Management of Chronic Heart Failure in Dialysis Patients: A Challenging but Rewarding Path.

Chronic heart failure (CHF) is a common complication and cause of death in dialysis patients. Although several clinical guidelines and expert consensus on heart failure (HF) in the general population have been issued in China and abroad, due to abnormal renal function or even no residual renal function (RRF) in dialysis patients, the high number of chronic complications, as well as the specificity, variability, and limitations of hemodialysis (HD) and peritoneal dialysis (PD) treatments, there are significant differences between dialysis patients and the general population in terms of the treatment and management of HF. The current studies are not relevant to all dialysis-combined HF populations, and there is an urgent need for high-quality studies on managing HF in dialysis patients to guide and standardize treatment. After reviewing the existing guidelines and literature, we focused on the staging and diagnosis of HF, management of risk factors, pharmacotherapy, and dialysis treatment in patients on dialysis. Based on evidence-based medicine and clinical trial data, this report reflects new perspectives and future trends in the diagnosis and treatment of HF in dialysis patients, which will further enhance the clinicians' understanding of HF in dialysis patients.

The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

Recent advances in biomimetic strategies for the immunotherapy of glioblastoma.

Immunotherapy is regarded as one of the most promising approaches for treating tumors, with a multitude of immunotherapeutic thoughts currently under consideration for the lethal glioblastoma (GBM). However, issues with immunotherapeutic agents, such as limited in vivo stability, poor blood-brain barrier (BBB) penetration, insufficient GBM targeting, and represented monotherapy, have hindered the success of immunotherapeutic interventions. Moreover, even with the aid of conventional drug delivery systems, outcomes remain suboptimal. Biomimetic strategies seek to overcome these formidable drug delivery challenges by emulating nature's intelligent structures and functions. Leveraging the variety of biological structures and functions, biomimetic drug delivery systems afford a versatile platform with enhanced biocompatibility for the co-delivery of diverse immunotherapeutic agents. Moreover, their inherent capacity to traverse the BBB and home in on GBM holds promise for augmenting the efficacy of GBM immunotherapy. Thus, this review begins by revisiting the various thoughts and agents on immunotherapy for GBM. Then, the barriers to successful GBM immunotherapy are analyzed, and the corresponding biomimetic strategies are explored from the perspective of function and structure. Finally, the clinical translation's current state and prospects of biomimetic strategy are addressed. This review aspires to provide fresh perspectives on the advancement of immunotherapy for GBM.

Exploring the potent hydrolytic activity of chitosan-cerium complex microspheres resin for organophosphorus pesticide degradation.

Chitosan is a biocompatible, non-toxic and renewable natural basic polysaccharide that can be cross-linked and reacted with Ce(IV) to form a physiologically active chitosan-Ce(IV) complex. To investigate this novel complex and its potential to hydrolyze phosphate ester bonds, chitosan-cerium complex microspheres resin (CS-CCMR) was prepared from chitosan and ceric ammonium nitrate by reversed-phase suspension cross-linking polymerization. CS-CCMR was characterized, its ability to hydrolyze disodium p-nitrobenzene phosphate (PNPP2Na) and organophosphorus pesticides was investigated, and the hydrolytic mechanism was explored. CS-CCMR was composed of dark yellow microspheres with smooth surfaces and dense pores. It was found that CS-CCMR contained 4.507 mg/g Ce(IV), indicating that coordination polymerization between Ce(IV) and chitosan was successful. The presence of Ce(IV) in CS-CCMR was confirmed by multiple analytical methods and it was found that coordination of Ce(IV) by chitosan was mediated by the nitrogen atom of the amino group and the oxygen atom of the hydroxyl group of chitosan. It was shown that CS-CCMR efficiently hydrolyzed the phosphate ester bonds of PNPP2Na and five organophosphorus pesticides. Hydrolysis of PNPP2Na is potentially accomplished by charge neutralization and nucleophilic substitution. The mechanism of parathion degradation by CS-CCMR involves modification of the nitro group to give aminoparathion, followed by cleavage of the P-O bond to generate diazinphos. Consequently, the novel chitosan-Ce(IV) complex exhibits great efficiency for hydrolysis of phosphate ester bonds and CS-CCMR is expected to be developed as an agent to reduce the possibility of contamination of fruit and vegetable drinks by organophosphorus pesticides.

PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR.

