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Abstract The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80–1.40), 1.24 (95% CI 0.89–1.74) and 1.47 (95% CI 1.04–2.08) fold risk for proteinuria with a trend test P trend

Objective To reveal the structures and evolutionary patterns of faults in the central and northern parts of Tazhong Uplift, Tarim Basin, Methods this paper systematically discusses the types of fault structures, geometric characteristics, differential activity mechanisms, and tectonic evolution processes in this area by analysing detailed structural interpretations and coherent slices of combined large 3D seismic data along with the regional dynamic background. Results The results show that there are 4 types and 7 evolution stages of faults in the central and northern parts of Tazhong Uplift, among which thrust faults and strike-slip faults are particularly common. On the plane, NW arc thrust faults intersect with NE-, NW- and NS-striking strike-slip faults; vertically, the fault stratification and differential activity characteristics are obvious. In the Lower Ordovician and the belowing layers, faults developed in large numbers and were mainly linear in their trending directions. As for the Middle Ordovician-Middle and Lower Devonian layers, faults are mostly in the echelon type. In the Upper Devonian-Permian layers, a few faults developed in the Tazhong Ⅱ fault zone and the southwestern end of the Shunbei 5 fault zone. Conclusion The fault activity in the study area was controlled by stress sites exhibiting diverse properties across multiple phases and directions and experienced an extremely complex evolutionary history: In the Early Caledonian period, a small number of normal faults, such as the Tazhong Ⅱ fault zone, were mainly active; in the Middle Caledonian Ⅰ period, the fault activity was very strong and was characterized by coevolution and mutual coupling of thrust faults and strike-slip faults. The strike-slip faults obviously cut or restricted the thrust faults. The fault activity of the Middle Caledonian Ⅲ period basically inherited the tectonic framework of the Middle Caledonian Ⅰ period, but the characteristics of transtensional fault activity in the Shunbei 4 and 5 fault zones are significant. From the Late Caledonian to Early Hercynian, some of the faults inherited activities with obvious transtensional characteristics. Conversely, in the Indochina-Yanshan period, only a few faults inherited activity, and the development area of transtensinal fault is further expanded to the south. During the Himalayan period, the tectonic movement of this area was relatively stable, and the complex fault structures that formed in the early stage transitioned into the deep burial stage.

Abstract Background Vascular calcification (VC) is an independent risk factor for cardiovascular diseases. Recently, ferroptosis has been recognised as a novel therapeutic target for cardiovascular diseases. Although an association between ferroptosis and vascular calcification has been reported, the role and mechanism of iron overload in vascular calcification are still poorly understood. Specifically, further in-depth research is required on whether metalloproteins SLC39a14 and SLC39a8 are involved in ferroptosis induced by iron overload. Methods R language was employed for the differential analysis of the dataset, revealing the correlation between ferroptosis and calcification. The experimental approaches encompassed both in vitro and in vivo studies, incorporating the use of iron chelators and models of iron overload. Additionally, gain- and loss-of-function experiments were conducted to investigate iron’s effects on vascular calcification comprehensively. Electron microscopy, immunofluorescence, western blotting, and real-time polymerase chain reaction were used to elucidate how Slc39a14 and Slc39a8 mediate iron overload and promote calcification. Results Ferroptosis was observed in conjunction with vascular calcification (VC); the association was consistently confirmed by in vitro and in vivo studies. Our results showed a positive correlation between iron overload in VSMCs and calcification. Iron chelators are effective in reversing VC and iron overload exacerbates this process. The expression levels of the metal transport proteins Slc39a14 and Slc39a8 were significantly upregulated during calcification; the inhibition of their expression alleviated VC. Conversely, Slc39a14 overexpression exacerbates calcification and promotes intracellular iron accumulation in VSMCs. Conclusions Our research demonstrates that iron overload occurs during VC, and that inhibition of Slc39a14 and Slc39a8 significantly relieves VC by intercepting iron overload-induced ferroptosis in VSMCs, providing new insights into the VC treatment. Graphical Abstract

Abstract Background Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population. Methods In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC. Results Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC. Conclusion lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC.

