Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.

Valve-in-valve implantation to seal post-dilation-induced annular rupture in transcatheter aortic valve replacement.

An 85-year-old woman was admitted to our hospital with severe symptomatic aortic stenosis. Preoperative computed tomography and transesophageal echocardiography (TEE) revealed a type I bicuspid aortic valve.

Long-term outcomes in patients with bicuspid valve stenosis and aortic dilation undergoing transcatheter valve implantation.

BACKGROUND: To date, whether ascending aorta dilation (AAD) should be considered a contraindication for transcatheter aortic valve replacement (TAVR) remains a topic of debate.. OBJECTIVE: The study investigated the clinical outcome of TAVR in patients with bicuspid aortic valve stenosis (BAV-AS) complicated by AAD. METHODS: We included patients with BAV-AS who underwent TAVR between 2012 and 2019. We collected patient perioperative clinical data., tracked clinical outcomes for over four years post-TAVR, and obtained echocardiography images one year postoperatively. The Kaplan-Meier method was employed for analyzing both unadjusted and adjusted survival data, which was compared using the log-rank test. COX regression and nomograms were used to assess the impact of AAD on post-TAVR clinical outcomes in patients with aortic stenosis (AS), with all-cause mortality as the primary clinical endpoint. RESULTS: A total of 111 BAV patients were included in this study. Long-term follow-up showed an increased mortality risk in patients with BAV-AAD (adjusted Kaplan-Meier analysis: P = .02/0.001). Cox correlation analysis indicated that age (OR = 1.137; P = .034), AAD (OR = 3.51; P = .038), and postoperative left ventricular pressure (LVSP) (OR: 0.959; P = .044) were predictive factors for mortality more than four years after TAVR in patients with BAV. The area under the curve of the Nomogram predicting long-term survival for the training set of patients based on the above metrics was 0.845 (95% CI: 0.696-0.994). Short-term cardiac ultrasound follow-up showed a more rapid rate of AA expansion (0.29 [0-0.34] vs. -1 [-3.3-1] mm/month, P = .001) and a smaller proportion of AA diameter reduction (7.1% vs. 53.7%, P = .001) in patients who died. CONCLUSIONS: Patients with BAV-AAD-AS treated with TAVR have an increased risk of long-term mortality, and clinical prediction models, including AAD age and postoperative LVSP, may predict long-term patient survival. CONDENSED ABSTRACT: The study investigated the clinical outcome of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (BAV-AS) complicated by ascending aorta dilation (AAD). Patients with BAV-AAD-AS treated with TAVR have an increased risk of long-term mortality. AAD, age and postoperative LVSP, may predict long-term patient survival. Short-term cardiac ultrasound follow-up showed a more rapid rate of AA expansion and a smaller proportion of AA diameter reduction in patients who died. A high postoperative AAD expansion rate may indicate an adverse clinical outcome. Surgery regimens for tolerable BAV-AADs and can be considered as a treatment option.

[Prdx1 regulates macrophage polarization by maintaining mitochondrial homeostasis].