Cancer stem cells (CSCs) are responsible for tumor chemoresistance, and the aryl hydrocarbon receptor (AHR) is indispensable for maintaining CSC characteristics. Here, we aimed to investigate how the interaction between progesterone receptor membrane component 1 (PGRMC1) and AHR contributes to the maintenance of CSC phenotypes in non-small cell lung cancer (NSCLC). Clinical data and tissue microarray analyses indicated that patients with elevated PGRMC1 expression had poorer prognoses. Moreover, PGRMC1 overexpression enhanced CSC phenotypes and chemotherapy resistance in vitro and in vivo by modulating AHR ubiquitination. We then determined the specific interaction sites between PGRMC1 and AHR. Mass spectrometry screening identified tripartite motif containing 56 (TRIM56) as the E3 ligase targeting AHR. Notably, PGRMC1 overexpression inhibited the interaction between TRIM56 and AHR. Overall, our study revealed a regulatory mechanism that involves PGRMC1, AHR, and TRIM56, providing insights for developing CSC-targeting strategies in NSCLC treatment.

Longitudinal measurement invariance and psychometric properties of the Patient Health Questionnaire-Four in China.

BACKGROUND: Depression and anxiety symptoms among medical students are often a concern. The Patient Health Questionnaire-Four (PHQ-4), an important tool for depression and anxiety screening, is commonly used and easy to administer. This study aimed to assess and update the longitudinal measurement invariance and psychometric properties of the simplified Chinese version. METHODS: A three-wave longitudinal survey was conducted among healthcare students using the PHQ-4. Structural validity was based on one-factor, two-factor, and second-order factor models, construct validity was based on the Self-Rated Health Questionnaire (SRHQ), Sleep Quality Questionnaire (SQQ), and Rosenberg Self-Esteem Scale (RSES), and longitudinal measurement invariance (LMI), internal consistency, and test-retest reliability were based on structural consistency across three time points. RESULTS: The results of the confirmatory factor analysis indicated that two-factor model was the best fit, and LMI was supported at three time points. Inter-factor, factor-total, and construct validity correlations of the PHQ-4 were acceptable. Additionally, Cronbach's alpha, McDonald's omega, and the intraclass correlation coefficient demonstrated acceptable/moderate to excellent reliability of the PHQ-4. CONCLUSIONS: This study adds new longitudinal evidence that the Chinese version of the PHQ-4 has promising LMI and psychometric properties. Such data lends confidence to the routine and the expanded use of the PHQ-4 for routine screening of depression and anxiety in Chinese healthcare students.

A longitudinal examination of the measurement properties and invariance of the Sleep Condition Indicator in Chinese healthcare students.

BACKGROUND: The Sleep Condition Indicator (SCI), an insomnia measurement tool based on the updated Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria with sound psychometric properties when applied in various populations, was evaluated here among healthcare students longitudinally, to demonstrate its measurement properties and invariance in this particularly high-risk population. METHODS: Healthcare students of a Chinese university were recruited into this two-wave longitudinal study, completing the simplified Chinese version of the SCI (SCI-SC), Chinese Regularity, Satisfaction, Alertness, Timing, Efficiency, Duration (RU_SATED-C) scale, Chinese Patient Health Questionnaire-4 (PHQ-4-C), and sociodemographic variables questionnaire (Q-SV) between September and November 2022. Structural validity, measurement invariance (MI), convergent and discriminant validity, internal consistency, and test-retest reliability of the SCI-SC were examined. Subgroups of gender, age, home location, part-time job, physical exercise, and stress-coping strategy were surveyed twice to test cross-sectional and longitudinal MI. RESULTS: We identified 343 valid responses (62.9% female, mean age = 19.650 ± 1.414 years) with a time interval of seven days. The two-factor structure was considered satisfactory (comparative fit index = 0.953-0.989, Tucker-Lewis index = 0.931-0.984, root means square error of approximation = 0.040-0.092, standardized root mean square residual = 0.039-0.054), which mostly endorsed strict invariance except for part-time job subgroups, hence establishing longitudinal invariance. The SCI-SC presented acceptable convergent validity with the RU_SATED-C scale (r ≥ 0.500), discriminant validity with the PHQ-4-C (0.300 ≤ r < 0.500), internal consistency (Cronbach's alpha = 0.811-0.835, McDonald's omega = 0.805-0.832), and test-retest reliability (intraclass correlation coefficient = 0.829). CONCLUSION: The SCI-SC is an appropriate screening instrument available for assessing insomnia symptoms among healthcare students, and the promising measurement properties provide additional evidence about validity and reliability for detecting insomnia in healthcare students.

Ultrasonic Imaging of Deeper Bone Defect Using Virtual Source Synthetic Aperture with Phased Shift Migration: A Phantom Study.