Abstract Background Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1–T2 SGSCC. We also enrolled 109 patients with T1–T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1–T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA). Results Our investigation identified nine prognostic indicators for T1–T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II–IV), grade (III–IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1–T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve. Conclusion Nomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1–T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1–T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1–T2 SGSCC patients.

Abstract. Background:. Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them. Methods:. This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated. Results:. When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899–0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796–0.995) and 0.870 (95% CI, 0.769–0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model. Conclusions:. DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo.

As a pathological hallmark of type 2 diabetes mellitus (T2DM), islet amyloid is formed by the aggregation of islet amyloid polypeptide (IAPP). Endoplasmic reticulum (ER) stress interacts with IAPP aggregates and has been implicated in the pathogenesis of T2DM. To examine the role of ER stress in T2DM, we cloned the hIAPP promoter and analyzed its promoter activity in human β-cells. We found that ER stress significantly enhanced hIAPP promoter activity and expression in human β-cells via triggering X-box binding protein 1 (XBP1) splicing. We identified a binding site of XBP1 in the hIAPP promoter. Disruption of this binding site by substitution or deletion mutagenesis significantly diminished the effects of ER stress on hIAPP promoter activity. Blockade of XBP splicing by MKC3946 treatment inhibited ER stress-induced hIAPP up-regulation and improved human β-cell survival and function. Our study uncovers a link between ER stress and IAPP at the transcriptional level and may provide novel insights into the role of ER stress in IAPP cytotoxicity and the pathogenesis of T2DM.

Among the green-cyan phosphors widely used in white LEDs, the full width at half maximum, thermal stability and quantum efficiency are key performance indicators. This kind of phosphor should have stable peak shape and peak position when working at different temperatures. It should simultaneously exhibit ultrawideband emission, which is conducive to the realization of two-color white light and simplification of the preparation process of white LED devices. In this paper, a series of KAlSiO4:Eu2+, Mn2+ luminescent materials were synthesized by a high-temperature recalcination strategy. Phase analysis and refinement results showed that the samples were effectively synthesized. After the first calcination, a bright green powder was obtained. The main emission peak was at 514 nm, and the FWHM was 30 nm. After recalcination, the color of the light emission from the representative samples changed from green to cyan-green, which was very close to white light, under near-UV irradiation. The emission range was wide, including blue and green light, and the full width at half maximum could reach 150 nm. After recalcination, the emission intensity of the representative samples increased by 3.4 times, and the quantum efficiency reached 90 % under near-UV excitation. The emission intensity at 150 °C was 82 % of that at room temperature. The Raman spectra showed that recalcination had a good effect on the lattice symmetry of the samples and promoted their luminescence intensity. The experimental value of the optical bandgap of the matrix was 5.6 eV, whereas the DFT-calculated bandgap was 4.8 eV, indicating good thermal stability. The chromaticity shift of the sample at high temperatures was very small, indicating good chromaticity stability. A commercial broadband red powder and representative samples after refiring were combined with 365 nm near-UV chips. The color rendering index of the white LED devices exhibited under different driving currents was greater than 90, indicating that the refiring strategy successfully improved the luminous performance of the representative samples. KAlSiO4:Eu2+, Mn2+ phosphors were verified to have good application prospects in the field of white LED lighting. This work provides a new idea and technology for calcination and color control of luminescent phosphors.

IntroductionSotorasib and adagrasib have been widely used for the non-small cell lung cancer (NSCLC) patients harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation. It's necessary to assess their safety profiles in the real-world population.MethodsA retrospective pharmacovigilance was conducted to examine adverse events (AEs) associated with sotorasib and adagrasib therapies using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was performed employing Venn analysis and four data-mining algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS).ResultsThe most commonly reported system organ classes (SOCs) for both adagrasib and sororasib were general, gastrointestinal, and investigations disorders. Notably, sotorasib exhibited significant signals for neoplasms and hepatobiliary disorders in four algorithms. Specifically, AEs related to neoplasms were predominantly associated with lung malignancies, all of which were consistent with the therapeutic indications of KRAS G12C mutation inhibitor. A total of 19 common AEs were identified in sotorasib and adagrasib, spanning gastrointestinal, general, hepatobiliary, investigations, metabolism, musculoskeletal, neoplasms, and respiratory disorders. 4 severe AEs (SAEs) were identified in sotorasib, with 3 SAEs displaying significant signals in four algorithms, including drug-induced liver injury, pancreatitis, and hepatic failure. In adagrasib, only 2 SAEs were detected, with renal failure showing significant signals in four algorithms.ConclusionThis study offers a comprehensive evaluation of the major safety signals associated with sotorasib and adagrasib, providing valuable information for clinicians regarding drug selection and safety considerations, thereby facilitating the design of future prospective safety studies.

