Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Neighborhood Racial and Ethnic Segregation and the Risk of Dementia in Older Adults Living with Kidney Failure.

BACKGROUND: Dementia disproportionately impacts older minoritized adults with kidney failure. To better understand the mechanism of this disparity, we studied the role of racial and ethnic segregation (segregation hereafter), a form of structural racism recently identified as a mechanism in numerous other health disparities. METHODS: We identified 901,065 older adults (age ≥55) with kidney failure from 2003 to 2019 using the United States Renal Data System (USRDS). We quantified dementia risk across tertiles of residential neighborhood segregation score using cause-specific hazard models, adjusting for individual and neighborhood-level factors. We included an interaction term to quantify the differential effect of segregation on dementia diagnosis by race and ethnicity. RESULTS: We identified 79,851 older adults with kidney failure diagnosed with dementia between 2003 and 2019 (median follow-up: 2.2 years). Compared to those in low-segregation neighborhoods, older adults with kidney failure in high-segregation neighborhoods had a 1.63-fold (95% confidence interval (CI):1.60-1.66) higher risk of dementia diagnosis, an association that differed by race and ethnicity (Asian: adjusted hazard ratio [aHR]=1.26, 95%CI:1.15-1.38; Black: aHR=1.66, 95%CI:1.61-1.71; Hispanic: aHR=2.05, 95%CI:1.93-2.18; White: aHR=1.59, 95%CI:1.55-1.64;Pinteraction<0.001). Notably, older Asian (aHR=1.76, 95%CI:1.64-1.89), Black (aHR=2.65, 95%CI:2.54-2.77), Hispanic (aHR=2.15, 95%CI:2.04-2.26), and White (aHR=2.20, 95%CI:2.09-2.31) adults with kidney failure residing in minority-predominant high-segregation neighborhoods had a higher risk of dementia diagnosis compared to older White adults with kidney failure in White-predominant high-segregation neighborhoods. Moreover, older adults with kidney failure receiving care at dialysis facilities located in high-segregation neighborhoods also experienced a higher risk of dementia diagnosis (aHR=1.53, 95%CI:1.50-1.56); this association differed by race and ethnicity (Pinteraction<0.001). CONCLUSIONS: Residing in or receiving care at dialysis facilities located in high-segregation neighborhoods was associated with a higher risk of dementia diagnosis among older individuals with kidney failure, particularly minoritized individuals.

GHA-DenseNet prediction and diagnosis of malignancy in femoral bone tumors using magnetic resonance imaging.

Background and objective: Due to their aggressive nature and poor prognosis, malignant femoral bone tumors present considerable hurdles. Early treatment commencement is essential for enhancing vital and practical outcomes. In this investigation, deep learning algorithms will be used to analyze magnetic resonance imaging (MRI) data to identify bone tumors that are malignant. Methodology: The study cohort included 44 patients, with ages ranging from 17 to 78 (22 women and 22 males). To categorize T1 and T2 weighted MRI data, this paper presents an improved DenseNet network model for the classification of bone tumor MRI, which is named GHA-DenseNet. Based on the original DenseNet model, the attention module is added to solve the problem that the deep convolutional model can reduce the loss of key features when capturing the location and content information of femoral bone tumor tissue due to the limitation of local receptive field. In addition, the sparse connection mode is used to prune the connection mode of the original model, so as to remove unnecessary and retain more useful fast connection mode, and alleviate the overfitting problem caused by small dataset size and image characteristics. In a clinical model designed to anticipate tumor malignancy, the utilization of T1 and T2 classifier output values, in combination with patient-specific clinical information, was a crucial component. Results: The T1 classifier's accuracy during the training phase was 92.88% whereas the T2 classifier's accuracy was 87.03%. Both classifiers demonstrated accuracy of 95.24% throughout the validation phase. During training and validation, the clinical model's accuracy was 82.17% and 81.51%, respectively. The clinical model's receiver operating characteristic (ROC) curve demonstrated its capacity to separate classes. Conclusions: The proposed method does not require manual segmentation of MRI scans because it makes use of pretrained deep learning classifiers. These algorithms have the ability to predict tumor malignancy and shorten the diagnostic and therapeutic turnaround times. Although the procedure only needs a little amount of radiologists' involvement, more testing on a larger patient cohort is required to confirm its efficacy.

A Mammography-Based Radiomic Nomogram for Predicting Malignancy in Breast Suspicious Microcalcifications.

