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Abstract Over the past few decades, the expanded applications of in-vivo confocal microscopy (IVCM) have greatly enhanced the knowledge of a variety of conjunctival diseases. IVCM allows non-invasively detailed observation of tarsal, palpebral and bulbar conjunctiva, from the superficial to the substantia propria at the cellular level. IVCM has been shown as a powerful tool for the assessment of morphological changes in both physiological and pathological conditions. High-resolution images of different cellular phenotypes, together with quantifiable results, open new insights into understanding the mechanisms of conjunctival diseases, as well as provide valuable and longitudinal information for the diagnosis and therapeutic evaluation. This review aims to provide an overview of the current knowledge on the applications of IVCM on conjunctival disorders, including aging changes, dry eye-related morphological changes, glaucoma and glaucoma surgery-related morphological changes, conjunctival neoplasm, pterygium, allergic conjunctivitis, trachomatous scarring, and the conjunctiva-associated lymphoid tissue (CALT) changes. In this review, we highlight the key findings of previous studies and discusses the current limitations and challenges of IVCM in assessing the structural characteristics of the conjunctiva. Furthermore, we consider possible future directions for unlocking the full potential of IVCM applications. The insights presented here will contribute to a more comprehensive understanding of the applications of IVCM in conjunctival diseases.

Abstract Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, with a rising incidence. Traditional treatments, such as thyroidectomy and radiotherapy, often lead to significant side effects, including impaired thyroid function. Therefore, there is an urgent need for non-invasive therapeutic approaches. This study aims to explore the potential of photobiomodulation therapy (PBMT), a non-invasive treatment using specific wavelengths of light, in the management of PTC. Methods We investigated the effects of blue light PBMT on PTC cells, focusing on the Retinal-OPSIN 3 (OPN3) complex’s role in mediating cellular responses. Blue light exposure was applied to PTC cells, and subsequent changes in cellular proliferation, cell cycle progression, and protein expression were analyzed. Statistical tests, including one-way ANOVA and t-tests, were used to evaluate the significance of the findings. Results Blue light exposure led to the dissociation of 11-cis-retinal from OPN3, resulting in the accumulation of all-trans retinal. This accumulation disrupted cellular proliferation pathways and induced G0/G1 cell cycle arrest in PTC cells. The Retinal-OPN3 complex was found to be a key mediator in these processes, demonstrating that thyroid cells can respond to specific light wavelengths and utilize their photoreceptive potential for therapeutic purposes. Conclusions Our findings suggest that PBMT, through the modulation of the Retinal-OPN3 complex, offers a promising non-invasive approach for treating PTC. This study highlights the therapeutic potential of light signal transduction in non-ocular tissues and opens new avenues for non-invasive cancer therapies.

Abstract Background Edaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context. Methods Cost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1–4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed. Results In the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection. Conclusions Using 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.

Abstract Background Pulmonary fibrosis is a serious interstitial lung disease with no viable treatment except for lung transplantation. Glucagon-like peptide-1 receptor (GLP-1R), commonly regarded as an antidiabetic target, exerts antifibrotic effects on various types of organ fibrosis. However, whether GLP-1R modulates the development and progression of pulmonary fibrosis remains unclear. In this study, we investigated the antifibrotic effect of GLP-1R using in vitro and in vivo models of pulmonary fibrosis. Methods A silica-induced pulmonary fibrosis mouse model was established to evaluate the protective effects of activating GLP-1R with liraglutide in vivo. Primary cultured lung fibroblasts treated with TGF-β1 combined with IL-1β (TGF-β1 + IL-1β) were used to explore the specific effects of liraglutide, MCC950, and 3PO on fibroblast activation in vitro. Cell metabolism assay was performed to determine the glycolytic rate and mitochondrial respiration. RNA sequencing was utilized to analyse the underlying molecular mechanisms by which liraglutide affects fibroblast activation. ChIP‒qPCR was used to evaluate histone lactylation at the promoters of profibrotic genes in TGF-β1 + IL-1β- or exogenous lactate-stimulated lung fibroblasts. Results Activating GLP-1R with liraglutide attenuated pulmonary inflammation and fibrosis in mice exposed to silica. Pharmacological inhibition of the NLRP3 inflammasome suppressed PFKFB3-driven glycolysis and vice versa, resulting in decreased lactate production in TGF-β1 + IL-1β-stimulated lung fibroblasts. Activating GLP-1R inhibited TGF-β1 + IL-1β-induced fibroblast activation by disrupting the interaction between the NLRP3 inflammasome and PFKFB3-driven glycolysis and subsequently prevented lactate-mediated histone lactylation to reduce pro-fibrotic gene expression. In addition, activating GLP-1R protected mitochondria against the TGF-β1 + IL-1β-induced increase in oxidative phosphorylation in fibroblasts. In exogenous lactate-treated lung fibroblasts, activating GLP-1R not only repressed NLRP3 inflammasome activation but also alleviated p300-mediated histone lactylation. Finally, GLP-1R activation blocked silica-treated macrophage-conditioned media-induced lung fibroblast activation. Conclusions The antifibrotic effects of GLP-1R activation on pulmonary fibrosis could be attributed to the inhibition of the interaction between NLRP3 inflammasome and PFKFB3-driven glycolysis, and histone lactylation in lung fibroblasts. Thus, GLP-1R is a specific therapeutic target for the treatment of pulmonary fibrosis.

