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Global climate change has become one of the most large-scale, widespread, and far-reaching challenges facing mankind. Against this background, China has proposed a "dual-carbon" target in 2020, which greatly demonstrates China's determination and commitment to carbon emission reduction, and the burden of realizing the "dual-carbon" target is mainly borne by heavy polluters. The burden of achieving the "dual-carbon" goal is mainly borne by the heavily polluting firms. Although this has increased the economic burden of the firms to a certain extent, carbon information disclosure reduces the degree of information asymmetry and also obtains the support of the government, which improves the financial performance of the firms. Based on the data of A-share listed companies in Shanghai and Shenzhen in the heavy pollution industry in 2013-2023, this paper analyzes the relationship between carbon information disclosure, and corporate financial performance according to signaling theory, rent-seeking theory, and sustainable development theory. It is found that enhanced corporate carbon disclosure can significantly improve corporate financial performance, and the main effect is realized through reducing debt financing costs and increasing the proportion of institutional investors' shareholding. In the heterogeneity analysis, this paper finds that the main effect is more significant in the samples of firms located in the western region and the central region. Based on existing research, this paper deepens the study of the relationship between carbon disclosure and corporate financial performance. By integrating the multiple perspectives of signaling theory, rent-seeking theory and sustainable development theory, this paper systematically analyzes how creditors, institutional investors and other stakeholders play a role in the dynamic interaction between carbon disclosure and corporate financial performance, and reveals the motives and mechanisms behind the behaviors of these stakeholders. In order to further refine the analysis path, this paper constructs an intermediary model in order to deconstruct the deep logic of the path and mechanism through which carbon disclosure indirectly affects corporate financial performance. This model not only enhances the theoretical explanatory power, but also provides a more refined analytical framework for empirical testing, which helps to reveal the "black box" mechanism of carbon disclosure's impact on corporate financial performance. In addition, in view of China's vast territory and the uneven level of economic development between regions, this paper adopts a differentiated analysis strategy, based on the economic characteristics of the regions where the heavy polluters are located, and divides the whole sample into three sub-samples for independent regression analysis. This heterogeneity test incorporates inter-regional development differences into the scope of analysis, making the research conclusions more geographically specific and policy-guiding significance. By comparing and analyzing the differences in the impact of carbon disclosure on the financial performance of enterprises in different regions, this paper provides a reference for the government to formulate differentiated carbon disclosure policies in the future, accurately promote the construction of the carbon trading market, and efficiently achieve the carbon emission reduction targets at the national level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/objectives: Sepsis-related acute kidney injury (SA-AKI) is a severe condition characterized by high mortality rates. The utility of the sCAR (secrum creatinine/albumin) and LAR (Lactate dehydrogenase/albumin) as diagnostic markers for persistent severe SA-AKI remains unclear., Methods: We acquired training set data from the MIMIC-IV database and validation set data from the First Affiliated Hospital of Harbin Medical University. Logistic regression analysis was used to identify key predictors of persistent severe SA-AKI, considering factors such as sCAR, LAR, PAR (Platelet/albumin), BAR (BUN/albumin), and LAO (Lactic/albumin). Independent predictors, sCAR and LAR, were combined into a composite Log(sCAR)&#95;Log(LAR) score, denoted as the Log(sCAR)&#95;Log(LAR) score. Possible confounding factors were screened out by univariate logistic regression, and multivariable logistic regression was applied to evaluate the association of Log (sCAR) &#95;Log (LAR) score with persistent severe sepsis and other secondary clinical outcomes. The ROC curve was utilized to obtain the best cutoff value of the Log(sCAR)&#95;Log(LAR) score. The Kaplan-Meier curve was used to evaluate the prognosis predictive ability of the risk model., Results: Logistic regression analysis indicated that sCAR and LAR independently predicted persistent severe SA-AKI. This led to the creation of Log(sCAR)&#95;Log(LAR) score on the base of logarithms of sCAR and LAR. ROC curve analysis showed that the Log(sCAR)&#95;Log(LAR) score was more effective in predicting persistent severe SA-AKI (AUC = 0.71) than Log(sCAR) (AUC = 0.69), Log(LAR) (AUC = 0.65), SOFA score (AUC = 0.66) and Δ Scr (AUC = 0.70). Multivariate regression identified that the SOFA score, PT, ΔScr, Tbil, chronic liver disease, and Vasopressor use as independent risk factors for persistent severe SA-AKI (P < 0.05). A basic clinical prediction model was created using these variables, and its predictive ability, recognition capability, and clinical utility improved with the inclusion of the Log(sCAR)&#95;Log(LAR) score. The model's predictive ability for secondary outcomes, such as renal replacement therapy (RRT), also improved with the addition of the Log(sCAR)&#95;Log(LAR) score. The sensitivity analysis further corroborated the stability of the Log(sCAR)&#95;Log(LAR) score in predicting persistent severe SA-AKI and secondary outcomes, such as RRT., Conclusions: The Log(sCAR)&#95;Log(LAR) score effectively predicted persistent severe SA-AKI, potentially aiding intensive care physicians in risk assessment., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethical Committee of the First Affiliated Hospital of Harbin Medical University (No. MR-23-24-039837). Consent for publication: My co-authors have all contributed to approve of this submission. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Acer griseum (Franch.) Pax is an endangered species endemic to China, mainly scattered in the Qinling-Daba Mountains. The genetic diversity of 17 natural populations were analyzed by nuclear DNA (nDNA) and chloroplast DNA (cpDNA) to explore the driving forces for its microevolution. A high level of genetic diversity (nDNA: H e = 0.296, cpDNA: H t = 0.806) was found in A. griseum . Genetic variation was mainly within populations (92.52%) based on nDNA, while it was mainly among populations (96.26%) based on cpDNA. The seventeen populations were divided into two groups, corresponding to the subtropical zone (Group I) and temperate zone (Group II), with haplotype 4 (Hap4) and Hap5 being the most common haplotypes, respectively. Consequently, genes associated with heat and heavy metal stress were identified in Group I, while genes related to salt and drought stress were identified in Group II. Haplotype differentiation was driven by the heterogeneous microenvironment caused by the uplifting of the Qinling-Daba Mountains, which was a vital source of its high genetic diversity. Furthermore, the uplifted Qinling-Daba mountains may bridge high pollen flow among populations, whereas rivers can result in low seed flow among populations, which has led to the incongruent genetic structure between nDNA and cpDNA. This study represents a new perspective that geological events, especially orogeny, play an important role in plant microevolution through the establishment of maternal genetic structure and provides a meaningful conservation strategy for A. griseum . Overall, the Qinling-Daba Mountains not only are cradles for the genetic diversity of A. griseum but also provided refugia for it during the Quaternary glacial period.