RATIONALE AND OBJECTIVES: Preoperative accurate identification of benign and malignant breast lesions is vital for patients to achieve individualized treatment. This study aimed to develop and validate a mammography-based radiomic nomogram for predicting malignant risk of breast suspicious microcalcifications (MCs). MATERIALS AND METHODS: 496 patients with histologically confirmed breast suspicious MCs were randomly divided into the training set (n = 346) and validation set (n = 150). Radiomics features was extracted from the craniocaudal and mediolateral oblique images. Least absolute shrinkage and selection operator algorithm were used to select radiomics features, then radiomics score (Rad-score) was calculated. Univariate analysis was used to identify malignant MCs-related clinical independent risk factors. Multivariate logistic regression was used to establish a clinical-radiomics model by incorporating Rad-score and clinic factors. A nomogram was developed to visualize the clinical-radiomics model. The receiver operating characteristic curve, calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. RESULTS: The Rad-score was consisted of 29 optimal radiomics features. We developed a nomogram by incorporating Rad-score, menopause status, MCs morphology and distribution, the area under the curve value of the combined model was 0.926(95% confidence interval [CI]: 0.878-0.975) for the validation set. The calibration curves and DCA indicated the combined model had favorable calibration and clinical utility. CONCLUSION: The combined model could be considered as a potential imaging marker to predict malignant risk of breast suspicious MCs.

Age Disparities in Access to First and Repeat Kidney Transplantation.

BACKGROUND: Evidence suggests that older patients are less frequently placed on the waiting list for kidney transplantation (KT) than their younger counterparts. The trends and magnitude of this age disparity in access to first KT and repeat KT (re-KT) remain unclear. METHODS: Using the US Renal Data System, we identified 2 496 743 adult transplant-naive dialysis patients and 110 338 adult recipients with graft failure between 1995 and 2018. We characterized the secular trends of age disparities and used Cox proportional hazard models to compare the chances of listing and receiving first KT versus re-KT by age (18-64 y versus ≥65 y). RESULTS: Older transplant-naive dialysis patients were less likely to be listed (adjusted hazard ratio [aHR] = 0.18; 95% confidence interval [CI], 0.17-0.18) and receive first KT (aHR = 0.88; 95% CI, 0.87-0.89) compared with their younger counterparts. Additionally, older patients with graft failure had a lower chance of being listed (aHR = 0.40; 95% CI, 0.38-0.41) and receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.81). The magnitude of the age disparity in being listed for first KT was greater than that for re-KT ( Pinteraction < 0.001), and there were no differences in the age disparities in receiving first KT or re-KT ( Pinteraction = 0.13). Between 1995 and 2018, the age disparity in listing for first KT reduced significantly ( P < 0.001), but the age disparities in re-KT remained the same ( P = 0.16). CONCLUSIONS: Age disparities exist in access to both first KT and re-KT; however, some of this disparity is attenuated among older adults with graft failure. As the proportion of older patients with graft failure rises, a better understanding of factors that preclude their candidacy and identification of appropriate older patients are needed.

Association of Postoperative Delirium With Incident Dementia and Graft Outcomes Among Kidney Transplant Recipients.

BACKGROUND: Kidney transplant (KT) recipients have numerous risk factors for delirium, including those shared with the general surgical population (eg, age and major surgery) and transplant-specific factors (eg, neurotoxic immunosuppression medications). Evidence has linked delirium to long-term dementia risk in older adults undergoing major surgery. We sought to characterize dementia risk associated with post-KT delirium. METHODS: Using the United States Renal Data System datasets, we identified 35 800 adult first-time KT recipients ≥55 y. We evaluated risk factors for delirium using logistic regression. We evaluated the association between delirium and incident dementia (overall and by subtype: Alzheimer's, vascular, and other/mixed-type), graft loss, and death using Fine and Gray's subhazards models and Cox regression. RESULTS: During the KT hospitalization, 0.9% of recipients were diagnosed with delirium. Delirium risk factors included age (OR = 1.40, 95% CI, 1.28-1.52) and diabetes (OR = 1.38, 95% CI, 1.10-1.73). Delirium was associated with higher risk of death-censored graft loss (aHR = 1.52, 95% CI, 1.12-2.05) and all-cause mortality (aHR = 1.53, 95% CI, 1.25-1.89) at 5 y post-KT. Delirium was also associated with higher risk of dementia (adjusted subhazard ratio [aSHR] = 4.59, 95% CI, 3.48-6.06), particularly vascular dementia (aSHR = 2.51, 95% CI, 1.01-6.25) and other/mixed-type dementia (aSHR = 5.58, 95% CI, 4.24-7.62) subtypes. The risk of all-type dementia associated with delirium was higher for younger recipients aged between 55 and 64 y ( Pinteraction = 0.01). CONCLUSIONS: Delirium is a strong risk factor for subsequent diagnosis of dementia among KT recipients, particularly those aged between 55 and 64 y at the time of transplant. Patients experiencing posttransplant delirium might benefit from early interventions to enhance cognitive health and surveillance for cognitive impairment to enable early referral for dementia care.

