MicroRNA-139-5p mediates BMSCs impairment in diabetes by targeting HOXA9/c-Fos.

The properties and functions of BMSCs were altered by the diabetic microenvironment, and its mechanism was not very clear. In recent years, the regulation of the function of BMSCs by microRNA has become a research hotspot, meanwhile, HOX genes also have been focused on and involved in multiple functions of stem cells. In this study, we investigated the role of miR-139-5p in diabetes-induced BMSC impairment. Since HOXA9 may be a target gene of miR-139-5p, we speculated that miR-139-5p/HOXA9 might be involved in regulating the biological characteristics and the function of BMSCs in diabetes. We demonstrated that the miR-139-5p expression was increased in BMSCs derived from STZ-induced diabetic rats. MiR-139-5p mimics were able to inhibit cell proliferation, and migration and promoted senescence and apoptosis in vitro. MiR-139-5p induced the down-regulated expression of HOXA9 and c-Fos in BMSCs derived from normal rats. Moreover, miR-139-5p inhibitors reversed the tendency in diabetic-derived BMSCs. Further, gain-and-loss function experiments indicated that miR-139-5p regulated the functions of BMSCs by targeting HOXA9 and c-Fos. In vivo wound model experiments showed that the downregulation of miR-139-5p further promoted the epithelialization and angiogenesis of diabetic BMSC-mediated skin. In conclusion, induction of miR-139-5p upregulation mediated the impairment of BMSCs through the HOXA9/c-Fos pathway in diabetic rats. Therefore, miR-139-5p/HOXA9 might be an important therapeutic target in treating diabetic BMSCs and diabetic complications in the future.

Association Between Triglyceride Glucose Index with Cognitive Impairment and Dementia in Adult Population: A Meta-Analysis.

The current understanding of the correlation between insulin resistance (IR) and cognitive dysfunction is limited. Therefore, the objective of this systematic review and meta-analysis was to assess the association between the triglyceride glucose (TyG) index, a recently suggested indicator of IR, and cognitive impairment and dementia in the adult population. Observational studies pertinent to our research were identified through comprehensive searches of the PubMed, Embase, and Web of Science databases. To account for potential heterogeneity, the random-effects models were employed to aggregate the findings. This meta-analysis included ten observational studies involving 5602409 participants. Compared to those with the low TyG index, subjects with the high TyG index were significantly associated with the risk of cognitive impairment [risk ratio (RR): 1.39, 95% confidence interval (CI): 1.22 to 1.59, p<0.001; I2=45%) and dementia (RR: 1.30, 95% CI: 1.06 to 1.60, p=0.01; I2=50%). The association was consistent for Alzheimer's disease (RR: 1.35, 95% CI: 1.04 to 1.76, p=0.03; I2=54%) and vascular dementia (RR: 1.18, 95% CI: 1.13 to 1.24, p<0.001; I2=0%). Subgroup analyses showed that the association between TyG index with cognitive impairment and dementia were stronger in cross-sectional studies than that in cohort studies (p for subgroup difference=0.02), but not significantly modified by age, sex, or diabetic status of the participants. In conclusion, a high TyG index may be associated with higher risk of cognitive impartment and dementia in adult population.

Scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair in rheumatic mitral disease.

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.

Outcomes of non-angiosarcoma radiation-associated soft tissue sarcomas of the chest.

BACKGROUND: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest. METHODS: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy. RESULTS: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%. CONCLUSION: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies.

Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Association between Chinese visceral adiposity index and risk of stroke incidence in middle-aged and elderly Chinese population: evidence from a large national cohort study.

BACKGROUND: Abdominal obesity has long been considered as a crucial risk factor of stroke. Chinese visceral adiposity index (CVAI), a novel surrogate indicator of abdominal obesity, has been confirmed as a better predictor for coronary heart disease than other indicators in Asian population. However, the data on the relationship of CVAI with stroke is limited. The objective of our study is evaluating the relationship between CVAI and stroke incidence. METHODS: In the present study, we enrolled 7242 middle-aged and elderly residents from the China Health and Retirement Longitudinal Study (CHARLS) and placed them into groups according to quartile of CVAI. The outcome of interest was stroke. Kaplan-Meier curves were used to estimate the cumulative incidences of stroke. Cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were performed to evaluate the relationship between CVAI and incident stroke. Multiple sensitivity analyses and subgroups analyses were performed to test the robustness of the findings. RESULTS: During a median 84 months of follow-up, 612 (8.45%) participants experienced incident stroke, and the incidences of stroke for participants in quartiles (Q) 1-4 of CVAI were 4.42%, 7.29%, 9.06% and 13.04%, respectively. In the fully adjusted model, per 1.0-SD increment in CVAI has a significant increased risk of incident stroke: hazard ratio (HR) [95% confidence interval (CI)] was 1.17 (1.07-1.28); compared with participants in Q1 of CVAI, the HRs (95% CI) of incident stroke among those in Q2-4 were 1.47 (1.10-1.95), 1.62 (1.22-2.15), and 1.70 (1.28-2.27), respectively. Subgroups analyses suggested the positive association was significant in male participants, without diabetes, hypertension and heart disease. The findings were robust in all the sensitivity analyses. Additional, RCS curves showed a significant dose-response relationship of CVAI with risk of incident stroke (P for non-linear trend = 0.319). CONCLUSION: Increased CVAI is significantly associated with higher risk of stroke incidence, especially in male individuals, without hypertension, diabetes and heart disease. The findings suggest that baseline CVAI is a reliable and effective biomarker for risk stratification of stroke, which has far-reaching significance for primary prevention of stroke and public health.

