Outcomes of Mitral Valve Repair for Posterior Leaflet Prolapse, Anterior Leaflet Prolapse, and Bileaflet Prolapse.

Background: Mitral valve repair (MVr) is an effective treatment for degenerative mitral regurgitation (DMR).And the outcomes and repair rates for posterior leaflet prolapse (PLP), anterior leaflet prolapse (ALP), and bileaflet prolapse (BLP) vary. This study aimed to compare the outcomes of mitral valve repair for patients with PLP, ALP, and BLP. Methods: From 2010 to 2019, 1192 patients with degenerative mitral valve regurgitation underwent surgery at our hospital. And 1069 patients were identified. The average age of all patients was (54.74 ± 12.17) years old for all patients. 273 patients (25.5%) had ALP, 148 patients (13.8%) had BLP, and 648 patients (60.6%) had PLP. All patients were followed up for an average duration of 5.1 years. We compared the outcomes of patients with ALP, PLP, and BLP. Results: Patients with ALP were the youngest of the 3 groups and had the highest prevalence of atrial fibrillation. Patients with PLP had the highest prevalence of hypertension, whereas patients with BLP and ALP had larger left ventricular end-diastolic and left ventricular end-systolic diameters. ALP and BLP repairs had a longer cardiopulmonary bypass and aortic cross-clamp time.10 patients dead in-hospital, 5 patients had PLP, 3 had ALP, and 2 had BLP. The 10-year survival cumulative incidences of reoperation among ALP, BLP, and PLP repairs were not significantly different. ALP repair still had higher cumulative incidences of recurrent mitral regurgitation (MR) compared to PLP. Conclusions: The rates of long-term survival and freedom from reoperation were not significantly different among patients with ALP, BLP, and PLP. ALP repair has higher cumulative incidences of recurrent MR compared to PLP.

Peripheral blood indicators and COVID-19: an observational and bidirectional Mendelian randomization study.

Blood is critical for health, supporting key functions like immunity and oxygen transport. While studies have found links between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we analyzed clinical data (n = 2,293, aged 18-65 years) from Guangzhou Medical University's first affiliated hospital (2022-present), identifying 34 significant indicators differentiating COVID-19 patients from healthy controls. Utilizing bidirectional Mendelian randomization analyses, integrating data from over 2.46 million participants from various large-scale studies, we established causal links for six blood indicators with COVID-19 risk, five of which is consistent with our observational findings. Specifically, elevated Troponin I and Platelet Distribution Width levels are linked with increased COVID-19 susceptibility, whereas higher Hematocrit, Hemoglobin, and Neutrophil counts confer a protective effect. Reverse MR analysis confirmed four blood biomarkers influenced by COVID-19, aligning with our observational data for three of them. Notably, COVID-19 exhibited a positive causal relationship with Troponin I (Tnl) and Serum Amyloid Protein A, while a negative association was observed with Plateletcrit. These findings may help identify high-risk individuals and provide further direction on the management of COVID-19.

The genetic etiology of body fluids on chronic obstructive airways disease.

BACKGROUND: Numerous studies have documented significant alterations in the bodily fluids of Chronic Obstructive Pulmonary Disease (COPD) patients. However, existing literature lacks causal inference due to residual confounding and reverse causality. METHODS: Summary-level data for COPD were obtained from two national biobanks: the UK Biobank, comprising 1,605 cases and 461,328 controls, and FinnGen, with 6,915 cases and 186,723 controls. We also validated our findings using clinical data from 2,690 COPD patients and 3,357 healthy controls from the First Affiliated Hospital of Guangzhou Medical University. A total of 44 bodily fluid biomarkers were selected as candidate risk factors. Mendelian randomization (MR) and meta-analyses were used to evaluate the causal effects of these bodily fluids on COPD and lung function (FEV1/FVC). RESULTS: Mendelian randomization (MR) and meta-analyses, by integrating data from the UK Biobank and FinnGen cohort, found that 3 bodily fluids indicators (HDLC, EOS, and TP) were causally associated with the risk of COPD, two (EOS and TP) of which is consistent with our observational findings. Moreover, we noticed EOS and TP were causally associated with the risk of lung function (FEV1/FVC). CONCLUSIONS: The MR findings and clinical data highlight the independent and significant roles of EOS and TP in the development of COPD and lung function (FEV1/FVC), which might provide a deeper insight into COPD risk factors and supply potential preventative strategies.

