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Abstract Background Chronic low-grade inflammation may mediate the relationship between obesity and diabetes, yet clinical research in this area remains scarce. Thus, this study aimed to explore the mediating role of chronic low-grade inflammation in this relationship using the National Health and Nutrition Examination Survey (NHANES). Methods This study involved 2,482 participants enrolled in the NHANES between 2005 and 2016. Based on the complex sampling survey weights of NHANES, logistic regression models were fitted, adjusting for various covariates to investigate the relationship between BMI, INFLA score, and diabetes. Moreover, weighted quantile sum (WQS) regression models were fitted to analyze the proportional contribution of individual components within the INFLA score. Finally, mediation analysis was conducted to quantitatively assess the magnitude of the mediating effect of the INFLA score on the relationship between BMI and diabetes. Results After adjusting for all potential confounding factors, a significant positive correlation was noted between INFLA score and diabetes [OR (95% CI), 1.038(1.003–1.075), p = 0.035]. Additionally, a significant positive correlation was observed between the high INFLA group and diabetes compared to the low INFLA group [OR (95% CI), 1.599(1.031–2.481), p = 0.037]. WQS regression models revealed that the proportional contributions of C-reactive protein, white blood cell count, platelet count, and neutrophil-to-lymphocyte ratio (NLR) were 55.5%, 34.8%, 8.46%, and 1.19%, respectively. Finally, the results of the mediation analysis indicated that the indirect effect of the INFLA score accounted for 10.20%. Conclusions Chronic low-grade inflammation was associated with diabetes and partially mediates the relationship between obesity and diabetes.

Spontaneous celiac artery dissection is uncommon. Abdominal pain is a common clinical presentation. Conservative medical treatments, endovascular interventions, and open surgery are used to treat spontaneous celiac artery dissection. A 49-year-old male patient visited our hospital, with back and subxiphoid pain that had persisted for 11 hours. He has been smoking 40 cigarettes a day for 20 years. The blood pressure was 180/100mmHg. Aortic computed tomography angiography (CTA) images revealed dissection of the celiac artery, common hepatic artery, left hepatic artery, right hepatic artery, and splenic artery. Urapidil hydrochloride and isosorbide dinitrate were administered to lower the blood pressure to approximately 110/70 mmHg. However, the back and subxiphoid pain persisted without relief. Angiography was performed and a vascular stent (BARD, LIFE STENT, VASCULAR, 8 × 60) was implanted into the celiac artery without involving the branches. Pain was immediately relieved after interventional therapy. The patient was discharged after 4 days. A subsequent aortic CTA after 10 months confirmed that the celiac artery dissection had still not reoccurred.

Abstract Background Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. Methods RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. Results Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. Conclusions METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.

Abstract Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet‐induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination‐proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

Cisplatin is commonly used in treating osteosarcoma, however, chemoresistance reduces its efficacy and results in a poor prognosis. Lycorine, a Chinese herbal medicine component, possesses anti-tumor and anti-inflammatory properties. This study aims to investigate the combined impact of lycorine and cisplatin on osteosarcoma and its molecular mechanism. The combination of lycorine and cisplatin exhibited a synergistic effect evaluated by MTT and Zheng-Jun Jin’s method. Lycorine and cisplatin synergistically inhibit proliferation, migration, invasion, and induce apoptosis of osteosarcoma cells. Pharmacological analysis predicts 13 key targets, including Wnt/β-Catenin and STAT3. After treatment with this combination, key molecules in Wnt/β-Catenin and STAT3 pathways were significantly inhibited. In an orthotopic tumor model, the combination significantly reduces lung metastasis. The present work suggests that a combination of lycorine with cisplatin can effectively inhibit OS cells by suppressing the Wnt/β-Catenin and STAT3 signaling pathways synergistically. This is expected to enhance the therapeutic effect of OS.

ObjectiveTo address the research gap in the epidemiology of pediatric respiratory tract infections (RTIs) in Luzhou, Southern Sichuan, China, by analyzing respiratory pathogens in a large pediatric cohort from 2018 to 2021, covering the pre- and during-COVID-19 periods.MethodsThis study conducted a retrospective analysis of children with RTIs in Luzhou from July 2018 to January 2021. Strict exclusion criteria were applied to ensure an accurate representation of the pediatric population. Pathogen detection included viruses, bacteria, and atypical agents.ResultsPathogens were identified in 52.8% of 12,546 cases. Viruses accounted for 32.2% of infections, bacteria for 29.8%, and atypical agents for 29.7%, with significant findings of Staphylococcus aureus, Moraxella catarrhalis, and Mycoplasma pneumoniae. Age-related analysis indicated a higher incidence of bacterial infections in infants and viral infections in preschool-aged children, with atypical pathogens being most prevalent in 3–5-year-olds. Gender-based analysis, adjusted for age, revealed similar overall pathogen presence; however, females were more susceptible to viral infections, while males were more prone to Streptococcus pneumoniae. Notably, there was an unusual increase in pathogen cases during spring, potentially influenced by behavioral changes and public health measures related to COVID-19. Co-infections were identified as a significant risk factor for the development of pneumonia.ConclusionThe study provides essential insights into the epidemiology of respiratory pathogens in pediatric populations, emphasizing the need for healthcare strategies tailored to age, gender, and seasonality. The findings highlight the impact of environmental and public health factors, including COVID-19 measures, on respiratory pathogen prevalence, underscoring the importance of targeted diagnostic and treatment protocols in pediatric respiratory infections.

A pre-metastatic niche (PMN) is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs. Extracellular vesicles (EVs) play a role in intercellular communication by delivering cargoes, such as noncoding RNAs (ncRNAs). The pivotal role of extracellular vesicle-derived noncoding RNAs (EV-ncRNAs) in the PMN has attracted increasing attention. In this review, we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression, vascular permeability and angiogenesis, inflammation, metabolic reprogramming, and fibroblast alterations. In particular, we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers. Finally, we discussed the promising clinical applications of EV-ncRNAs, including their potential as diagnostic and prognostic markers and therapeutic targets.