Association between non-insulin-based insulin resistance indices and cardiovascular events in patients undergoing percutaneous coronary intervention: a retrospective study.

BACKGROUND: Insulin resistance (IR) has been confirmed that getting involved in the pathophysiological process of cardiovascular diseases (CVD). Recently, increasing evidence suggests metabolic score for insulin resistance (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index are simple and reliable surrogates for IR. However, their abilities in predicting cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) are not well explored. Therefore, this study aimed to investigate the association and evaluate the predictive performance of each index. METHODS: A total of 2533 consecutive participants undergoing PCI were included in this study, and the data from 1461 patients were used to determine the correlation of these non-insulin-based IR indices with major adverse cardiac and cerebrovascular events (MACCEs) via performing the multivariate logistic models and restricted cubic splines (RCS). RESULTS: During a median of 29.8 months follow-up, 195 cases of 1461 patients experienced incident MACCEs. In the overall population, both univariate and multivariate logistic regression analyses indicated no statistically significant connection between these IR indices and MACCEs. Subgroup analyses revealed significant interactions between age subgroups and TyG-BMI index, as well as METS-IR, and between sex subgroups and TyG index. In elderly patients, per 1.0-SD increment in TyG-BMI index and METS-IR had a significant association with MACCEs, with odds ratios (ORs) [95% confidence interval (CI)] of 1.24 (1.02-1.50) and 1.27 (1.04-1.56), respectively (both P < 0.05). Moreover, in female patients, all the IR indices showed significant associations with MACCEs. Multivariable-adjusted RCS curves demonstrated a linear relationship between METS-IR and MACCEs in elderly and female patients, respectively. However, all the IR indices failed to enhance the predictive performance of the basic risk model for MACCEs. CONCLUSION: All the four IR indices showed a significant association with MACCEs in female individuals, whereas only TyG-BMI index and METS-IR showed associations in elderly patients. Although the inclusion of these IR indices did not improve the predictive power of basic risk model in either female or elderly patients, METS-IR appears to be the most promising index for secondary prevention of MACCEs and risk stratification in patients undergoing PCI.

Influence of the Au-Ti Active Site of the Titanosilicate MWW Zeolite on the Catalytic Activity of Ethane Dehydrogenation in the Presence of O2.

The titanosilicate zeolite with a MWW topology structure was synthesized by the atom-planting method through the dehydrochlorination of the hydroxyl group in the deboronated ERB-1 zeolite (D-ERB-1) and TiCl4, and Au was further loaded with the deposition precipitation method to apply for the ethane direct dehydrogenation (DH) and dehydrogenation of ethane in the presence of O2 (O2-DH). It was found that Au nanoparticles (NPs) below 5 nm exhibited good activity for ethane direct dehydrogenation and O2-DH. The addition of titanium can not only anchor more Au but also make Au have a more dispersed homogeneous distribution. The ethane O2-DH catalytic performances of Au-loaded Ti-incorporated D-ERB-1 (Ti-D-ERB-1) were compared to those of Au-loaded ZnO-D-ERB-1 and pure silicate D-ERB-1. The results confirm that ethane O2-DH catalyzed by Au-Ti paired active sites is a tandem reaction of catalytic ethane DH and selective H2 combustion (SHC) of generated H2. According to the experimental results and calculated kinetic parameters, such as the activation energy of DH and SHC reaction heat of O2-DH, SHC catalyzed by the Au/Ti-D-ERB-1 catalyst containing the Au-Ti active site can not only break the ethane dehydrogenation thermodynamic equilibrium limitation to improve the ethylene yield but also suppress the CO2 and CO selectivity.

Multiphoton breakdown of acetylene; formation of organic building block fragments.