Outcomes of Mitral Valve Repair for Degenerative Mitral Disease: A Single-Centre 10-Year Experience.

OBJECTIVE: To evaluate the long-term outcomes of degenerative mitral valve (MV) repair. METHODS: This study analysed 1,069 patients who underwent MV repair due to degenerative MV disease at Beijing Anzhen Hospital from January 2010 to December 2019. All patients were clinically followed until December 2019, with an average follow-up period of 4.7 years. Perioperative complications, 30-day mortality, long-term outcomes, and risk factors of all-cause death and recurrent mitral regurgitation (MR) were summarised. RESULTS: Ten patients died in the hospital and 33 died during the follow-up period. Recurrent MR occurred in 113 patients. Fourteen patients underwent re-operation. Rates of long-term survival, absence of recurrent MR, and no re-operation were 94.0% (91.6%-96.6%), 81.2% (77.3%-85.3%), and 98.2% (97.2%-99.3%), respectively. The risk factors for long-term all-cause death included age and an ejection fraction (EF) <60%. The risk factors for recurrent MR included age, female sex, E-wave velocity, anterior prolapse, residual 1+MR postoperatively, and lower body mass index. CONCLUSIONS: Mitral valve repair is an effective treatment for degenerative MV disease that, in an experienced heart centre, can be performed with low mortality, recurrence, and re-operation rates. Advanced age and an EF <60% were risk factors for long-term all-cause death. Age, female sex, residual 1+MR postoperatively, lower body mass index, higher peak E-wave velocity, and anterior prolapse were risk factors for recurrent MR.

Impact of ultra-low temperature storage on serum sIgE detection and allergic disease biobank feasibility.

Research has shown that the concentration and composition of biological samples may change after long-term ultra-low temperature storage. Consequently, this study examined the effect of ultra-low temperature storage on serum sIgE detection by comparing sIgE concentrations at various durations from the time of sample storage to subsequent testing. We selected 40 serum samples from the Guangzhou Medical University Affiliated First Hospital Biobank, which had been tested for house dust mites, dog hair, tobacco mold, cockroaches, and cow milk allergen sIgE. Samples were categorized by storage duration: 14 samples stored for 10 years, 12 for 5 years, and 14 for 3 years. They were also classified by sIgE positive levels: 15 samples at levels 1-2, 15 at levels 3-4, and 10 at levels 5-6. The allergen sIgE of these samples was retested using the same technology. Regardless of the type of allergen or the level of positivity, the majority of sIgE concentrations measured at the time of storage were higher than the current measurements, but the difference was not statistically significant. The correlation between the sIgE results at the time of storage and the current results was high for samples stored for 10 years (rs = 0.991, P < 0.001) and 5 years (rs = 0.964, P < 0.001). Serum allergen sIgE is stable when stored under ultra-low temperature conditions, making the construction of a biological sample bank for allergic diseases feasible. This will facilitate researchers in quickly obtaining samples, conducting technical research, and translating findings, thereby promoting the development of the field of allergy through integration of industry, academia, and research.

Outcome of mitral repair combined with Cox-maze procedure for atrial functional mitral regurgitation with heart failure with recovered ejection fraction.