Abstract Background Females with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group. Objective The primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs). Methods A total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02). Results According to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM. Conclusion(s) Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Abstract Background Trachelospermum jasminoides has medicinal and ornamental value and is widely distributed in China. Although the chloroplast genome has been documented, the mitochondrial genome has not yet been studied. Results The mitochondrial genome of T. jasminoides was assembled and functionally annotated using Illumina and nanopore reads. The mitochondrial genome comprises a master circular molecular structure of 605,764 bp and encodes 65 genes: 39 protein-coding genes, 23 transfer RNA (tRNA) genes and 3 ribosomal RNA genes. In addition to the single circular conformation, we found many alternative conformations of the T. jasminoides mitochondrial genome mediated by 42 repetitive sequences. Six repetitive sequences (DRS01–DRS06) were supported by nanopore long reads, polymerase chain reaction (PCR) amplifications, and Sanger sequencing of the PCR products. Eleven homologous fragments were identified by comparing the mitochondrial and chloroplast genome sequences, including three complete tRNA genes. Moreover, 531 edited RNA sites were identified in the protein-coding sequences based on RNA sequencing data, with nad4 having the highest number of sites (54). Conclusion To our knowledge, this is the first description of the mitochondrial genome of T. jasminoides. Our results demonstrate the existence of multiple conformations. These findings lay a foundation for understanding the genetics and evolutionary dynamics of Apocynaceae.

Abstract Background Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer’s solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke. Methods Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins. Results Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived. Conclusions NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

Abstract Background With the increasing prevalence of obesity, there is growing awareness of the impact of overweight and obesity on total hip arthroplasty (THA). Research exploring the accuracy of acetabular component orientation in THA between robotic-assisted and manual techniques across different BMI categories is insufficient. Methods This prospective study evaluated 221 patients who underwent THA with a Robotic Interactive Orthopaedic Arm system and 252 patients who underwent manual THA between March 2022 and January 2024. The patients were divided into four groups according to their BMI. We analysed whether there were differences in the accuracy of acetabular component positioning between robotic-assisted THA and manual THA across different BMI categories. Results In the overweight group, robotic-assisted THA achieved a significantly higher rate of abductions within the target range (73/6) than manual THA (62/28) (p = 0.000). Both abductions and anteversions within the target range were also significantly more frequent in the robotic-assisted THA group (69/10) than in the manual THA group (56/34) (p = 0.000). Among the obese patients, robotic-assisted THA showed a perfect record for anteversions within the target range (29/0), markedly outperforming manual THA (39/6) (p = 0.040). Conclusion In the overweight (24 kg/m² ≤ BMI

Abstract Background Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids. Method We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20–22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo. Results ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments. Conclusions Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars. Graphical Abstract

Abstract Background The mandibular retromolar space (RMS) has not been extensively studied in relation to various sagittal skeletal classes and patterns of third-molar eruption. The objective of this study was to test the null hypothesis that there is no difference in the mandibular RMS among normodivergent subjects with different skeletal classes and patterns of mandibular third-molar eruption, using cone-beam computed tomography (CBCT). Method A total of 105 normodivergent patients (20–40 years) were included in this study. Participants were categorized into Class I, II and III groups based on ANB and further impacted and erupted groups based on the eruption patterns of the mandibular third molars. Measurements of the mandibular RMS were taken at four planes parallel to the occlusal plane, along the cusp line. Comparative analyses were conducted among the three sagittal groups and between the impacted and erupted groups. Results The Class II group exhibited a statistically smaller RMS (P

Abstract Background There is a serious public health concern regarding the emergence of carbapenem-resistant Escherichia coli (CREC). The purpose of this study is to identify the molecular characterization and risk factors of CREC in Fujian province, China. Methods A total of 48 CREC isolates were collected from various clinical samples. The strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Susceptibility to antibiotics was determined by the standard broth microdilution method. Polymerase chain reaction (PCR) was used to screen common drug resistance genes. Multilocus sequence typing (MLST) was used to type isolates. RT-qPCR was used to detect gene expression of acrA, acrB, and tolC. Conjugation assays were used to analyze the transferability of plasmids carrying mcr-1 or bla NDM. Risk factors for CREC infection were identified by logistic regression analysis. Results 48 CREC strains were collected, with 81.25% producing carbapenemase (CP-CREC), and 18.75% were not producing carbapenemase (no-CP-CREC). They belonged to 21 sequence type (STs) and five unknown STs. Perianal swabs were the main sample type, with 25 patients found to have hematological malignancies. All isolates of CP-CREC were found to contain bla NDM (bla NDM−5 (n = 32), bla NDM−1 (n = 5), bla NDM−4 (n = 1), and bla NDM−13 (n = 1)), among which one isolate co-existence bla NDM−5 and bla OXA−48. Two bla NDM-positive strains, specifically bla NDM−5 and bla NDM−4, were found to co-habor mcr-1 with ST617. Conjugation assays confirmed that bla NDM−1, bla NDM−13, and most bla NDM−5(68.75%, 22/32) could be transferred between E. coli strains. Four of the 9 non-CP-CREC isolates had deletions in ompC and ompF with bla CTX−M production, while the other five showed high expression of acrA, acrB, and tolC. Antibiotics usage, antifungal treatment, detection of other pathogens (prior to CREC infection), and respiratory disease were identified as independent risk factors for CREC infection. The area under the receiver operating characteristic curve for the scoring system was 0.937. Youden’s index, with sensitivity and specificity of 0.96 and 0.78, was maximal when 2 points were scored. Conclusions In CP-CREC, carbapenem resistance is caused primarily by multiple types of bla NDM, while non-CP-CREC is caused by loss of porin protein or high expression of efflux pumps coupled with carrying bla CTX−M. CREC isolates were highly diverse in terms of ST, with a total of 21 STs identified. Here, we first describe a clinical strain of CREC from China both mcr-1 and bla NDM −4 with ST617. An easy-to-use scoring system was developed to diagnose CREC infections.