Objectives: Neuroblastoma (NB), a pediatric malignancy of the peripheral nervous system, is characterized by epigenetic and transcriptional (EP-TF) anomalies. This study aimed to develop an EP-TF clinical prognostic model for NB using CRISPR-Cas9 knockout screening.Results: An integrative analysis was conducted using CRISPR-Cas9 screening in vitro and in vivo with public NB datasets to identify 35 EP-TF genes that exhibited the highest expression in NB and were highly dependent on cancer viability. After univariate analysis, 27 of these 35 genes were included in the least absolute shrinkage and selection operator screen. We established and biologically validated a prognostic EP-TF model encompassing RUVBL1, LARP7, GTF3C4, THAP10, SUPT16H, TIGD1, SUV39H2, TAF1A, SMAD9, and FEM1B across diverse NB cohorts. MYCN serves a potential upstream regulator of EP-TF genes. The high-risk subtype exhibited traits associated with the malignant cell cycle, MYCN-linked signaling and chromatin remodeling, all of which are correlated with poor prognosis and immunosuppression. MEK inhibitors have emerged as promising therapeutic agents for targeting most EP-TF risk genes in NB.Conclusion: Our novel prognostic model shows significant potential for predicting and evaluating the overall survival of NB patients, offering insights into therapeutic targets.

Aortic aneurysm and dissection (AAD) are severe vascular diseases with high mortality rates. However, the causal relationship between serum uric acid levels and the occurrence of AAD remains a subject of controversy. To address this issue, we conducted a two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal association between these factors. We obtained single-nucleotide polymorphisms (SNPs) data related to serum uric acid levels from the FinnGen study and data on AAD from the UK Biobank. Various two-sample MR methods, including inverse variance weighted (IVW) analysis, MR-Egger regression analysis, weighted median analysis, and contamination mixture method, were employed to assess the causal relationship between serum uric acid and the risk of AAD. Sensitivity analysis was conducted to evaluate the stability and reliability of the results. The findings revealed a positive association between serum uric acid levels and the risk of aortic aneurysm (AA) (odds ratio [OR] = 1.200, 95 % confidence interval [CI]: 1.020–1.400, P = 0.0239). However, no significant correlation was observed between serum uric acid levels and the occurrence of aortic dissection (AD) (OR = 0.893, 95 % CI = 0.602–1.326, P = 0.576). Our study, which employed MR analysis, identified a positive association between serum uric acid levels and the risk of AA. However, we did not observe a significant correlation with AD.

Introduction: The production of bone-like structural scaffolds through bone tissue engineering technology is a promising method for bone regeneration to repair bone defects. Deer antler, an easily harvested and abundantly sourced initial bone tissue structure, resembles the composition and structure of human cancellous bone and can serve as a new material for allogeneic bone transplantation.Methods: This study involved the preparation and characterization of antler powder/chitosan/β-glycerophosphate sodium/polyvinyl alcohol (AP/CS/β-GP/PVA) porous hydrogel scaffolds to verify their material properties and osteogenic mechanisms. The microstructure, hydrophilicity, and mechanical properties of the scaffolds were studied using Scanning Electron Microscopy (SEM), contact angle measurement, and a universal material testing machine. The interactions between the various components were investigated using Fourier-Transform Infrared Spectroscopy (FTIR). Biocompatibility, osteogenic properties, and expression of osteogenesis-related proteins of the scaffolds were evaluated through Cell Counting Kit-8 (CCK-8) assays, alkaline phosphatase staining, Alizarin Red staining, live/dead cell staining, and Western blot analysis.Results: The results showed that as the content of deer antler powder increased, both the hydrophilicity and mechanical properties of the scaffold materials improved, while the porosity slightly decreased with an increase in deer antler powder content. Cell culture experiments demonstrated that scaffolds with a higher proportion of deer antler powder were beneficial for the proliferation and differentiation of mouse pre-osteoblast (MC3T3-E1) cells, with the scaffolds containing 10% and 8% deer antler powder showing the best effects. The upregulation of RUNX2, OCN, OSX, and OPN protein expression may promote differentiation.Discussion: Therefore, the AP/CS/β-GP/PVA hydrogel scaffolds have the potential to become a promising biomaterial for bone tissue engineering.