OBJECTIVES: Atrial functional mitral regurgitation (AFMR) in patients with heart failure with recovered ejection fraction has received insufficient attention. This study analysed the prognosis and outcomes of mitral valve (MV) repair combined with the Cox-maze procedure. METHODS: A prospective cohort study of patients with AFMR with left ventricular ejection fraction (LVEF) <40% was conducted. All patients received guideline-directed medical therapy. Those with recovered ejection fraction underwent MV repair combined with the Cox-maze procedure. Mortality, atrial fibrillation (AF) recurrence, mitral regurgitation (MR) and postoperative tricuspid regurgitation were assessed using the inverse probability weighting (IPW) method. RESULTS: In total, 312 patients were enrolled in this study between 2010 and 2019, 247 of whom underwent MV repair combined with the Cox-maze procedure [full recovery (LVEF > 50%): n = 132, partial recovery (LVEF of 40-50%): n = 115]. IPW-adjusted survival of patients with LVEF ≥50% and LVEF 40-50% showed no significant difference [hazard ratio (HR): 2.18, 95% confidence interval: 0.46-10.38, P = 0.33]. However, patients with LVEF ≥50% had better IPW-adjusted long-term freedom from recurrent MR [HR: 2.44 (1.28-4.63), P = 0.0065] and AF recurrence [HR: 1.85 (1.06-3.21), P = 0.030] than those with LVEF of 40-50%. CONCLUSIONS: MV repair combined with the Cox-maze procedure was effective and feasible in patients with severe AFMR with heart failure with recovered ejection fraction. Additionally, patients with LVEF ≥50% after guideline-directed medical therapy undergoing these combined procedures had better long-term freedom from recurrent AF and MR than those with LVEF of 40-50%.

Outcomes of pregnancy in mice with pulmonary hypertension induced by Hypoxia/SU5416.

BACKGROUND: Pulmonary hypertension (PH) seriously affects the health of patients. We have found in clinical studies that PH has adverse effects on both maternal and offspring. OBJECTIVE: To establish a animal model of PH induced by hypoxia/SU5416 and observe the effects of PH on pregnant mice and their fetuses. METHODS: Twenty-four C57 mice aged 7-9 weeks were selected and divided into 4 groups with 6 mice in each group. ① Female mice with normal oxygen; ② Female mice with hypoxia/SU5416; ③ Pregnant mice with normal oxygen; ④ Pregnant mice with hypoxia/SU5416. After 19 days, weight, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were compared in each group. Lung tissue and right ventricular blood were collected. The number and weight of fetal mice were also compared between the two pregnant groups. RESULTS: There was no significant difference in RVSP and RVHI between female and pregnant mice under the same condition. Compared with normal oxygen condition, two groups of mice in hypoxia/SU5416 had poor development, RVSP and RVHI were significantly increased, the number of fetal mice was small, hypoplasia, degeneration and even abortion. CONCLUSION: The model of mice PH was successfully established. PH affects the development and health of female and pregnant mice, and seriously affects the fetuses.

Surgery Before Pregnancy in Women with Congenital Heart Disease: A Retrospective Study.

BACKGROUND: This study aimed to investigate if surgery before pregnancy would result in better maternal and fetal outcomes in patients with congenital heart disease. METHODS: A retrospective study was conducted using data collected from the medical records of pregnant patients with congenital heart disease, who were seen at Beijing Anzhen Hospital between 2010 and 2019. The patients were divided into surgical and non-surgical groups, and the differences in outcomes were compared. RESULTS: A total of 999 patients with congenital heart disease (mean age, 28.7±4.3 years) were enrolled, with 403 (40.0%) and 596 (60.0%) in the surgical and non-surgical groups, respectively. The percentages of almost all adverse events were higher in the non-surgical group than in the surgical group. The adverse events included preterm delivery (9.9 vs. 17.1%), low birth weight (6.5 vs. 11.6%), heart failure (2.7 vs. 6.7%), cesarean section (75.7 vs. 85.9%), pulmonary hypertension (13.6 vs. 36.2%), and death (0.5 vs. 2.3%) (all P < 0.05). A total of 16 (1.6%) patients died, including 14 and two in the non-surgical and surgical groups, respectively. Regardless of the type of congenital heart disease, preterm delivery and low birth weight were more common in the non-surgical group compared with the surgical group, and there were no statistical between group differences in the other remaining events. CONCLUSIONS: In the non-surgical group, the results were similar regardless of the type of congenital heart disease, except for preterm delivery and low birth weight. The overall outcome of the surgical group was better than that of the non-surgical group, and surgery before pregnancy reduced maternal and infant risk.

Sex Differences in the Outcomes of Degenerative Mitral Valve Repair.