Summary: Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

Background Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive.Results The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379–3 p to promote M2 macrophage polarization.Conclusion circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor–macrophage interaction potentially affecting CRC metastatic nodule formation.

ObjectiveThe coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model.MethodsIn this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome.ResultsOur results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group.ConclusionHere, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.

Duchenne muscular dystrophy (DMD MIM#310200) is a degenerative muscle disease caused by mutations in the dystrophin gene located on Xp21.2. The clinical features encompass muscle weakness and markedly elevated serum creatine kinase levels. An 8-year-old Chinese boy was diagnosed with Duchenne muscular dystrophy (DMD). Whole exome gene sequencing was conducted and the Sanger method was used to validate sequencing. A deletion (c.5021del) in exon 35 of the dystrophin gene was identified, which was predicted to generate a frameshift mutation and create an early termination codon (p.Leu1674CysfsTer47). It has a pathogenic effect against dystrophin in the muscle cell membrane of the patient. As such, prednisone treatment at a dose of 0.75 mg/kg.d was administered. After one month, a notable reduction in fall frequency was observed. Our new finding will expand the pathogenic mutation spectrum causing DMD.

Abstract Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.

Abstract Osteoporosis is a systemic metabolic bone disorder for which inflammatory cytokines play an important role. To develop new osteoporosis treatments, strategies for improving the microenvironment for osteoblast and osteoclast balance are needed. Tumor necrosis factor-α (TNF-α) plays an important role in the initiation and development of osteoporosis. Atsttrin is an engineered protein derived from the growth factor, progranulin (PGRN). The present study investigates whether Atsttrin affects osteoclast formation and osteoblast formation. Here we show Atsttrin inhibits TNF-α-induced osteoclastogenesis and inflammation. Further mechanistic investigation indicates Atsttrin inhibits TNF-α-induced osteoclastogenesis through the TNFR1 signaling pathway. Moreover, Atsttrin rescues TNF-α-mediated inhibition of osteoblastogenesis via the TNFR1 pathway. Importantly, the present study indicates that while Atsttrin cannot directly induce osteoblastogenesis, it can significantly enhance osteoblastogenesis through TNFR2-Akt-Erk1/2 signaling. These results suggest that Atsttrin treatment could potentially be a strategy for maintaining proper bone homeostasis by regulating the osteoclast/osteoblast balance. Additionally, these results provide new insights for other bone metabolism-related diseases.

Abstract Tumor angiogenesis plays vital roles in the growth and metastasis of cancer. RNA methylation is one of the most common modifications and is widely observed in eukaryotes and prokaryotes. Accumulating studies have revealed that RNA methylation affects the occurrence and development of various tumors. In recent years, RNA methylation has been shown to play an important role in regulating tumor angiogenesis. In this review, we mainly elucidate the mechanisms and functions of RNA methylation on angiogenesis and progression in several cancers. We then shed light on the role of RNA methylation-associated factors and pathways in tumor angiogenesis. Finally, we describe the role of RNA methylation as potential biomarker and novel therapeutic target.

Abstract Breast cancer metastasis is a complex, multi-step process, with high cellular heterogeneity between primary and metastatic breast cancer, and more complex interactions between metastatic cancer cells and other cells in the tumor microenvironment. High-resolution single-cell transcriptome sequencing technology can visualize the heterogeneity of malignant and non-malignant cells in the tumor microenvironment in real time, especially combined with spatial transcriptome analysis, which can directly compare changes between different stages of metastatic samples. Therefore, this study takes single-cell analysis as the first perspective to deeply explore special or rare cell subpopulations related to breast cancer metastasis, systematically summarizes their functions, molecular features, and corresponding treatment strategies, which will contribute to accurately identify, understand, and target tumor metastasis-related driving events, provide a research basis for the mechanistic study of breast cancer metastasis, and provide new clues for its personalized precision treatment.

Abstract The significant impact of vegetation restoration on the turnover of organic carbon (OC) is mainly attributed to biological processes. However, the contribution of abiotic processes associated with reactive oxygen species (ROS) during vegetation restoration has remained largely overlooked. Therefore, we systematically explored ROS distribution and production mechanisms in sandy soil and their corresponding effects on OC oxidation through field monitoring and incubation experiments. The cumulative concentrations of hydroxyl radicals (•OH) produced within 24 h varied in different soils undergoing vegetation restoration, ranging from 2.36 to 22.05 μmol kg‒1, which were derived from the Fenton-like reaction of hydrogen peroxide (H2O2) and biotic-induced Fe(II). In addition, during the oxidation of reductive SOC, H2O2 can be formed and react with Fe(II) to generate •OH. Further, •OH significantly induced the abiotic transformation of OC, accounting for 15.93%‒25.80% of carbon dioxide (CO2) efflux. Specifically, 1 mol •OH can induce the production of 0.01–0.02 mol CO2 for particulate organic carbon (POC) and 0.03‒0.23 mol CO2 for mineral-associated organic carbon (MOC), as demonstrated by chemical quenching and sterilisation experiments. This indicated that MOC was more sensitive to •OH attacks. Collectively, our findings provide insights into the accumulation of ROS in sandy soils during vegetation restoration, with •OH playing a key role in SOC oxidation, as well as the patterns of SOC turnover and its response to changes in the soil environment. Graphical Abstract