Ultrasound imaging for bone is a difficult task in the field of medical ultrasound. Compared with other phase array techniques, the synthetic aperture (SA) has a better lateral resolution but a limited imaging depth due to the limited ultrasonic energy emitted by the single emitter in each transmission. In contrast, the virtual source (VS) synthetic aperture allows a simultaneous multi-element emission and could provide a higher ultrasonic incident energy in each transmission. Therefore, the VS might achieve a high imaging quality at a deeper depth for bone imaging than the traditional SA. In this study, we proposed the virtual source phase shift migration (VS-PSM) method to achieve ultrasonic imaging of the deeper bone defect featured in the multilayer structure. The proposed VS-PSM method was validated using standard soft tissue phantom and printed bone phantom with artificial defects. The image quality was evaluated in terms of contrast-to-noise ratios (CNR) and amplitudes of scatters and defects at different imaging depths. The results showed that the VS-PSM method could achieve a high imaging quality of the soft tissues with a significant improvement in the scattering amplitude and without a significant sacrifice of the lateral and axial resolution. The PSM was superior to the DAS in suppressing the background noise in the images. Compared with the traditional SA-PSM, the VS-PSM method could image deeper bone defects at different ultrasonic frequencies, with an average improvement of 50% in CNR. In conclusion, this study demonstrated that the proposed VS-PSM method could image deeper bone defects and might help the diagnosis of bone disease using ultrasonic imaging.

Assessment of psychometric performance for the Chinese version of the Brief Inventory of Perceived Stress integrating exploratory graph analysis and confirmatory factor analysis.

OBJECTIVE: This study was to evaluate measurement properties of the Chinese version of the Brief Inventory of Perceived Stress (BIPS-C) and confirm possible solutions for measuring the constructs underlying perceived stress. METHODS: A total of 1356 community residents enrolled and were randomly split into two halves. The first half was used to explore the underlying constructs of the BIPS-C by exploratory graph analysis (EGA) and the second half was used to compare and confirm the constructs by confirmatory factor analysis (CFA). RESULTS: The EGA identified a one-factor model of the BIPS-C with an accuracy of 99.3%. One-factor, three-factor, second-order, and bifactor models were compared by CFAs. The bifactor model with one general and three specific factors was found to be the most adequate [comparative fit index (CFI) = 0.990; Tucker-Lewis index (TLI) = 0.979; root mean square error of approximation (RMSEA) = 0.058] and was superior to the other models. The related bifactor indices showed a stronger existence of the general factor. The bifactor model of the BIPS-C also showed adequate internal consistency with McDonald's omega and omega subscales ranging from moderate to strong (0.677-0.869). CONCLUSION: The BIPS-C demonstrates sufficient measurement properties for assessing general perceived stress.

Experimental confirmation and bioinformatics reveal biomarkers of immune system infiltration and hypertrophy ligamentum flavum.

Background: Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended. Objective: The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum. Methods: The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting. Results: Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine-cytokine receptor interaction, and TGF-ß signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group. Conclusion: The TGF-ß signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.

Beyond VICs: Shedding light on the overlooked VECs in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is prevalent in developed nations and has emerged as a pressing global public health concern due to population aging. The precise etiology of this disease remains uncertain, and recent research has primarily focused on examining the role of valvular interstitial cells (VICs) in the development of CAVD. The predominant treatment options currently available involve open surgery and minimally invasive interventional surgery, with no efficacious pharmacological treatment. This article seeks to provide a comprehensive understanding of valvular endothelial cells (VECs) from the aspects of valvular endothelium-derived nitric oxide (NO), valvular endothelial mechanotransduction, valvular endothelial injury, valvular endothelial-mesenchymal transition (EndMT), and valvular neovascularization, which have received less attention, and aims to establish their role and interaction with VICs in CAVD. The ultimate goal is to provide new perspectives for the investigation of non-invasive treatment options for this disease.

Cellulose nanofiber-based hybrid hydrogel electrode with superhydrophilicity enabling flexible high energy density supercapacitor and multifunctional sensors.

Flexible hybrid hydrogels (GO/AC/CNFn) with a 3D porous network structure and superhydrophilic property are synthesized by cross-linking and self-assembling graphene oxide (GO) and activated carbon (AC) with cellulose nanofiber (CNF) during microwave hydrothermal process. In this ternary composite hydrogel, CNF molecular chains bridge GO sheets to build the 3D skeleton and anchor AC particles within GO nanosheets, forming ordered architecture of GO/AC/CNFn hydrogel that simultaneously possesses high flexibility and excellent mechanical integrity. When using this hydrogel as additive-free electrode, the presence of AC provides developed porous structure and density to promote high volumetric capacitance, while the heteroatom nitrogen groups tune the surface property of the composite with increased electrical conductivity. Benefited from the optimized structure, GO/AC/CNF1 electrode delivers an ultra-high mass specific capacitance of 627 F/g and volume specific capacitance of 618 F/cm3 at 0.5 A/g in three-electrode system in 1 M H2SO4 electrolyte, which is kinetically demonstrated to be essentially originated from the capacitive contributions. The energy density reaches 32.2 Wh/kg at a power density of 150 W/kg for the fabricated flexible solid-state symmetric supercapacitor. Moreover, the obtained flexible device could sensitively response at varied physiological signals, shedding fresh lights on their potential applications in signal sensors and portable electronics.

Psychometric properties of the ultra-brief self-report Patient Health Questionnaire-4 (PHQ-4) to assess anxiety and depression in Arabic-speaking adults.

BACKGROUND: Anxiety and depression are psychiatric disorders that often coexist and share some features. Developing a simple and cost-effective tool to assess anxiety and depression in the Arabic-speaking population, predominantly residing in low- and middle-income nations where research can be arduous, would be immensely beneficial. The study aimed to translate the four-item composite Patient Health Questionnaire - 4 (PHQ-4) into Arabic and evaluate its psychometric properties, including internal reliability, sex invariance, composite reliability, and correlation with measures of psychological distress. METHODS: 587 Arabic-speaking adults were recruited between February and March 2023. An anonymous self-administered Google Forms link was distributed via social media networks. We utilized the FACTOR software to explore the factor structure of the Arabic PHQ-4. RESULTS: Confirmatory factor analysis (CFA) indicated that fit of the two-factor model of the PHQ-4 scores was modest (χ2/df = .13/1 = .13, RMSEA = .001, SRMR = .002, CFI = 1.005, TLI = 1.000). Internal reliability was excellent (McDonald's omega = .86; Cronbach's alpha = .86). Indices suggested that configural, metric, and scalar invariance were supported across sex. No significant difference was found between males and females in terms of the PHQ-4 total scores, PHQ-4 anxiety scores, and PHQ-4 depression scores. The total score of the PHQ-4 and its depression and anxiety scores were significantly and moderately-to-strongly associated with lower wellbeing and higher Depression Anxiety and Stress Scale (DASS) total and subscales scores. CONCLUSION: The PHQ-4 proves to be a reliable, valid, and cost-effective tool for assessing symptoms related to depression and anxiety. To evaluate the practical effectiveness of the Arabic PHQ-4 and to further enhance the data on its construct validity, future studies should assess the measure in diverse contexts and among specific populations.

Transseptal approach versus retrograde aortic approach in mapping and ablation of ventricular arrhythmias from anterolateral papillary muscles.

INTRODUCTION: The anterior and lateral position of the anterolateral papillary muscle (ALPM) has found to be reached with better catheter stability and less mechanical bumping via the transseptal (TS) compared to the retrograde aortic (RA) approach. The aim of this study is to compare the TS and RA approaches on mapping and ablation of ventricular arrhythmias (VAs) arising from ALPMs. METHODS: Thirty-two patients with ALPM-VAs undergoing mapping and ablation via the TS approach were included and compared with 31 patients via the RA approach within the same period. Acute success was compared, as well as other outcomes including misinterpreted mapping results due to bumping, radiofrequency (RF) attempts, procedural time and success rate at 12-month follow-up. RESULTS: Acute success was achieved in more cases in the TS group (96.4% vs. 72.0%, p = .020). During activation mapping, bump-provoked premature ventricular complexes (PVCs) misinterpreted as clinical PVCs were more common in the RA group (30.0% vs. 58.3%, p = .036), leading to more RF attempts (3.5 ± 2.7 vs. 7.2 ± 6.8, p = .006). Suppression of VAs were finally achieved in the unsuccessful cases by changing to the alternative approach, but the procedural time was significantly less in the TS group (90.0 ± 33.0 vs. 113.7 ± 41.1 min, p = .027) with less need to change the approach, although follow-up success rates were similar (75.0% vs. 71.0%, p = .718). CONCLUSION: A TS rather than RA approach as the initial approach appears to facilitate mapping and ablation of ALPM-VAs, specifically by decreasing the possibility of misleading mapping results caused by bump-provoked PVC, and increase the acute success rate thereby.

Adult Female Patient with Untreated Truncus Arteriosus Type I and Torsion of Small Bowel Gastrointestinal Stromal Tumor: A Rare Case Report.

BACKGROUND Persistent truncus arteriosus is a rare congenital cyanotic heart defect characterized by a single ventricular outflow tract. Without surgical intervention, it has a poor prognosis in infancy. Here, we report an adult female patient with uncorrected truncus arteriosus type I, who presented with acute-onset abdominal pain due to torsion of a small bowel gastrointestinal stromal tumor (GIST). CASE REPORT A 41-year-old woman came to our Emergency Department with acute-onset lower abdominal pain for 2 days. Congenital heart disease, truncus arteriosus, had been diagnosed at birth, and there had been no surgical intervention. Abdominal computed tomography revealed a 10×9×12-cm mixed-density mass in the pelvic capacity. Transthoracic echocardiography revealed a 33-mm ventricular septal defect. The ascending aorta originated mainly from the right ventricle, and the pulmonary artery originated from the beginning of the aorta (type I truncus arteriosus, according to Collett and Edwards classification). After a quick and detailed preoperative workup, the patient underwent tumor resection by open surgery with general anesthesia. CONCLUSIONS This is the first case to report emergency surgery for a patient with uncorrected persistent truncus arteriosus due to torsion of a small bowel GIST. A multidisciplinary team with deep understanding of the disease entity was crucial. By considering the fixed hemodynamic and respiratory physiology, overtreatment and unrealistic goals were avoided. Eventually, the patient was discharged after being hospitalized for 2 weeks.

Socio-Demographic and Preoperative Clinical Factors Associated With 5-Year Weight Trajectories After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Objective: To determine whether socio-demographic and preoperative clinical factors contribute to the percent total body weight loss (%TBWL) after bariatric surgery (BS). Background: BS is the most effective long-term treatment for medically complicated obesity. More information is needed about the factors that contribute to postoperative %TBWL in large and ethnically diverse cohorts. Methods: This retrospective study conducted in the Kaiser Permanente Northern California region included 7698 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 2009 and March 2015. Trajectory analyses were conducted from 5-year follow-up data to assign patients to "low," "average," or "high" postoperative %TBWL groups. We then evaluated whether age, sex, race/ethnicity, neighborhood deprivation index and preoperative body mass index (BMI)/weight loss, diabetes, hypertension, and sleep apnea contributed to postoperative %TBWL using logistic regression models. Results: Of 7698 patients (83.2% women), 48.6% underwent a RYGB and 51.4% underwent a SG. Postoperative %TBWL trajectories over 5 years were obtained in 6229 (81%) of 7698 eligible patients. About 27.8% and 29.3% of patients followed the "low" postoperative %TBWL trajectory, for RYGB and SG, respectively. Men, older patients, and Asian, Black, and Hispanic/Latino patients were more likely to be classified in the low postoperative %TBWL group. Patients showing lower postoperative %TBWL had a lower preoperative BMI (but lost less weight before surgery) and were more likely to have preoperative comorbidities. Conclusions: This study confirms and extends prior findings of the effects of several demographic and preoperative clinical factors on postoperative weight loss. Findings could improve the support of patients to achieve desired surgical outcomes.

How denitrifiers defense ciprofloxacin: Insights from intracellular and extracellular stress response.

Overuse of antibiotics has led to their existence in nitrogen-containing water. The impacts of antibiotics on bio-denitrification and the metabolic response of denitrifiers to antibiotics are unclear. We systematically analyzed the effect of ciprofloxacin (CIP) on bio-denitrification and found that 5 mg/L CIP greatly inhibited denitrification with a model denitrifier (Paracoccus denitrificans). Nitrate reduction decreased by 32.89 % and nitrous oxide emission increased by 75.53 %. The balance analysis of carbon and nitrogen metabolism during denitrification showed that CIP exposure blocked electron transfer and reduced the flow of substrate metabolism used for denitrification. Proteomics results showed that CIP exposure induced denitrifiers to use the pentose phosphate pathway more for substrate metabolism. This caused a substrate preference to generate NADPH to prevent cellular damage rather than NADH for denitrification. Notably, despite denitrifiers having antioxidant defenses, they could not completely prevent oxidative damage caused by CIP exposure. The effect of CIP exposure on denitrifiers after removal of extracellular polymeric substances (EPS) demonstrated that EPS around denitrifiers formed a barrier against CIP. Fluorescence and infrared spectroscopy revealed that the binding effect of proteins in EPS to CIP prevented damage. This study shows that denitrifiers resist antibiotic stress through different intracellular and extracellular defense strategies.

Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. METHODS: Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. RESULTS: According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81-0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. CONCLUSIONS: Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition.

Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.

Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion.

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.