Abstract Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Abstract Background Premarital sexual behavior (PSB) is a controversial topic in China. However, in recent times, changes in attitudes have led to PSB being more common among college students. This study investigated the attitudes of Chinese undergraduates toward PSB to identify whether a typological classification exists among them. Methods A total of 278 undergraduate students from two public universities in Mainland China completed a 17-item survey that included five dimensions( emotions, responsiveness, sexual health, sexual freedom, and condemnation) on attitudes toward PSB. Data were collected online from April 2023 to July 2023. Results The PSB questionnaire demonstrated good reliability and construct validity in this study, with a Cronbach’s α of 0.759 and a KMO value of 0.769. Meanwhile, a series of models were estimated specifying one through five latent classes and three typologies on the attitude were identified: “Affective,”“Avoidant,” and “Open.” After the best fitting model was determined, multiple analysis of variance testing of different factors such as gender, year of study and where one came from were found to have significant effects on attitude complexity (p

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix (ECM) deposition. However, current treatments are not satisfactory. Therefore, more effective therapies need to be explored. Cepharanthine (CEP) is a naturally occurring alkaloid that has recently been reported to have multiple pharmacological effects, particularly in chronic inflammation. Methods For in vivo experiments, first, a pulmonary fibrosis murine model was generated via tracheal injection of bleomycin (BLM). Second, the clinical manifestations and histopathological changes of the mice were used to verify that treatment with CEP might significantly reduce BLM-induced fibrosis. Furthermore, flow cytometric analysis was used to analyze the changes in the number of M2 macrophages in the lung tissues before and after treatment with CEP to explore the relationship between macrophage M2 polarization and pulmonary fibrosis. In vitro, we constructed two co-culture systems (THP-1 and MRC5 cells, RAW264.7 and NIH 3T3 cells), and measured the expression of fibrosis-related proteins to explore whether CEP could reduce pulmonary fibrosis by regulating macrophage M2 polarization and fibroblast activation. Results The results showed that the intranasal treatment of CEP significantly attenuated the symptoms of pulmonary fibrosis induced by BLM in a murine model. Our findings also indicated that CEP treatment markedly reduced the expression of fibrosis markers, including TGF-β1, collagen I, fibronectin and α-SMA, in the mouse lung. Furthermore, in vitro studies demonstrated that CEP attenuated pulmonary fibrosis by inhibiting fibroblast activation through modulating macrophage M2 polarization and reducing TGF-β1 expression. Conclusions This study demonstrated the potential and efficacy of CEP in the treatment of pulmonary fibrosis. In particular, this study revealed a novel mechanism of CEP in inhibiting fibroblast activation by regulating macrophage M2 polarization and reducing the expression of fibrosis-associated factors. Our findings open a new direction for future research into the treatment of pulmonary fibrosis.

Abstract Background Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. Methods Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. Results By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. Conclusions Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts. Graphical Abstract

Abstract Background Benzyl acetate is an aromatic ester with a jasmine scent. It was discovered in plants and has broad applications in food, cosmetic, and pharmaceutical industries. Its current production predominantly relies on chemical synthesis. In this study, Escherichia coli was engineered to produce benzyl acetate. Results Two biosynthetic routes based on the CoA-dependent β-oxidation pathway were constructed in E. coli for benzyl acetate production. In route I, benzoic acid pathway was extended to produce benzyl alcohol by combining carboxylic acid reductase and endogenous dehydrogenases and/or aldo-keto reductases in E. coli. Benzyl alcohol was then condensed with acetyl-CoA by the alcohol acetyltransferase ATF1 from yeast to form benzyl acetate. In route II, a plant CoA-dependent β-oxidation pathway via benzoyl-CoA was assessed for benzyl alcohol and benzyl acetate production in E. coli. The overexpression of the phosphotransacetylase from Clostridium kluyveri (CkPta) further improved benzyl acetate production in E. coli. Two-phase extractive fermentation in situ was adopted and optimized for benzyl acetate production in a shake flask. The most optimal strain produced 3.0 ± 0.2 g/L benzyl acetate in 48 h by shake-flask fermentation. Conclusions We were able to establish the whole pathway for benzyl acetate based on the CoA-dependent β-oxidation in single strain for the first time. The highest titer for benzyl acetate produced from glucose by E. coli is reported. Moreover, cinnamyl acetate production as an unwanted by-product was very low. Results provided novel information regarding the engineering benzyl acetate production in microorganisms. Graphical abstract