PURPOSE: This study explored the sex differences in the outcomes of degenerative mitral valve repair (MVr). METHODS: From 2010 to 2019, 1069 patients who underwent MVr due to degenerative mitral disease at Beijing Anzhen Hospital were analyzed. The average patient follow-up was 5.1 years (interquartile range: 5-7 years). The primary endpoint was overall survival. Secondary endpoints were freedom from reoperation and recurrent mitral regurgitation. A propensity-matched analysis was used to compare the outcomes of males and females. RESULTS: Females were older, had a higher prevalence of atrial fibrillation and moderate-to-severe tricuspid regurgitation, and had smaller left atrial, left ventricular end-diastolic, and left ventricular end-systolic diameters. Males were more likely to undergo concomitant coronary artery bypass grafting and had longer cardiopulmonary bypass and aortic cross-clamp times. The in-hospital mortality was <1% (10/1,069). After propensity score matching of 331 pairs of patients, most variables were well balanced. Before and after propensity score matching, the long-term survival and freedom from reoperation rates were similar. Males had higher durability after surgery compared with females. CONCLUSIONS: Females were referred to surgery later and had more complications than males. Long-term survival and freedom from reoperation rates were not significantly different between the sexes.

Childbearing Performances and Outcomes of Female Patients with Rheumatic Mitral Valve Diseases after Different Mitral Interventions.

PURPOSE: This study aimed to illustrate how percutaneous balloon mitral valvuloplasty (PBMV) and mitral valve (MV) surgeries influence women of childbearing age with rheumatic mitral valve diseases (RMVDs) from two aspects, including clinical outcomes and their postoperative childbearing performances. METHODS: Female patients with RMVD who were of childbearing age and underwent MV interventions between 2007 and 2019 at Beijing Anzhen Hospital were identified. Outcomes included all-cause deaths, repeated MV interventions, and atrial fibrillation. A survey about childbearing attempts and complications during pregnancy was also performed during follow-up. RESULTS: A total of 379 patients were involved in this study, consisting of 226 cases of mitral valve replacements, 107 cases of mitral valve repairs (MVrs), and 46 cases of PBMVs. PBMV was associated with higher possibilities of repeated MV interventions (P <0.05). Postoperative childbearing attempts were more frequently observed among bioprosthesis, MVr, and PBMV (P <0.05). However, PBMV and MVr showed a higher incidence of cardiac complications during pregnancy as compared to prosthesis replacement (P <0.05). CONCLUSIONS: MVr and PBMV are not recommended to young female patients for higher incidences of postoperative complications. Safe pregnancy is more likely to be present among patients with biological prosthesis.

Pregnancy outcomes of women with Eisenmenger syndrome: A single-center study.

BACKGROUND: To explore the outcomes of mothers with Eisenmenger syndrome (ES) and their offspring. METHODS: Pregnant women with ES admitted to the Beijing Anzhen Hospital between 2010 and 2019 were retrospectively analyzed and followed up. RESULTS: Forty-two parturient women with ES were recruited, with an average age of 26.7 years (standard deviation [SD], ±4.0 years). The average gestational age was 33.7 weeks (SD, ±2.5 weeks). The average percutaneous oxygen saturation was 84.1 (±9.2), and 40 (95.2%) had caesarean delivery. The average pulmonary artery systolic pressure was 107.5 mmHg (SD, ±20.3 mmHg). Twelve (28.6%) women experienced pulmonary hypertensive crisis; 11 (26.2%) of these women died. Regarding the offspring, the average fetal weight was 1778.1 g (SD, ±555.3 g), six (14.3%) died, and congenital heart disease was diagnosed in three (7.1%). There were significant differences in age, gestational age, percutaneous oxygen saturation, Apgar score, and heart failure between the maternal death and non-death groups (P < 0.05). Death was mainly related to pulmonary hypertensive crisis and heart failure. CONCLUSIONS: We recommend pregnancy termination if ES occurs during early pregnancy; however, patients should be informed of the risks if it occurs during late pregnancy. Multidisciplinary cooperation should be strengthened to improve the prognosis of the mothers and their offspring.

Radiofrequency Ablation in Patients Undergoing Mitral Valve Surgery with or without Giant Left Atria.

PURPOSE: We aimed to compare the efficacy of radiofrequency ablation (RFA) in patients undergoing mitral valve (MV) surgery with or without giant left atria. METHODS: This retrospective, single-center, cohort study investigated patients who underwent MV surgery and concomitant RFA from 2009 to 2019. Patients were divided into non-giant left atria (diameter ≤65 mm, n = 1543) and giant left atria (diameter >65 mm, n = 241) groups. Five-year freedom from atrial tachyarrhythmia recurrence and thromboembolic event (TE) rates were assessed with death as the competing risk factor with and without propensity-score matching. RESULTS: Patients with giant left atria had higher mortality (10.8% versus 6.2%, P = 0.008) and readmission rates for heart failure than those without (12.0% versus 6.8%, P = 0.004). Atrial tachyarrhythmia recurrence rates were higher in patients with giant left atria than in those without (49% versus 24% at 5 years, P <0.001), but the cumulative incidence of TEs before (P = 0.944) and after (P = 0.695) propensity-score matching was comparable. CONCLUSIONS: RFA effectively prevented TEs in patients with giant left atria, despite significant atrial tachyarrhythmia recurrence. Atrial tachyarrhythmia recurrence did not increase the risk of TEs. A lower success rate should be considered when deciding whether to perform surgical ablation in patients with giant left atria.

Maternal and fetal outcomes of pregnant women with pulmonary arterial hypertension associated with congenital heart disease in Beijing, China: A retrospective study.

As pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) may increase maternal and fetal risk, this study explored the pregnancy outcomes of Chinese women with PAH-CHD. The clinical data of pregnant women with PAH-CHD admitted to the Beijing Anzhen Hospital from 2010 to 2019 were retrospectively analyzed; these patients and their offspring were followed up, with a mean period of 5.9 ± 2.7 years. Overall, 260 patients with PAH-CHD were included. The mean maternal age was 27.7 ± 4.1 years, and 205 (78.8%) patients were nulliparous. The estimated systolic pulmonary artery pressure was 40-50 mmHg in 34.6% of the patients, 50-70 mmHg in 23.1%, and >70 mmHg in 42.3%. More than 96% of patients were diagnosed with PAH-CHD before pregnancy. During pregnancy, heart failure occurred in 19.2% of the patients. Cesarean delivery was performed in 88.1% (15.0% emergency) of the patients. Complications included fetal distress (5.8%), preterm delivery (34.2%), and low birth weight (33.8%). A total of 15 mothers (5.8%) died, with the highest mortality rate in those with Eisenmenger syndrome (10/43, 23.3%), and 10 offspring died (3.8%), two (0.8%) following hospital discharge and eight (3.1%) while in hospital. Although most pregnant women with PAH-CHD were able to have children, PAH increased the maternal and fetal risk. Thus, an individualized risk-based approach with shared decision-making may be more appropriate in pregnant women with PAH-CHD.

MicroRNA-146b-5p promotes atrial fibrosis in atrial fibrillation by repressing TIMP4.

Alteration of tissue inhibitors of matrix metalloproteinases (TIMP)/matrix metalloproteinases (MMP) associated with collagen upregulation has an important role in sustained atrial fibrillation (AF). The expression of miR-146b-5p, whose the targeted gene is TIMPs, is upregulated in atrial cardiomyocytes during AF. This study was to determine whether miR-146b-5p could regulate the gene expression of TIMP4 and the contribution of miRNA to atrial fibrosis in AF. Collagen synthesis was observed after miR-146b-5p transfection in human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs)-fibroblast co-culture cellular model in vitro. Furthermore, a myocardial infarction (MI) mouse model was used to confirm the protective effect of miR-146b-5p downregulation on atrial fibrosis. The expression level of miR-146b-5p was upregulated, while the expression level of TIMP4 was downregulated in the fibrotic atrium of canine with AF. miR-146b-5p transfection in hiPSC-aCMs-fibroblast co-culture cellular model increased collagen synthesis by regulating TIMP4/MMP9 mediated extracellular matrix proteins synthesis. The inhibition of miR-146b-5p expression reduced the phenotypes of cardiac fibrosis in the MI mouse model. Fibrotic marker MMP9, TGFB1 and COL1A1 were significantly downregulated, while TIMP4 was significantly upregulated (at both mRNA and protein levels) by miR-146b-5p inhibition in cardiomyocytes of MI heart. We concluded that collagen fibres were accumulated in extracellular space on miR-146b-5p overexpressed co-culture cellular model. Moreover, the cardiac fibrosis induced by MI was attenuated in antagomiR-146 treated mice by increasing the expression of TIMP4, which indicated that the inhibition of miR-146b-5p might become an effective therapeutic approach for preventing atrial fibrosis.

Pregnancy Complications and Outcomes Among Women With Congenital Heart Disease in Beijing, China.

OBJECTIVE: To conduct a comparative analysis of the complications and outcomes in pregnant women with and without congenital heart disease (CHD) in Beijing, China. METHODS: We compared pregnancy-related complications and outcomes experienced by women with and without CHD throughout 19,424 deliveries in Beijing Anzhen Hospital between 2010 and 2019, including cardiovascular and obstetric factors, fetal events, delivery methods, and other complications over a mean 5-years post-delivery follow-up period. RESULTS: There were 1,040 women with CHD (5.35% of all deliveries). Compared to women without CHD, these women had longer hospital stays (7.83 ± 4.65 vs. 4.93 ± 3.26 days) and a higher death rate (1.92 vs. 0.02%). They also had a greater risk of comorbidities, including pre-term delivery (odds ratio: 13.65 vs. 6.71), heart failure (odds ratio: 4.90 vs. 0.40), and arrhythmia (odds ratio 12.69 vs. 4.69). Pulmonary hypertension, New York Heart Association functional class III~IV, and no congenital heart disease surgery prior to pregnancy were associated with adverse events such as cesarean section, pre-term delivery, and heart failure. The fetuses of mothers with CHD were more likely to be born pre-term (odds ratio: 13.65 vs. 6.71) and have low birth weight (odds ratio: 8.56 vs. 4.36). Eleven infants (1.82%) born to mothers with CHD and four infants (0.64%) born to mothers without CHD were diagnosed with CHD. CONCLUSIONS: Women with CHD generally increase maternal and infant risk during pregnancy and the perinatal period. Pulmonary hypertension, decrease in cardiac function, and no previous CHD surgery increase the risk in women with CHD. Greater attention should be paid to pregnant women with CHD and their fetuses, newborns.

Surgical outcome for hypertrophic cardiomyopathy patients with extreme interventricular septal thickness: a propensity score matched study.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) with extreme interventricular septal thickness (IVST) is associated with a higher incidence of adverse cardiovascular events. However, the results of these patients who underwent septal myectomy are unclear. METHODS: We studied 47 HCM patients with IVST ≥30 mm who underwent septal myectomy between 2011 and 2018 in Anzhen Hospital. After a 2:1 propensity score matching, the study cohort included 141 patients and 94 patients with IVST <30 mm. RESULTS: Patients with IVST ≥30 mm had a longer clinical course of disease, high incidence of syncope, palpitation, and moderate or severe mitral regurgitation. After a mean follow-up of 34.0±21.3 months, 6 patients died, including 5 with IVST ≥30 mm and 1 with IVST <30 mm. The 5-year survival free of all-cause mortality was significantly higher in patients with IVST ≥30 mm than in those with IVST <30 mm (98.9% vs. 85.7%, P=0.03). Multivariable Cox analysis revealed that IVST ≥30 mm (HR: 1.12, 95% CI: 1.01-1.25, P=0.028) was an independent risk factor for all-cause mortality. Meanwhile, left ventricular end diastole diameter (HR: 0.72, 95% CI: 0.54-0.97, P=0.031) and age (HR: 0.91, 95% CI: 0.83-0.99, P=0.025) were also independent risk factors for all-cause mortality in this special cohort. Furthermore, the incidence of NYHA class III or IV was significantly higher in patients with IVST ≥30 mm. CONCLUSIONS: The surgical outcome was poor in a matched cohort of HCM patients with IVST ≥30 mm, which was mainly reflected by mortality and the incidence of NYHA class III or IV.

Catheter ablation or surgical therapy in moderate-severe tricuspid regurgitation caused by long-standing persistent atrial fibrillation. Propensity score analysis.