Objective: The aim of this study is to comprehensively investigate the prevalence and distribution patterns of three common genetic variants associated with hearing loss (HL) in Chinese neonatal population. Methods: Prior to June 30, 2023, an extensive search and screening process was conducted across multiple literature databases. R software was utilized for conducting meta-analyses, cartography, and correlation analyses. Results: Firstly, our study identified a total of 99 studies meeting the inclusion criteria. Notably, provinces such as Qinghai, Tibet, Jilin, and Heilongjiang lack large-scale genetic screening data for neonatal deafness. Secondly, in Chinese newborns, the carrier frequencies of GJB2 variants (c.235delC, c.299_300delAT) were 1.63 % (95 %CI 1.52 %–1.76 %) and 0.33 % (95 %CI 0.30 %–0.37 %); While SLC26A4 variants (c.919-2A > G, c.2168A > G) exhibited carrier rates of 0.95 % (95 %CI 0.86 %–1.04 %) and 0.17 % (95 %CI 0.15 %–0.19 %); Additionally, Mt 12S rRNA m.1555 A > G variant was found at a rate of 0.24 % (95 % CI 0.22 %–0.26 %). Thirdly, the mutation rate of GJB2 c.235delC was higher in the east of the Heihe-Tengchong line, whereas the mutation rate of Mt 12S rRNA m.1555 A > G variant exhibited the opposite pattern. Forthly, no significant correlation exhibited the opposite pattern of GJB2 variants, but there was a notable correlation among SLC26A4 variants. Lastly, strong regional distribution correlations were evident between mutation sites from different genes, particularly between SLC26A4 (c.919-2A > G and c.2168A > G) and GJB c.299_300delAT. Conclusions: The most prevalent deafness genes among Chinese neonates were GJB2 c.235delC variant, followed by SLC26A4 c.919-2A > G variant. These gene mutation rates exhibit significant regional distribution characteristics. Consequently, it is imperative to enhance genetic screening efforts to reduce the incidence of deafness in high-risk areas.

Abstract A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin‐3‐gallate‐coated hydroxyapatite nanorods in O‐carboxymethyl chitosan cross‐linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin‐3‐gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1‐related pathway) in vitro and in vivo.

Objective: Peripheral blood routine parameters (PBRPs) are simple and easily acquired markers to identify ulcerative colitis (UC) and Crohn's disease (CD) and reveal the severity, whereas the diagnostic performance of individual PBRP is limited. We, therefore used four machine learning (ML) models to evaluate the diagnostic and predictive values of PBRPs for UC and CD. Methods: A retrospective study was conducted by collecting the PBRPs of 414 inflammatory bowel disease (IBD) patients, 423 healthy controls (HCs), and 344 non-IBD intestinal diseases (non-IBD) patients. We used approximately 70 % of the PBRPs data from both patients and HCs for training, 30 % for testing, and another group for external verification. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnosis and prediction performance of these four ML models. Results: Multi-layer perceptron artificial neural network model (MLP-ANN) yielded the highest diagnostic performance than the other three models in six subgroups in the training set, which is helpful for discriminating IBD and HCs, UC and CD, active CD and remissive CD, active UC and remissive UC, non-IBD and HCs, and IBD and non-IBD with the AUC of 1.00, 0.988, 0.942, 1.00, 0.986, and 0.97 in the testing set, as well as the AUC of 1.00, 1.00, 0.773, 0.904, 1.00 and 0.992 in the external validation set. Conclusion: PBRPs-based MLP-ANN model exhibited good performance in discriminating between UC and CD and revealing the disease activity; however, a larger sample size and more models need to be considered for further research.

Abstract Background Data on persistent candidemia (PC), a recognized complication of candidemia, are lacking in China. This study aimed to investigate the clinical characteristics and risk factors for the mortality of PC among adults in China. Methods This 6-year retrospective study analyzed the prevalence, species distribution, antifungal susceptibility, risk factors, and patient mortality of PC among adults in three regional tertiary teaching hospitals in China from 2016 to 2021. We collected electronic laboratory records data of PC and non-PC patients and used the Student test or Mann–Whitney U test for a retrospective study. Logistic regression was used to identify risk factors associated with persistent candidemia. Results The definition of PC was fulfilled by 36 patients (13.7%, 36/263). The mean age of the patients was 59.9 years (60 years for patients with PC; 59.8 years for those with non-PC; P > 0.05) and 131 (60.1%) were men [16 with PC (44.4%), 115 with non-PC (63.2%), P 0.05). The 30-day mortality rate was 20.2% (16.7% with PC vs. 20.9% with non-PC, P > 0.05). Multivariable regression analysis showed that use of broad-spectrum antibiotics (odds ratio (OR), 5.925; 95% confidence interval (CI), 1.886–18.616, P = 0.002), fluconazole (OR, 3.389; 95% CI, 1.302–8.820, P = 0.012) and C. parapsilosis infection (OR, 6.143; 95% CI, 2.093–18.031, P = 0.001) were independent predictors of PC, sex (male) (OR, 0.199; 95% CI, 0.077–0.518, P = 0.001) was the protective factor for PC. Respiratory dysfunction (OR, 5.763; 95% CI, 1.592–20.864, P = 0.008) and length of hospital stay(OR, 0.925; 95% CI, 0.880–0.973, P = 0.002) were independent predictors of 30-day mortality in patients with non-PC. C. tropicalis bloodstream infection (OR, 12.642; 95% CI, 1.059–150.951; P = 0.045) was an independent predictor of 30-day mortality in patients with PC. Conclusions The epidemiological data of patients with PC and non-PC were different in the distribution of Candida species, the mean annual incidence and independent predictors of 30-day mortality. Flucytosine and amphotericin B could be used as first-choice drugs in the presence of PC infections.