In order to investigate the role of Prdx1 in macrophage polarization, mouse leukemia cells of monocyte macrophage (RAW264.7) were treated with lipopolysaccharides (LPS)+ interferon gamma (IFNγ) or IL-4 to induce type 1 macrophage (M1) and type 1 macrophage (M2) macrophages, respectively. The Prdx1 gene knockout cells (Prdx1-/-) were used for the study. Flow cytometry was conducted to detect M1/M2 macrophage markers, and ELISA kits were used to measure M1/M2 cytokine levels. Inducible nitric-oxide synthase (iNOS) activity, arginase-1 (Arg-1) activity, and oxidative damage were also assessed. The Seahorse XFe24 Extracellular Flux Analyzer was employed to measure extracellular acidification rate and oxygen consumption rate. The mitochondrial membrane potential was analyzed using the mitochondrial membrane potential dye (JC-1) fluorescent probe, and mitochondrial superoxide was detected through fluorescence staining. Additionally, the impact of adding a mitochondrial reactive oxygen species (ROS) scavenger on RAW264.7 macrophage polarization was examined. The results demonstrated an increase in ROS, hydrogen peroxide, and 8-hydroxy-2 deoxyguanosine (8-OHDG). Cytotoxicity and mitochondrial toxic effects, including mitochondrial superoxide accumulation, decreased adenosine-triphosphate (ATP) production, reduced mitochondrial membrane potential, and decreased mitochondrial DNA copy number, were observed. Furthermore, down-regulation of translocase of inner mitochondrial membrane 23 (TIM23) mitochondrial protein and mitochondrial stress protein heat shock protein 60 (HSP60) was noted. The extra cellular acidification rate (ECAR) in M1 macrophage polarization in RAW264.7 cells was increased, while oxygen consumption rate (OCR) in M2 macrophages was reduced. These findings indicate that Prdx1 knockout in RAW264.7 cells can inhibit M2 macrophage polarization but promote M1 macrophage polarization by impairing mitochondrial function and reducing oxidative phosphorylation.

A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib.

Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.

Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI.

[Research progress on distal interlocking screws of cephalomedullary nails in intertrochanteric fractures].

Objective: To summarize the new research progress in distal interlocking screws of cephalomedullary nails for the treatment of intertrochanteric fractures. Methods: Relevant domestic and foreign literature was extensively reviewed to summarize the static/dynamic types of distal interlocking screw holes, biomechanical studies, clinical studies and application principles, effects on toggling in the cavity, and related complications of distal interlocking screws. Results: The mode of the distal interlocking screw holes can be divided into static and dynamic. Distal interlocking screws play the role of anti-rotation, maintaining femur length, resisting compression stress, increasing torque stiffness, resisting varus stress, etc. The number of the screws directly affects the toggling of the main nail in the cavity. At present, regardless of whether long or short nails are used, distal interlocking screws are routinely inserted in clinical practice. However, using distal interlocking screws can significantly increase the duration of anesthesia and operation, increase fluoroscopy exposure time, surgical blood loss, and incision length. There is a trend of trying not to use distal interlocking screws in recent years. No significant difference is found in some studies between the effectiveness of dynamic and static interlocking for AO/Orthopaedic Trauma Association (AO/OTA) 31-A1/2 fractures. At present, the selection of the number and mode of distal interlocking screws is still controversial. When inserting distal interlocking screws, orthopedists should endeavor to minimize the occurrence of complications concerning miss shot, vascular injuries, local stress stimulation, and peri-implant fractures. Conclusion: Distal interlocking screws are mainly used to prevent rotation. For stable fractures with intact lateral walls, long cephalomedullary nails can be used without distal interlocking screws. For any type of intertrochanteric fractures, distal interlocking screws are required when using short cephalomedullary nails for fixation. Different interlocking modes, the number of interlocking screws, and the application prospects of absorbable interlocking screws may be future research directions.

A novel detection method based on MIRA-CRISPR/Cas13a-LFD targeting the repeated DNA sequence of Trichomonas vaginalis.