Large bony Bankart injuries are typically stabilized using screws or plates or multiple anchors. Here, the “door-locking” technique, using a single-row anchor, can provide effective fixation for massive bony Bankart injuries. This technique offers several advantages over open fixation surgery or other techniques that use more than 2 suture anchors, including simpler surgical procedures, lower medical costs, and satisfactory clinical outcomes.

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare.Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn’s disease (CD)] and DD using the Mendelian randomization (MR) analysis.Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy.Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98–1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94–1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92–1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method.Conclusion: This study’s findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.

Xin Ma,&ast; Junxia Jiao,&ast; Mayila Aierken,&ast; Hong Sun, Li Chen Department of Clinical Laboratory, Urumqi Friendship Hospital, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Sun; Li Chen, Department of Clinical Laboratory, Urumqi Friendship Hospital, No. 558 Shengli Road, Tianshan District, Urumqi, Xinjiang Uygur Autonomous Region, 830049, People’s Republic of China, Tel +86-13899816208 ; +86-13579401192, Email ma.xin228@163.com; CLDYX624@163.comPurpose: In vitro experiments explored how the hypoxia-induced factor-1α (HIF-1α) regulates the regulation of pyroptosis in microglial cells (BV 2) in acute ischemic stroke through ROS/NLRP3 pathway.Methods: The microglia acute phase oxygen-glucose deprivation/reoxygenation (OGD/R) was established, CCK-8 was applied to determine the optimal timing of intervention modeling. HIF-1α was overexpressed with stabilizer GF-4592 and HIF-1α small molecule interfering RNA (HIF-1α-siRNA), which was divided into group A (blank group), group B (OGD/R model group), group C (model+FG-4592 intervention group), group D (model+siRNA negative control group) and group E (model+HIF-1α-siRNA group). Cell proliferation of different groups was measured by CCK-8 assay. Pyroptosis and intracellular ROS levels were measured by flow cell technology. IL-18, IL-1β levels were measured by ELISA. HIF-1α, GSDMD-D, GSDMD-N, clean-Caspase-1 and NLRP3 protein expression levels were measured by Western blot. On the above experiments, ROS and NLRP3 response experiments were performed to explore how HIF-1α regulates pyroptosis through ROS/NLRP3 pathway.Results: Hypoxia for 6 h then reoxygenation for 12 h was the optimal intervention time. Compared with groups B and D, cell proliferation in group C was significantly enhanced, pyroptosis, intracellular levels of ROS, IL-18, IL-1β and the expression of GSDMD-D, GSDMD-N, clean-Caspase-1, and NLRP3 proteins were significantly decreased in group C (P < 0.05). However, in group E, the performance of these test indicators were exactly the opposite, and the difference was statistically significant (P < 0.05). Through ROS and NLRP3 response experiments, it was found that HIF-1α Inhibition of Pyroptosis by inhibiting ROS/NLRP3 pathway.Conclusion: Overexpression of HIF-1α factor can inhibit microglia pyroptosis. HIF-1α factor has an inhibitory effect on the ROS/NLRP 3 pathway, which can inhibit the pyroptotic process in microglia.Keywords: hypoxia-inducible factor-1α, acute ischemic stroke, microglial pyroptosis, reactive oxygen species, nucleotide-binding oligomerization domain-like receptor protein 3