Abstract Background The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. Methods 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017–2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. Results In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11–2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04–3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745–0.819), which was assessed by DCA to be clinically important. Conclusion In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Abstract Accurate fluorescence imaging of nanocarriers in vivo remains a challenge owing to interference derived mainly from biological tissues and free probes. To address both issues, the current study explored fluorophores in the near-infrared (NIR)-II window with aggregation-caused quenching (ACQ) properties to improve imaging accuracy. Candidate fluorophores with NIR-II emission, ACQ984 (λ em = 984 nm) and IR-1060 (λ em = 1060 nm), from the aza-BODIPY and cyanine families, respectively, were compared with the commercial fluorophore ICG with NIR-II tail emission and the NIR-I fluorophore P2 from the aza-BODIPY family. ACQ984 demonstrates high water sensitivity with complete fluorescence quenching at a water fraction greater than 50%. Physically embedding the fluorophores illuminates various nanocarriers, while free fluorophores cause negligible interference owing to the ACQ effect. Imaging based on ACQ984 revealed fine structures in the vascular system at high resolution. Moreover, good in vivo and ex vivo correlations in the monitoring of blood nanocarriers can be established, enabling real-time noninvasive in situ investigation of blood pharmacokinetics and dynamic distribution in various tissues. IR-1060 also has a good ACQ effect, but the lack of sufficient photostability and steady post-labeling fluorescence undermines its potential for nanocarrier bioimaging. P2 has an excellent ACQ effect, but its NIR-I emission only provides nondiscriminative ambiguous images. The failure of the non-ACQ probe ICG to display the biodistribution details serves as counterevidence for the improved imaging accuracy by NIR-II ACQ probes. Taken together, it is concluded that fluorescence imaging of nanocarriers based on NIR-II ACQ probes enables accurate in vivo bioimaging and real-time in situ pharmacokinetic analysis.

Abstract Background Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. Methods Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. Results A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein–Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test 0.3 & P 0.3 & P

Abstract Background Healthcare-associated infections (HAIs) are important indicators of healthcare quality. The aseptic non touch technique (ANTT), a standardised aseptic technique, is a crucial preventative measure against HAIs. However, there is insufficient evidence currently available regarding ANTT awareness and proficiency among nurses. This study aimed to investigate the status of ANTT proficiency in a cohort of nurses and analyse the associated risk factors, with the ultimate goal of providing a reference for promoting the application of ANTT in clinical practice. Methods The study population was sampled from nurses working in a tertiary hospital in Zhejiang Province, China, in January 2024. A cross-sectional survey was conducted using a self-designed questionnaire to assess ANTT knowledge. Multivariate linear regression analysis was used to analyse the risk factors influencing ANTT knowledge in nurses. Results A total of 458 nurses were included in this study. The cohort had an overall score of 49.7% correct responses on the ANTT knowledge questionnaire, with a mean score of 12.4 ± 2.4 out of 25, and 30.1% of the nurses felt that they did not need training related to ANTT. Multivariate linear regression analysis indicated that professional title, educational level, and the need for ANTT training were independently associated with ANTT knowledge in nurses. Nurses with Master’s degrees and associated chief nurses were observed to have higher levels of ANTT knowledge compared to the rest. Conclusions ANTT knowledge is insufficient among nurses in China, and its importance is not widely recognised. Continuous efforts are required to strengthen this knowledge. Constructing sustained, multiform, and stratified training programmes may represent an effective method to strengthen ANTT knowledge among nurses and promote its clinical use.

Abstract Background Herpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare. Case Presentation This article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve. Conclusions Secondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

Abstract Background Pneumoconiosis has a significant impact on the quality of patient survival due to its difficult staging diagnosis and poor prognosis. This study aimed to develop a computer-aided diagnostic system for the screening and staging of pneumoconiosis based on a multi-stage joint deep learning approach using X-ray chest radiographs of pneumoconiosis patients. Methods In this study, a total of 498 medical chest radiographs were obtained from the Department of Radiology of West China Fourth Hospital. The dataset was randomly divided into a training set and a test set at a ratio of 4:1. Following histogram equalization for image enhancement, the images were segmented using the U-Net model, and staging was predicted using a convolutional neural network classification model. We first used Efficient-Net for multi-classification staging diagnosis, but the results showed that stage I/II of pneumoconiosis was difficult to diagnose. Therefore, based on clinical practice we continued to improve the model by using the Res-Net 34 Multi-stage joint method. Results Of the 498 cases collected, the classification model using the Efficient-Net achieved an accuracy of 83% with a Quadratic Weighted Kappa (QWK) score of 0.889. The classification model using the multi-stage joint approach of Res-Net 34 achieved an accuracy of 89% with an area under the curve (AUC) of 0.98 and a high QWK score of 0.94. Conclusions In this study, the diagnostic accuracy of pneumoconiosis staging was significantly improved by an innovative combined multi-stage approach, which provided a reference for clinical application and pneumoconiosis screening.