BACKGROUND: Trichomonas vaginalis is a protozoan parasite, widely recognized as the most prevalent non-viral sexually transmitted infection (STI) globally. This infection is linked to various complications, including pelvic inflammatory disease, adverse pregnancy outcomes, and an increased risk of acquiring HIV. Current molecular detection methods for T. vaginalis are often costly and technically challenging. METHODS: We developed a novel detection method for T. vaginalis using a multi-enzyme isothermal rapid amplification-clustered regularly interspaced short palindromic repeats (MIRA-CRISPR)/Cas13a-lateral flow device (LFD). This assay targets the repeated DNA sequence (GenBank: L23861.1) of T. vaginalis and is performed at a constant temperature of 37 °C for approximately 1 hour. RESULTS: The detection limit of genomic DNA (gDNA) using our protocol was 1 × 10-4 ng/µl. Specificity was confirmed by the absence of cross-reaction with gDNA from various other microorganisms such as Staphylococcus aureus, Lactobacillus taiwanensis, Escherichia coli, Monilia albicans, Giardia lamblia, or Toxoplasma gondii. Among 30 clinical samples tested, the positive rates of T. vaginalis detection were 33.33% (10/30) by wet mount microscopy, 40% (12/30) by nested polymerase chain reaction (PCR), 40% (12/30) by MIRA-CRISPR/Cas13a-LFD, and 40% (12/30) by the culture method. Compared with the culture method, the gold standard for diagnosing trichomoniasis, wet mount microscopy showed a sensitivity of 83.3% and moderate diagnostic agreement (kappa value = 0.87). Both nested PCR and MIRA-CRISPR/Cas13a-LFD exhibited 100% sensitivity and excellent diagnostic agreement (kappa value = 1). CONCLUSIONS: The MIRA-CRISPR/Cas13a-LFD method is a convenient, rapid, stable, and accurate diagnostic tool for detecting T. vaginalis. This method has the potential to enhance the diagnosis and management of vaginitis, offering a significant improvement over existing diagnostic techniques.

Depression promotes breast cancer progression by regulating amino acid neurotransmitter metabolism and gut microbial disturbance.

INTRODUCTION: Breast cancer (BC) is the most prevalent type of cancer and has the highest mortality among women worldwide. BC patients have a high risk of depression, which has been recognized as an independent factor in the progression of BC. However, the potential mechanism has not been clearly demonstrated. METHODS: To explore the correlation and mechanism between depression and BC progression, we induced depression and tumor in BC mouse models. Depression was induced via chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS). Amino acid (AA) neurotransmitter-targeted metabonomics and gut microbiota 16S rDNA gene sequencing were employed in the mouse model after evaluation with behavioral tests and pathological analysis. RESULTS: The tumors in cancer-depression (CD) mice grew faster than those in cancer (CA) mice, and lung metastasis was observed in CD mice. Metabonomics revealed that the neurotransmitters and plasma AAs in CD mice were dysregulated, namely the tyrosine and tryptophan pathways and monoamine neurotransmitters in the brain. Gut microbiota analysis displayed an increased ratio of Firmicutes/Bacteroides. In detail, the abundance of f_Lachnospiraceae and s_Lachnospiraceae increased, whereas the abundance of o_Bacteroidales and s_Bacteroides_caecimuris decreased. Moreover, the gut microbiota was more closely associated with AA neurotransmitters than with plasma AA. CONCLUSION: Depression promoted the progression of BC by modulating the abundance of s_Lachnospiraceae and s_Bacteroides_caecimuris, which affected the metabolism of monoamine neurotransmitters in the brain and AA in the blood.

Mean compression ratio of a self-expandable valve is associated with the need for pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: The risk and timing of permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR) is still hard to predict. We aimed to analyze the relationship between the compression ratio of a self-expandable valve (SEV) and the need for PPMI after TAVR. METHODS: A total of 106 patients who were implanted with the VitaFlow transcatheter aortic valve system and for whom complete imaging information was available were included in this retrospective cohort study. Eight lines perpendicular to the long axis of the SEV were drawn (the top and bottom of the SEV and the intersection of each row of wires) for measurement purposes. The compression ratio was calculated as 1 - (in vivo meridian/in vitro meridian) and compared between patients undergoing and those not undergoing PPMI after adjusting for implantation depth. Multivariable logistic regression and Cox proportional hazards models were used to assess factors associated with the risk and timing of the need for PPMI. RESULTS: Fifteen (14.2%) patients underwent PPMI after TAVR. Patients with a higher mean compression ratio (20%, odds ratio [OR] = 214.82; p < 0.001) and prior right bundle branch block (OR = 51.77; p = 0.015) had a higher risk of the need for PPMI after TAVR. These two factors were also associated with the timing of PPMI, according to the Cox proportional hazards model. CONCLUSIONS: The compression ratio of the SEV was positively associated with the risk of PPMI after TAVR, and the association was most significant in the annular and supravalvular planes. The compression ratio may also affect the time to PPMI.

How much of the superolateral femoral neck should be removed in intramedullary nail fixation for intertrochanteric fracture?

The objective of this study was to measure how much of the superolateral femoral neck should be removed to reduce the incidence of wedge effect. Simulating surgery: Computed Tomography images of 131 intertrochanteric fracture patients were included, three-dimensionally reconstructed, virtually reduced and implanted with Proximal Femoral Nail Antirotation blade-Ⅱ(PFNA-Ⅱ) nail. The antero-posterior length and media-lateral width of the intersection between superolateral femoral neck and PFNA-Ⅱ nail were measured. Retrospective study: The pre- and postoperative CT of 30 patients were collected. The average varus angle of the neck-shaft angle and the correlation between the angles and the difference in the actual and estimated width of the fragments removed were measured. Models of 108 patient were selected for analysis. The average antero-posterior length and media-lateral width were 14.46 mm (14.00-14.93 mm) and 9.33 mm (8.79-9.87 mm), respectively. The AO/OTA classification was not significantly associated with the outcome, but the gender was. In the retrospective study, the mean value of the varus angles was -4.58° (SE = 6.85°), and the difference of width was strongly positively correlated with the varus angle with a correlation coefficient of 0.698. Results obtained in this study can improve the understanding of this region and help surgeons to make appropriate preoperative planning to reduce the incidence of wedge effect. Retrospective study provided effective proof of the reliability of this study.

Discovery of novel harmine derivatives as GSK-3ß/DYRK1A dual inhibitors for Alzheimer's disease treatment.

Multitarget-directed ligands (MTDLs) have recently attracted significant interest due to their superior effectiveness in multifactorial Alzheimer's disease (AD). Combined inhibition of two important AD targets, glycogen synthase kinase-3ß (GSK-3ß) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), may be a breakthrough in the treatment of AD. Based on our previous work, we have designed and synthesized a series of novel harmine derivatives, investigated their inhibition of GSK-3ß and DYRK1A, and evaluated a variety of biological activities. The results of the experiments showed that most of these compounds exhibited good activity against GSK-3ß and DYRK1A in vitro. ZLQH-5 was selected as the best compound due to the most potent inhibitory effect against GSK-3ß and DYRK1A. Molecular docking studies demonstrated that ZLQH-5 could form stable interactions with the ATP binding pocket of GSK-3ß and DYRK1A. In addition, ZLQH-5 showed low cytotoxicity against SH-SY5Y and HL-7702, good blood-brain barrier permeability, and favorable pharmacokinetic properties. More importantly, ZLQH-5 also attenuated the tau hyperphosphorylation in the okadaic acid SH-SY5Y cell model. These results indicated that ZLQH-5 could be a promising dual-target drug candidate for the treatment of AD.

When NIPT meets WES, prenatal diagnosticians face the dilemma: genetic etiological analysis of 2,328 cases of NT thickening and follow-up of pregnancy outcomes.

Objective: To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or diagnostic action with a NT thickening of 95th percentile-3.50 mm. Methods: A retrospective analysis of 2,328 pregnancies with NT ≥ 95th percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, or cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, and cord blood), and real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), chromosome microarray analysis (CMA), or whole exome sequencing (WES) were provided to identify genetic etiologies. Results: In this study, the incidence of chromosomal defects increased with NT thickness. When NT ≥ 6.5 mm, 71.43% were attributed to genetic abnormalities. The 994 gravidas with fetal NT thickening underwent short tandem repeat (STR), CS, and CMA. In 804 fetuses with normal karyotypes, CMA detected 16 (1.99%) extra pathogenic or likely pathogenic copy number variations (CNVs). The incremental yield of CMA was only 1.16% (3/229) and 3.37% (10/297) in the group with NT 95th percentile-2.99 mm and NT 3.0-3.49 mm, separately. Among the 525 gravidas with fetal NT thickening who underwent STR, CMA, and WES, the incremental yield of WES was 4.09% (21/513). In the group of NT 95th percentile-2.99 mm, there were no additional single-nucleotide variations (SNVs) detected in WES, while in 143 cases with NT of 3.0-3.49 mm, the incremental yield of WES was 5.59% (8/143). Conclusion: In the group of NT 95th percentile-3.0 mm, since chromosomal aneuploidy and chromosomal copy number variation were the primary causes and the additional contribution of CMA and WES was not significant, we recommend NIPT-Plus for pregnant women with a NT thickening of 95th percentile-3.0 mm first. In addition, comprehensive prenatal genetic testing involving CMA and WES can benefit pregnancies with NT thickening of 3.0-3.49 mm.