Abstract Taking NVP-BEZ235 (BEZ235) as an example to screen drug response-related genes (DRRGs) and explore their potential value in triple-negative breast cancer (TNBC). Through high-throughput technique, multidimensional transcriptome expression data (mRNA, miRNA and lncRNA) of BEZ235-treated and -untreated MDA-MB-468 cell lines were obtained. Combined with transcriptome data of the MDA-MB-468 cells and TCGA-TNBC tissues, differential gene expression analysis and WGCNA were performed to identify DRRGs associated with tumor trait by simulating the drug response microenvironment (DRM) of BEZ235-treated patients. Based on DRRGs, we constructed a ceRNA network and verified the expression levels of three key molecules by RT-qPCR, which not only demonstrated the successful construction of a BEZ235-treated cell line model but also explained the antitumor mechanism of BEZ235. Four molecular subtypes related to the DRM with survival difference were proposed using cluster analysis, namely glycolysis subtype, proliferation depression subtype, immune-suppressed subtype, and immune-activated subtype. A novel prognostic signature consisting of four DRRGs was established by Lasso–Cox analysis, which exhibited outstanding performance in predicting overall survival compared with several excellent reported signatures. The high- and low-risk groups were characterized by enrichment of metabolism-related pathways and immune-related pathways, respectively. Of note, the low-risk group had a better response to immune checkpoint blockade. Besides, pRRophetic analysis found that patients in the low-risk group were more sensitive to methotrexate and cisplation, whereas more resistant to BEZ235, docetaxel and paclitaxel. In conclusion, the DRRGs exemplified by BEZ235 are potential biomarkers for TNBC molecular typing, prognosis prediction and targeted therapy. The novel DRRGs-guided strategy for predicting the subtype, survival and therapy efficacy, might be also applied to more cancers and drugs other than TNBC and BEZ235.

Summary: The disturbance of hepatic lipid metabolism has a strong association with non-alcoholic fatty liver disease (NAFLD) and diabetes. Mof, an acetyltransferase involved in obesity and carbon metabolism, has not been thoroughly examined in its connection to hepatic metabolism. We aimed to explore the impact of Mof on hepatic lipid metabolism. The alteration of Mof expression was found in both obese mice and NAFLD human liver. The genes regulated by Mof were closely associated with lipid metabolism. In normal mice or hepatic cells, the down-regulation or inhibition of Mof resulted in increased lipid accumulation due to decreased PPARα expression. Conversely, in diet-induced obesity (DIO) mice or hepatic cells treated with palmitic acid, the inhibition of Mof led to improved lipid metabolism, attributed to the reduction in p-mTOR/mTOR levels. In summary, Mof exhibited distinct roles in lipid metabolism under different conditions. The inhibition of Mof may hold potential as a therapeutic target for hepatic lipid metabolism disturbances.

Machine learning (ML) includes a broad class of computer programs that improve with experience and shows unique strengths in performing tasks such as clustering, classification and regression. Over the past decade, microbial communities have been implicated in influencing the onset, progression, metastasis, and therapeutic response of multiple cancers. Host-microbe interaction may be a physiological pathway contributing to cancer development. With the accumulation of a large number of high-throughput data, ML has been successfully applied to the study of human cancer microbiomics in an attempt to reveal the complex mechanism behind cancer. In this review, we begin with a brief overview of the data sources included in cancer microbiomics studies. Then, the characteristics of the ML algorithm are briefly introduced. Secondly, the application progress of ML in cancer microbiomics is also reviewed. Finally, we highlight the challenges and future prospects facing ML in cancer microbiomics. On this basis, we conclude that the development of cancer microbiomics can not be achieved without ML, and that ML can be used to develop tumor-targeting microbial therapies, ultimately contributing to personalized and precision medicine.

Abstract In recent years, tumor immunotherapy has made significant progress. However, tumor immunotherapy, particularly immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors), benefits only a tiny proportion of patients in solid cancers. The tumor microenvironment (TME) acts a significant role in tumor immunotherapy. Studies reported that tumor-associated macrophages (TAMs), as one of the main components of TME, seriously affected the therapeutic effect of PD-1/PD-L1 inhibitors. In this review, we analyzed TAMs from epigenetic and single-cell perspectives and introduced the role and mechanisms of TAMs in anti-programmed death protein 1(anti-PD-1) therapy. In addition, we summarized combination regimens that enhance the efficacy of tumor PD-1/PD-L1 inhibitors and elaborated on the role of the TAMs in different solid cancers. Eventually, the clinical value of TAMs by influencing the therapeutic effect of tumor PD-1/PD-L1 inhibitors was discussed. These above are beneficial to elucidate poor therapeutic effect of PD-1/PD-L1 inhibitors in solid tumors from the point of view of TAMs and explore the strategies to improve its objective remission rate of solid cancers.

Mesh division plays an important role in applications of the finite element method (FEM). The proposed research shows that under the same order, the equilateral triangular meshes have the most uniform dispersion distribution. The isosceles triangles with equal base and height have more uniform dispersion error than the square meshes, while the maximum phase error is similar. Taking the rectangular waveguide as an example, the relative errors in the cut-off frequency are analyzed based on different meshes. The numerical results show that under the same interpolation order and node numbers, the relative error of isosceles triangles with equal base and height for TE10 mode is the smallest. The results are useful in choosing appropriate element order, node density and mesh shape when applying FEM.

BackgroundIntervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.ObjectiveThis study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.MethodsWe exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.ResultsDigoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.ConclusionThese findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.

Introduction Isthmin-1 (Ism-1) is a novel adipokine. However, little is known regarding the association between Ism-1 and type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between serum Ism-1 levels and glomerular filtration rate (GFR) in patients with T2DM.Research design and methods A total of 209 patients with T2DM were recruited into this retrospective study. Clinical data were collected. Fasting blood samples were collected for serum Ism-1 testing using ELISA kits. Based on the estimated glomerular filtration rate (eGFR), participants were divided into the normal eGFR group (n=167) and the decreased eGFR group (n=42). The relationship between Ism-1 and eGFR was assessed using linear and binary logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was employed to examine the predictive efficacy of Ism-1 for distinguishing patients with eGFR 1.297 ng/mL) had predictive efficacy in patients with eGFR

Colistin is highly promising against multidrug-resistant and extensively drug-resistant bacteria clinically. Bacteria are resistant to colistin mainly through mcr and chromosome-mediated lipopolysaccharide (LPS) synthesis-related locus variation. However, the current understanding cannot fully explain the resistance mechanism in mcr-negative colistin-resistant strains. Significantly, the contribution of efflux pumps to colistin resistance remains to be clarified. This review aims to discuss the contribution of efflux pumps and their related transcriptional regulators to colistin resistance in various bacteria and the reversal effect of efflux pump inhibitors on colistin resistance. Previous studies suggested a complex regulatory relationship between the efflux pumps and their transcriptional regulators and LPS synthesis, transport, and modification. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), 1-(1-naphthylmethyl)-piperazine (NMP), and Phe-Arg-β-naphthylamide (PAβN) all achieved the reversal of colistin resistance, highlighting the role of efflux pumps in colistin resistance and their potential for adjuvant development. The contribution of the efflux pumps to colistin resistance might also be related to specific genetic backgrounds. They can participate in colistin tolerance and heterogeneous resistance to affect the treatment efficacy of colistin. These findings help understand the development of resistance in mcr-negative colistin-resistant strains.