Abstract Background At present, good results have been obtained in the treatment of hematogenous osteomyelitis(HO) in children by the use of drug-loaded calcium sulfate, but there are few clinical studies reported. The aim of this study was to investigate the clinical efficacy of radical debridement combined with drug-laden calcium sulphate antibiotics in paediatric haematogenous osteomyelitis. Methods In this study, we retrospectively analyzed the clinical data of 15 cases of pediatric hematogenous osteomyelitis admitted to our hospital in recent years. A total of 15 pediatric patients with HO treated in our hospital from January 2018 to February 2022 were included for evaluation. Results All 15 patients were treated with drug-laden calcium sulfate, and the antibiotic of choice was vancomycin in 14 cases and vancomycin combined with gentamicin in 1 case. The follow-up period ranged from 12 to 36 months, with a mean follow-up time of 24.73 months, and all children were treated with drug-laden calcium sulfate with satisfactory clinical outcomes. The results of serological examination showed that the preoperative white blood cell count level, C-reactive protein and erythrocyte sedimentation rate were higher than the postoperative ones, and the differences were statistically significant (P

Abstract Background Ferroptosis is closely associated with the pathophysiological processes of many diseases, such as infection, and is characterized by the accumulation of excess lipid peroxides on the cell membranes. However, studies on the ferroptosis-related diagnostic markers in tuberculosis (TB) is still lacking. Our study aimed to explore the role of ferroptosis-related biomarkers and molecular subtypes in TB. Methods GSE83456 dataset was applied to identify ferroptosis-related genes (FRGs) associated with TB, and GSE42826, GSE28623, and GSE34608 datasets for external validation of core biomarkers. Core FRGs were identified using weighted gene co-expression network analysis (WGCNA). Subsequently, two ferroptosis-related subtypes were constructed based on ferroptosis score, and differently expressed analysis, GSEA, GSEA, immune cell infiltration analysis between the two subtypes were performed.Affiliations: Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.correctly Results A total of 22 FRGs were identified, of which three genes (CHMP5, SAT1, ZFP36) were identified as diagnostic biomarkers that were enriched in pathways related to immune-inflammatory response. In addition, TB patients were divided into high- and low-ferroptosis subtypes (HF and LF) based on ferroptosis score. HF patients had activated immune- and inflammation-related pathways and higher immune cell infiltration levels than LF patients. Conclusion Three potential diagnostic biomarkers and two ferroptosis-related subtypes were identified in TB patients, which would help to understand the pathogenesis of TB.Author names: Kindly check and confirm the process of the author names [2,4]correctly

Background: The challenge of emerging antimicrobial resistance and variation in antibiotic use across provinces in China call for knowledge on antibiotic utilization at the regional level. This study aims to evaluate the long-term trends and patterns of antibiotic usage in Xinjiang Province, the largest provincial-level division located in the northwest of China, aiming to provide evidence in enhancing provincial antimicrobial stewardship (AMS) and developing policy measures to optimize regional antimicrobial use. Methods: This was an ecological study with temporal trend analysis on inpatient antibiotic utilization, with antibiotic use data from 92 public hospitals covered by Xinjiang’s Center for Antibacterial Surveillance from 2012 to 2022. Antibiotic use was measured by the number of daily defined doses per 100 patient days (DDDs/100 pds). Patterns of antibiotic use were described by Anatomical Therapeutic Chemical (ATC) subgroups and the Access, Watch, Reserve (AWaRe) classification. The Average Annual Percent Change (AAPC) of antibiotic use and the corresponding 95% confidence intervals (CIs) were calculated to describe the trend of antibiotic use over time. Joinpoint regression was performed using the Weighted Bayesian Information Criteria (WBIC) model with a parametric method. A pairwise comparison between secondary and tertiary hospitals was conducted to explore disparities in antibiotic use across hospital levels. The most commonly used antibiotics were also analyzed. Results: The total inpatient antibiotic use in Xinjiang was 27.6 DDDs/100 patient days in 2022, with a significant decreasing trend during 2012–2022 (AAPC, −2.0%; 95% CI, −3.6% to −0.4%). The Watch group antibiotics were the most used AWaRe category, with the Access-to-Watch ratio decreasing significantly from 46.4% to 24.4% (AAPC, −6.8%; 95% CI, −8.4% to −5.1%). No significant difference was found in the trend of total antibiotic use between secondary and tertiary hospitals, but there were disparities across hospital levels in subgroups. Third-generation cephalosporins, second-generation cephalosporins, and fluoroquinolones remained the top three antibiotic class throughout the study period. The number of antibiotics accounting for 90% of the total antibiotic use decreased from 34 antibiotics in 2012 to 18 antibiotics in 2022. Conclusions: The decreasing trend of inpatient antibiotic use in Xinjiang’s public hospitals reflects the effects of continuous AMS implementation. Patterns of antibiotic use underscore the need for further efforts on evidence-based antibiotic selection and for analyses on the appropriateness of antibiotic use.

