS) and its influence on the clinical outcomes of in vitro fertilization-embryo transfer.Methods:This was a prospective study. By using convenient sampling method, 421 patients with PCOS (PCOS group) and 372 control infertility patients (control group) in the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from April 2022 to January 2024 were investigated for basic information, physical examination, laboratory examination and follow-up of clinical outcomes. The total score of AL was calculated using 16 related indicators of cardiovascular system, metabolic system and immune system, and AL>3 was used as the judgment criteria for the high level AL group and the low level AL group. The differences in general data, embryo development and clinical outcomes between the groups were compared.Results:There were 222 cases (52.7%, 222/421) in PCOS low level AL group and 199 cases (47.3%, 199/421) in PCOS high level AL group. There were 214 patients (57.5%, 214/372) in the control low level AL group and 158 patients (42.5%, 158/372) in the control high level AL group. Embryo development outcomes: number of oocytes retrieved (median: 12, 12, 19, 14, respectively; P<0.001), number of two pronuclei (median: 8, 7, 11, 8, respectively; P<0.001), number of fertilization (median: 9, 9, 13, 10, respectively; P<0.001), number of metaphase of meiosis Ⅱ oocytes (median: 9, 8, 13, 10, respectively; P<0.001), number of transferable embryos (median: 5, 5, 7, 6, respectively; P<0.001), number of high-quality embryos (median: 4, 3, 6, 5, respectively; P<0.001), gonadotropin(Gn) starting dosage (median: 150, 200, 150, 200 U, respectively; P<0.001), total dosage of Gn (median: 1 800, 2 075, 1 575, 2 025 U, respectively; P<0.001), duration of Gn used (median: 10, 10, 10, 10 days, respectively; P=0.027) in the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group were significantly different. Pairings between groups showed that number of oocytes retrieved, number of two pronuclei, number of fertilization, number of metaphase of meiosis Ⅱ oocytes and number of transferable embryos in PCOS high level AL group were lower than those in PCOS low level AL group (all P<0.05); Gn starting dosage and total dosage of Gn in PCOS low level AL group were lower than those in the other three groups (all P<0.05); duration of Gn used in PCOS high level AL group was higher than that PCOS low level AL group ( P<0.05). Clinical outcomes: the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group underwent fresh transplantation [27.4% (57/208), 24.4% (38/156), 15.1% (32/212), 17.1% (33/193), respectively; P=0.006] and the proportion of transplanted day 5 embryos [82.7% (172/208), 77.6% (121/156), 91.0% (193/212), 86.5% (167/193), respectively; P=0.018] were statistically significant. There were no significant differences in fertilization rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate and early abortion rate among the four groups (all P>0.05). Conclusion:The high level of AL in PCOS patients may affect the outcomes of embryo development, and more attention should be paid to AL in PCOS patients to reduce stress.

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 investigate the status of allostatic load (AL) in patients with polycystic ovary syndrome (PCOS) and its influence on the clinical outcomes of in vitro fertilization-embryo transfer.Methods:This was a prospective study. By using convenient sampling method, 421 patients with PCOS (PCOS group) and 372 control infertility patients (control group) in the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from April 2022 to January 2024 were investigated for basic information, physical examination, laboratory examination and follow-up of clinical outcomes. The total score of AL was calculated using 16 related indicators of cardiovascular system, metabolic system and immune system, and AL>3 was used as the judgment criteria for the high level AL group and the low level AL group. The differences in general data, embryo development and clinical outcomes between the groups were compared.Results:There were 222 cases (52.7%, 222/421) in PCOS low level AL group and 199 cases (47.3%, 199/421) in PCOS high level AL group. There were 214 patients (57.5%, 214/372) in the control low level AL group and 158 patients (42.5%, 158/372) in the control high level AL group. Embryo development outcomes: number of oocytes retrieved (median: 12, 12, 19, 14, respectively; P<0.001), number of two pronuclei (median: 8, 7, 11, 8, respectively; P<0.001), number of fertilization (median: 9, 9, 13, 10, respectively; P<0.001), number of metaphase of meiosis Ⅱ oocytes (median: 9, 8, 13, 10, respectively; P<0.001), number of transferable embryos (median: 5, 5, 7, 6, respectively; P<0.001), number of high-quality embryos (median: 4, 3, 6, 5, respectively; P<0.001), gonadotropin(Gn) starting dosage (median: 150, 200, 150, 200 U, respectively; P<0.001), total dosage of Gn (median: 1 800, 2 075, 1 575, 2 025 U, respectively; P<0.001), duration of Gn used (median: 10, 10, 10, 10 days, respectively; P=0.027) in the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group were significantly different. Pairings between groups showed that number of oocytes retrieved, number of two pronuclei, number of fertilization, number of metaphase of meiosis Ⅱ oocytes and number of transferable embryos in PCOS high level AL group were lower than those in PCOS low level AL group (all P<0.05); Gn starting dosage and total dosage of Gn in PCOS low level AL group were lower than those in the other three groups (all P<0.05); duration of Gn used in PCOS high level AL group was higher than that PCOS low level AL group ( P<0.05). Clinical outcomes: the control low level AL group, control high level AL group, PCOS low level AL group and PCOS high level AL group underwent fresh transplantation [27.4% (57/208), 24.4% (38/156), 15.1% (32/212), 17.1% (33/193), respectively; P=0.006] and the proportion of transplanted day 5 embryos [82.7% (172/208), 77.6% (121/156), 91.0% (193/212), 86.5% (167/193), respectively; P=0.018] were statistically significant. There were no significant differences in fertilization rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate and early abortion rate among the four groups (all P>0.05). Conclusion:The high level of AL in PCOS patients may affect the outcomes of embryo development, and more attention should be paid to AL in PCOS patients to reduce stress.

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 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.

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.