Cuproptosis, a copper-induced mechanism of mitochondrial-related cell death, has been implicated as a breakthrough in the treatment of cancer and has become a new treatment strategy. Furthermore, long non-coding RNA (lncRNA) can change the biological activities of tumor cells. Worldwide, lung squamous cell carcinoma (LUSC) is among the most common annoying tumors. LncRNAs related to cuproptosis are not researched at LUSC. Our research intends to develop a signature on the basis of cuproptosis-associated lncRNAs, which can predict LUSC prognosis and investigate LUSC immunological features. The TCGA database was used to retrieve LUSC transcriptome, clinical, and gene mutation data. For statistical analysis, we utilized the R program. We created a signature consisting of three cuproptosis-related lncRNAs in this investigation (including AC002467.1, LINC01740, and LINC02345). Survival analyses and Receiver Operating Characteristic curves demonstrated that this signature possessed powerful predictive capability. The signature’s ability to predict was confirmed by a Receiver Operating Characteristic curve and principal component analysis. Notably, the patient with a high-risk score and a high tumor mutation burden level had a lower survival time. Furthermore, the tumor immune dysfunction and exclusion analysis showed that these individuals with low-risk scores may benefit from immunotherapy. The signature constructed by three cuproptosis-associated lncRNAs may be prognostic markers of LUSC. It contributes to immunotherapy and offers LUSC’s therapy a new treatment direction.

In this work, 532 nm laser was used as the pump source and pressurized ethane was used as Raman active medium; 631.3 nm first Stokes (S1) and 776.0 nm second Stokes (S2) Raman lasers were generated. By the optimization of ethane pressure and focus lens, S2 and backwards first Stokes Raman conversion could be reduced, while the conversion of S1 could be improved. Under 2.0 MPa ethane and focal length of 1.5 m, the maximum S1 conversion efficiency of 84.5% was achieved. Up to 68.7 mJ S1 Raman laser was obtained, and the corresponding peak power is 17.2 MW. By the comparison of the threshold of methane Raman laser, Raman gain coefficients of ethane were estimated to be 0.50 × 10−12 m/W at 0.5 MPa and 0.76 × 10–12 m/W at 1.4 MPa ethane respectively.

Abstract This study assessed the value of circRNAs (circular RNAs) as prognostic markers in BC (breast cancer). We searched pertinent studies on the PubMed, Embase, and Web of Science online databases published according to PRISMA guidelines. A random-effects model for meta-analysis was used to assess the combined effect size of the HRs (hazard ratios) of the included studies. The heterogeneity test used Cochran's Q-test and I 2 statistics. Thirty of the 520 trials retrieved were included in the systematic review. A total of 11 chemotherapeutic agents were used in the included studies. A total of 30 studies on 30 circRNAs were included in the systematic review. Of the 30 relevant circRNAs, 28 were upregulated and two were downregulated in breast cancer versus normal samples, and both were associated with increased drug resistance. Nine of 30 studies were used for the meta-analysis. The results of the meta-analysis showed that the groups with circRNA upregulation and circRNA downregulation showed the same prognostic risk (HR = 1.37, 95% Cl: 0.80–2.36, I 2 = 63.7%). The results of subgroup analysis showed that both upregulated circRNAs (HR = 2.24, 95% Cl: 1.34–3.75, I 2 = 0%) and downregulated circRNAs (HR = 0.61, 95% Cl: 0.45–0.83, I 2 = 0%) were associated with poor BC prognosis. Collectively, the results of all relevant articles collected indicated that circRNAs showed good potential as possible clinical biomarkers of chemoresistance in BC patients.

Abstract Background Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin β1 (Itgb1) is the major integrin subunit that mediates iPSC-ECM adhesion, suggesting that knocking out Itgb1 might be an effective method for enhancing the therapeutic efficacy of iPSCs. Methods We knocked out Itgb1 in mouse iPSCs and evaluated its effects on the therapeutic potential of topically applied iPSCs, as well as their underlying in vivo and in vitro mechanisms. Results The Itgb1-knockout (Itgb1-KO) did not change iPSC pluripotency, function, or survival in the absence of embedding in an ECM gel but did accelerate wound healing, angiogenesis, blood perfusion, and survival in skin-wound lesions. However, embedding in an ECM gel inhibited the in vivo effects of wild-type iPSCs but not those of Itgb1-knockout iPSCs. Additionally, in vitro results showed that Itgb1-knockout decreased iPSC-ECM adhesion while increasing ECM-crossing migration. Moreover, ECM coating on the culture surface did not change cell survival, regardless of Itgb1 status; however, the in vivo and in vitro functions of both Itgb1-knockout and wild-type iPSCs were not affected by the presence of agarose gel, which does not contain integrin-binding sites. Knockout of Integrin α4 (Itga4) did not change the above-mentioned cellular and therapeutic functions of iPSCs. Conclusions Itgb1-knockout increased iPSCs migration and the wound-healing-promoting effect of topically applied iPSCs. These findings suggest the inhibition of Itgb1 expression is a possible strategy for increasing the efficacy of iPSC therapies.