BACKGROUND: This study aimed to describe the mid-term outcomes of different treatments in patients with atrial fibrillation caused tricuspid regurgitation. METHODS: A retrospective study of patients diagnosed as atrial fibrillation caused moderate-severe tricuspid regurgitation undergoing ablation (n = 411) were reviewed. The surgical cohort (n = 114) underwent surgical ablation and tricuspid valve repair; the catheter cohort (n = 279) was selected from those patients who had catheter ablation. RESULTS: The estimated actuarial 5-year survival rates were 96.8% (95% CI: 92.95-97.78) and 92.0% (95% CI: 85.26-95.78) in the catheter and surgical cohort, respectively. Tethering height was showed as independent risk factors for recurrent atrial fibrillation and tricuspid regurgitation in both cohorts. A matched group analysis using propensity-matched was conducted after categorizing total patients by tethering height < 6 mm and ≥ 6 mm. Kaplan-Meier analysis showed in patients with tethering height < 6 mm, there were no differences in survival from mortality, stroke, recurrent atrial fibrillation and tricuspid regurgitation between two groups. In patients with tethering height ≥ 6 mm, there were significantly higher cumulative incidence of stroke (95% CI, 0.047-0.849; P = 0.029), recurrent atrial fibrillation (95% CI, 0.357-09738; P = 0.039) and tricuspid regurgitation (95% CI, 0.359-0.981; P = 0.042) in catheter group. CONCLUSIONS: Atrial fibrillation caused tricuspid regurgitation resulted in less leaflets coaptation, which risk the recurrence of atrial fibrillation and tricuspid regurgitation. Patients whose tethering height was less than 6 mm showed satisfying improvement in tricuspid regurgitation with the restoration of sinus rhythm after catheter ablation. However, in patients with severe leaflets tethering, the results favored surgical over catheter.

Discovery of a non-zwitterionic oseltamivir analogue as a potent influenza a neuraminidase inhibitor.

The most of potent neuraminidase inhibitors as zwitterions with poor lipophilicity suffered from the poor oral bioavailability. Herein, we describe a rational journey to discover a non-zwitterionic neuraminidase inhibitor 24a containing urea. It showed potent inhibitions against neuraminidases from group 1(H5N1 and H1N1) and group 2 (H3N2) subtypes and exhibited more strong inhibitory activities against neuraminidases from H274Y mutants than oseltamivir carboxylate. Whether administrated by orally or intravenous injection, the pharmacokinetic profile of compound 24a in SD rats were improved compared to oseltamivir carboxylate.

NF-κB "decoy" inhibits COX-2 expression in epileptic rat brain.

There is a need to investigate the role of nuclear factor kappa B in the regulation of cyclooxygenase-2 expression in the epileptic rat brain and cultured hippocampal neurons. Immunofluorescence and polymerase chain reaction was used to detect the expression of nuclear factor kappa B and cyclooxygenase-2. In cultured hippocampal neurons and rat brain: the control group compared with the normal group, nuclear factor kappa B expression in the hippocampal dentate gyrus, cerebral cortex, the piriform cortex brain regions were significantly increased (P < 0.01). This is accompanied by a significant increase in cyclooxygenase-2 protein and mRNA expressions in the hippocampus (P < 0.01). In the experimental group compared to the control group, the nuclear factor-kappa B expression in the hippocampal dentate gyrus, cerebral cortex, piriform cortex, and other brain regions was significantly lower (P < 0.01), with the accompanying decrease in cyclooxygenase-2 protein and mRNA expression (P < 0.01) in the hippocampus. In conclusion, κB-decoy can inhibit nuclear factor kappa B activation in epileptic rat brain and cyclooxygenase-2 overexpression.

Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A.

Influenza A neuraminidase plays an indispensable role in the process of replication and transmission of influenza, so the neuraminidase inhibition can prevent the reproduction of the viruses therefore achieve the effect of treatment of influenza. However, drug resistance of neuraminidase inhibitors such as oseltamivir highlights the need to develop novel structural neuraminidase inhibitors. Here we explored a series of oseltamivir derivatives bearing pyridyl group. Among them, compound 23b exhibiting potent inhibitory activity against neuraminidase from H5N1 subtype was comparable to oseltamivir carboxylate. Cytopathic effect inhibition assay in MDCK cells indicated that compound 23b exerted powerful inhibitions on influenza viruses. And compound 23b were nontoxic to MDCK cells. Meanwhile, compound 23b showed high stability towards rat liver microsomes, human liver microsomes and human plasma. This research enriched the structural type of neuraminidase inhibitors.