Abstract Background Salt is an important factor that affects crop productivity. Plant hexokinases (HXKs) are key enzymes in the glycolytic pathway and sugar signaling transduction pathways of plants. In previous studies, we identified and confirmed the roles of GmHXK2 in salt tolerance. Results In this study, we analyzed the tissue-specific expression of GmHXK2 at different growth stages throughout the plant’s life cycle. The results showed that GmHXK2 was expressed significantly in all tissues at vegetative stages, including germination and seedling. However, no expression was detected in the pods, and there was little expression in flowers during the later mature period. Arabidopsis plants overexpressing the GmHXK2 (OE) had more lateral roots. The OE seedlings also produced higher levels of auxin and ascorbic acid (AsA). Additionally, the expression levels of genes PMM, YUC4/YUC6/YUC8, and PIN/LAX1,LAX3, which are involved respectively in the synthesis of AsA and auxin, as well as polar auxin transport, were upregulated in OE plants. This upregulation occurred specifically under exogenous glucose treatment. AtHKT1, AtSOS1, and AtNHX1 were up-regulated in OE plants under salt stress, suggesting that GmHXK2 may modulate salt tolerance by maintaining ion balance within the cells and alleviating damage caused by salt stress. Additionally, we further confirmed the interaction between GmHXK2 and the protein GmPMM through yeast two-hybridization and bimolecular fluorescence complementation assays, respectively. Conclusion The expression of GmHXK2 gene in plants is organ-specific and developmental stage specific. GmHXK2 not only regulates the synthesis of AsA and the synthesis and distribution of auxin, but also promotes root elongation and induces lateral root formation, potentially enhancing soil water absorption. This study reveals the crosstalk between sugar signaling and hormone signaling in plants, where GmHXK2 acts as a glucose sensor through its interaction with GmPMM, and sheds light on the molecular mechanism by which GmHXK2 gene is involved in salt tolerance in plants.

Abstract Background Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. Methods We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM−)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman’s analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. Results In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM−) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM−) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = − 0.399; radial, r = − 0.362; circumferential, r = − 0.389) (all P

Abstract Background Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length. Methods In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed. Results We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation. Conclusions Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.

Abstract Background Escherichia. coli is the most frequent host for New Delhi metallo-β-lactamase (NDM) which hydrolyzes almost all β-lactams except aztreonam. The worldwide spread of blaNDM-carrying E. coli heavily threatens public health. Objective This study aimed to explore the global genomic epidemiology of blaNDM- carrying E. coli isolates, providing information for preventing the dissemination of such strains. Methods Global E. coli genomes were downloaded from NCBI database and blaNDM was detected using BLASTP. Per software was used to extract meta information on hosts, resources, collection data, and countries of origin from GenBank. The sequence types (STs) and distribution of antimicrobial resistance gene (ARG) were analyzed by CLC Workbench; Plasmid replicons, serotypes and virulence genes (VFs) were analyzed by submitting the genomes to the websites. Statistical analyses were performed to access the relationships among ARGs and plasmid replicons. Results Until March 2023, 1,774 out of 33,055 isolates collected during 2003–2022 were found to contain blaNDM in total. Among them, 15 blaNDM variants were found with blaNDM-5 (74.1%) being most frequent, followed by blaNDM-1 (16.6%) and blaNDM-9 (4.6%). Among the 213 ARGs identified, 27 blaCTX-M and 39 blaTEM variants were found with blaCTX-M-15 (n = 438, 24.7%) and blaTEM-1B (n = 1092, 61.6%) being the most frequent ones, respectively. In addition, 546 (30.8%) plasmids mediated ampC genes, 508 (28.6%) exogenously acquired 16 S rRNA methyltransferase encoding genes and 262 (14.8%) mcr were also detected. Among the 232 distinct STs, ST167 (17.2%) were the most prevalent. As for plasmids, more than half of isolates contained IncFII, IncFIB and IncX3. The VF terC, gad, traT and iss as well as the serotypes O101:H9 (n = 231, 13.0%), O8:H9 (n = 115, 6.5%) and O9:H30 (n = 99, 5.6%) were frequently observed. Conclusions The study delves into the intricate relationship between plasmid types, virulence factors, and ARGs, which provides valuable insights for clinical treatment and public health interventions, and serves as a critical resource for guiding future research, surveillance, and implementation of effective strategies to address the challenges posed by blaNDM-carrying E. coli. The findings underscore the urgent need for sustained global collaboration, surveillance efforts, and antimicrobial stewardship to mitigate the impact of these highly resistant strains on public health.

Abstract Purpose The risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion. Methods This retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis. Results Risk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively. Conclusions Risk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.

Abstract Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.

Abstract Background Citrus is a major fruit crop, and RNA-sequencing (RNA-seq) data can be utilized to investigate its gene functions, heredity, evolution, development, and the detection of genes linked to essential traits or resistance to pathogens. However, it is challenging to use the public RNA-seq datasets for researchers without bioinformatics training, and expertise. Results OrangeExpDB is a web-based database that integrates transcriptome data of various Citrus spp., including C. limon (L.) Burm., C. maxima (Burm.) Merr., C. reticulata Blanco, C. sinensis (L.) Osbeck, and Poncirus trifoliata (L.) Raf., downloaded from the NCBI SRA database. It features a blast tool for browsing and searching, enabling quick download of expression matrices for different transcriptome samples. Expression of genes of interest can be easily generated by searching gene IDs or sequence similarity. Expression data in text format can be downloaded and presented as a heatmap, with additional sample information provided at the bottom of the webpage. Conclusions Researchers can utilize OrangeExpDB to facilitate functional genomic analysis and identify key candidate genes, leveraging publicly available citrus RNA-seq datasets. OrangeExpDB can be accessed at http://www.orangeexpdb.com/ .