Objectives: This study was aimed at describing antibiotic susceptibility patterns and developing a predictive model by assessing risk factors for carbapenem-resistant Pseudomonas aeruginosa (CRPA). Methods: A retrospective case-control study was conducted at a teaching hospital in China from May 2019 to July 2021. Patients were divided into the carbapenem-susceptible P. aeruginosa (CSPA) group and the CRPA group. Medical records were reviewed to find an antibiotic susceptibility pattern. Multivariate analysis results were used to identify risk factors and build a predictive model. Results: A total of 61 among 292 patients with nosocomial pneumonia were infected with CRPA. In the CSPA and CRPA groups, amikacin was identified as the most effective antibiotic, with susceptibility of 89.7%. The CRPA group showed considerably higher rates of resistance to the tested antibiotics. Based on the results of mCIM and eCIM, 28 (45.9%) of 61 isolates might be carbapenemase producers. Independent risk factors related to CRPA nosocomial pneumonia were craniocerebral injury, pulmonary fungus infection, prior use of carbapenems, prior use of cefoperazone-sulbactam, and time at risk (≥15 d). In the predictive model, a score >1 point indicated the best predictive ability. Conclusions: CRPA nosocomial pneumonia could be predicted by risk factor assessment particularly based on the underlying disease, antimicrobial exposure, and time at risk, which could help prevent nosocomial pneumonia.

Over the last decade, event prediction has drawn attention from both academic and industry communities, resulting in a substantial volume of scientific papers published in a wide range of journals by scholars from different countries and disciplines. However, thus far, a comprehensive and systematic survey of recent literature has been lacking to quantitatively capture the research progress as well as emerging trends in the event prediction field. Aiming at addressing this gap, we employed CiteSpace software to analyze and visualize data retrieved from the Web of Science (WoS) database, including authors, documents, research institutions, and keywords, based on which the author co-citation network, document co-citation network, collaborative institution network, and keyword co-occurrence network were constructed. Through analyzing the aforementioned networks, we identified areas of active research, influential literature, collaborations at the national level, interdisciplinary patterns, and emerging trends by identifying the central nodes and the nodes with strong citation bursts. It reveals that sensor data has been widely used for predicting weather events and meteorological events (e.g., monitoring sea surface temperature and weather sensor data for predicting El Nino). The real-time and multivariable monitoring features of sensor data enable it to be a reliable source for predicting multiple types of events. Our work offers not only a comprehensive survey of the existing studies but also insights into the development trends within the event prediction field. These findings will assist researchers in conducting further research in this area and draw a large readership among academia and industrial communities who are engaged in event prediction research.

Fine particulate matter (PM2.5) has attracted more and more attention in the field of environmental pollution and public health. Previous studies have found that PM2.5 can be inhaled and deposit in the airway and alveoli, and even spread to the whole-body tissues and organs through blood, resulting in various toxic effects. The malignant transformation of lung epithelial cells associated with long-term exposure to PM2.5 may play an important role in the occurrence and development of lung cancer. This paper reviewed recent studies on the mechanisms of malignant transformation of lung epithelial cells associated with PM2.5 exposure, and discussed the main biological mechanisms, including epigenetics, tumor microenvironment, and other biological pathways. Besides, the potential research directions of malignant transformation of lung epithelial cells associated with PM2.5 exposure were proposed. This work aims to provide a scientific basis and reference for public health management and air quality assessment.

Electrochemical enzymatic biosensors represent a promising, low-cost technology for point-of-care (POC) diagnostics that allows fast response and simple sample processing procedures. In this review, we summarize up-to-date literature on NAD+/NADH (β-nicotinamide adenine dinucleotide)-dependent electrochemical dehydrogenase biosensors and highlight their applications in human physiological fluids. A brief comparison of various enzyme immobilization procedures is first presented, discussing preparation processes and principal analytical performance characteristics. In the following section, we briefly discuss classes of biosensors based on redox mediators-mediated electron transfer systems (METs). Finally, the conclusion section summarizes the ongoing challenges in the fabrication of NAD+-dependent electrochemical dehydrogenase biosensors and gives an outlook on future research studies.

A novel photodetecting device architecture that combines the optoelectronic property advantages of a perovskite and the amplification properties of a Si metal–oxide–semiconductor field‐effect transistor (MOSFET) to innovate a photodetecting system with ultrahigh sensitivity, especially in low‐light intensity, is demonstrated. This perovskite‐based MOSFET photodetector (PM‐PD) can respond as low as 116 nW cm−2 with extremely high responsivity 4200 A W−1. The perovskite is part of the gate dielectric to modulate the MOSFET drain current when the light intensity is changed. A direct bandgap, organic–inorganic hybrid halide perovskite with a large optical absorption coefficient, can enhance photodetector performance. However, perovskite materials are not good conductors for transporting photogenerated electrons and holes compared with single‐crystal silicon. Therefore, the perovskite was utilized as a dielectric where the capacitance is used instead. In the proposed PM‐PD architecture, changing the width‐to‐length (W/L) ratio of perovskite capacitor electrodes, can modulate the dark current from picoamperes to microamperes providing a tunable parameter for optimizing photodetecting performance. Furthermore, the capacitance of the perovskite can be modulated by frequency, which facilitates matching the capacitance of perovskite and MOSFET gate oxide—another important requirement for optimal photodetecting performance. Finally, our novel PM‐PD is commensurate with potential 3D monolithic integration.

Abstract Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, − 0.76−− 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, − 0.97−− 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, − 1.13−− 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, − 1.49−− 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.

The clinical presentation of primary hyperparathyroidism (PHPT) differs between patients from developed and developing countries. In China, the clinical pattern has changed over the past few decades. Our aim was to elucidate general changes in the clinical characteristics of PHPT from 2010 to 2021. We enrolled 343 patients with PHPT at the Qilu Hospital of Shandong University, Jinan, China, from January 2010 to May 2021, including both surgical and non-surgical patients. Patients were divided into two subgroups, 2010–2016 (group A, n = 152) and 2017–2021 (group B, n = 191), based on the time span. We compared clinical manifestations and laboratory result data between these two groups. The mean patient age was 52.59 ± 13.55 years, and the male-to-f emale ratio was 1:2.54. Of the 343 patients, 183 (53.35%) had symptomatic PHPT; bone pain, urolithiasis, and fatigue were the most common symptoms. Post-operative pathology showed that 96.20% of the patients had parathyroid adenoma, whereas 2.41% had parathyroid carcinoma. Great changes occurred between 2010 and 2021; the percentage of patients with asymptomatic PHPT (aPHPT) increased from 36.18% in group A to 54.97% in grou p B. Moreover, patients in group B showed significantly lower serum calcium, alkaline ph osphatase, parathyroid hormone, and urinary phosphate levels but higher serum 25-hydroxyvitamin D levels than those in group A. Clinical presentations in group B were also m ilder. In conclusion, the clinical characteristics of Chinese PHPT patients changed dramatically from 2010 to 2021, with asymptomatic PHPT (aPHPT becoming the predominant type over the last 3 years.