Radiomic Nomogram for Predicting Axillary Lymph Node Metastasis in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: The detection of axillary lymph node metastasis (ALNM) in patients with breast cancer is a crucial determinant in the decision-making process for axillary surgery and potential therapies. The objective of this study was to develop and validate a radiomics nomogram that integrates radiomics features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with clinical factors to predict ALNM in patients with breast cancer. MATERIALS AND METHODS: A total of 177 patients with breast cancer were randomly divided into a training set (n = 123) and a validation set (n = 54) using a 7:3 ratio. From the DCE-MRI images, 2818 radiomics features were extracted from the primary tumor and axillary lymph node (ALN). Subsequently, optimal features were selected through the least absolute shrinkage and selection operator algorithm to construct the Radscore. Clinical factors were identified using univariate logistic regression analysis and included in a multivariate logistic regression analysis. Using the Radscore and clinical factors, a radiomics nomogram was developed using the Support Vector Machine method. The predicting efficacy of our model was visually appraised utilizing a receiver operator characteristic (ROC) curve, while its clinical application and predictive accuracy were assessed through decision curve analysis (DCA) and calibration curves, respectively. RESULTS: The results revealed Ki67, multifocality, and MRI-reported ALN status as independent risk factors for ALNM. The radiomics nomogram demonstrated good calibration and discrimination with areas under the ROC curve of 0.92 (95% confidence interval [CI], 0.88-0.97) in the training set and 0.90 (95% CI, 0.72-0.90) in the validation set. DCA revealed the clinical usefulness of the radiomics nomogram. CONCLUSION: The DCE-MRI-based radiomics nomogram is a reliable tool for assessing ALNM in patients with breast cancer.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. RESEARCH QUESTION: What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH?. STUDY DESIGN AND METHODS: A total of 135 age- and BMI-matched patients with PAH and 49 control subjects were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. RESULTS: Compared with the control subjects, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8 mL vs 3.5 ± 0.7 mL; P = .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear = .001), right ventricular end-diastolic volume index (P < .001), right ventricular cardiac output (P = .003), N-terminal pro-brain natriuretic peptide (P = .030), and the risk of clinical worsening (P = .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95% CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95% CI, 1.5-30.2) for high-level EATV in patients with PAH. INTERPRETATION: Patients with PAH had a decreased EATV compared with control subjects. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis.

OBJECTIVE: The purpose of this study was to explore the expression level of SNHG4 in patients with COPD and its diagnostic value in COPD, to probe the biological function of SNHG4 in COPD at the cellular level, and to reveal the interaction between SNHG4 and miR-144-3p/EZH2 axis. METHODS: The serum levels of SNHG4, miR-144-3p and EZH2 in healthy people and patients with COPD were detected by RT-qPCR. The diagnostic value of SNHG4 in COPD was evaluated by ROC curve. Pearson method was chosen to estimate the correlation between SNHG4 and clinical indicators in patients with COPD. Cigarette smoke extract (CSE) was obtained, and Beas-2B cells were exposed with 2% CSE to establish an inflammatory cell model of COPD in vitro. MTT assay was used to detect cell viability, flow cytometry was used to evaluate cell apoptosis, and ELISA was performed to detect inflammatory cytokines. Dual-luciferase reporting assay was carried out to verify the targeting of lncRNA-miRNA or miRNA-mRNA. RESULTS: (1) The expression of SNHG4 is decreased in patients with COPD, and the expression level in acute exacerbation COPD was lower than that in stable COPD. SNHG4 demonstrated high diagnostic accuracy in distinguishing between stable and acute exacerbation COPD. (2) The expression of SNHG4 was decreased in CSE-induced Beas-2B cells, and overexpression of SNHG4 was beneficial to alleviate CSE-induced apoptosis and inflammation. (3) The expression of miR-144-3p is up-regulated in patients with COPD and CSE-induced Beas-2B cells. MiR-144-3p has a targeting relationship with SNHG4, which is negatively regulated by SNHG4. Overexpression of miR-144-3p could counteract the beneficial effects of increased SNHG4 on CSE-induced cells. (4) The expression of EZH2 is reduced in patients with COPD and CSE-induced Beas-2B cells. Bioinformatics analysis and luciferase reporter gene confirmed that EZH2 is the downstream target gene of miR-144-3p and is negatively regulated by miR-144-3p. CONCLUSION: The expression of SNHG4 decreased in patients with COPD, and it may promote the progression of COPD by inhibiting the viability, promoting apoptosis and inflammatory response of bronchial epithelial cells via regulating the miR-144-3p/EZH2 axis.

Evolving Trends in Kidney Transplant Outcomes Among Older Adults: A Comparative Analysis Before and During the COVID-19 Pandemic.

Background: Advancements in medical technology, healthcare delivery, and organ allocation resulted in improved patient/graft survival for older (age ≥65) kidney transplant (KT) recipients. However, the recent trends in these post-KT outcomes are uncertain in light of the mounting burden of cardiovascular disease, changing kidney allocation policies, heterogeneity in candidates' risk profile, and the coronavirus disease 2019 pandemic. Thus, we examined secular trends in post-KT outcomes among older and younger KT recipients over the last 3 decades. Methods: We identified 73 078 older and 378 800 younger adult (aged 18-64) recipients using Scientific Registry of Transplant Recipients (1990-2022). KTs were grouped into 6 prepandemic eras and 1 postpandemic-onset era. Kaplan-Meier and Cox proportional hazards models were used to examine temporal trends in post-KT mortality and death-censored graft failure. Results: From 1990 to 2022, a 19-fold increase in the proportion of older KT recipients was observed compared to a 2-fold increase in younger adults despite a slight decline in the absolute number of older recipients in 2020. The mortality risk for older recipients between 2015 and March 14, 2020, was 39% (adjusted hazard ratio [aHR] = 0.61, 95% confidence interval [CI], 0.50-0.75) lower compared to 1990-1994, whereas that for younger adults was 47% lower (aHR = 0.53, 95% CI, 0.48-0.59). However, mortality risk during the pandemic was 25% lower (aHR = 0.75, 95% CI, 0.61-0.93) in older adults and 37% lower in younger adults (aHR = 0.63, 95% CI, 0.56-0.70) relative to 1990-1994. For both populations, the risk of graft failure declined over time and was unaffected during the pandemic relative to the preceding period. Conclusions: The steady improvements in 5-y mortality and graft survival were disrupted during the pandemic, particularly among older adults. Specifically, mortality among older adults reflected rates seen 20 y prior.

Suberoylanilide hydroxamic acid upregulates reticulophagy receptor expression and promotes cell death in hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common clinical condition with a poor prognosis and few effective treatment options. Potent anticancer agents for treating HCC must be identified. Epigenetics plays an essential role in HCC tumorigenesis. Suberoylanilide hydroxamic acid (SAHA), the most common histone deacetylase inhibitor agent, triggers many forms of cell death in HCC. However, the underlying mechanism of action remains unclear. Family with sequence similarity 134 member B (FAM134B)-induced reticulophagy, a selective autophagic pathway, participates in the decision of cell fate and exhibits anticancer activity. This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death. AIM: To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death. METHODS: The viability, apoptosis, cell cycle, migration, and invasion of SAHA-treated Huh7 and MHCC97L cells were measured. Proteins related to the reticulophagy pathway, mitochondria-endoplasmic reticulum (ER) contact sites, intrinsic mitochondrial apoptosis, and histone acetylation were quantified using western blotting. ER and lysosome colocalization, and mitochondrial Ca2+ levels were characterized via confocal microscopy. The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization. Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region. RESULTS: After SAHA treatment, the proliferation of Huh7 and MHCC97L cells was significantly inhibited, and the migration and invasion abilities were greatly blocked in vitro. This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner. Following treatment with SAHA, ER-phagy was activated, thereby triggering autophagy-mediated cell death of HCC cells in vitro. Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region. Further, SAHA disturbed the Ca2+ homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells. Additionally, SAHA decreased the mitochondrial membrane potential levels, thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro. CONCLUSION: SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway, thereby enhancing HCC cell death.