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and insidious postoperative complication. This study aimed to evaluate the relationship between the triglyceride-glucose index (TyG) and MINS in advanced-age patients. Methods We performed a single-center retrospective study including patients ≥ 65 years of age who underwent non-cardiac surgery. The relationship between TyG and MINS was investigated using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis involved three models: Model I adjusted for preoperative factors, Model II adjusted for surgery-related factors, and Model III adjusted for both preoperative and surgery-related factors. Propensity score matching (PSM) was used to reduce the confounding effects of covariates. Subgroup analyses were then performed to evaluate the relationship between TyG and MINS in various subsamples. Results A total of 7789 patients were studied, among whom 481 (6.2%) developed MINS. A cut-off value of TyG of 8.57 was determined using a receiver operating characteristic (ROC) curve to be associated with the best predictive performance. Participants with TyG ≥ 8.57 were at a higher risk of developing MINS than those with TyG

Abstract Background Patients with a Breast Imaging Reporting and Data System (BI-RADS) 4 mammogram are currently recommended for biopsy. However, 70–80% of the biopsies are negative/benign. In this study, we developed a deep learning classification algorithm on mammogram images to classify BI-RADS 4 suspicious lesions aiming to reduce unnecessary breast biopsies. Materials and methods This retrospective study included 847 patients with a BI-RADS 4 breast lesion that underwent biopsy at a single institution and included 200 invasive breast cancers, 200 ductal carcinoma in-situ (DCIS), 198 pure atypias, 194 benign, and 55 atypias upstaged to malignancy after excisional biopsy. We employed convolutional neural networks to perform 4 binary classification tasks: (I) benign vs. all atypia + invasive + DCIS, aiming to identify the benign cases for whom biopsy may be avoided; (II) benign + pure atypia vs. atypia-upstaged + invasive + DCIS, aiming to reduce excision of atypia that is not upgraded to cancer at surgery; (III) benign vs. each of the other 3 classes individually (atypia, DCIS, invasive), aiming for a precise diagnosis; and (IV) pure atypia vs. atypia-upstaged, aiming to reduce unnecessary excisional biopsies on atypia patients. Results A 95% sensitivity for the “higher stage disease” class was ensured for all tasks. The specificity value was 33% in Task I, and 25% in Task II, respectively. In Task III, the respective specificity value was 30% (vs. atypia), 30% (vs. DCIS), and 46% (vs. invasive tumor). In Task IV, the specificity was 35%. The AUC values for the 4 tasks were 0.72, 0.67, 0.70/0.73/0.72, and 0.67, respectively. Conclusion Deep learning of digital mammograms containing BI-RADS 4 findings can identify lesions that may not need breast biopsy, leading to potential reduction of unnecessary procedures and the attendant costs and stress.

Abstract Background The relationship between the triglyceride–glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes. Methods We used data from the 2003–2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted. Results The study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes. Conclusions A higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients.

Abstract Background Although studies have demonstrated the value of the triglyceride–glucose (TyG) index for cardiovascular disease (CVD) and cardiovascular mortality, however, few studies have shown that the TyG index is associated with all-cause or CVD mortality in young patients with diabetes. This study aimed to investigate the association between the TyG index and all-cause and CVD mortality in young patients with diabetes in the United States. Methods Our study recruited 2440 young patients with diabetes from the National Health and Nutrition Examination Survey (NHANES) 2001–2018. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Cox regression modeling was used to investigate the association between TyG index and mortality in young patients with diabetes. The nonlinear association between TyG index and mortality was analyzed using restricted cubic splines (RCS), and a two-segment Cox proportional risk model was constructed for both sides of the inflection point. Results During a median follow-up period of 8.2 years, 332 deaths from all causes and 82 deaths from cardiovascular disease were observed. Based on the RCS, the TyG index was found to have a U-shaped association with all-cause and CVD mortality in young patients with diabetes, with threshold values of 9.18 and 9.16, respectively. When the TyG index was below the threshold value (TyG index

Abstract Background and Aim The impact of trace elements and heavy metals on human health has attracted widespread attention. However, the correlation between urinary chromium concentrations and blood pressure remains unclear and inadequately reported, and the aim of this study was to investigate the relationship between urinary chromium concentrations and blood pressure in adults in the United States (US). Methods We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 for this study. Multivariate logistic regression and multivariate linear regression were used to explore the association of urinary chromium concentrations with hypertension and blood pressure. Additionally, we also performed subgroup analysis and restricted cubic splines (RCS). Results A total of 2958 participants were enrolled in this study. The overall mean systolic blood pressure and diastolic blood pressure were 123.98 ± 0.60, 72.66 ± 0.57 mmHg, respectively. The prevalence of hypertension was found in 41.31% of the whole participants. In the fully adjusted model, we did not observe a correlation between urinary chromium concentrations and the risk of hypertension and systolic blood pressure. However, we found a negative association between urinary chromium concentrations and diastolic blood pressure. In subgroup analysis, we observed a positive association between urinary chromium and the risk of hypertension among participants older than 60 years of age and those who were Non-Hispanic Black. The interaction term highlighted the influence of age and race on this positive association. We also found a negative association of urinary chromium with diastolic blood pressure in male, participants who were current smokers, overweight, and other races, as well as those without alcohol use and anti-hypertensive drug use. However, the interaction term only revealed the influence of alcohol consumption on the negative association. Conclusion Our study suggested that urinary chromium concentrations may show a negative association with diastolic blood pressure and this association was significantly dependent on alcohol consumption. Besides, a positive association between urinary chromium and the risk of hypertension was also found among participants older than 60 years of age and those who were Non-Hispanic Black.