Abstract SHORT syndrome (short stature, hyperextensibility, ocular depression [deeply set eyes], Rieger anomaly and teething delay) is very rare, with a few cases reported in the literature. We report a case of SHORT syndrome with a novel PIK3R1 mutation (c.2008delT) and complicated with severe insulin resistance. Although no treatment guidelines are available to relieve insulin resistance in SHORT syndrome, our treatment plans, including lifestyle intervention combined with metformin and pioglitazone, were carried out for this patient. After the intervention, insulin resistance and hyperinsulinemia in this patient were significantly decreased during a 6‐month follow up, which showed the effect of our therapeutic strategies.

Abstract Background Vascular endothelial dysfunction, arteriosclerosis and atherosclerotic plaque are well-known risk factors for cardiovascular disease (CVD). Studies on vascular health markers have been well-established, however, there is still a lack of related research on combined vascular structure and function indicators. Method Beijing vascular health stratification (BVHS) is an evaluation system aiming at vascular health, combined the endothelial function, arteriosclerosis, atherosclerotic plaque and vascular lumen stenosis to comprehensively assess the vascular health and grade it. This study will explore the predictive value of the combined evaluation of vascular structure and function for cardiovascular events and assess the predictive value of BVHS and compare it with the existing risk assessment systems. A total of 1500 subjects will be enrolled into the prospective cohort study from a community and will be followed up for at least 3 years from July 1, 2020 to June 30, 2023. Subjects aged 40 or above, without coronary heart disease, stroke or peripheral artery disease, with written informed consent will be included; subjects with end-stage hepatorenal diseases (uremia, renal failure, cirrhosis, liver failure), mental disorders or cognitive disorders, with any other factors that the researcher thinks are not suitable for the study will be excluded. Traditional cardiovascular risk factors will be collected as adjusted confounders. Discussion BVHS is a potential and scientific vascular health evaluation system. The study will be the first to grade vascular health by combing various vascular indicators and explore the prediction value and compare with other risk prediction system in general Chinese population. Trial registration: The trial is registered on http://www.chictr.org.cn/ (ChiCTR2000034085).

Vibrio cholerae is a bacterium ubiquitous in aquatic environments which can cause widespread infection worldwide. V. cholerae gradually became a rare species of bacteria in clinical microbiology laboratories with the control of the cholera epidemic. In this study, we isolated a V. cholerae strain, named VCHL017, from the blood of an elderly patient without gastrointestinal symptoms. The patient had a history of hookworm infection and multiple myeloma. Furthermore, she was immunocompromised, and received long-term chemotherapy and antimicrobial agents. VCHL017 was inoculated on blood agar and thiosulfate citrate bile salt sucrose plates (TCBS) to observe morphological characteristics. Then this isolate was identified by matrix-assisted laser desorption/ionization time-of-flight spectrometry (MALDI-TOF MS). The minimum inhibitory concentrations (MICs) for cefazolin, ceftazidime, cefepime, meropenem, tetracycline, ciprofloxacin, chloramphenicol, and gentamicin of VCHL017 were determined by the microbroth dilution method. PCR and serum agglutination tests were used to determine whether the serogroups of the isolate belonged to the O1/O139 and cholera toxin encoding genes. Finally, the genomic features and phylogeny of VCHL017 were analyzed by whole genome sequencing (WGS). VCHL017 was a non-O1/O139 V cholerae strain that did not carry the ctxA gene. Antimicrobial susceptibility tests revealed that VCHL017 was susceptive to chloramphenicol and tetracycline. Although it did not carry the genes encoding the cholera toxin, WGS indicated that VCHL017 carried a variety of other virulence factors. By calculating the average nucleotide identity (ANI), we precisely identified the species of VCHL017 as V. cholerae. There are also A171S and A202S missense mutations in gyrA of VCHL017. The phylogenetic analysis indicated that VCHL017 was closely related to V. cholerae strains isolated from aquatic environments. Our results suggest that continuous monitoring is necessary for non-O1/O139 V cholerae strains isolated from outside the digestive tract, which could be pathogenic through multiple virulence factors.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become one of the leading causes of healthcare-associated infections globally, particularly in intensive care units (ICUs). Cross-transmission of microorganisms between patients and the hospital environment may play a crucial role in ICU-acquired CRAB colonization and infection. The control and treatment of CRAB infection in ICUs have been recognized as a global challenge because of its multiple-drug resistance. The main concern is that CRAB infections can be disastrous for ICU patients if currently existing limited therapeutic alternatives fail in the future. Therefore, the colonization, infection, transmission, and resistance mechanisms of CRAB in ICUs need to be systematically studied. To provide a basis for prevention and control countermeasures for CRAB infection in ICUs, we present an overview of research on CRAB in ICUs, summarize clinical infections and environmental reservoirs, discuss the drug resistance mechanism and homology of CRAB in ICUs, and evaluate contemporary treatment and control strategies.

BackgroundCircular RNAs (circRNAs) are receiving increasing attention as novel biomarkers. Our goal was to investigate the diagnostic, clinicopathological, and prognostic utility of circRNAs in prostate cancer (PCa).MethodsRelevant literature was searched in PubMed, Web of Science, and EMBASE. Sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR), positive likelihood ratio (PLR), and the area under the curve (AUC) were calculated to evaluate the diagnostic accuracy of circRNA expression. circRNAs’ clinical, pathological, and prognostic value was examined using pooled odds ratios (ORs) and hazard ratios (HRs).ResultsThis meta-analysis included 23 studies, with 5 for diagnosis, 16 for clinicopathological parameters, and 10 for prognosis. For diagnostic value, the pooled sensitivity, pooled specificity, PLR, NLR, DOR, and AUC were 0.82, 0.62, 2.17, 0.29, 7.37, and 0.81, respectively. Upregulation of carcinogenic circRNAs was associated with poor clinical parameters (Gleason score: OR = 0.222, 95% CI: 0.145–0.340; T classification: OR = 0.274, 95% CI: 0.175–0.430; lymph node metastasis: OR = 0.353, 95% CI: 0.175–0.716; tumor size: OR = 0.226, 95% CI: 0.099–0.518) and could predict poor survival outcomes (HR = 2.408, 95% CI: 1.559–3.720, p < 0.001). Conversely, downregulation of tumor-suppressor circRNAs was also associated with poor clinical parameters (Gleason score: OR = 1.689, 95% CI: 1.144–2.493; T classification: OR = 2.586, 95% CI: 1.779–3.762) and worse prognosis (HR = 1.739, 95% CI: 1.147–2.576, p = 0.006).ConclusionOur results showed that circRNAs might be useful biomarkers for the diagnosis and prognosis of PCa.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021284785.

Extensively drug-resistant and hypervirulent Klebsiella pneumoniae (XDR-hvKp) is a new problem for patients in Intensive Care Unit (ICU) and can become an even more severe threat if resistant to tigecycline, considered one of the ‘last lines of defense’ drugs. This study collected seven non-replicated tigecycline-resistant XDR-hvKp from seven patients and performed genome analysis and epidemiological investigation using whole genome equencing (WGS) and other methods. All strains in this study were identified as ST11-KL64 and showed high resistance to antibiotics such as β-lactams, aminoglycosides, quinolones, and tigecycline, and one strain was also resistant to colistin. All strains were determined to be hvKp by the results of serum resistance assay and Galleria mellonella infection models. All strains had resistance genes blaCTX-M-65,blaKPC-2,blaLAP-2,blaTEM-1B, rmtB, and qnrS1 and virulence factors such as rmpA, rmpA2, and aerobactin (iucABCD, iutA). The expression of the AcrAB-TolC efflux pump was upregulated in all strains, and the expression levels of the gene pmrK was significantly upregulated in colistin-resistant strain DP compared to colistin-sensitive strain WT in this study. In conclusion, we described an outbreak caused by tigecycline-resistant XDR-hvKp in the ICU of a teaching hospital in southwest China. The spread of these superbugs poses a great threat to patients and therefore requires us to closely monitor these XDR-hvKp and develop relevant strategies to combat them.

Introduction Isthmin-1 (Ism-1), as a novel adipokine, plays a role in glucose homeostasis and lipid metabolism. However, the relationship between Ism-1 and type 2 diabetes mellitus (T2DM) remains unclear. This study aims to investigate the association of serum Ism-1 levels with albuminuria and insulin resistance in patients with T2DM and preserved renal function.Research design and methods A total of 150 patients with T2DM were recruited. The presence of albuminuria was evaluated by urinary albumin:creatinine ratio (UACR) in first morning urine sample. Serum Ism-1 levels were tested by ELISA. Homeostasis model assessments were used to evaluate insulin resistance. Binary logistic regression and multivariable linear regression analyses were used to assess the association of serum Ism-1 levels with albuminuria. Multivariable linear regression analyses were performed to explore the correlation of serum Ism-1 levels with insulin resistance.Results Compared with the normal-albuminuria and microalbuminuria groups, serum Ism-1 levels were significantly higher in the macroalbuminuria group (p

Objective To investigate the relationship between thyroid hormone concentrations and β-cell function in euthyroid patients with obesity and type 2 diabetes. Methods We performed a single-center cross-sectional study of 254 patients with type 2 diabetes mellitus aged ≥40 years. The participants were allocated to an obesity group or non-obesity group on the basis of their body mass index (BMI). Their β-cell function was assessed by measuring C-peptide concentration during a 75-g oral glucose tolerance test (OGTT); and their serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone concentrations were measured. Results The serum FT3 concentration and the C-peptide concentrations at five time points of the OGTT were significantly higher in the obesity group than in the non-obesity group. FT3 was positively associated with the β-cell function of the obesity group, but not that of the non-obesity group, in multiple linear regression analysis, after adjustment for potential confounding factors. Serum FT3 concentration was also significantly associated with indices of obesity (BMI, waist circumference, body fat percentage, fat mass, fat mass/height 2 and visceral fat area). Conclusions Obesity-associated high serum FT3 concentrations might affect β-cell function in euthyroid patients with obesity and type 2 diabetes.

Ultrasonic elliptical vibration cutting has a wide range of applications in the field of precision cutting of difficult-to-machine metal materials. However, due to its intermittent cutting characteristics and the weak rigidity of the horn, cutting chatter is prone to occur during its cutting process, which has an important impact on cutting surface quality and tool wear. In this paper, the rigid/viscoplastic rod model is used to simulate the horn in the ultrasonic elliptical vibration cutting device, and the influence factors of the amplitude-frequency response of the horn are analyzed. The influence of cutting speed and cutting depth on cutting chatter was studied by ultrasonic elliptical vibration cutting experiment of tungsten heavy alloy, and the influence of cutting chatter on cutting surface morphology and diamond tool wear was studied. The research shows that cutting speed will change the excitation frequency of the horn, and reasonable cutting speed can inhibit the occurrence of cutting chatter and avoid resonance of the horn. The cutting depth will affect the excitation amplitude and amplify the vibration amplitude when chatter or resonance occurs. The experimental results show that in ultrasonic elliptical vibration cutting of heavy tungsten alloy, chatter suppression can significantly improve the quality of the cutting surface and reduce the wear of diamond tools.