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body’s innate immune defenses and compromise the liver’s ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis.

Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient’s symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient’s clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman’s disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman’s disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Perovskite solar cells (PSCs) are believed to be optimistic for commercial deployment soon since the power conversion efficiency of PSCs presently reaches up to 26.10 % due to the intensive efforts these years. The two-step method is comparatively more suitable for scalable perovskite films, where lead halides and ammonium salts are prepared in separate precursors and deposited sequentially. Therefore, the reactivity between these two precursors governs the quality of final perovskite films and the intrinsic non-radiative recombination (NRR) at the perovskite's interfaces. Herein, we empowered both types of precursors, one by one and then simultaneously, with triethylsilane (TES) to investigate its effect on the (FAPbI3)1-x (MAPbBr3)x perovskite's morphological and optoelectronic properties. TES, with ethyl moieties and metalloid center, in ammonium salts delivers homogeneous perovskites' crystals and inhibits the NRR of perovskite films by reducing the defects and trap states. As a result, the optimized devices exhibit not only improved device performance (particularly for the increased fill factors and open circuit voltages) but also enhanced stabilities.

Summary: Alzheimer’s disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aβ is a typical AD hall marker, but Aβ-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aβ-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aβ-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.

Background: Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC). Objectives: We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC. Design: This is a single-center prospective observational study. Methods: FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO. Results: CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb versus 2.8 ± 2.3 ppb, p 5 ppb) had more proximal reflux events (24 ± 15 versus 9 ± 9 episodes, p = 0.001) and a higher level of pepsin (984.8 ± 492.5 versus 634.5 ± 626.4 pg/ml, p = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ 2 = 3.963, p = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 versus 4.8 ± 2.6 ppb, p

BackgroundAlthough previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare.AimOur study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD.MethodsData from the 2017–2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia.ResultsThe findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004–1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162–3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022–1.071), under/normal weight (OR = 1.077, 95% CI, 1.009–1.150), overweight (OR = 1.040, 95% CI, 1.010–1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012–1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596–0.628).ConclusionThis study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings.

Background Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. Material/Methods A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. Results A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11–1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82–6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Conclusions Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.

BackgroundWe aimed to explore the inter-connection between depression and HRQOL dimensions in cancer patients using a network approach, which might provide new insights for precise interventions to improve cancer patients’ overall HRQOL.MethodsBetween June 1, 2016, and August 31, 2017, a total of 1735 eligible patients with heterogeneous types of cancer were recruited. The Zung Self-Rating Depression Scale (SDS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used to measure patients’ depression status and HRQOL, respectively. A regularized partial correlation network was established. Central and bridge symptoms/functions were identified using expected influence and bridge expected influence. A directed acyclic graph (DAG) was used to explore the possible causal relationship between depression and HRQOL dimensions.ResultsIn this study, depression and 15 dimensions of the EORTC-QLQ-C30 scale were highly inter-correlated and could be represented as a network. We found that nearly two-thirds of cancer patients experienced various degrees of depression, and depression was consistently the central symptom in the network, in addition to nausea/vomiting, pain, and physical function. DAG and bridge symptoms indicated that depression might influence overall HRQOL in cancer patients mainly through emotional function, pain, physical function, and sleeplessness, particularly in cancer patients with moderate-to-severe depression. The disparity in network structures between mild and moderate-to-severe depression suggested that the relationship between depression and HRQOL dimensions might be bidirectional.ConclusionThe prevalence of depression remained high in Chinese patients with cancer, and depression may influence various symptoms and functions within the HRQOL network. Screening and early treatment of depression were warranted to improve the overall HRQOL of cancer patients, in addition to adequate treatment of pain and nausea/vomiting and improvement in physical function.