Abstract Background The association between the triglyceride-glucose (TyG) index and the likelihood of developing cardiovascular disease (CVD) in the general elderly population in the United States aged 60 and above is not well understood. The objective of our study was to examine the relationship between the TyG index and CVD likelihood in the general elderly population over 60 years of age in the United States. Methods Data for this cross-sectional study were sourced from the 2003–2018 National Health and Nutrition Examination Survey. Weighted multivariable regression analysis and subgroup analysis were conducted to estimate the independent relationship between the TyG index and the likelihood of CVD. Non-linear correlations were explored using restricted cubic splines. Results A total of 6502 participants were included, with a mean TyG index of 8.75 ± 0.01. The average prevalence of CVD was 24.31% overall. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 19.91%; Quartile 2: 21.65%; Quartile 3: 23.82%; Quartile 4: 32.43%). For CVD, a possible association between the TyG index and the odds of CVD was observed. Our findings suggest a nonlinear association between the TyG index and the odds of CVD. The threshold of 8.73 for the likelihood of CVD. Interaction terms were employed to assess heterogeneities among each subgroup, revealing a significant difference specifically in alcohol consumption. This suggests that the positive association between the TyG index and the likelihood of CVD is dependent on the drinking status of the participants. Conclusion A higher TyG index is linked to an increased likelihood of CVD in US adults aged ≥ 60 years. TyG index is anticipated to emerge as a more effective metric for identifying populations at early likelihood of CVD.

Abstract Background Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. Methods Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. Results The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. Conclusions Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Abstract Introduction Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation over intubation (CAB) can improve outcomes in patients with exsanguinating injuries. Methods A prospective observational study involving international trauma centers was conducted. Patients with systolic blood pressure below 90 who were intubated within 30 min of arrival were included. Prioritizing circulation (CAB) was defined as delaying intubation until blood products were started, and/or bleeding control was performed before securing the airway. Demographics, clinical data, and outcomes were recorded. Results The study included 278 eligible patients, with 61.5% falling within the “CAB” cohort and 38.5% in the “ABC” cohort. Demographic and disease characteristics, including age, sex, ISS, use of blood products, and other relevant factors, exhibited comparable distributions between the two cohorts. The CAB group had a higher proportion of penetrating injuries and more patients receiving intubation in the operating room. Notably, patients in the CAB group demonstrated higher GCS scores, lower SBP values before intubation but higher after intubation, and a significantly lower incidence of cardiac arrest and post-intubation hypotension. Key outcomes revealed significantly lower 24-hour mortality in the CAB group (11.1% vs. 69.2%), a lower rate of renal failure, and a higher rate of ARDS. Multivariable logistic regression models showed a 91% reduction in the odds of mortality within 24 h and an 89% reduction at 30 days for the CAB cohort compared to the ABC cohort. These findings suggest that prioritizing circulation before intubation is associated with improved outcomes in patients with exsanguinating injuries. Conclusion Post-intubation hypotension is observed to be correlated with worse outcomes. The consideration of prioritizing circulation over intubation in patients with exsanguinating injuries, allowing for resuscitation, or bleeding control, appears to be associated with potential improvements in survival. Emphasizing the importance of circulation and resuscitation is crucial, and this approach might offer benefits for various bleeding-related conditions.

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).

Abstract Background Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. Methods Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. Results Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609—54.769; p = 0.013). Conclusions Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.

Abstract Background Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer’s disease (AD). Numerous studies have asserted a close association between neuroinflammation and disrupted cerebral energetics. During AD progression and other neurodegenerative disorders, a persistent state of chronic neuroinflammation reportedly exacerbates cytotoxicity and potentiates neuronal death. Here, we assessed the impact of a neuroinflammatory challenge on metabolic demand and microvascular hemodynamics in the somatosensory cortex of an AD mouse model. Methods We utilized in vivo 2-photon microscopy and the phosphorescent oxygen sensor Oxyphor 2P to measure partial pressure of oxygen (pO2) and capillary red blood cell flux in cortical microvessels of awake mice. Intravascular pO2 and capillary RBC flux measurements were performed in 8-month-old APPswe/PS1dE9 mice and wildtype littermates on days 0, 7, and 14 of a 14-day period of lipopolysaccharide-induced neuroinflammation. Results Before the induced inflammatory challenge, AD mice demonstrated reduced metabolic demand but similar capillary red blood cell flux as their wild type counterparts. Neuroinflammation provoked significant reductions in cerebral intravascular oxygen levels and elevated oxygen extraction in both animal groups, without significantly altering red blood cell flux in capillaries. Conclusions This study provides evidence that neuroinflammation alters cerebral oxygen demand at the early stages of AD without substantially altering vascular oxygen supply. The results will guide our understanding of neuroinflammation’s influence on neuroimaging biomarkers for early AD diagnosis.

Abstract Background Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. Methods A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question ‘Do you feel you have more problems with memory than most?’ in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient’s age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People’s Hospital during the morning of the survey. Results The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). Conclusions This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.