Analysis of relationship between P wave dispersion and diagnosis of pulmonary arterial hypertension and risk stratification.

BACKGROUND: The aim of this study was to measure the P-wave dispersion(PWD) in the ECG of patients with pulmonary arterial hypertension(PAH). METHODS: A total of 103 PAH patients were collected, including 55 patients related with congenital heart disease(CHD) and 44 patients with idiopathic pulmonary arterial hypertension(IPAH). In addition, 30 CHD patients without PAH (nPAH-CHD group) and 30 healthy controls (HCG group) were collected as control. Patients in the PAH group were categorized into the low-risk group (30 cases), moderate-risk group (53 cases) and high-risk group (20 cases), followed by comparison of PWD difference between groups. The ROC curve was used to evaluate the diagnostic efficacy of PWD on PAH-CHD and IPAH. RESULTS: The levels of PWD and maximum P wave duration(Pmax) in PAH-CHD and IPAH group were significantly higher than those in nPAH-CHD and HCG group (P < 0.05). PWD level was positively correlated with right ventricular end-diastolic diameter(RVD), right atrial end-systolic diameter(RAS), mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance(PVR)(r = 0.407, 0.470, 0.477, 0.423, P < 0.001), and was negatively correlated with systolic displacement of tricuspid valve annulus(TAPSE) level (r = -0.551, P < 0.001). After risk quantification in 103 PAH patients, we found that PWD was significantly different among the low-risk, moderate-risk and high-risk groups (43.89 ± 9.91 vs. 51.29 ± 6.61, 62.15 ± 10.44, P < 0.001). CHD-PAH and IPAH were identified by PWD with a cut off value of 41.5 ms (P < 0.001), and a cut off value of 41.45 ms (P < 0.001), respectively. CONCLUSIONS: PWD might be an effective ECG indicator for PAH, which might be used as a relatively economical indicator for PAH patients to assist in early diagnosis, disease severity assessment and prognosis evaluation.

Evaluating the role of serum uric acid in the risk stratification and therapeutic response of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD).

Background: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease that negatively impacts quality of life, exercise capacity, and mortality. This study sought to investigate the relationship between serum uric acid (UA) level and the disease severity and treatment response of patients with PAH and congenital heart disease (PAH-CHD). Methods: This study included 225 CHD patients and 40 healthy subjects. Serum UA was measured in all patients, and UA levels and haemodynamic parameters were re-evaluated in 20 patients who had received PAH-specific drug treatment for at least 7 ± 1 month. Results: Serum UA levels were significantly higher in PAH-CHD patients than in CHD patients with a normal pulmonary artery pressure and normal subjects (347.7 ± 105.7 µmol/L vs. 278.3 ± 84.6 µmol/L; 347.7 ± 105.7 µmol/L vs. 255.7 ± 44.5 µmol/L, p < 0.05). UA levels in the intermediate and high risk groups were significantly higher than those in the low-risk group (365.6 ± 107.8 µmol/L vs. 311.2 ± 82.8 µmol/L; 451.6 ± 117.6 µmol/L vs. 311.2 ± 82.8 µmol/L, p < 0.05). Serum UA levels positively correlated with mean pulmonary arterial pressure, WHO functional class, pulmonary vascular resistance, and NT-proBNP (r = 0.343, 0.357, 0.406, 0.398; p < 0.001), and negatively with mixed venous oxygen saturation (SvO2) and arterial oxygen saturation (SaO2) (r = -0.293, -0.329; p < 0.001). UA significantly decreased from 352.7 ± 97.5 to 294.4 ± 56.8 µmol/L (p = 0.001) after PAH-specific drug treatment for at least 6 months, along with significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance and increases in cardiac index and mixed SvO2. Conclusion: Serum UA can be used as a practical and economic biomarker for risk stratification and the evaluation of PAH-specific drug treatment effects for patients with PAH-CHD.

Differential expression spectrum and targeted gene prediction of tRNA-derived small RNAs in idiopathic pulmonary arterial hypertension.

