Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective: To investigate the effects of C1q tumor necrosis factor⁃related protein 3 (CTRP3) ⁃enhanced Sendai virus (SeV) vector⁃overexpressing Gata4 , Mef2c , and Tbx5 (SeVGMT) in the treatment of myocardial in⁃farction (MI) mice and to analyze whether ubiquitin carboxyl⁃terminal hydrolase L1 (UCHL1) mediates this thera⁃peutic pathway. Methods: The mice were divided into 7 groups ( n = 12) : Sham group , MI group , SeVGMT group , CTRP3⁃Lv group , UCHL1 ⁃sh group , SeVGMT + CTRP3⁃Lv group , and SeVGMT + CTRP3⁃Lv + UCHL1 ⁃sh group. In the Sham group , only the skin was incised without ligation , while the coronary artery was ligated 2 - 3 mm below the left atrial appendage in mice in other groups. PBS was injected at three points in the myocardial infarction boundary in the Sham and MI groups 30 minutes after ligation. Mice in other groups were injected with SeVGMT , CTRP3-Lv , or UCHL1-sh according to their grouping. Four weeks after treatment , fractional shortening (FS) , ejection fraction (EF) , left ventricular end-diastolic diameter (LVIDd) , left ventricular end-systolic diameter (LVIDs) , heart rate (HR) , mean arterial pressure (MAP) , serum creatine kinase isoenzyme MB (CK-MB) , myocardial troponin I ( cTnI) and lactate dehydrogenase ( LDH) levels , and myocardial tumor necrosis factor-α (TNF-α ) , interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in mice were detected. The pathological changes of myocardial tissue were detected by 2 , 3 , 5-triphenyltetrazolium chloride ( TTC) , hematoxylin-eosin ( HE) , Masson trichrome and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The mRNA expressions of CTRP3 and UCHL1 were detected by qRT-PCR. The protein expressions of CTRP3 , UCHL1 , collagen Ⅰ , collagen Ⅲ , Bcl-2-associated X (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) in myocardial tissue were detected by Western blot or immunohistochemical staining. Results: Compared with SeVGMT group and CTRP3-Lv group , the levels of EF , FS , HR and MAP in SeVGMT + CTRP3-Lv group increased (P < 0. 05) . The levels of LVIDd , LVIDs , CK-MB , cTnI , LDH , TNF-α , IL-1β and IL-6 decreased (P < 0. 05) . MI area , fibrosis area and TUNEL positive rate decreased (P < 0. 05) , the protein levels collagen Ⅰ , collagen Ⅲ and Bax decreased (P < 0. 05) , and Bcl-2 protein levels increased (P < 0. 05) . The mRNA and protein levels and relative staining intensity of CTRP3 and UCHL1 increased (P < 0. 05) . Compared with SeVGMT + CTRP3-Lv group , the addition of UCHL1-sh treatment ( SeVGMT + CTRP3-Lv + UCHL1-sh group) significantly weakened the influence of SeVGMT + CTRP3-Lv on the above indexes (P < 0. 05) . Conclusion CTRP3 mediated UCHL1 enhances the therapeutic effect of SeVGMT reprogrammed CFs on MI in mice.

Objective To investigate the efficiency and mechanism of C1q tumor necrosis factor-related protein 3(CTRP3)on reprogramming of cardiac fibroblasts(CFs)into induced cardiomyocyte-like cells(iCMs)by Sendai virus(SeV)vector overexpressing Gata4,Mef2c and Tbx5(SeVGMT).Methods CFs were divided into Control,NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh groups.NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh were transfected into CFs using Lipofectamine 3000 reagent for 48 hours.Lipofectamine 3000 reagent was then mixed with SeVGMT and incubated at room temperature for 48 hours,the culture medium was then replaced,and cells were cultured for 21 days.Cell morphology was observed under a microscope at 0,3,7,14,and 21 days.Expression levels of the myocardial-specific proteins α-myosin heavy chain(α-MHC),α-actin,cardiac troponin T(cTnT),connexin 43(Cx43),cardiac muscle α-actin(Actc1),and myosin heavy chain 6(Myh6)were detected at different time points by immunofluorescence,quantitative reverse transcription-polymerase chain reaction,and Western blot,and the proportions of beating cells at different time points were calculated.Results The relative fluorescence intensity and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs in each group increased with increasing culture time(P＜0.05),with significantly higher expression levels of myocardial-specific proteins at 14 days of culture than at 7 days(P＜0.05).The relative fluorescence intensities and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs at 3,7,14,and 21 days of culture were significantly increased in the CTRP3-Lv group compared with the NC-Lv group(P＜0.05),but were significantly decreased in CFs in the CTRP3-sh group compared with the NC-sh group(P＜0.05).Beating cells appeared in CFs in each group at 7 days of culture.The proportion of beating cells in each group increased with increasing culture time(P＜0.05),and the proportion was significantly higher at 14 days than at 7 days(P＜0.05).The proportion of beating cells among CFs was increased in the CTRP3-Lv group at 7,14,and 21 days of culture compared with the NC-Lv group(P＜0.05),while the proportion of beating cells in the CTRP3-sh group was decreased compared with the NC-sh group(P＜0.05).Conclusions CTRP3 can enhance SeVGMT reprogramming of CFs into iCMs.

Objective To investigate the efficiency and mechanism of C1q tumor necrosis factor-related protein 3(CTRP3)on reprogramming of cardiac fibroblasts(CFs)into induced cardiomyocyte-like cells(iCMs)by Sendai virus(SeV)vector overexpressing Gata4,Mef2c and Tbx5(SeVGMT).Methods CFs were divided into Control,NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh groups.NC-Lv,CTRP3-Lv,NC-sh,and CTRP3-sh were transfected into CFs using Lipofectamine 3000 reagent for 48 hours.Lipofectamine 3000 reagent was then mixed with SeVGMT and incubated at room temperature for 48 hours,the culture medium was then replaced,and cells were cultured for 21 days.Cell morphology was observed under a microscope at 0,3,7,14,and 21 days.Expression levels of the myocardial-specific proteins α-myosin heavy chain(α-MHC),α-actin,cardiac troponin T(cTnT),connexin 43(Cx43),cardiac muscle α-actin(Actc1),and myosin heavy chain 6(Myh6)were detected at different time points by immunofluorescence,quantitative reverse transcription-polymerase chain reaction,and Western blot,and the proportions of beating cells at different time points were calculated.Results The relative fluorescence intensity and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs in each group increased with increasing culture time(P＜0.05),with significantly higher expression levels of myocardial-specific proteins at 14 days of culture than at 7 days(P＜0.05).The relative fluorescence intensities and mRNA and protein levels of α-MHC,α-actin,cTnT,Cx43,Actc1,and Myh6 in CFs at 3,7,14,and 21 days of culture were significantly increased in the CTRP3-Lv group compared with the NC-Lv group(P＜0.05),but were significantly decreased in CFs in the CTRP3-sh group compared with the NC-sh group(P＜0.05).Beating cells appeared in CFs in each group at 7 days of culture.The proportion of beating cells in each group increased with increasing culture time(P＜0.05),and the proportion was significantly higher at 14 days than at 7 days(P＜0.05).The proportion of beating cells among CFs was increased in the CTRP3-Lv group at 7,14,and 21 days of culture compared with the NC-Lv group(P＜0.05),while the proportion of beating cells in the CTRP3-sh group was decreased compared with the NC-sh group(P＜0.05).Conclusions CTRP3 can enhance SeVGMT reprogramming of CFs into iCMs.

Objective: To investigate the health literacy and its influencing factors among residents in areas out of poverty in Kunming City, so as to provide insights into formulating health education strategies. Methods: A total of 1 916 permanent residents at ages of 15 to 69 years were sampled in three areas out of poverty in Kunming City using the multi-stage stratified random sampling method and probability proportionate to size sampling method from August to October, 2020. Health literacy was investigated using the Questionnaire on the Health Literacy among Chinese Residents, the level of health literacy was analyzed and weighted by the population of the China's Seventh National Population Census. Factors affecting health literacy among residents in areas out of poverty were identified using a multivariable logistic regression model. Results: A total of 1 916 questionnaires were allocated, and 1 908 valid questionnaires were recovered, with an effective recovery rate of 99.58%. The respondents included 997 men (52.25%) and 911 women (47.75%), and had a mean age of (45.58±14.28) years. The level of health literacy was 21.38%. Multivariable logistic regression analysis identified age (15 to 24 years, OR=5.087, 95%CI: 1.573-16.450; 25 to 34 years, OR=6.016, 95%CI: 1.991-18.183; 35 to 44 years, OR=7.526, 95%CI: 2.541-22.289; 45 to 54 years, OR=4.800, 95%CI: 1.640-14.050), educational level (junior high school, OR=5.333, 95%CI: 3.100-9.175; high school/vocational high school/technical secondary school, OR=19.895, 95%CI: 10.418-37.966; college or above, OR=27.580, 95%CI: 12.349-61.597) as factors affecting health literacy among residents in areas out of poverty in Kunming City. Conclusion The level of health literacy is 21.38% among residents in areas out of poverty in Kunming City, and age and educational level are associated factors.

Background::The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis (AS), and the impact of sizing strategies and related procedural outcomes.Methods::Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to 2019. The anatomy and morphology of the aortic root were assessed. "Downsize" strategy was preformed when patients had complex morphology. The clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing strategy. The primary outcome was device success rate, and secondary outcomes included Valve Academic Research Consortium-3 clinical outcomes variables based on 1-year follow-up.Results::A total of 293 patients were enrolled. Among them, 95 patients (32.4%) had bicuspid aortic valve. The calcium volume (Hounsfield Unit-850) of aortic root was 449.90 (243.15-782.15) mm 3. Calcium is distributed mostly on the leaflet level. Downsize strategy was performed in 204 patients (69.6%). Compared with the patients who performed annular sizing strategy, those received downsize strategy achieved a similar device success rate (82.0% [73] vs. 83.3% [170], P= 0.79). Aortic valve gradients (downsize strategy group vs. annular sizing group, 11.28 mmHg vs. 11.88 mmHg, P = 0.64) and percentages of patients with moderate or severe paravalvular regurgitation 2.0% (4/204) vs. 4.5% (4/89), P = 0.21) were similar in the two groups at 30 days after TAVR. These echocardiographic results were sustainable for one year. Conclusions::Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic root. Calcium is distributed mostly on the leaflet level. Compare with annular sizing strategy, downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.

Objective:To investigate the role of TSLP and NF-κB in the pathogenesis of adenomyosis.Methods:Immunohisto-chemistry was employed to detect the expression of TSLP and NF-κB p65 in the endometrial glandular cell and stromal cell of 35 adeno-myosis patients and 20 hysteromyoma patients as control , and analyze the correlation of the two proteins.The concentration of TSLP was measured by specific ELISA in the serum of healthy subjects besides of the patients with adenomyosis and hysteromyoma .Results:TSLP and NF-κB p65 were both positively expressd in the glandular cells and stromal cells of ectopic and eutopic endometrium of patients with adenomyosis , their expression was significantly higher than that of the control group ( P<0.01 ) , and the expression of TSLP and NF-κB p65 in ectopic endometrium was significantly higher than that in eutopic endometrium ( P<0.01 ).There was positive correlation between TSLP and NF-κB p65 in ectopic endometrium.The concentration of TSLP was higher in the serum of patients with adenomyosis.Conclusion:The TSLP is highly expressed in endometrial glandular and stromal cells of patients with adenomyosis , and there is higher level of TSLP in serum , and there is correlation between the expression of TSLP and NF-κB in ectopic endometrium.

Objective To explore the scanning technique and image quality of coronary artery imaging with dual-source CT without oral Betaloc preparation in the patients with high heart rate.Methods 412 cases were undergone coronary imaging with dual-source CT (including plain and enhanced scans) ,among them,there were 30 cases with heart rate more than 100 bpm.Multi-planar reconstruction(MPR),maximum intensity projection(MIP) and volume rendering (VR) were performed using contrast-enhanced images.The image quality was classified into 3 grades, and coronary segments named according to AHA standard were evaluated.Results The average heart rate during enhanced scan in the 30 cases was (115.6?11.8)(101～139)bpm,the average breath hold time was (5.7?1.2) s.The best reconstruction phase was in the systolic phase. Altogether 424 coronary segments were evaluated, among them 93.9%(398/424)belonged to the first grade,5.0%(21/424)belonged to the second grade,and 1.2%(5/424) belonged to the third grade. Conclusion Without oral administration of Betaloc preparation, good coronary artery images can be obtained in the patients with high heart rate by dual-source CT.