Abstract Background The medical students’ knowledge and attitude toward brain death has not been investigated in China. The aims of this study were to assess the knowledge and attitude toward brain death among medical students in China and assess the influence of medical education on the knowledge and attitude. Methods An online questionnaire consisting of 17 questions was developed and completed by undergraduates majoring in clinical medicine in China Medical University. The students’ demographic data, knowledge and attitude toward brain death were collected and analyzed. Results A total of 1075 medical students participated in the survey, and 1051 of them completed the valid questionnaire. The exploratory factor analysis grouped the 17 items into four dimensions, which explained 63.5% of the total variance. These dimensions were named as knowledge (5 items), attitude (5 items), concern (3 items) and education needs (4 items) respectively. The global Cronbach α of the questionnaire was 0.845 and the Cronbach α of the four dimensions ranged from 0.756 to 0.866. The mean dimension scores of knowledge, attitude, concern and education needs was 3.67 ± 0.89, 3.67 ± 0.87, 3.10 ± 1.03 and 4.12 ± 0.72 respectively. The clinical students had a better knowledge than the preclinical students (P

Abstract Background A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. Methods A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. Results In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. Conclusions This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Abstract Background The efficacy of surgical treatment for benign prostatic hyperplasia (BPH) patients with detrusor underactivity (DU) remains controversial. Methods To summarize relevant evidence, three databases (PubMed, Embase, and Web of Science) were searched from database inception to May 1, 2023. Transurethral surgical treatment modalities include transurethral prostatectomy (TURP), photoselective vaporization of the prostate (PVP), and transurethral incision of the prostate (TUIP). The efficacy of the transurethral surgical treatment was assessed according to maximal flow rate on uroflowmetry (Q max), International Prostate Symptom Score (IPSS), postvoid residual (PVR), quality of life (QoL), voided volume, bladder contractility index (BCI) and maximal detrusor pressure at maximal flow rate (PdetQmax). Pooled mean differences (MDs) were used as summary statistics for comparison. The quality of enrolled studies was evaluated by using the Newcastle–Ottawa Scale. Sensitivity analysis and funnel plots were applied to assess possible biases. Results In this study, 10 studies with a total of 1142 patients enrolled. In BPH patients with DU, within half a year, significant improvements in Q max (pooled MD, 4.79; 95% CI, 2.43–7.16; P

Abstract Background Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. Methods Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. Results Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. Conclusion Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

Abstract Background Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. Methods We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI

Abstract Background Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. Methods In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. Results GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. Conclusion GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.

Abstract Background Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with a subset of tumors developing inside the liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, an emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered copper metabolism and comparatively higher copper needs, cuproptosis may play a role in the development of ICC. However, studies investigating this possibility are currently lacking. Methods Single-cell and bulk RNA sequence data were analyzed, and correlations were established between the expression of cuproptosis-related molecules and ICC patient survival. Genes with predicting survival were used to create a CUPT score using Cox and LASSO regression and tumor mutation burden (TMB) analysis. The CIBERSORT software was employed to characterize immune cell infiltration within the tumors. Furthermore, immune infiltration prediction, biological function enrichment, and drug sensitivity analyses were conducted to explore the potential implications of the cuproptosis-related signature. The effects of silencing solute carrier family 39 member 4 gene (SLC39A4) expression using siRNA were investigated using assays measuring cell proliferation, colony formation, and cell migration. Key genes of cuproptosis were detected by western blotting. Results The developed CUPT score divided patients into high and low CUPT score groups. Those with a low score had significantly better prognosis and longer survival. In contrast, high CUPT scores were associated with worse clinical outcomes and significantly higher TMB. Comparisons of the two groups also indicated differences in the immune infiltrate present in the tumors. Finally, we were able to identify 95 drugs potentially affecting the cuproptosis pathway. Some of these might be effective in the treatment of ICC. The in vitro experiments revealed that suppressing the expression of SLC39A4 in ICC cell lines resulted in reduced cell proliferation, colony formation, and cell migration. It also led to an increase in cell death and the upregulation of key genes associated with cuproptosis, namely ferredoxin 1 (FDX1) and dihydrolipoyl transacetylase (DLAT). These findings strongly suggest that this cuproptosis-associated molecule may play a pivotal role in the development and metastasis of ICC. Conclusions Changes in the expression of a cuproptosis-related gene signature can predict the clinical prognosis of ICC with considerable accuracy. This supports the notion that cuproptosis influences the diversity and complexity of the immune microenvironment, mutational landscape, and biological behavior of ICC. Understanding this pathway better may hold promise for the development of innovative strategies in the management of this disease.

Abstract Background Burnout is a common issue among medical professionals, and one of the well-studied predisposing factors is the Big Five personality traits. However, no studies have explored the relationships between these traits and burnout from a trait-to-component perspective. To understand the specific connections between each Big Five trait and burnout components, as well as the bridging effects of each trait on burnout, we employed network analysis. Methods A cluster sampling method was used to select a total of 420 Chinese medical personnel. The 15-item Chinese Big Five Personality Inventory-15 (CBF-PI-15) assessed the Big Five personality traits, while the 15-item Maslach Burnout Inventory-General Survey (MBI-GS) assessed burnout components. Network analysis was used to estimate network structure of Big Five personality traits and burnout components and calculate the bridge expected influence. Results The study revealed distinct and clear relationships between the Big Five personality traits and burnout components. For instance, Neuroticism was positively related to Doubt significance and Worthwhile, while Conscientiousness was negatively related to Accomplish all tasks. Among the Big Five traits, Neuroticism displayed the highest positive bridge expected influence, while Conscientiousness displayed the highest negative bridge expected influence. Conclusions The network model provides a means to investigate the connections between the Big Five personality traits and burnout components among medical professionals. This study offers new avenues for thought and potential targets for burnout prevention and treatment in medical personnel, which can be further explored and tested in clinical settings.

Abstract Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract