Smartphone addiction habit is positively associated with coronary artery disease and its severity in Chinese adults: a case-control study.

Background: Coronary artery disease (CAD) has a high incidence and poor prognosis worldwide. It has been confirmed that smartphone addiction (SA) habit can increase the incidence of hypertension and obesity in adolescents. However, the association of SA with CAD and its severity in Chinese adults remains largely unknown. Methods: A total of 700 Chinese adults (aged 18-70 years) including 350 CAD patients and 350 control subjects were enrolled. The Smartphone Addiction Scale Short Version (SAS-SV) was used to measure SA habit, and the Pittsburgh sleep quality index (PSQI) was used to assess sleep quality. Multiple logistic regression was employed to analyze the relationship between SA habit and CAD. Results: After adjusting for age, smoking, hypertension, type 2 diabetes mellitus, and other risk factors, there was a significant association between SA habit and CAD in adults (p < 0.001). Subgroup analysis showed that there were statistical differences in the correlation between SA habit and CAD in the hypertension, ≤55 years age old, and female subgroups. Moreover, we performed a subgroup analysis based on the number of coronary artery lesions. The result showed that the rate of SA habit in the three-vessel disease group was the highest (p < 0.001). We applied Gensini score to evaluate the severity of coronary artery lesions (median Gensini score, 34) and divided all CAD patients into high Gensini score group (>34) and low Gensini score group (≤34), respectively. Compared with low Gensini score group, patients in high Gensini score group were more likely to have SA habit (p = 0.049). Conclusions: There is a positive association of SA habit with CAD and its severity in Chinese adults.

Effect of Ropivacaine Combined with Nalbuphine on Pain during Anaesthesia Recovery in Patients with Prostatic Hyperplasia Undergoing Transurethral Resection of Prostate.

BACKGROUND: As a frequent disease, prostatic hyperplasia could be treated by transurethral resection of prostate (TURP). However, postoperative pain may affect the prognosis of patients to some extent, so exploring reasonable anaesthetic drugs is an important measure to reduce the recovery period of anaesthesia. This study used the combination of ropivacaine and nalbuphine for intraoperative anaesthesia in patients undergoing TURP to investigate its effect on pain during anaesthesia recovery. METHODS: A retrospective study was conducted on the clinical data of 205 patients with prostatic hyperplasia who underwent TURP in our hospital from June 2020 to December 2022. All patients experienced epidural anaesthesia, and 110 patients who used ropivacaine combined with nalbuphine were included in the study group, whereas 95 patients who used ropivacaine and lidocaine were classified as the control group. The Visual Analogue Scale was used to evaluate the pain conditions of patients. The levels of pain mediators, such as substance P (SP), bradykinin (BK) and histamine (HIS), the stress levels, including cortisol (Cort), adrenocorticotropic hormone (ACTH) and norepinephrine (NE), and the incidence of adverse reactions were compared between the two groups. RESULTS: At T0 (postoperative 30 min), T1 (postoperative 60 min), T2 (postoperative 2 h) and T3 (postoperative 4 h), the study group had significantly lower pain scores (p < 0.01), levels of SP, BK and HIS (p < 0.001), and levels of Cort, ACTH and NE (p < 0.05) than the control group. No statistical difference was observed in the incidences of adverse reactions between the two groups (p > 0.05). CONCLUSIONS: The combination of ropivacaine and nalbuphine has a notable analgesic effect during anaesthesia recovery in patients undergoing TURP. It inhibits the secretion of pain and physical stress indicators and relieves postoperative pain to a large extent.

Eco-friendly Nanoparticles Synthesized from Salvia sclarea Ethanol Extract Protect against STZ-induced Diabetic Nephropathy in Rats via Antioxidant, Anti-inflammatory, and Apoptosis Mechanisms.

Recent global scientific attention has been directed towards eco-friendly synthesis and versatile applications of silver nanoparticles (AgNPs) due to their effectiveness against specific cells and tissues. This study aimed to develop a green synthesis method for AgNPs using ethanolic extract from Salvia sclarea aerial parts, and to assess their protective efficacy against streptozotocin (STZ)-induced diabetic nephropathy in rats. Additionally, antioxidant, anti-inflammatory, and apoptosis studies were conducted to understand their mode of action. Characterization via ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and X-ray diffraction (XRD) confirmed the formation of ethanol extract of Salvia sclarea silver nanoparticles (EESS AgNPs), with a distinctive absorption peak at 400 nm. Scanning electron microscopy (SEM) analysis revealed predominantly spherical and quasi-spherical shapes of the synthesized nanoparticles. The treatment procedure spanned for a period of 12 weeks in diabetic rats and were evaluated for inflammatory markers (tumor necrosis factor-α, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) and apoptosis markers (Bcl-2, Bax, cleaved-caspase-3). Results demonstrated that treatment with EESS AgNPs significantly reduced blood glucose levels compared to the diabetic group. Additionally, EESS AgNPs treatment led to a significant decrease in levels of pro-inflammatory cytokines TNF-α, IL-1ß, and PKC-ꞵ in renal cells. Furthermore, EESS AgNPs effectively modulated antioxidant enzyme concentrations, including GSH, SOD, GPx, and CAT, bringing them to acceptable levels. Administration of EESS AgNPs also resulted in a significant decrease in protein levels of Bax and activated caspase-3, while increasing expression of the anti-apoptotic protein Bcl-2 in renal cells of STZ-induced diabetic rats. In conclusion, EESS AgNPs demonstrate potent anti-hyperglycemic effects, potentially mitigating diabetic nephropathy by suppressing hyperglycemiainduced oxidative stress, apoptosis, and inflammation in renal cells of diabetic rats.

Dual Template Molecularly Imprinted Polymers Targeting Blockade of CD47 for Enhanced Macrophage Phagocytosis and Synergistic Antimetabolic Therapy.

Glycinamide ribonucleotide formyltransferase (GARFT) is an important enzyme in the folate metabolism pathway, and chemical drugs targeting GARFT have been used in tumor treatments over the past few decades. The development of novel antimetabolism drugs that target GARFT with improved performance and superior activity remains an attractive strategy. Herein, we proposed a targeted double-template molecularly imprinted polymer (MIP) for enhancing macrophage phagocytosis and synergistic antimetabolic therapy. The double-template MIP was prepared by imprinting the exposed peptide segment of the extracellular domain of CD47 and the active center of GARFT. Owing to the imprinted cavities on the surface of MIP, it can actively target cancer cells and mask the "do not eat me" signal upon binding to CD47 thereby blocking the CD47-SIRPα pathway and ultimately enhancing phagocytosis by macrophages. In addition, MIP can specifically bind to the active center of GARFT upon entry into the cells, thereby inhibiting its catalytic activity and ultimately interfering with the normal expression of DNA. A series of cell experiments demonstrated that MIP can effectively target CD47 overexpressed 4T1 cancer cells and inhibit the growth of 4T1 cells. The enhanced phagocytosis ability of macrophages-RAW264.7 cells was also clearly observed by confocal imaging experiments. In vivo experiments also showed that the MIP exhibited a satisfactory tumor inhibition effect. Therefore, this study provides a new idea for the application of molecular imprinting technology to antimetabolic therapy in conjunction with macrophage-mediated immunotherapy.

Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.

Development of a Prognostic Model for Gastric Cancer Based on Apoptosis- and Hypoxia-Related Genes: Predictive Insights into Survival and Immune Landscape.

Gastric cancer (GC) is the fifth most prevalent malignancy worldwide, characterized by poor prognosis. Apoptosis is interacted with hypoxia in tumorigenesis. This study attempted to delineate potential value of apoptosis and hypoxia-related genes (AHRGs) in prognosis of gastric cancer. Differential expression analysis was performed on GC transcriptomic data from TCGA. Apoptosis-related genes (ARGs) and hypoxia-related genes (HRGs) were obtained from MSigDB, followed by intersecting them with differentially expressed genes (DEGs) in GC. A prognostic model was constructed using univariate, LASSO, and multivariate regression analyses. The model was validated using a Gene Expression Omnibus dataset. DEGs between risk groups were subjected to enrichment analysis. A nomogram was plotted by incorporating clinical information. Non-negative matrix factorization based on core prognostic genes from the multifactorial model was employed to cluster tumor samples. The subsequent analyses involved immunophenoscore, immune landscape, Tumor Immune Dysfunction and Exclusion (TIDE) score, and chemosensitivity for distinct subtypes. A prognostic model based on AHRGs was established, and its predictive capability was verified in external cohorts. Riskscore was determined as an independent prognostic factor, and it was used, combined with other clinical features, to plot a prognostic nomogram. Patients were clustered into cluster1 and cluster2 based on prognostic model genes. Cluster2 showed poorer prognosis and IPS scores, higher immune cell infiltration, immune function and TIDE scores than cluster1. Distinct therapeutic potential for various chemotherapeutic agents was observed between the two clusters. The developed AHRG scoring introduced a novel and effective avenue for predicting GC prognosis and identifying potential targets for further investigation.

Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on "Enucleation" or "Nucleus-Retaining" of Cornus officinalis Fruits.

The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.

Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

The role of cardiac remodeling associated with renal function in mediating cardiovascular event outcomes.

The potential impact of renal function-related cardiovascular remodeling on associated cardiovascular risk has not been previously investigated. Hence, we conducted multiple mediation analyses in the UK Biobank study to evaluate this association. Using multiple Cox models, we found lower renal function (estimated glomerular filtration rate based on cystatin C, eGFR-cysC) was independently related to increased risks of various cardiovascular events and mortalities. Multivariable linear regression revealed a progressive relationship between declining eGFR-cysC and adverse left ventricular (LV) remodeling and impaired systolic function. In Cox models, larger LV volume, mass, as well as decreased systolic function, were significantly correlated with adverse events, particularly in heart failure. Mediation analyses showed that undesirable LV remodeling and cardiometabolic diseases were independent mediators. Our study explores the connections between reduced renal function and poor cardiovascular phenotypes, as well as their significant independent role in mediating renal function-cardiovascular outcome relationships.

Analysis of Risk Factors for Postoperative Dysuria in Patients Undergoing Thoracotomy under General Anaesthesia.

BACKGROUND: Thoracotomy under general anaesthesia is one of the most difficult surgeries and is prone to result in postoperative complications. This study explored risk factors for postoperative dysuria in patients undergoing thoracotomy under general anaesthesia to provide a reference for the formulation and selection of subsequent clinical management programs. METHODS: Patients undergoing thoracotomy under general anaesthesia (n = 179) admitted to our hospital from June 2019 to June 2021 were selected. They were divided into dysuria group (n = 79) and normal urination group (n = 100) according to whether they had dysuria after surgery. Logistic regression analysis was conducted to explore risk factors affecting postoperative dysuria. RESULTS: Univariate analysis showed that dysuria was related to gender, age, surgical time, intraoperative and postoperative infusion volume, usage time of analgesic pump and retention time of urethral catheter (p < 0.001). Logistic regression analysis showed that male, age ≥60 years, surgical time ≥120 min, intraoperative infusion volume >1200 mL, postoperative infusion volume >800 mL, analgesic pump usage time ≥18 h and urethral catheter retention time of ≥72 h were risk factors for postoperative dysuria. CONCLUSIONS: The occurrence of postoperative dysuria in patients undergoing thoracotomy under general anaesthesia is related to gender, age, surgical time, intraoperative infusion volume, postoperative infusion volume, usage time of analgesic pump and retention time of urethral catheter. Clinical attention should be given to this patient group, and targeted intervention measures should be implemented.

Effect of icariin on depressive behaviour in rat pups. Evidences for its mechanism of action by integrating network pharmacology, metabolomics and gut microbiota composition.

BACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear. PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups. METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing. RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour. CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.

Resveratrol Promotes Proliferation, Antioxidant Properties, and Progesterone Production in Yak (Bos grunniens) Granulosa Cells.

Resveratrol (RES) is a class of natural polyphenolic compounds known for its strong anti-apoptotic and antioxidant properties. Granulosa cells (GCs) are one of the important components of ovarian follicles and play crucial roles in follicular development of follicles in the ovary. Here, we explored the effects of RES on the proliferation and functions of yak GCs. Firstly, we evaluated the effect of RES dose and time in culture on the viability of GCs, and then the optimum treatment protocol (10 µM RES, 36 h) was selected to analyze the effects of RES on the proliferation, cell cycle, apoptosis, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) accumulation, lipid droplet content, ATP production, and steroidogenesis of GCs, as well as the expression of related genes. The results show that RES treatment significantly (1) increased cell viability and proliferation and inhibited cell apoptosis by upregulating BCL-2 and SIRT1 genes and downregulating BAX, CASP3, P53, and KU70 genes; (2) increased the proportion of GCs in the S phase and upregulated CCND1, PCNA, CDK4, and CDK5 genes; (3) reduced ROS accumulation and MDA content and increased GSH content, as well as upregulating the relative expression levels of CAT, SOD2, and GPX1 genes; (4) decreased lipid droplet content and increased ATP production; (5) promoted progesterone (P4) secretion and the expression of P4 synthesis-related genes (StAR, HSD3B1, and CYP11A1); and (6) inhibited E2 secretion and CYP19A1 expression. These findings suggest that RES at 10 µM increases the proliferation and antioxidant properties, inhibits apoptosis, and promotes ATP production, lipid droplet consumption, and P4 secretion of yak GCs.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

Validation of the European Kidney Function Consortium Equation in Chinese Adult Population: An Equation Standing on the Shoulders of Predecessors.

BACKGROUND: Equations based on serum creatinine (SCr) have been extensively applied to estimate glomerular filtration rate (GFR), but their performance is debatable. In 2021, the European Kidney Function Consortium (EKFC) published one novel SCr-based formula, which combined the feature of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and full age spectrum (FAS) equations, but its potential applications remain unknown. We seek to assess the appropriateness of the three equations in Chinese adults. METHODS: A total of 3,692 participants (median age, 54 years) were included. Reference GFR (rGFR) was measured by the 99mTc-DTPA renal dynamic imaging method. Estimated GFR (eGFR) was calculated by the CKD-EPI, FAS, and EKFC equations. Correlation coefficients and Bland-Altman analysis were adopted to evaluate their validity. The performance was assessed in subgroups according to age, sex, rGFR, and SCr, considering the bias, accuracy, and precision. RESULTS: The average rGFR was 74.2 mL/min/1.73 m2. eGFR by EKFC showed a relatively stronger correlation with rGFR (R = 0.749) and a larger area under the receiver operating characteristic curve (0.902). EKFC was significantly less biased and exhibited the highest P30 in the entire population (bias = 3.61, P30 = 73.3%). It also performed well in all analyzed subgroups, especially in participants with normal or slightly impaired renal function (rGFR≥60 mL/min/1.73 m2), and low SCr. CONCLUSIONS: Compared to the other two SCr-based formulas, EKFC performed better in the Chinese. Thus, it might serve as a good alternative, until a more suitable formula is developed for the Chinese population.

Tea polyphenols protect against Flavobacterium columnare-induced gill injury via suppression of oxidative stress, inflammation, and apoptosis in grass carp.

Flavobacterium columnare (F. columnare) is one of the deadliest fish pathogens causing bacterial gill rot disease in various freshwater fish species globally. Tea polyphenols (TPs) are an inexpensive product extracted from tea that have received much attention as a feed additive in aquaculture. The current study was designed to investigate the underlying mechanisms and protective effects of dietary TPs against F. columnare-induced gill injury via suppression of oxidative stress, apoptosis, and inflammation in grass carp. TPs were not supplemented to the diet (control) and were supplemented at 40, 80, 120, 160 or 200 mg/kg diet. The feeding experiment was carried out for 60 days, followed by a 3-Day F. columnare challenge test. The results showed that 120 mg/kg TPs in the diet exerted the following five protective effects in fish gill: (1) control gill-rot disease and improved histopathology, (2) inhibit excessive apoptosis, (3) enhance the activity of antioxidant enzymes and upregulate related gene expression via the Nrf2/Keap1 pathway, (4) increase the activity of immune enzymes, And (5) mediate inflammatory cytokine gene expression via the JAK/STAT3 pathway. Taken together, dietary supplementation with TPs is a compelling approach to protect the gill function of fish against F. columnare.

Thiol-Based Modification of MarR Protein VnrR Regulates Resistance Toward Nitrofuran in Vibrio cholerae By Promoting the Expression of a Novel Nitroreductase VnrA and of NO-Detoxifying Enzyme HmpA.

Aims: Epidemiological investigations have indicated low resistance toward nitrofuran in clinical isolates, suggesting its potential application in the treatment of multidrug-resistant bacteria. Therefore, it is valuable to explore the mechanism of bacterial resistance to nitrofuran. Results: Through phenotypic screening of ten multiple antibiotic resistance regulator (MarR) proteins in Vibrio cholerae, we discovered that the regulator VnrR (VCA1058) plays a crucial role in defending against nitrofuran, specifically furazolidone (FZ). Our findings demonstrate that VnrR responds to FZ metabolites, such as hydroxylamine, methylglyoxal, hydrogen peroxide (H2O2), ß-hydroxyethylhydrazine. Notably, VnrR exhibits reversible responses to the addition of H2O2 through three cysteine residues (Cys180, Cys223, Cys247), leading to the derepression of its upstream gene, vnrA (vca1057). Gene vnrA encodes a novel nitroreductase, which directly contributes to the degradation of FZ. Our study reveals that V. cholerae metabolizes FZ via the vnrR-vnrA system and achieves resistance to FZ with the assistance of the classical reactive oxygen/nitrogen species scavenging pathway. Innovation and Conclusion: This study represents a significant advancement in understanding the antibiotic resistance mechanisms of V. cholerae and other pathogens. Our findings demonstrate that the MarR family regulator, VnrR, responds to the FZ metabolite H2O2, facilitating the degradation and detoxification of this antibiotic in a thiol-dependent manner. These insights not only enrich our knowledge of antibiotic resistance but also provide new perspectives for the control and prevention of multidrug-resistant bacteria.

Secondary ocular hypertension due to tentorial dural arteriovenous fistula: a case report.

BACKGROUND: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported. CASE PRESENTATIONS: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups. CONCLUSION: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension.

The prevalence, related factors and interventions of oncology nurses' burnout in different continents: A systematic review and meta-analysis.

BACKGROUND: Burnout is a significant occupational problem among oncology nurses, affecting their physical and mental health and the quality of medical care. Besides, there is a gradually increasing trend that we should pay more attention to. OBJECTIVES: To investigate the prevalence, influencing factors and interventions of oncology nurses' burnout among different continents. DESIGN: Systematic review and meta-analysis. DATA SOURCES: English literature in PubMed, EMBASE, MEDLINE/EBSCOhost, CINAHL Complete and Web and of Science were searched before 1 March 2022. RESULTS: Twenty studies included 5904 oncology nurses in this review. Meta-analysis was performed in 19 of the studies. First, the pooled mean scores estimate for emotional exhaustion (EE) was 22.13 (95% CI: 19.69-24.58), depersonalization (DP) was 6.89 (95% CI: 5.67-8.10) and personal accomplishment (PA) was 32.86 (95% CI: 29.34-36.37). A high level of burnout was defined as a high level of EE (score ≥ 27), a high level of DP (score ≥ 10), and a low level of PA (score ≤ 33). Of these, 36.40% of nurses reported high EE, 28.26% reported high DP and 28.68% reported low levels of PA. Furthermore, there are differences in the prevalence, influencing factors and intervention measures of burnout among oncology nurses in different regions. The highest pooled mean scores for EE and DP were found in Asia. And the highest pooled mean scores for PA were found in the Americas. The factors that influence burnout among Asian oncology nurses are mostly personal-related factors such as empathy and personality traits, while the factors that influence burnout among European oncology nurses are work-related factors. This review included three intervention studies from Europe and the Americas, with fewer intervention studies on burnout in oncology nurses in Asia. CONCLUSION: Oncology nurses in Asia had the highest pooled mean scores for EE and DP, and the highest mean scores for the PA pool in the Americas. There are regional differences in the prevalence and factors influencing burnout among oncology nurses, but there are few interventions for it. Therefore, future interventions should be developed to address the differences that exist in different regions. RELEVANCE TO CLINICAL PRACTICE: Burnout among oncology nurses in different regions is a concern, and this review may provide a reference for managers to target interventions to alleviate burnout among oncology nurses.

Elucidating the cell metabolic heterogeneity during hematopoietic lineage differentiation based on Met-Flow.

Cell metabolism is critically involved in the differentiation of the hematopoietic lineage and, therefore, has attracted the attention of researchers, however, in-depth studies on cellular metabolic activity of hematopoietic cells (HCs) require attention. This investigation compared the metabolic activity of HCs at critical lineage differentiation stages, including hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and differentiated blood cells, via multiple methods and basic reference values. Primary metabolic processes of HCs, including anabolism, catabolism, phosphate, and glucose metabolism, were analyzed, and their maps were drawn. The data revealed that GLUT1 expression in HSCs was substantially higher than in all progenitor cells and mature myeloid blood cells, indicating their strong glucose uptake capacity. In myeloid differentiation, the ACAC expression of HPC2 was markedly higher than in neutrophils and monocytes. The ACAC, ASS1, ATP5A, and PRDX2 of HPC2 expression in lymphoid differentiation was substantially greater than in B and Natural-killer cells. CLP, CMP, GMP, MEP, and HPC1 inherit increased glucose uptake stem cell properties. In lymphocyte subsets, the expression of ACAC, ASS1, ATP5A, CPT1A, and PRDX2 in CD4+ T subgroups (naive and memory CD4+ T and nTreg) were elevated than in B subgroups (pro-, pre-, immature and mature Bs) and CD8+ T subgroups. Furthermore, leukemia stem cells (LSCs) had increased levels of ACAC, CPT1A, G6PD, IDH2, and PRDX2 than leukemia cells, indicating a stronger metabolic capacity of LSCs than differentiated leukemia cells.