Titanium exposure and gestational diabetes mellitus: associations and potential mediation by perturbation of amino acids in early pregnancy.

BACKGROUND: Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. METHODS: The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. RESULTS: As parameterized in tertiles, titanium showed positive dose-response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. CONCLUSIONS: In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.

CCL2/CCR2 axis promotes perineural invasion of salivary adenoid cystic carcinoma via ITGß5-mediated nerve-tumor interaction.

Perineural invasion (PNI) is a notorious feature of salivary adenoid cystic carcinoma (SACC) and other neurotropic tumors. The pathogenesis of PNI that involves the molecular communication between the tumor and the suffered nerve is elusive. The in vitro co-culture assays of SACC cells with dorsal root ganglia (DRG) or neural cells showed that nerve-derived CCL2 activated CCR2 expression in SACC cells, promoting the proliferation, adhesion, migration, and invasion of SACC cells via the ERK1/2/ITGß5 pathway. Meanwhile, SACC-derived exosomes delivered ITGß5 to promote the neurite outgrowth of neural cells or DRG. Blocking of CCL2/CCR2 axis or ITGß5 inhibited the PNI of SACC cells in models in vitro by 3D co-culture of DRG with SACC cells and in vivo by xenografting SACC cells onto the murine sciatic nerve. High levels of ITGß5 in tissues or plasma exosomes were significantly correlated with CCL2 and CCR2 expression in the tissues and associated with PNI and poor prognosis of SACC cases. Our findings revealed a novel reciprocal loop between neural and tumor cells driven by the CCL2/CCR2 axis and exosomal ITGß5 during PNI of SACC. The present study may provide a prospective diagnostic and anti-PNI treatment strategy for SACC patients via targeting the nerve-tumor interactions.

Unveiling the common laws of extracellular polymeric substances (EPS) properties on short-chain fatty acids production from sludge by EPS disintegration pretreatment.

The production of short-chain fatty acids (SCFAs) from sludge is promising, but the efficiency and product quality often vary because of extracellular polymeric substances (EPS) characteristics and pretreatment principles. This study adopted specific EPS disintegration pretreatment to treat different types of sludge. By correlation coefficient matrix analysis and correlation dynamics change resolution, the intrinsic relationships between the nature of EPS and the production of SCFAs from sludge was unveiled. We demonstrate that tight-bound EPS (TB-EPS) is a principal carbon reservoir, positively impacting SCFAs yields, in the fermentation system with EPS as the main fermentation substrate, it can contribute about 29.2 % for SCFAs growth during fermentation. Conversely, TB-EPS exhibits a negative correlation during fermentation due to EPS-SCFAs interconversion, while loosely bound EPS (LB-EPS) correlates positively. Proteins and polysaccharides in TB-EPS, especially proteins, significantly enhance individual SCFAs yields, predominantly acetic, propionic, and isovaleric acids. The findings would provide a theoretical basis for developing pretreatments and process-control technologies aimed at improving SCFAs production efficiency and quality.

Cinobufacini Inhibits Survival and Metastasis of Hepatocellular Carcinoma via c-Met Signaling Pathway.

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS: CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.