Mass resolved REMPI spectra and electron and ion velocity map images were recorded for REMPI of acetylene in the case of two-photon resonant excitations to low lying 3p and 4p Rydberg states. Combined data analysis of ion signal intensities and electron and ion kinetic energy release distribution revealed multiphoton-fragmentation processes in terms of photodissociation and photoionization channels to form the molecular ion, C2H2+ and the fragment ions H+, C+, CH+, CH2+, C2+ and C2H+. The ratio of fragment ion formation over the parent ion formation increases with excitation energy. To a large extent, multiphoton-fragmentation involves the initial breakdown of the molecule into ground and excited state neutral fragments by two-, three- and four-photon dissociation processes prior to multiphoton ionization. The three-photon dissociation processes via superexcited molecular state(s) are found to be the most important and electronically excited fragment species playing a significant role in the overall multiphoton-fragmentation. Furthermore, the data are indicative of the involvement of secondary photodissociation processes and provide information on fragment energetics as well as state interactions. The question, whether acetylene could be an important source of building block fragments for the formation of organic molecules in interstellar space, is addressed.

Noninvasive assessment of myocardial work during left ventricular isovolumic relaxation in patients with diastolic dysfunction.

BACKGROUND: This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD). METHODS: This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC. RESULTS: The total myocardial work during IVR (MWIVR), myocardial constructive work during IVR (MCWIVR), myocardial wasted work during IVR (MWWIVR), and myocardial work efficiency during IVR (MWEIVR) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWEIVR and MCWIVR were significantly correlated with the LV E/e' ratio and left atrial volume index, MWEIVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWEIVR corrected by IVRT also exhibited a significant correlation with tau. CONCLUSIONS: MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function.

Left atrial reservoir strain measurements derived from intracardiac echocardiography in patients with atrial fibrillation: comparison with transthoracic echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) provides accurate left atrial (LA) anatomical information in the procedure of atrial fibrillation (AF) ablation but lacks LA functional assessment. LA reservoir strain (LASr) is an excellent marker of LA reservoir function. This study aimed to assess the agreement between LASr derived from ICE and transthoracic echocardiography (TTE) in AF patients and analyze the reproducibility of LASr assessed by ICE combined with speckle tracking imaging. METHODS: This study prospectively enrolled 110 patients with a clinical diagnosis of AF who were ready for AF ablation, including 71 patients with paroxysmal AF and 39 with persistent AF. TTE and ICE examinations were performed on each individual before AF ablation. LASr measurements derived from ICE and TTE images were using dedicated LA-tracking software. Pearson correlation coefficients (r) and Bland-Altman plots were used to evaluate the agreement of LASr between the two modalities. Intraclass correlation coefficients (ICCs) were used to assess intra- and inter-observer reproducibility. RESULTS: The agreement between LASr obtained from ICE and TTE, especially between LASrLPV (LASr derived from LA left pulmonary vein view of ICE) and LASrTTE (LASr derived from TTE) were good in both paroxysmal and persistent AF patients [r = 0.890 (P < 0.001) for overall population; r = 0.815 (P < 0.001) and Bias ± LOA: -0.3 ± 9.9% for paroxysmal AF; r = 0.775 (P < 0.001) and Bias ± LOA: -2.6 ± 3.9% for persistent AF, respectively]. But the values of LASr derived from ICE were slightly lower than those of TTE, especially in patients with persistent AF. The ICCs for LASr derived from ICE were excellent (all ICCs > 0.90). CONCLUSIONS: In patients with AF, LASr derived from ICE demonstrated excellent reproducibility and showed good agreement with LASr obtained from TTE. Obtaining LASr from ICE images may be a supplementary method to evaluate LA reservoir function in AF patients and expands the potential of ICE in the field of cardiac function assessment.

Comparative characterization of SARS-CoV-2 variants of concern and mouse-adapted strains in mice.

SARS-CoV-2 has evolved into a panel of variants of concern (VOCs) and constituted a sustained threat to global health. The wildtype (WT) SARS-CoV-2 isolates fail to infect mice, while the Beta variant, one of the VOCs, has acquired the capability to infect standard laboratory mice, raising a spreading risk of SARS-CoV-2 from humans to mice. However, the infectivity and pathogenicity of other VOCs in mice remain not fully understood. In this study, we systematically investigated the infectivity and pathogenicity of three VOCs, Alpha, Beta, and Delta, in mice in comparison with two well-understood SARS-CoV-2 mouse-adapted strains, MASCp6 and MASCp36, sharing key mutations in the receptor-binding domain (RBD) with Alpha or Beta, respectively. Our results showed that the Beta variant had the strongest infectivity and pathogenicity among the three VOCs, while the Delta variant only caused limited replication and mild pathogenic changes in the mouse lung, which is much weaker than what the Alpha variant did. Meanwhile, Alpha showed comparable infectivity in lungs in comparison with MASCp6, and Beta only showed slightly lower infectivity in lungs when compared with MASCp36. These results indicated that all three VOCs have acquired the capability to infect mice, highlighting the ongoing spillover risk of SARS-CoV-2 from humans to mice during the continued evolution of SARS-CoV-2, and that the key amino acid mutations in the RBD of mouse-adapted strains may be referenced as an early-warning indicator for predicting the spillover risk of newly emerging SARS-CoV-2 variants.

High energy state interactions, energetics and multiphoto-fragmentation processes of HI.

Mass resolved multiphoton ionization data for two-photon resonant excitations (REMPI) in the 69 000-79 000 cm-1 region were recorded for HI. REMPI spectra of fragment and molecular ions were derived from the data and analysed to obtain information relevant to the state interactions, energetics and photofragmentation processes of intermediate Rydberg and ion-pair states (HI**). Spectral perturbations observed as line shifts and intensity anomalies acted complementarily to demonstrate the effects of the state interactions. The interaction strength and character mixing of Rydberg states and Rydberg and ion-pair states of different interaction types and the states energetics were quantified by deperturbation analysis for the high energy region of 75 000-79 000 cm-1, which is dense in states. Energetics of new, not previously observed, Rydberg states, detected in the lower energy excitation region of 69 000-75 000 cm-1 was characterized by simulation calculations. Ion intensity borrowing effects, found in the spectra of interacting states, are evidence of alterations in two-photon transition probabilities due to state mixing. Based on variations in relative spectral line intensities the major photofragmentation processes involved are proposed. These involve one-photon excitation of the intermediate states (HI**) to form repulsive superexcited states (HI#) followed by autoionization, dissociation, photodissociation and photoionization processes to form ions. The importance of state interactions in multiphoton-fragmentation processes is evident from the work.

Initial experiences of transapical beating-heart mitral valve repair with a novel artificial chordal implantation device.

BACKGROUND: Severe mitral regurgitation (MR) is associated with progressive heart failure and impairment of survival. Degenerative MR accounts for most MV repair surgeries. Conventional mitral valve repair surgery requires cardiopulmonary bypass and is associated with significant morbidity and risks. Transapical beating-heart mitral valve repair by artificial chordae implantation with transesophageal echocardiography (TEE) guidance has the potential to significantly reduce surgical morbidity. We report the first-in-human experience of degenerative MR repair using a novel artificial chordae implantation device (MitralstitchTM system). METHODS: Ten patients with severe MR underwent transapical artificial chordae implantation using MitralstitchTM system. The procedure was performed through a small left thoracotomy under general anesthesia and TEE guidance. Patients underwent transthoracic echocardiography and other assessments during the follow-up. RESULTS: All 10 patients with an average age of 63.7 ± 9.6 years successfully received transapical artificial chordae implantation. Their MR reduced from severe to none or trace in five patients, mild in five patients before discharge. Five patients received one artificial chordal implantation, four patients received two, and one patient received three and edge-to-edge repair by locking two of them. The safety and efficacy endpoint were achieved in all patients at 1-month follow-up. At 1-year follow-up, six patients had mild MR, three patients had moderate MR, one patient had recurrence of severe MR and underwent surgical repair. CONCLUSIONS: The results of this first-in-human study show safety and feasibility of transapical mitral valve repair using MitralStitch system. Patient selection and technical refinement are crucial to improve the outcomes.

The progress in the classification and treatment of scaphoid nonunion.

Scaphoid fracture is the most common carpal fracture, accounting for 50%-80% of all carpal fractures in the Youngers and manual workers. The nonunion rate of scaphoid fractures was approximately 10-15%. Scaphoid nonunion can lead to wrist deformity, wrist collapse, ischemic necrosis, and traumatic osteoarthritis resulting in the loss of wrist function and seriously influence the patients' lives. Achieving bony union is essential for the treatment of scaphoid nonunion. Although many surgical procedures including various forms of bone grafting have been developed to improve bony union, there is no conclusion about which method is the most effective and optimal. In this review, we provide an overview of the diagnostic, classification and progress in the treatments of scaphoid nonunion fractures.

A Three-Dimensional Finite Element Analysis Model of SAW Torque Sensor with Multilayer Structure.