Advances in application of novel magnetic resonance imaging technologies in liver disease diagnosis.

Liver disease is a major health concern globally, with high morbidity and mor-tality rates. Precise diagnosis and assessment are vital for guiding treatment approaches, predicting outcomes, and improving patient prognosis. Magnetic resonance imaging (MRI) is a non-invasive diagnostic technique that has been widely used for detecting liver disease. Recent advancements in MRI technology, such as diffusion weighted imaging, intravoxel incoherent motion, magnetic resonance elastography, chemical exchange saturation transfer, magnetic resonance spectroscopy, hyperpolarized MR, contrast-enhanced MRI, and ra-diomics, have significantly improved the accuracy and effectiveness of liver disease diagnosis. This review aims to discuss the progress in new MRI technologies for liver diagnosis. By summarizing current research findings, we aim to provide a comprehensive reference for researchers and clinicians to optimize the use of MRI in liver disease diagnosis and improve patient prognosis.

Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs.

Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance.

A prediction model for permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: This study aims to develop a post-procedural risk prediction model for permanent pacemaker implantation (PPMI) in patients treated with transcatheter aortic valve replacement (TAVR). METHODS: 336 patients undergoing TAVR at a single institution were included for model derivation. For primary analysis, multivariate logistic regression model was used to evaluate predictors and a risk score system was devised based on the prediction model. For secondary analysis, a Cox proportion hazard model was performed to assess characteristics associated with the time from TAVR to PPMI. The model was validated internally via bootstrap and externally using an independent cohort. RESULTS: 48 (14.3%) patients in the derivation set had PPMI after TAVR. Prior right bundle branch block (RBBB, OR: 10.46; p < 0.001), pre-procedural aortic valve area (AVA, OR: 1.41; p = 0.004) and post- to pre-procedural AVA ratio (OR: 1.72; p = 0.043) were identified as independent predictors for PPMI. AUC was 0.7 and 0.71 in the derivation and external validation set. Prior RBBB (HR: 5.07; p < 0.001), pre-procedural AVA (HR: 1.33; p = 0.001), post-procedural AVA to prosthetic nominal area ratio (HR: 0.02; p = 0.039) and post- to pre-procedural troponin-T difference (HR: 1.72; p = 0.017) are independently associated with time to PPMI. CONCLUSIONS: The post-procedural prediction model achieved high discriminative power and accuracy for PPMI. The risk score system was constructed and validated, providing an accessible tool in clinical setting regarding the Chinese population.

Discrete unified gas kinetic scheme for continuum compressible flows.

In this paper, a discrete unified gas kinetic scheme (DUGKS) is proposed for continuum compressible gas flows based on the total energy kinetic model [Guo et al., Phys. Rev. E 75, 036704 (2007)1539-375510.1103/PhysRevE.75.036704]. The proposed DUGKS can be viewed as a special finite-volume lattice Boltzmann method for the compressible Navier-Stokes equations in the double distribution function formulation, in which the mass and momentum transport are described by the kinetic equation for a density distribution function (g), and the energy transport is described by the other one for an energy distribution function (h). To recover the full compressible Navier-Stokes equations exactly, the corresponding equilibrium distribution functions g^{eq} and h^{eq} are expanded as Hermite polynomials up to third and second orders, respectively. The velocity spaces for the kinetic equations are discretized according to the seventh and fifth Gauss-Hermite quadratures. Consequently, the computational efficiency of the present DUGKS can be much improved in comparison with previous versions using more discrete velocities required by the ninth Gauss-Hermite quadrature.

Impact of current targeted drug therapy on the prognosis of Eisenmenger syndrome: A large-scale retrospective analysis.

BACKGROUND: Data regarding the prognosis of Eisenmenger syndrome (ES) and effect of targeted drugs are limited. This study aimed to analyze the prognosis and impact of targeted drug therapy on the survival rate of patients with ES in the Chinese population. METHODS: The data of patients with ES referred to our hospital between January 2010 and December 2020 were retrospectively analyzed. Data included baseline demographics, echocardiographic parameters, and clinical diagnoses. All patients were followed up via telephone interviews in February 2022. The primary endpoint was mortality. RESULTS: Overall, 1,021 patients with ES were included. The 1-, 3-, 5-, 7-, 10-, and 12-year survival rates were 91.6%, 84.2%, 80.7%, 73.8%, 71.4%, and 69.9%, respectively. Patients with atrial septal defects had the best prognosis than those with ventricular septal defects, patent ductus arteriosus, and complex congenital heart disease (CHD) (P < 0.0001). Patients who visited between 2016 and 2020 received increased targeted drug therapy and had a better prognosis than those who visited between 2010 and 2015 (all P < 0.05). Cox regression analysis revealed age, pulmonary arterial systolic pressure, post-tricuspid shunt CHD, targeted drugs, and year of the first hospital visit to be predictors of death (P < 0.05). CONCLUSIONS: Survival rates associated with an increased use of combined targeted drugs significantly improved in patients with ES. However, numerous factors that predict increased mortality remain to be elucidated.

Consistent lifting relations for the initialization of total-energy double-distribution-function kinetic models.

A lifting relation connecting the distribution function explicitly with the hydrodynamic variables is necessary for the Boltzmann equation-based mesoscopic approaches in order to correctly initialize a nonuniform hydrodynamic flow. We derive two lifting relations for Guo et al.'s total-energy double-distribution-function (DDF) kinetic model [Z. L. Guo et al., Phys. Rev. E 75, 036704 (2007)1539-375510.1103/PhysRevE.75.036704], one from the Hermite expansion of the conserved and nonconserved moments, and the second from the O(τ) Chapman-Enskog (CE) approximation of the Maxwellian exponential equilibrium. While both forms are consistent to the compressible Navier-Stokes-Fourier system theoretically, we stress that the latter may introduce numerical oscillations under the recently optimized discrete velocity models [Y. M. Qi et al., Phys. Fluids 34, 116101 (2022)10.1063/5.0120490], namely a 27 discrete velocity model of the seventh-order Gauss-Hermite quadrature (GHQ) accuracy (D3V27A7) for the velocity field combined with a 13 discrete velocity model of the fifth-order GHQ accuracy (D3V13A5) for the total energy. It is shown that the Hermite-expansion-based lifting relation can be alternatively derived from the latter approach using the truncated Hermite-polynomial equilibrium. Additionally, a relationship between the order of CE expansions and the truncated order of Hermite equilibria is developed to determine the minimal order of a Hermite equilibria required to recover any multiple-timescale macroscopic system. Next, three-dimensional compressible Taylor-Green vortex flows with different initial conditions and Ma numbers are simulated to demonstrate the effectiveness and potential issues of these lifting relations. The Hermite-expansion-based lifting relation works well in all cases, while the Chapman-Enskog-expansion-based lifting relation may produce numerical oscillations and a theoretical model is developed to predict such oscillations. Furthermore, the corresponding lifting relations for Qi et al.'s total energy DDF model [Y. M. Qi et al., Phys. Fluids 34, 116101 (2022)10.1063/5.0120490] are derived, and additional simulations are performed to illustrate the generality of our approach.