Short-Term Supraorbital Nerve Stimulation and Pain Relief for Acute and Subacute Ophthalmic Herpetic Neuralgia: A Randomized Controlled Crossover Trial.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a kind of refractory disease, and treating it is important for preventing postherpetic neuralgia (PHN). But the evidence surrounding the current treatment options for these conditions is controversial, so exploring reasonable clinical treatment strategies for HZO is necessary. Neuromodulation is an excellent modality for the treatment of various neuropathic pain conditions. This trial was designed to evaluate the effectiveness of short-term supraorbital nerve stimulation (SNS) and the supraorbital nerve block (SNB) for HZO. OBJECTIVES: To determine whether short-term SNS relieves acute and subacute ophthalmic herpetic neuralgia. STUDY DESIGN: This prospective randomized controlled crossover trial compared short-term SNS to SNB. SETTING: The operating room of a pain clinic. METHODS: Patients with acute or subacute ophthalmic herpetic neuralgia were recruited. The patients were randomly assigned to receive either SNS or SNB. The primary outcome being measured was each patient's Visual Analog Scale (VAS) score at 4 weeks. The secondary outcomes under measurement were the proportion of patients who achieved ≥ 50% pain relief, sleep quality, medicine consumption, and adverse events. Crossover after 4 weeks was permitted, and patients were followed up to 12 weeks. RESULTS: Overall, 50 patients were included (n = 25/group). At 4 weeks, the patients who received SNS achieved greater pain relief, as indicated by their significantly different VAS scores from those of the SNB group (mean difference: -1.4 [95% CI, -2.29 to -0.51], P < 0.05). Both groups showed a significant decrease in pain level from the baseline (all P < 0.05). Overall, 72% and 44% of the SNS and SNB patients experienced ≥ 50% pain relief, respectively (OR: 0.31 [95% CI, 0.09 to 0.99], P < 0.05), and 68% and 32% of SNS and SNB patients, respectively, had VAS scores < 3 (OR: 0.22 [95% CI, 0.07 to 0.73], P < 0.05). Compared to the SNB group, the SNS group had better sleep quality, lower ophthalmic neuralgia, a lower proportion of further treatment, and lower analgesic intake. Overall, 18 patients received SNS alone, and 16 patients crossed over from SNB to SNS. The VAS scores, sleep quality, ophthalmic neuralgia, and trend of medicine intake were not significantly different between the groups (all P > 0.05). No serious complications occurred. LIMITATIONS: This study was nonblind. CONCLUSIONS: Short-term SNS is effective for controlling acute or subacute ophthalmic herpetic neuralgia. Combining SNS with SNB yields no additional benefits.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Peroxiredoxin-1 as a molecular chaperone that regulates glutathione S-transferase P1 activity and drives mutidrug resistance in ovarian cancer cells.

Ovarian cancer is among the most prevalent gynecological malignancies around the globe. Nonetheless, chemoresistance continues to be one of the greatest obstacles in the treatment of ovarian cancer. Therefore, understanding the mechanisms of chemoresistance and identifying new treatment options for ovarian cancer patients is urgently required. In this study, we found that the mRNA and protein expression levels of PRDX1 were significantly increased in cisplatin resistant A2780/CDDP cells. Cell survival assays revealed that PRDX1 depletion substantially increased ovarian cancer cell sensitivity to cisplatin, docetaxel, and doxorubicin. Additionally, PRDX1 significantly increased GSTP1 activity, resulting in multidrug resistance. Biochemical experiments showed that PRDX1 interacted with GSTP1 through Cysteine 83, which regulated GSTP1 activity as well as chemotherapy resistance in ovarian cancer cells. Our findings indicate that the molecular chaperone activity of PRDX1 is a promising new therapeutic target for ovarian cancer.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study.

BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear. METHODS: Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined. RESULTS: In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in DNMT3A, TET2, RUNX1, and ASXL1. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (P<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257-3.816]; P=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1ß and interleukin-6 and lower interleukin-4 and IgG galactosylation levels. CONCLUSIONS: This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

Congenital thrombophilia in East-Asian venous thromboembolism population: a systematic review and meta-analysis.

Background: Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis. Methods: Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical. Results: Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study. Conclusion: The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.

Comparison of the effect of two commercialized vitrification carriers on pregnancy outcomes in freeze-thaw cycles.

OBJECTIVE: This study aimed to compare the effects of two brands of commercial vitrification carriers on pregnancy outcomes in freeze-thaw cycles. METHODS: We included 4871 patients who underwent a "freeze all" strategy using the commercial carriers J.Y. straw and OYASHIPS straw in the Reproductive Center of the First Hospital of Jilin University. The pregnancy outcomes of cleavage-stage embryos and blastocysts were studied separately. Detailed data and the safety of children born from mothers with the two types of carriers were also compared. RESULTS: Patients who used J.Y. straw had similar clinical pregnancy and live birth rates with one and two cleavage-stage embryo transplantation to those who used OYASHIPS straw. In patients who had blastocyst transplantation, the clinical pregnancy rate of one blastocyst transplanted in those who used OYASHIPS straw was significantly higher than that in those who used J.Y. straw (57.85% vs 47.09%). Among children born from mothers who used J.Y. straw, the congenital disability rate was significantly higher than that in those with OYASHIPS straw. CONCLUSION: The OYASHIPS straw carrier is cheap and can achieve clinical pregnancy and live birth outcomes comparable to those of J.Y. straw. Therefore, OYASHIPS straw is a good alternative option.

Role of ferroptosis in esophageal cancer and corresponding immunotherapy.

Esophageal cancer (EC) is one of the most common digestive system malignancies in the world. The combined modality treatment of EC is usually surgery and radiation therapy, however, its clinical efficacy for advanced patients is relatively limited. Ferroptosis, a new type of iron-dependent programmed cell death, is different from apoptosis, necrosis and autophagy. In recent years, many studies have further enlightened that ferroptosis plays an essential role in the occurrence, development and metastasis of tumors. Targeting ferroptosis stimulates a new direction for further exploration of oncologic treatment regimens. Furthermore, ferroptosis has a critical role in the immune microenvironment of tumors. This paper reviews the mechanism of ferroptosis and the ferroptosis research progress in the treatment of EC. We further elaborate the interaction between ferroptosis and immunotherapy, and the related mechanisms of ferroptosis participation in the immunotherapy of EC, so as to provide new directions and ideas for the treatment of EC.

Human Plasma IgG N-Glycome Profiles Reveal a Proinflammatory Phenotype in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The pathological mechanism of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood, and inflammation has been reported to be one of its etiological factors. IgG regulates systemic inflammatory homeostasis, primarily through its N-glycans. Little is known about IgG N-glycosylation in CTEPH. We aimed to map the IgG N-glycome of CTEPH to provide new insights into its pathogenesis and discover novel markers and therapies. METHODS: We characterized the plasma IgG N-glycome of patients with CTEPH in a discovery cohort and validated our results in an independent validation cohort using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Thereafter, we correlated IgG N-glycans with clinical parameters and circulating inflammatory cytokines in patients with CTEPH. Furthermore, we determined IgG N-glycan quantitative trait loci in CTEPH to reveal partial mechanisms underlying glycan changes. RESULTS: Decreased IgG galactosylation representing a proinflammatory phenotype was found in CTEPH. The distribution of IgG galactosylation showed a strong association with NT-proBNP (N-terminal pro-B-type natriuretic peptide) in CTEPH. In line with the glycomic findings, IgG pro-/anti-inflammatory N-glycans correlated well with a series of inflammatory markers and gene loci that have been reported to be involved in the regulation of these glycans or inflammatory immune responses. CONCLUSIONS: This is the first study to reveal the full signature of the IgG N-glycome of a proinflammatory phenotype and the genes involved in its regulation in CTEPH. Plasma IgG galactosylation may be useful for evaluating the inflammatory state in patients with CTEPH; however, this requires further validation. This study improves our understanding of the mechanisms underlying CTEPH inflammation from the perspective of glycomics.

Percutaneous transluminal pulmonary angioplasty for Takayasu arteritis-associated pulmonary hypertension: A single-arm meta-analysis.

BACKGROUND: The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. OBJECTIVES: To examine the efficacy and safety of PTPA in TA-PH. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. RESULTS: Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). CONCLUSIONS: Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. REGISTRATION: PROSPERO CRD42022354087.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

Rhubarb Peony Decoction Downregulates the Expression of c-Fos after Intestinal Epithelial Cells Hypoxia-reoxygenation Injury.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury occurs in several clinical situations and after intestinal transplantation. This study aimed to examine the role of rhubarb peony decoction (RPD) in intestinal I/R injury. METHODS: Different concentrations of RPD were set to treat IEC-6 and Caco-2 cells. Cell proliferation and apoptosis were measured by CCK-8 and flow cytometry assays. High-throughput transcriptome sequencing was performed on IEC-6 cells treated with hypoxia-reoxygenation (HR) or HR and RPD. RESULTS: RPD treatment significantly promoted the proliferation of IEC-6 and Caco-2 cells and inhibited apoptosis. Sequencing results identified 109 significantly up-regulated genes and 36 significantly down-regulated genes in the RPD group. In addition, the results of western blot suggested that HR induced the expression of c-Fos, and the treatment of RPD prevented the HR-induced c- Fos expression. Importantly, knockdown of c-Fos rescued the HR-inhibited cell proliferation and HR-induced apoptosis. CONCLUSIONS: In conclusion, RPD was beneficial in protecting the survival of intestinal epithelial cells under HR stress. Furthermore, the increase in c-Fos expression after HR stress was closely related to the proliferation and apoptosis of intestinal epithelial cells.

Development of a customized mask retainer for improving the fit performance of surgical masks.

This study introduces a customized mask retainer to improve the fit performance of surgical masks using various advanced digital techniques. The participant's 3D face scans with and without a surgical mask were taken by using a smartphone. The mask retainer was designed using the 3D face scan data based on the facial anthropometric landmarks. The fitting was inspected and adjusted using the masked face scan data. The retainer was fabricated using a 3D printer. The effectiveness of the retainer on the augmentation of the fit of the surgical mask was tested according to the Chinese Standard (GB 19083-2010). A questionnaire was used to assess the effect of wearing surgical masks with and without retainers and N95 respirators on subjective perception of discomfort. The effectiveness test of the retainer on the augmentation of the fit performance showed a better than 25-fold increase in the overall fit factor, meeting the fit requirement for KN95 respirators in China. The subjective perception of discomfort of wearing N95 was significantly greater than surgical mask with and without retainers. The fit factor results indicated that by using the retainer, the overall fit factors and that of each exercise significantly increased compared to that of the group with the surgical mask alone. And compared with N95, the surgical mask with the retainer significant improved comfort. The surgical mask with the retainer can provide an alternative of personal protective equipment for healthcare workers.

Time-Velocity Integral of Left Ventricular Outflow Tract Predicts Worse Long-Term Survival in Pulmonary Arterial Hypertension.

Background: The time-velocity integral of the left ventricular outflow tract (TVILVOT) has been demonstrated to correlate with heart failure hospitalization and mortality, but the association of TVILVOT with the severity and prognosis of pulmonary arterial hypertension (PAH) has not been evaluated. Objectives: The aim of this study was to investigate the predictive value of baseline TVILVOT in PAH. Methods: A total of 225 consecutive patients with a diagnosis of incident PAH were prospectively studied and echocardiology-derived TVILVOT was measured at enrollment followed by right heart catheterization examination within 48 hours. Cox proportional hazards analysis was performed to assess the association between baseline variables and mortality. Results: During a median follow-up period of 33.8 months, 44 patients died of cardiovascular events. Baseline TVILVOT was significantly lower in the nonsurvivors compared with the survivors (P < 0.001). Baseline TVILVOT was positively correlated with stroke volume obtained by right heart catheterization (r = 0.709; P < 0.001), and inversely correlated with N-terminal pro-B-type natriuretic peptide (r = -0.533; P < 0.001), pulmonary vascular resistance (r = -0.423; P < 0.001). Multivariate analysis showed that baseline TVILVOT (hazard ratio: 0.856; 95% CI: 0.780-0.941; P = 0.001) was an independent predictor of cardiovascular mortality in PAH. Patients with a baseline TVILVOT <17.1 cm (median value) had a significantly worse survival than those with a baseline TVILVOT ≥17.1 cm (P < 0.001). Conclusions: The findings of this study suggest that noninvasive TVILVOT provides a practical method to assess the severity and predict long-term outcome of PAH.

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension.

Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

A tartrate-EDTA-Fe complex mediates electron transfer and enhances ammonia recovery in a bioelectrochemical-stripping system.

Traditional bioelectrochemical systems (BESs) coupled with stripping units for ammonia recovery suffer from an insufficient supply of electron acceptors due to the low solubility of oxygen. In this study, we proposed a novel strategy to efficiently transport the oxidizing equivalent provided at the stripping unit to the cathode by introducing a highly soluble electron mediator (EM) into the catholyte. To validate this strategy, we developed a new kind of iron complex system (tartrate-EDTA-Fe) as the EM. EDTA-Fe contributed to the redox property with a midpoint potential of -0.075 V (vs. standard hydrogen electrode, SHE) at pH 10, whereas tartrate acted as a stabilizer to avoid iron precipitation under alkaline conditions. At a ratio of the catholyte recirculation rate to the anolyte flow rate (RC-A) of 12, the NH4 +-N recovery rate in the system with 50 mM tartrate-EDTA-Fe complex reached 6.9 ±â€¯0.2 g N m-2 d-1, approximately 3.8 times higher than that in the non-EM control. With the help of the complex, our system showed an NH4 +-N recovery performance comparable to that previously reported but with an extremely low RC-A (0.5 vs. 288). The strategy proposed here may guide the future of ammonia recovery BES scale-up because the introduction of an EM allows aeration to be performed only at the stripping unit instead of at every cathode, which is beneficial for the system design due to its simplicity and reliability.