A three-dimensional finite element analysis model of surface acoustic wave (SAW) torque sensor based on multilayer structure is proposed in this paper. Compared with the traditional saw torque sensor with quartz as piezoelectric substrate, the SAW torque sensor with multilayer structure has the advantages of fast propagation speed and high characteristic frequency. It is a very promising torque sensor, but there is very little related research. In order to successfully develop the sensor, it is essential to understand the propagation characteristics and torque sensing mode of SAW in multilayer structure. Therefore, in this study, we first established a multi-layered finite element analysis model of SAW device based on IDT/128° Y-X lithium niobate/diamond/Si (100). Then, the effects of different film thicknesses on the characteristic frequency, electromechanical coupling coefficient, s parameter, and mechanical quality factor of SAW device without changing the wavelength are analyzed. Then, based on the finite element analysis, a three-dimensional research model of a new SAW torque sensor suitable for small diameter torsion bar (d = 10 mm) is established, and the relationship between saw device deformation and torque under the condition of small torque (±40 Nm) is tested. The shape variable is introduced into the finite element analysis model of multi-layer SAW device. Finally, the relationship between saw torque sensor with multi-layer structure and torque is established by using the deformation relationship, which shows the perfect curve of sensor performance.

Risk factors for postoperative recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery and the association between tricuspid annular circumference and secondary tricuspid regurgitation.

BACKGROUND: To identify the association between tricuspid annular circumference and secondary tricuspid regurgitation and analyze the risk factors of recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery. METHODS: From October 2018 to June 2019, a total of 117 patients receiving concomitant tricuspid annuloplasty within left heart surgery were enrolled. Severity of tricuspid regurgitation was classified as 4 subtypes: normal, mild, moderate and severe. Perioperative data and mid-term outcome were collected. Tricuspid annular circumference (TAC) was measured under cardiac arrest during surgery procedure by cardioplegia. Optimal TAC and TAC index (TAC/body surface area, BSA) cutoffs of significant tricuspid annulus dilatation (moderate and severe) were obtained. Univariable and multivariable logistic regression analyses were performed to identify the risk factors of postoperative recurrent tricuspid regurgitation. The follow up period is 13-19 months (mean 15.5 ± 3.2 months). RESULTS: There was 1 patient was excluded who died after surgery. A total of 116 patients receiving tricuspid annuloplasty were included. Optimal cutoffs of significant tricuspid annulus dilatation were recommended (TAC 11.45 cm, Sensitivity 82.89%, Specificity 73.68%, AUC 0.915; TAC index 7.09 cm/m2, Sensitivity 73.68%, Specificity 85%, AUC 0.825, respectively). Based on findings of multivariable logistic regression, it has been showed that TAC index and postoperative atrial fibrillation were the independent risk factors of recurrent regurgitation after surgery. Optimal TAC index cutoff to predict recurrent tricuspid regurgitation was 7.86 cm/m2 CONCLUSIONS: The severity of secondary tricuspid regurgitation is associated with the tricuspid annular circumference. The cut-offs of significant tricuspid regurgitation (more than moderate) were TAC 11.45 cm and TAC index 7.09 cm/m2, respectively. Clinically, concomitant tricuspid annuloplasty is relative safe and effective. TAC index ≥ 7.86 cm/m2 and postoperative atrial fibrillation are the risk factors of recurrent significant tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.

The B55α subunit of PP2A drives a p53-dependent metabolic adaptation to glutamine deprivation.

Glutamine is an essential nutrient for cancer cell survival and proliferation, yet the signaling pathways that sense glutamine levels remain uncharacterized. Here, we report that the protein phosphatase 2A (PP2A)-associated protein, α4, plays a conserved role in glutamine sensing. α4 promotes assembly of an adaptive PP2A complex containing the B55α regulatory subunit via providing the catalytic subunit upon glutamine deprivation. Moreover, B55α is specifically induced upon glutamine deprivation in a ROS-dependent manner to activate p53 and promote cell survival. B55α activates p53 through direct interaction and dephosphorylation of EDD, a negative regulator of p53. Importantly, the B55α-EDD-p53 pathway is essential for cancer cell survival and tumor growth under low glutamine conditions in vitro and in vivo. This study delineates a previously unidentified signaling pathway that senses glutamine levels as well as provides important evidence that protein phosphatase complexes are actively involved in signal transduction.

Clinical characteristics of concurrent primary aldosteronism and renal artery stenosis: A retrospective case-control study.

Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016.  Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis.  Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.

New Internet-Based Warfarin Anticoagulation Management Approach After Mechanical Heart Valve Replacement: Prospective, Multicenter, Randomized Controlled Trial.

BACKGROUND: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. OBJECTIVE: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. METHODS: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. RESULTS: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). CONCLUSIONS: The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-032949.