Background: Idiopathic pulmonary arterial hypertension (PAH) is a potentially fatal pulmonary vascular disease with an extremely poor natural course. The limitations of current treatment and the unclear etiology and pathogenesis of idiopathic PAH require new targets and avenues of exploration involved in the pathogenesis of PAH. tRNA-derived small RNAs (tsRNAs), a new type of small non-coding RNAs, have a significant part in the progress of diverse diseases. However, the potential functions behind tsRNAs in idiopathic PAH remain unknown. Methods: Small RNA microarray was implemented on three pairs of plasma of idiopathic PAH patients and healthy controls to investigate and compare tsRNAs expression profiles. Validation samples were used for real-time polymerase chain reaction (Real-time PCR) to verify several dysregulated tsRNAs. Bioinformatic analysis was adopted to determine potential target genes and mechanisms of the validated tsRNAs in PAH. Results: Microarray detected 816 statistically significantly dysregulated tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated in PAH. Eight validated tsRNAs in the results of Real-time PCR were concordant with the small RNA microarray: four upregulated (tRF3a-AspGTC-9, 5'tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulated (5'tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1). The Gene Ontology analysis has shown that the verified tsRNAs are related to cellular macromolecule metabolic process, regulation of cellular process, and regulation of cellular metabolic process. It is disclosed that potential target genes of verified tsRNAs are widely involved in PAH pathways by Kyoto Encyclopedia of Genes and Genomes. Conclusion: This study investigated tsRNA profiles in idiopathic PAH and found that the dysregulated tsRNAs may become a novel type of biomarkers and possible targets for PAH.

Morphology and Ultrastructure of the Female Reproductive Apparatus of an Asexual Strain of the Endoparasitoid Meteorus pulchricornis (Wesmael) (Hymenoptera, Braconidae).

Meteorus pulchricornis (Wesmael) is a solitary endoparasitoid of lepidopteran pests and a good candidate for the control of Spodoptera frugiperda. To elucidate the structure of the female reproductive apparatus, which may play a role in facilitating successful parasitism, we presented the description of the morphology and ultrastructure of the whole female reproductive system in a thelytokous strain of M. pulchricornis. Its reproductive system includes a pair of ovaries without specialized ovarian tissues, a branched venom gland, a venom reservoir, and a single Dufour gland. Each ovariole contains follicles and oocytes at different stages of maturation. A fibrous layer, possibly an egg surface protector, coats the surface of mature eggs. The venom gland consists of secretory units (including secretory cells and ducts) with abundant mitochondria, vesicles and end apparatuses in the cytoplasm, and a lumen. The venom reservoir is comprised of a muscular sheath, epidermal cells with few end apparatuses and mitochondria, and a large lumen. Furthermore, venosomes are produced by secretory cells and delivered into the lumen via the ducts. As a result, myriad venosomes are observed in the venom gland filaments and the venom reservoir, suggesting that they may function as a parasitic factor and have important roles in effective parasitism.

Differences in right ventricular function and response to targeted therapy between patients with IPAH and PAH-CHD.

Background and aims: Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disorder characterized by elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Right heart failure is a life-threatening complication of PAH and predicts a poor prognosis. PAH associated with congenital heart disease (PAH-CHD) and idiopathic PAH (IPAH) are two prevalent PAH subtypes in China. In this section, we set out to explore baseline right ventricular (RV) function and its response to targeted agents between IPAH and PAH-CHD. Methods and results: Consecutive patients diagnosed with IPAH or PAH-CHD by right heart catheterization (RHC) in the Second Xiangya Hospital from November 2011 to June 2020 were included. All patients received PAH-targeted therapy and the RV function was assessed by echocardiography at baseline and during follow-up. A total of 303 patients (age, 36.23 ± 13.10 years; women, 213 (70.3%); mean PAP [mPAP], 63.54 ± 16.12 mmHg; PVR, 14.74 ± 7.61 WU) with IPAH (n = 121) or PAH-CHD (n = 182) were included in this study. Compared with PAH-CHD, patients with IPAH had worse baseline RV function. As of the latest follow-up, forty-nine patients with IPAH and six patients with PAH-CHD died. Kaplan-Meier analyses showed better survival in PAH-CHD versus IPAH. After PAH-targeted therapy, patients with IPAH had less improvement in 6 MWD, World Health Organization functional class, and RV functional parameters compared with patients with PAH-CHD. Conclusion: Compared with patients with PAH-CHD, patients with IPAH had worse baseline RV function, unfavourable prognosis, and inadequate response to targeted treatment.

Trends in the survival benefit of repeat kidney transplantation over the past 3 decades.

Repeat kidney transplantation (re-KT) is the preferred treatment for patients with graft failure. Changing allocation policies, widening the risk profile of recipients, and improving dialysis care may have altered the survival benefit of a re-KT. We characterized trends in re-KT survival benefit over 3 decades and tested whether it differed by age, race/ethnicity, sex, and panel reactive assay (PRA). By using the Scientific Registry of Transplant Recipient data, we identified 25 419 patients who underwent a re-KT from 1990 to 2019 and 25 419 waitlisted counterfactuals from the same year with the same waitlisted time following graft failure. In the adjusted analysis, a re-KT was associated with a lower risk of death (adjusted hazard ratio [aHR] = 0.63; 95% confidence interval [CI], 0.61-0.65). By using the 1990-1994 era as a reference (aHR = 0.77; 95% CI, 0.69-0.85), incremental improvements in the survival benefit were noted (1995-1999: aHR = 0.72; 95% CI, 0.67-0.78: 2000-2004: aHR = 0.59; 95% CI, 0.55-0.63: 2005-2009: aHR = 0.59; 95% CI, 0.56-0.63: 2010-2014: aHR = 0.57; 95% CI, 0.53-0.62: 2015-2019: aHR = 0.64; 95% CI, 0.57-0.73). The survival benefit of a re-KT was noted in both younger (age = 18-64 years: aHR = 0.63; 95% CI, 0.61-0.65) and older patients (age ≥65 years: aHR = 0.66; 95% CI, 0.58-0.74; Pinteraction = .45). Patients of all races/ethnicities demonstrated similar benefits with a re-KT. However, it varied by the sex of the recipient (female patients: aHR = 0.60; 95% CI, 0.56-0.63: male patients: aHR = 0.66; 95% CI, 0.63-0.68; Pinteraction = .004) and PRA (0-20: aHR = 0.69; 95% CI, 0.65-0.74: 21-80: aHR = 0.61; 95% CI, 0.57-0.66; Pinteraction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; Pinteraction< .001). Our findings support the continued practice of a re-KT and efforts to overcome the medical, immunologic, and surgical challenges of a re-KT.

Effect of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension on treatment and outcomes of pregnancy.

BACKGROUND: The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. METHODS: A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35-60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value < 0.05 was set to be statistically significant. RESULTS: 149 pregnancies were found in 143 women with PH. Overall, 46 pregnancies were elective abortions, remaining 49 and 54 pregnancies completing delivery in the pre-MDT group and post-MDT group, respectively. Five (10.2%) mother and seven (8.6%) neonatal died in the former, while no maternal deaths but 1.9% neonatal death occurred in the latter. In subgroup analysis, maternal and fetal/neonatal complications were higher in patients with severe PH and World Health Organization functional class (WHO FC) III/IV and all maternal deaths occurred in class III/IV women. In pre-MDT and post-MDT groups, there were 8 and 22 pregnant women receiving the pulmonary-specific therapy and completing delivery, respectively. The percentage of heart failure and urgent cesarean of pre-MDT group was higher than the post-MDT group (30.6% vs. 12.9%, p = 0.02; 40.8% vs. 14.8%, p = 0.01, respectively). CONCLUSION: Implementing the MDT decreased the rate of urgent caesarean section and heart failure in patients with PH and no maternal deaths occurred in the post-MDT group. Pregnant women with severe PH and WHO FC III/IV might have a poor prognosis, whereas the use of pulmonary-specific therapy might improve outcomes of pregnancy.

Genistein Promotes Anti-Heat Stress and Antioxidant Effects via the Coordinated Regulation of IIS, HSP, MAPK, DR, and Mitochondrial Pathways in Caenorhabditis elegans.

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected in Caenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR in C. elegans. The results indicate that genistein substantially extended the lifespan of C. elegans under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in C. elegans under hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2 and upregulated the expression of daf-16, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, and eat-2, whereas it downregulated the expression of age-1 and daf-2 in C. elegans; similarly, it upregulated the expression of daf-16, sod-3, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, jnk-1 skn-1, and eat-2, whereas it downregulated the expression of age-1, daf-2, gst-4, and hsp-12.6 in C. elegans at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2 conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2 conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects in C. elegans via insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.