Background: Alterations in lipid metabolism were reported to impact human fertility; however, there is limited evidence on the association of lipid metabolism with embryo implantation as well as the etiology of recurrent implantation failure (RIF), especially regarding arachidonic acid metabolism., Methods: Experimental verification research (16 RIF patients and 30 control patients) based on GEO database analysis (24 RIF patients and 24 control patients). The methods in bioinformatics included differential gene screening, functional enrichment analysis, protein-protein interaction network, cluster analysis, weighted gene co-expression network analysis, and so forth. RIF patients were recruited for the experimental validation section. The endometrial samples in the mid-luteal phase were collected and subjected to quantitative real-time PCR detection., Results: Genes related to oxidative stress were differentially expressed and 17 different types of immune cells exhibited diverse infiltration in three RIF subgroups with different arachidonic acid metabolism. HPGDS, ALOX12, and TBXAS1 showed a strong positive correlation with the infiltration of NK cell, on the contrary, GGT6, PLA2G12A, and PTGS2 showed a strong negative correlation. The overall expression of AAMRGs was positively correlated with the infiltration of activated CD8 T cell, macrophage, natural killer cell, and T follicular helper cell., Conclusions: The cluster of arachidonic acid metabolism-related genes (AAMRGs) was abnormally expressed and positively associated with excessive oxidative stress as well as extensive infiltration of immune cells, including NK cells among RIF patients. Considering the high heterogeneity of the etiology of RIF, our study utilized the expression of AAMRGs as a typing basis to provide a new understanding of endometrial receptivity from the perspective of lipid metabolism and immune regulation in unexplained RIF couples, providing directions for its etiology and future basic research., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sinonasal inverted papilloma (SNIP) is characterized by a high recurrence rate and potential for malignant transformation. Although metabolic reprogramming plays a role in benign neoplasms, the specific metabolic pathways and biomarkers involved in SNIP pathogenesis remain unclear. Methods: RNA sequencing on paired SNIP and normal tissues identified altered genes with enzyme annotations and metabolic pathways by intersecting our cohort data (GSE270193, N=2) with the GSE193016 (N=4) dataset using Ingenuity Pathway Analysis. Functional and interaction assessments were performed using Metascape and STRING, with further validation via tissue microarray from an independent SNIP cohort (N=30). Results: The estrogen biosynthesis pathway was significantly altered in both datasets. Five key biomarkers, AKR1B10, CYP1B1, CYP2C19, CYP3A5, and HSD17B13, were significantly altered in SNIP tissues. These markers, sharing Gene Ontology terms, showed significant correlations at both the transcript and protein levels. Functional analysis revealed enrichment in epithelial cell proliferation and regulation of EGFR signaling, suggesting a role in SNIP pathogenesis. Validation in an independent cohort confirmed elevated protein levels of these markers, all positively correlated with EGFR in SNIP tissues. Notably, AKR1B10, CYP2C19, and CYP3A5 exhibited specific expression patterns distinguishing SNIP from sinonasal squamous cell carcinoma. Conclusion: Altered estrogen biosynthesis signaling plays a role in SNIP pathogenesis, revealing distinct biomarkers that could serve as novel diagnostic markers and therapeutic targets for SNIP management., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Context.—: Fondaparinux monitoring is not required among noncritically ill patients due to a predictable dose-response effect. However, this is debatable among critically ill patients, because fondaparinux bioavailability can be influenced by complicated medical conditions., Objective.—: To investigate fondaparinux monitoring among the critically ill., Design.—: Retrospective analysis of patients admitted in intensive care unit from February 2021 to December 2021 who received prophylactic fondaparinux and had anti-Xa activity tests., Results.—: Of 156 anti-Xa values, 86 (55.1%) were within 0.10-0.50 μg/mL (the recommended prophylactic range), 38 (24.4%) were less than 0.10 μg/mL, and 32 (20.5%) were greater than 0.50 μg/mL, demonstrating an unpredictable dose-response effect. Among 70 patients, thrombotic tendency was controlled in 32 (45.7%), thrombosis progressed in 22 (31.4%), and bleeding events occurred in 16 (22.9%). Patients with progressed thrombosis had 17 of 54 (31.5%) anti-Xa values less than 0.10 μg/mL; even though this proportion was greater than that of patients with controlled thrombotic tendency (11 of 72, 15.3%), it was similar to that of patients with bleeding (10 of 30, 33.3%), indicating a weak practicability of anti-Xa for monitoring fondaparinux efficacy. Thrombin-antithrombin complex showed a gradual decline among patients with controlled thrombotic tendency but a bounce-back effect among patients with progressed thrombosis. Thrombelastography R value above the upper reference value occurred more frequently among patients with bleeding (4 of 6, 66.7%) compared to patients without bleeding (4 of 22, 18.2%) (P = .01)., Conclusions.—: The fondaparinux dose-response effect was unpredictable among the critically ill; anti-Xa activity combined with thrombin-antithrombin complex and thrombelastography can be helpful to guide a precise fondaparinux therapy in this population., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2025 College of American Pathologists.)

The causal relationship between visceral adipose tissue (VAT) and hypertension remains unclear. We aimed to examine the potential association between them using observational and two-sample Mendelian randomization (MR) analyses. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used, applying multivariable logistic regression analysis to investigate the association between VAT mass and hypertension risk. Independent genetic variants related to VAT mass were derived from genome-wide association studies (GWAS) in 325 153 UK Biobank participants. The primary analysis employed the random-effects inverse-variance weighted (IVW) method, with MR-Egger, weighted median, simple mode, and weighted mode as sensitivity analyses. A total of 7661 participants were included. After adjusting for confounding factors, increased VAT mass was associated with a higher risk of hypertension (quartile 4 vs. quartile 1: OR:1.85, 95% confidence intervals [CI]: 1.31-2.63). Furthermore, VAT mass exhibited greater accuracy than body mass index (BMI) in predicting hypertension (areas under the curve [AUC]: 0.701 vs. 0.676, p for comparison < 0.001). The MR analyses demonstrated a causal relationship between increased VAT mass and the risk of hypertension in primary analyses (odds ratio [OR]:1.768, 95% CI: 1.594-1.861). Consistent findings across various MR models substantiate the robustness and strength of this causal relationship. These analyses provide additional support for both the positive association and causal relationship between elevated VAT and the risk of developing hypertension, suggesting that targeted interventions for VAT may be beneficial in preventing hypertension., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity., Methods: The expression of miR-378a-5p was analyzed in CRC samples. CRC cell lines were treated with different doses of X-rays. Bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were used to detect the expressions and binding relationship of miR-378a-5p and low-density lipoprotein receptor-related protein 8 (LRP8). MiR-378a-5p inhibitor or/and siLRP8 were transfected into CRC cells with or without irradiation. Subsequently, clonogenic assay, flow cytometry and in vivo experiments including tumorigenesis assay, immunohistochemistry, RT-qPCR and Western blot were performed to clarify the role of miR-378a-5p/LRP8 axis in the radiosensitivity of CRC., Results: The down-regulated expression of miR-378a-5p in CRC is related to histological differentiation and tumor-node-metastasis (TNM) stage. After irradiation, the survival fraction of CRC cells was decreased, while the apoptotic rate and the level of miR-378a-5p were increased. Restrained miR-378a-5p repressed apoptosis and apoptosis-related protein expressions, yet promoted the proliferation and the radioresistance of cells by regulating β-catenin in CRC cells. LRP8 was highly expressed in CRC, and targeted by miR-378a-5p. SiLRP8 improved radiosensitivity and reversed the effect of miR-378a-5p down-regulation on CRC cells. Overexpressed miR-378a-5p and irradiation enhanced the level of miR-378a-5p, yet suppressed the expressions of Ki67 and LRP8 as well as tumorigenesis., Conclusion: MiR-378a-5p may exert a radiosensitizing effect on CRC through the LRP8/β-catenin axis, which may be a new therapeutic target for CRC radioresistance.

Identification of critical material attributes(CMAs) is a key issue in the quality control of large-scale TCM products like Jianwei Xiaoshi Tablets. This study focuses on the granules of Jianwei Xiaoshi Tablets, using tablet tensile strength as the primary quality attribute. A method for identifying the CMAs and a design space for the granules were established, along with a predictive model for the granule CMAs based on Fourier transform near-infrared spectroscopy(FT-NIR). First, granules of Jianwei Xiaoshi Tablets with different properties were prepared using a partial factorial design method from the design of experiments(DOE). The powder properties of the granules were measured. An orthogonal partial least squares(OPLS) model was established to correlate the powder properties with tensile strength. Based on the characteristics of the comprehensive variables extracted by OPLS, the independent variables with the greatest explanatory power for tensile strength were identified. FT-NIR technology was then employed to establish a predictive model for the granule CMAs. The final CMAs identified were hygroscopicity, moisture content, D&#95;(50), collapse angle, mass flow rate, and tapped density. The coefficients of determination of the prediction set(R■) and relative percentage deviation(RPD) of the prediction set for flowability, D&#95;(50), and moisture content were 0.891, 0.994, and 0.998; and 2.97, 12.4, and 20.7, respectively. The established OPLS model clearly identified the impact of various factors on tensile strength, demonstrating good fit results. The model exhibited high prediction accuracy and can be used for the rapid and accurate determination of CMAs in granules of Jianwei Xiaoshi Tablets.

The construction method and simulation parameter settings for the discrete element model of Jianwei Xiaoshi Granules, as the primary material of Jianwei Xiaoshi Tablets, are not yet clear. The accuracy of the simulation model significantly influences the dynamic response characteristics between granules. Therefore, it is necessary to calibrate the parameters to improve the accuracy of the simulation parameters. Using the repose angle of Jianwei Xiaoshi Granules as the response value, the response surface methodology was employed to optimize and calibrate the discrete element parameters. Physical experiments were conducted to determine the physical properties of Jianwei Xiaoshi Granules. Based on the Hertz-Mindlin with Johnson-Kendall-Roberts(JKR) V2 model and virtual simulation methods, a repose angle determination model was constructed in EDEM software. The repose angle was measured using image analysis and numerical fitting methods. The Plackett-Burman experiment was used to screen the initial parameters for significance in the discrete element simulation. The significant parameters were then subjected to a steepest ascent experiment to determine the optimal parameter range. Furthermore, based on the Box-Behnken experiment, a second-order regression equation between significant parameters and repose angle was established, with the repose angle of 37.64° in the physical experiment as the target value. The regression equation was optimized and solved. The significance screening experiment revealed that the granule-granule static friction coefficient, granule-granule rolling friction, and granule-steel plate rolling friction of Jianwei Xiaoshi Granules significantly influenced the simulated repose angle. The optimal parameter combination was found to be 0.330, 0.222, and 0.229. The simulation results with this optimal parameter combination showed that there was no significant difference between the simulated repose angle and the repose angle obtained in the physical experiment, with a relative error of 0.05%, which further validated the reliability of the calibrated discrete element parameters for Jianwei Xiaoshi Granules.

Kinsenoside is a rare and valuable glycoside with extensive bioactivities. However, the enzymatic synthesis of kinsenoside has been a challenging task due to the limited enzyme toolbox and unsatisfactory yield. Herein, the β-glucosidase from Dictyoglomus thermophilum (DtBGL) was heterologously expressed, purified and enzymatically characterized. The purified DtBGL was successfully immobilized on the metal-organic frameworks of UiO-66-NH 2 . The DtBGL@UiO-66-NH 2 was fully characterized using SEM, XRD, TGA and FTIR. The studies on enzymatic properties demonstrated that DtBGL@UiO-66-NH 2 exhibited increased catalytic activity and stability compared to the free DtBGL. Particularly, DtBGL@UiO-66-NH 2 could catalyze the synthesis of kinsenoside via the reverse hydrolysis reaction and the kinsenoside yield was 34.12 % under the optimized catalytic system, which was 1.9-fold higher compared with the free DtBGL. Moreover, DtBGL@UiO-66-NH 2 displayed good reusability with a kinsenoside yield of 27.02 % after reuse for 3 times. The present work not only identifies and characterizes a highly active β-glucosidase with reverse hydrolysis activity, but also proposes the immobilized enzyme as an effective catalyst for the industrial production of glycosides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There remain controversies regarding the surgical treatment of extrahepatic bile duct stones (EHBDSs) in clinical practice., Aim: To explore the curative effect of laparoscopic cholecystectomy (LC) plus common bile duct exploration (CBDE) for the surgical treatment of EHBDSs and to analyze the risk factors that affect postoperative stone recurrence., Methods: Eighty-two patients with EHBDSs admitted between March 2017 and March 2023 were selected. Among them, patients treated with open choledocholithotomy plus LC or open cholecystectomy (OC) were set as the control group ( n = 40), and those treated with LC plus CBDE served as the observation group ( n = 42). The surgical outcomes of the two groups were compared, the surgical complications and Gastrointestinal Quality of Life Index (GIQLI) scores were counted, and the one-year prognostic recurrence was recorded. Independent factors for postoperative recurrence were determined using univariate and multivariate analyses., Results: The two groups were comparable in the stone residual rate ( P > 0.05). The operation time ( P < 0.05), intraoperative bleeding ( P < 0.05), and total complication rate ( P = 0.005) were lower in the observation group than in the control group. The observation group exhibited a marked increase in the GIQLI score, which was higher than the control group ( P < 0.05). A lower one-year recurrence rate was determined in the observation group vs the control group ( P = 0.027). Sphincter of Oddi dysfunction [odds ratio (OR) = 5.712, P = 0.007] and the treatment scheme of open choledocholithotomy plus LC or OC (OR = 6.771, P = 0.008) were the independent risk factors for one-year recurrence in patients after surgery., Conclusion: LC plus CBDE for patients with EHBDSs can reduce stone residuals, intraoperative bleeding, complications, and postoperative recurrence., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: Sodium-glucose co-transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors., Methods and Results: Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90 413 patients were enrolled (age 66 ± 10.1 years, 35.7% female, follow-up 2.4 ± 0.3 years); as compared with placebo, SGLTis were associated with significantly lower risk of all-cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86-0.94, P < 0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82-0.92, P < 0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68-0.76, P < 0.01), HF events (RR: 0.72, 95% CI: 0.68-0.75, P < 0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88-0.93, P < 0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85-0.99, P = 0.03). Notably, the favourable effect of SGLTis on all-cause mortality was more pronounced in younger (<65 years) patients (RR: 0.86, 95% CI: 0.81-0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79-0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31-0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8 ± 12.4 years, 36.4% female, follow-up 3.4 ± 1.9 months); SGLTis were associated with significant improvement in QoL as compared with placebo., Conclusions: In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Melanoma is an aggressive tumor with a high mortality rate. Metformin, a commonly prescribed diabetes medication, has shown promise in cancer prevention and treatment. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA molecules that play a key role in tumor development by interacting with cellular chromatins. Despite the benefits of metformin, the anticancer mechanism underlying its effect on the regulation of lncRNAs in melanoma remains unclear., Methods: We investigated the lncRNA profiles of human melanoma cells with and without metformin treatment using a next-generation sequencing approach (NGS). Utilizing public databases, we analyzed the expression levels and clinical impacts of LINC00094 and miR-1270 in melanoma. The expression levels of LINC00094 and miR-1270 were verified in human cell lines and clinical samples by real-time PCR and in situ hybridization. The biological roles of LINC00094 and miR-1270 in cell growth, proliferation, cell cycle, apoptosis, and motility were studied using in vitro assays., Results: We identify a novel long noncoding RNA, namely LINC00094, whose expression considerably decreased in melanoma cells after metformin treatment. In situ hybridization analysis revealed substantially higher expression of LINC00094 in cutaneous melanoma tissue compared with adjacent normal epidermis and normal control tissues (P < 0.001). In nondiabetic patients with melanoma, the overall survival of high LINC00094 expression group was shorter than the low LINC00094 expression group with borderline statistical significance (log-rank test, P = 0.057). Coexpression analysis of LINC00094 indicated its involvement in the mitochondrial respiratory pathway, with its knockdown suppressing genes associated with mitochondrial oxidative phosphorylation, glycolysis, antioxidant production, and metabolite levels. Functional analysis revealed that silencing-LINC00094 inhibited the proliferation, colony formation, invasion, and migration of melanoma cells. Cell cycle analysis following LINC00094 knockdown revealed G1 phase arrest with reduced cell cycle protein expression. Combined TargetScan and reporter assays revealed a direct link between miR-1270 and LINC00094. Ectopic miR-1270 expression inhibited melanoma cell growth and motility while inducing apoptosis. Finally, through in silico analysis, we identified two miR-1270 target genes, CD276 and centromere protein M (CENPM), which may be involved in the biological functions of LINC00094., Conclusions: Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment., Competing Interests: Declarations Consent for publication All the authors have read and approved the final article. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To analyse risk factors for early neurological damage in young and middle-aged stroke cases., Methods: Totally 405 young and middle-aged stroke patients in the neurocritical care unit (NCU) were selected and divided into the developmental (260 patients) and validation (145 patients) sets. The 405 cases were also grouped based on whether early neurological deterioration (END) occurred. The influencing factors of END were analysed by logistic regression, followed by the construction of a nomogram for predicting the risk of END. The Bootstrap method was applied to internally verify the predictive value of the model, using validation set data., Results: Age, type of stroke, diabetes, mechanical ventilation, pulse, initial National Institute of Health stroke scale (NIHSS), Barthel index (BI), haemoglobin, hypersensitive C-reactive protein (hs-CRP), triglyceride glucose (TyG) index and CONUT showed statistically significant differences (p < 0.05). Logistic regression analysis revealed type of stroke, initial NIHSS, CONUT, TyG index and hs-CRP were risk factors for END in young and middle-aged stroke cases (OR > 1, p < 0.05). The area under the curve (AUC) for the developmental set was 0.842, and internal validation results showed a C-index of 0.843; the AUC for the validation set was 0.843., Conclusion: The nomogram constructed in this study has good predictive efficacy and can provide reference for early clinical prediction of END in young and middle-aged stroke cases., Relevance to Clinical Practice: The importance of this research lies in shedding light on the significant impact of early neurological deterioration on the health outcomes of young and middle-aged stroke patients, particularly in the short term. To guide clinical workers to identify risk factors early and improve the prognosis of stroke patients., (© 2024 John Wiley & Sons Ltd.)

Long-term biomonitoring of urinary metal ions is an essential tool for the epidemiological assessment of chronic exposure levels, enabling us to track changes in metal exposure over time and better understand its health implications. In this study, we evaluated the temporal trends of urinary metal ions among 1962 residents of Guangzhou, China, from 2018 to 2022. The total metal ion concentrations in the urine of the population did not change significantly between 2018 and 2019. With the onset of the COVID-19 pandemic in 2020, urinary total metal ion concentrations began to decline dramatically, reaching their lowest level in 2021. A rebound in concentrations was observed in 2022, which returned to the initial levels observed in 2018. Urine chromium and cadmium concentrations peaked in 2020, while urinary lead levels were the highest in 2021, and urinary nickel concentrations were the highest in 2022. Males consistently displayed higher urinary concentrations of lead and arsenic throughout each year of the study. Furthermore, minors consistently had higher urinary nickel levels than adults, whereas adults consistently had higher urinary cadmium concentrations than minors. Cluster analyses were conducted annually on urinary metal ions to examine the differences in their distribution and to evaluate changes in metal exposure patterns over time. The Monte Carlo simulations indicate that the whole population exhibits a high non-carcinogenic risk from arsenic exposure and significant carcinogenic risks associated with exposure to nickel, arsenic, chromium, and cadmium. The next two years were predicted by a gray prediction model, and the results are tested using mean absolute percentage error which demonstrating high accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Short videos have demonstrated huge potential in disseminating health information in recent years. However, to our knowledge, no study has examined information about colorectal polyps on short-video sharing platforms., Objective: This study aimed to analyze the content and quality of colorectal polyps-related videos on short-video sharing platforms., Methods: The terms "" (intestinal polyps) or "" (colonic polyps) or "" (rectal polyps) or "" (colorectal polyps) or "" (polyps of large intestine) were used to search in TikTok (ByteDance), WeChat (Tencent Holdings Limited), and Xiaohongshu (Xingyin Information Technology Limited) between May 26 and June 8, 2024, and then the top 100 videos for each search term on different platforms were included and recorded. The Journal of American Medical Association (JAMA) score, the Global Quality Scale (GQS), the modified DISCERN, and the Patient Education Materials Assessment Tool (PEMAT) were used to evaluate the content and quality of selected videos by 2 independent researchers. SPSS (version 22.0; IBM Corp) and GraphPad Prism (version 9.0; Dotmatics) were used for analyzing the data. Descriptive statistics were generated, and the differences between groups were compared. Spearman correlation analysis was used to evaluate the relationship between quantitative variables., Results: A total of 816 eligible videos were included for further analysis, which mainly conveyed disease-related knowledge (n=635, 77.8%). Most videos were uploaded by physicians (n=709, 86.9%). These videos had an average JAMA score of 2.0 (SD 0.6), GQS score of 2.5 (SD 0.8), modified DISCERN score of 2.5 (SD 0.8), understandability of 80.4% (SD 15.6%), and actionability of 42.2% (SD 36.1%). Videos uploaded by news agencies were of higher quality and received more likes and comments (all P<.05). The number of collections and shares of videos about posttreatment caveats were more than those for other content (P=.03 and P=.006). There was a positive correlation between the number of likes, comments, collections, and shares (all P<.001). The duration and the number of fans were positively correlated with the quality of videos (all P<.05)., Conclusions: There are numerous videos about colorectal polyps on short-video sharing platforms, but the reliability and quality of these videos are not good enough and need to be improved., (©Jia-Lun Guan, Su-Hong Xia, Kai Zhao, Li-Na Feng, Ying-Ying Han, Ji-Yan Li, Jia-Zhi Liao, Pei-Yuan Li. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.10.2024.)

Melanin is a natural pigment in the human body that is primarily found in the skin and hair. It protects the skin from damage by ultraviolet radiation. Although this pigment plays a crucial role in protecting the human body, it represents a challenge for pathologists to evaluate highly pigmented tissue samples from melanoma or pigmented skin lesions. Abundant melanin may obscure tissue morphology, which makes it very difficult for pathologists to make a differential diagnosis. Melanin pigment is brown-to-black and granular, and its distribution is often uneven in tissues. The presence of these pigments can complicate the analysis of immunohistochemistry (IHC) for 2 reasons. First, they have a direct physical masking effect on antigen-antibody interactions. Second, 3,3-diaminobenzidine, the most commonly used chromogen, has a brown color that is difficult to distinguish from melanin pigment. Therefore, melanin bleaching has become a crucial step in handling pigmented melanocytic lesions. Bleaching techniques aid pathologists in histopathologic examination of melanin-rich tissue. In this study, we integrated melanin bleaching and IHC on an automated IHC platform to set up a rapid and fully automated procedure. Bleaching steps were performed before antigen retrieval. Samples were treated with 1% hydrogen peroxide solution in Tris-HCl buffer (pH 10) at 80°C for 8 minutes, achieving optimal conditions for melanin bleaching while preserving tissue morphology and antigenicity. This rapid, effective, fully automated, and standardized workflow can be applied to routine staining procedures in clinical laboratories, thereby improving the quality of pathological diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Lung cancer is the leading cause of cancer-related deaths worldwide. Patients with lung cancer usually exhibit poor prognoses and low 5-year survival rates. Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both chronic lung dysfunctions resulting in lung fibrosis and increased risk of lung cancer. Myofibroblasts contribute to the progression of asthma, COPD and IPF, leading to fibrosis in the airway and lungs. A growing body of evidence demonstrates that metabolic reprogramming is a major hallmark of fibrosis, being important in the progression of fibrosis. Using gene expression microarray, we identified and validated that the lipid metabolic pathway was upregulated in lung fibroblasts upon interleukin (IL)-4, IL-13 and tumour necrosis factor (TNF)-α treatment. In this study, we described that prostaglandin E synthase (PTGES) was upregulated in lung fibroblasts after IL-4, IL-13 and TNF-α treatments. PTGES increased α-SMA levels and promoted lung fibroblast cell migration and invasion abilities. Furthermore, PTGES was upregulated in a lung fibrosis rat model in vivo. PTGES increased AKT phosphorylation, leading to activation of the HIF-1α-glycolysis pathway in lung fibroblast cells. HIF-1α inhibitor or 2-DG treatments reduced α-SMA expression in recombinant PTGES (rPTGES)-treated lung fibroblast cells. Targeting PGE 2 signalling in PTGES-overexpressing cells by a PTGES inhibitor reduced α-SMA expression. In conclusion, the results of this study demonstrate that PTGES increases the expression of myofibroblast marker via HIF-1α-dependent glycolysis and contributes to myofibroblast differentiation., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Electronic symptom monitoring via patient-reported outcomes in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery., Materials and Methods: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2022. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This instrument was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first-year post-surgery using the validated ePSA-Lung., Results: In total, 1037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 ( n =775), compliance ranged from 63.21 to 84.76% during the 1-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P <0.001)., Conclusions: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use., Methods: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days., Results: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; P interaction  = 0.07) or its individual components between bivalirudin and heparin groups., Conclusions: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI., Trial Registration: ClinicalTrials.gov NCT03822975., (© 2024. The Author(s).)

Sepsis associated Acute kidney injury (AKI) is a common clinical syndrome characterized by suddenly decreased in renal function and urinary volume. This study was designed to investigate the role of Aquaporin 1 (AQP1) and P53 in the development of sepsis-induced AKI and their potential regulatory mechanisms. Firstly, transcriptome sequencing analysis of mice kidney showed AQP1 expression was reduced and P53 expression was elevated in Cecal ligation and puncture (CLP)-induced AKI compared with controls. Bioinformatics confirmed that AQP1 expression was remarkably decreased and P53 expression was obviously elevated in renal tissues or peripheral blood of septic AKI patients. Moreover, we found in vivo experiments that AQP1 mRNA levels were dramatically decreased and P53 mRNA significantly increased following the increased expression of inflammation, apoptosis, fibrosis, NGAL and KIM-1 at various periods in septic AKI. Meanwhile, AQP1 and P53 protein levels increased significantly first and then decreased gradually in kidney tissue and serum of rats in different stages of septic AKI. Most importantly, in vivo and vitro experiments demonstrated that silencing of AQP1 greatly exacerbates renal or cellular injury by up-regulating P53 expression promoting inflammatory response, apoptosis and fibrosis. Overexpression of AQP1 prevented the elevation of inflammation, apoptosis and fibrosis by down-regulating P53 expression in Lipopolysaccharide (LPS)-induced AKI or HK-2 cells. Therefore, our results suggested that AQP1 plays a protective role in modulating AKI and can attenuate inflammatory response, apoptosis and fibrosis via downregulating P53 in septic AKI or LPS-induced HK-2cells. The pharmacological targeting of AQP1 mediated P53 expression might be identified as potential targets for the early treatment of septic AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Liao, Li, Liu, Luo, Diao, Wang and Jin.)

Plant-derived β-glucosidases hold promise for glycoside biosynthesis via reverse hydrolysis because of their excellent glucose tolerance and robust stability. However, their poor heterologous expression hinders the development of large-scale production and applications. In this study, we overexpressed apple seed β-glucosidase (ASG II) in Komagataella phaffii and enhanced its production from 289 to 4322 U L -1 through expression cassette engineering and protein engineering. Upon scaling up to a 5-L high cell-density fermentation, the resultant mutant ASG II V80A achieved a maximum protein concentration and activity in the secreted supernatant of 2.3 g L -1 and 41.4 kU L -1 , respectively. The preparative biosynthesis of salidroside by ASG II V80A exhibited a high space-time yield of 33.1 g L -1 d -1 , which is so far the highest level by plant-derived β-glucosidase. Our work addresses the long-standing challenge of the heterologous expression of plant-derived β-glucosidase in microorganisms and presents new avenues for the efficient production of salidroside and other natural glycosides., (© 2024 Wiley‐VCH GmbH.)

Using the sample of Chinese A-share listed firms from 2010 to 2020, this study examines the impact of non-controlling large shareholders (NCLSs) on corporate capital structure adjustment. The results show that NCLSs significantly increase the dynamic capital structure adjustment speed and reduce capital structure deviation. NCLSs have an asymmetric influence on capital structure adjustment speed for different deviation directions, i.e. compared to the speed of upward adjustment after a downward deviation of the capital structure, the effect of NCLSs on the speed of downward adjustment of the capital structure after an upward deviation is stronger. Whether in state-owned enterprises (SOEs) or non-state-owned enterprises (NSOEs), NCLSs significantly increase the dynamic capital structure adjustment speed. However, compared with SOEs, NCLSs in NSOEs have a more significant positive impact on the dynamic capital structure adjustment speed. The mechanism analysis suggests that reducing agency costs and mitigating financing constraints serve as the important channels through which NCLSs influence the dynamic adjustment of capital structure. This paper not only enriches and improves the theoretical basis of dynamic capital structure adjustment, but also helps to deepen the understanding of dynamic capital structure adjustment of Chinese listed firms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSV A ) and B (HRSV B ) of HRSV. Next, the Pyrococcus furiosus Argonaute ( PfAgo ) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/μL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSV A and HRSV B infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liao, Feng, Zhang, Yang, Zhan, Zeng, Huang, Lian, Ke, Cai, Zhang, Fang, Cai, Chen, Lin, Lin, Chen, Liu, Huang, Lin and Lin.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

Background: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC., Aim: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC., Methods: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines., Results: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC ( P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher ( P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC ( P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased ( P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) ( P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS., Conclusion: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated., Methods: Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death., Results: Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01-2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02-3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24-3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21-2.73, P = 0.0043), 2.76 (1.57-4.86, P = 0.0004), and 1.72 (1.09-2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75-4.49, P < 0.0001), cardiac death (aHR: 4.10, 95% CI: 2.18-7.70, P < 0.0001), and all-cause death (aHR: 3.00, 95% CI, 1.73-5.19, P < 0.0001) were significantly greater in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile). Notably, the RIR and RCR was associated with an increased risk of ischemic events especially in patients with adequate low-density lipoprotein cholesterol (LDL-C) control (LDL-C < 70 mg/dl) (P interaction =0.04). Furthermore, the RIR and RCR provide more accurate evaluations of risk in addition to the GRACE score in these patients [areas under the curve (AUC) for ischemic events: 0.64 vs. 0.66, P = 0.003]., Conclusion: Among ACS patients receiving contemporary statin treatment who underwent PCI, high risks of both residual inflammation and cholesterol, as assessed by hsCRP and RC, were strongly associated with increased risks of ischemic events, cardiac death, and all-cause death., (© 2024. The Author(s).)

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism., Methods: MyD88 knockout (MyD88 -/- ) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism., Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88 -/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed., Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1772/coif). The authors have no conflicts of interest to declare.

Sepsis is a severe inflammatory disorder that can lead to life-threatening multiple organ injury. Lipopolysaccharide (LPS)-induced inflammation is the leading cause of multiple organ failure in sepsis. This study aimed to explore the effect of a novel agent, 2-(4-hydroxy-3-methoxyphenyl)-benzothiazole (YL-109), on LPS-induced multiple organ injury and the molecular mechanisms underlying these processes. The results showed that YL-109 protected against LPS-induced high mortality, cardiac dysfunction, pulmonary and intestinal injury through inhibiting the proinflammatory response, NLRP3 expression and pyroptosis-associated indicators in mouse tissues. YL-109 suppressed LPS-initiated cytokine release, pyroptosis and pyroptosis-related protein expression in HL-1, IEC-6 and MLE-12 cells, which was consistent with the results of the in vivo experiments. Mechanistically, YL-109 reduces phosphorylated ERK (extracellular signal-regulated kinase) levels and NF-κB activation, which are achieved through upregulating CHIP (carboxy terminus of Hsc70-interacting protein) expression, thereby inhibiting c-Jun and c-Fos activation as well as NLRP3 expression. As an E3 ligase, CHIP overexpression obviously promoted the degradation of phosphorylated ERK and inhibited the expression of NF-κB-mediated NLRP3 in cells stimulated with LPS. The protective effects of YL-109 against cardiac, pulmonary and intestinal damage, inflammation and pyroptosis caused by LPS were eliminated in CHIP knockout mice. Our results not only reveal the protective effect and molecular mechanism of YL-109 against LPS-mediated organs damage but also provide additional insights into the effect of CHIP on negatively regulating pyroptosis and inflammatory pathways., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration., Methods: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset., Results: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis., Conclusion: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh 3 ) 3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.

Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct zyg -type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg -type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H 2 O 2 ). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H 2 O 2 synthesis rate of 3324 μmol g -1 h -1 , which makes the PTZ-COF one of the best crystalline porous photocatalysts in H 2 O 2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR , rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk., Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis., Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population., Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: To describe and conclude the in vitro fertilization (IVF) results of patients with X chromosome abnormality., Methods: A retrospective case series was conducted. According to the number of normal X, patients were allocated into two groups: Group A (patients with only a normal X, while other X has any types of abnormalities) and Group B (patients have two or more normal X chromosomes). Clinical data, including basic information, fertility information, and IVF outcomes, were collected., Results: Fourteen patients with X chromosome abnormality were included, among which 13 patients underwent a total of 29 cycles. Patients in Group B had five successful pregnancies and three live births, while no patient in Group A had a clinical pregnancy. Furthermore, the blastocyst formation rate and incidence of pregnancy were significantly lower in Group A (Z = -3.135, p = .002; Z = -2.946, p = .003, respectively). When controlled covariates, the karyotype of one normal X was also a risk factor for both blastocyst formation rate and success pregnancy (β = .820, 95% confidence interval [CI] = 0.458-1.116, β = .333, 95% CI = 0.017-0.494, respectively)., Conclusions: Our results revealed that women with only one normal X might suffer from worse IVF outcomes, mainly blastocyst formation rate, compared with those who had two or more normal X, including mosaic Turner syndrome and 47,XXX., (© 2024 Wiley Periodicals LLC.)

Objective: To investigate the clinical characteristics and prognosis of heavy alcohol consumption among young and middle-aged patients with acute cerebral infarction (ACI)., Methods: A total of 263 young and middle-aged ACI patients were included in the study from June 2018 to December 2020 and classified into heavy drinkers and non-heavy drinkers. Multivariate logistic regression analysis was conducted to assess the association between ACI and heavy alcohol consumption, considering clinical characteristics and one-year post-discharge prognosis., Results: Among the patients, 78 were heavy drinkers. Heavy drinkers were more likely to consume alcohol 24 h before ACI onset (OR 4.03, 95 % CI 2.26-7.20), especially in the form of liquor (OR 3.83, 95 % CI 1.59-9.20), and had a higher risk of diastolic blood pressure ≥90 mmHg upon admission (OR 2.02, 95 % CI 1.12-3.64). In the one-year post-discharge prognosis, heavy drinkers had a greater likelihood of poor prognosis at 3 months (OR 2.31, 95 % CI 1.01-5.25), were less likely to quit drinking after discharge (OR 0.36, 95 % CI 0.19-0.66), and had a higher risk of recurrent cerebral infarction (OR 2.79, 95 % CI 1.14-6.84)., Conclusions: Over the 12-month follow-up, young and middle-aged ACI patients with heavy alcohol consumption exhibited worse short-term prognosis. Controlling alcohol consumption levels may improve the prognosis of these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The asymmetric cross-coupling of unsaturated bonds, hampered by their comparable polarity and reactivity, as well as the scarcity of efficient catalytic systems capable of diastereo- and enantiocontrol, presents a significant hurdle in organic synthesis. In this study, we introduce a highly adaptable photochemical cobalt catalysis framework that facilitates chemo- and stereoselective reductive cross-couplings between common aldehydes with a broad array of carbonyl and iminyl compounds, including N -acylhydrazones, aryl ketones, aldehydes, and α-keto esters. Our methodology hinges on a synergistic mechanism driven by photoredox-induced single-electron reduction and subsequent radical-radical coupling, all precisely guided by a chiral cobalt catalyst. Various optically enriched β-amino alcohols and unsymmetrical 1,2-diol derivatives (80 examples) have been synthesized with good yields (up to 90% yield) and high stereoselectivities (up to >20:1 dr, 99% ee). Of particular note, this approach accomplishes unattainable photochemical asymmetric transformations of aldehydes with disparate carbonyl partners without reliance on any external photosensitizer, thereby further emphasizing its versatility and cost-efficiency.

In this study, an active and intelligent nanofilm for monitoring and maintaining the freshness of pork was developed using ethyl cellulose/gelatin matrix through electrospinning, with the addition of natural purple sweet potato anthocyanin. The nanofilm exhibited discernible color variations in response to pH changes, and it demonstrated a higher sensitivity towards volatile ammonia compared with casting film. Notably, the experimental findings regarding the wettability and pH response performance indicated that the water contact angle between 70° and 85° was more favorable for the smart response of pH sensitivity. Furthermore, the film exhibited desirable antioxidant activities, water vapor barrier properties and also good antimicrobial activities with the incorporation of ε-polylysine, suggesting the potential as a food packaging film. Furthermore, the application preservation outcomes revealed that the pork packed with the nanofilm can prolong shelf life to 6 days, more importantly, a distinct color change aligned closely with the points indicating the deterioration of the pork was observed, changing from light pink (indicating freshness) to light brown (indicating secondary freshness) and then to brownish green (indicating spoilage). Hence, the application of this multifunctional film in intelligent packaging holds great potential for both real-time indication and efficient preservation of the freshness of animal-derived food items., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Taking Chinese non-financial A-share companies listed on the Shenzhen Stock Exchange (SZSE) between 2003 and 2018 as a sample, this paper empirically examines whether and how institutional investors' site visits (SVs) affect corporate investment-cash flow sensitivity (ICFS). The results show that institutional investors' SVs can reduce ICFS, and this effect is more obvious for companies with fewer investment opportunities, larger sizes, higher internal cash flows, and higher agency costs, indicating that institutional investors' SVs primarily inhibit ICFS caused by agency conflicts rather than financing constraints. In addition, the inhibitory effect of institutional investors' SVs on ICFS exists mainly in companies with poor internal supervision governance and weak executive compensation incentive mechanisms, indicating that institutional investors' SVs and other forms of corporate governance mechanisms operate as substitutes in reducing ICFS. This paper reveals the important role of institutional investors' SVs in reducing ICFS, with important theoretical and practical implications for regulators to progressively regulate and promote this form of investor activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To develop and validate an effective nomogram for predicting poor response to orthokeratology., Methods: Myopic children (aged 8-15 years) treated with orthokeratology between February 2018 and January 2022 were screened in four hospitals of different tiers (i.e. municipal and provincial) in China. Potential predictors included 32 baseline clinical variables. Nomogram for the outcome (1-year axial elongation ≥0.20 mm: poor response; <0.20 mm: good response) was computed from a logistic regression model with the least absolute shrinkage and selection operator. The data from the First Affiliated Hospital of Chengdu Medical College were randomly assigned (7:3) to the training and validation cohorts. An external cohort from three independent multicentre was used for the model test. Model performance was assessed by discrimination (the area under curve, AUC), calibration (calibration plots) and utility (decision curve analysis)., Results: Between January 2022 and March 2023, 1183 eligible subjects were screened from the First Affiliated Hospital of Chengdu Medical College, then randomly divided into training (n = 831) and validation (n = 352) cohorts. A total of 405 eligible subjects were screened in the external cohort. Predictors included in the nomogram were baseline age, spherical equivalent, axial length, pupil diameter, surface asymmetry index and parental myopia (p < 0.05). This nomogram demonstrated excellent calibration, clinical net benefit and discrimination, with the AUC of 0.871 (95% CI 0.847-0.894), 0.863 (0.826-0.901) and 0.817 (0.777-0.857) in the training, validation and external cohorts, respectively. An online calculator was generated for free access (http://39.96.75.172:8182/#/nomogram)., Conclusion: The nomogram provides accurate individual prediction of poor response to overnight orthokeratology in Chinese myopic children., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known., Methods and Results: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways., Conclusion: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs)., Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk., Methods: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated., Results: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found., Conclusions: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients., (© 2024. The Author(s).)

Aim: To present the 1-year results of a prospective cohort study investigating the efficacy, potential mechanism, and safety of orthokeratology (ortho-k) with different back optic zone diameters (BOZD) for myopia control in children., Methods: This randomized clinical study was performed between Dec. 2020 and Dec. 2021. Participants were randomly assigned to three groups wearing ortho-k: 5 mm BOZD (5-MM group), 5.5 mm BOZD (5.5-MM group), and 6 mm BOZD (6-MM group). The 1-year data were recorded, including axial length, relative peripheral refraction (RPR, measured by multispectral refractive topography, MRT), and visual quality. The contrast sensitivity (CS) was evaluated by CSV-1000 instrument with spatial frequencies of 3, 6, 12, and 18 cycles/degree (c/d); the corneal higher-order aberrations (HOAs) were measured by iTrace aberration analyzer. The one-way ANOVA was performed to assess the differences between the three groups. The correlation between the change in AL and RPR was calculated by Pearson's correlation coefficient., Results: The 1-year results of 20, 21, and 21 subjects in the 5-MM, 5.5-MM, and 6-MM groups, respectively, were presented. There were no statistical differences in baseline age, sex, or ocular parameters between the three groups (all P >0.05). At the 1-year visit, the 5-MM group had lower axial elongation than the 6-MM group (0.07±0.09 vs 0.18±0.11 mm, P =0.001). The 5-MM group had more myopic total RPR (TRPR, P =0.014), with RPR in the 15°-30° (RPR 15-30, P =0.015), 30°-45° (RPR 30-45, P =0.011), temporal (RPR-T, P =0.008), and nasal area (RPR-N, P <0.001) than the 6-MM group. RPR 15-30 in the 5.5-MM group was more myopic than that in the 6-MM group ( P =0.002), and RPR-N in the 5-MM group was more myopic than that in the 5.5-MM group ( P <0.001). There were positive correlations between the axial elongation and the change in TRPR ( r =0.756, P <0.001), RPR 15-30 ( r =0.364, P =0.004), RPR 30-45 ( r =0.306, P =0.016), and RPR-N ( r =0.253, P =0.047). The CS decreased at 3 c/d ( P <0.001), and the corneal HOAs increased in the 5-MM group ( P =0.030)., Conclusion: Ortho-k with 5 mm BOZD can control myopia progression more effectively. The mechanism may be associated with greater myopic shifts in RPR., Competing Interests: Conflicts of Interest: Tang WT, None; Luo XN, None; Zhao WJ, None; Liao J, None; Xu XY, None; Zhang HD, None; Zhang L, None., (International Journal of Ophthalmology Press.)

Aims: Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH., Methods and Results: Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca 2+ influx and inducing phenotypic conversion of PASMCs., Conclusions: Nupr1 activation could promote Ca 2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy., (© 2024. The Author(s).)

Objective: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation., Methods: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms., Results: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model., Conclusion: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation., (© 2024. The Author(s).)

Aim: Limited data are available regarding ALI's clinical relevance and prognostic value in patients with hepatocellular carcinoma (HCC) after hepatectomy., Materials and Methods: HCC patients who received hepatectomy at the Meizhou People's Hospital from May 2011 to February 2022 were enrolled in the study cohort. The ALI was calculated as follows: ALI = BMI (kg/m 2 ) × ALB (g/dL)/(absolute neutrophil count/absolute lymphocyte count). The primary outcome was overall survival (OS). The secondary outcome was cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were performed, followed by nomogram construction and decision curve analysis (DCA)., Results: 425 HCC patients were enrolled for analyses. Lower preoperative ALI was significantly correlated with incomplete tumor capsule and advanced tumor stage. Lower preoperative ALI was an adverse independent prognostic factor for OS (HR: 1.512, 95% CI: 1.122-2.039, P 0.007) and CSS (HR: 1.754, 95% CI: 1.262-2.438, P <0.001) in HCC patients. The nomogram plot was built based on three (including age, TNM stage, and ALI) and two (including TNM stage and ALI) independent prognostic factors for OS and CSS, respectively. Further analyses indicated that the nomogram had better predictive value and some net benefit than the traditional TNM stage alone, especially in long-term OS., Conclusions: Our study further indicated that ALI could be a prognostic marker for OS and CSS in HCC patients after hepatectomy, especially in long-term OS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wen, Liu, Liao and Xu.)

Background: Performance status (PS) is associated with the severity of liver cirrhosis and is also an important survival determinant in hepatocellular carcinoma (HCC). Albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade have been proposed to evaluate liver dysfunction in HCC, but their role in patients with different PS is unclear. We aimed to investigate the prognostic role of ALBI and EZ-ALBI grade in a large HCC cohort with variable PS., Methods: A total of 3355 newly diagnosed HCC patients between 2002 and 2018 were identified and retrospectively analyzed. Independent prognostic predictors associated with survival were investigated using the Cox proportional hazards model., Results: Patients with poor PS had decreased survival compared with those with good PS. In the Cox model, creatinine ≥1.2 mg/dL, α-fetoprotein (AFP) ≥20 ng/mL, vascular invasion, distant metastasis, total tumor volume >100 cm 3 , presence of ascites, ALBI grades 2 and 3, EZ-ALBI grade 2 and grade 3, PS 1-4, and noncurative treatment were independently associated with higher mortality in the entire cohort (all p < 0.001). ALBI grade and EZ-ALBI grade can well stratify overall survival in subgroup patients with PS 0, PS 1-2, and PS 3-4 (all p < 0.001)., Conclusion: Patients with good PS have better long-term survival compared with those with poor PS. ALBI and EZ-ALBI grade can discriminate long-term outcome in the entire cohort as well as in patients with different PS. ALBI and EZ-ALBI are objective and feasible prognostic models to evaluate liver dysfunction in HCC patients independent of PS., Competing Interests: Conflicts of interest: Dr Teh-Ia Huo, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors., Methods: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error., Results: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25., Conclusion: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed. Transcriptome and real-time fluorescence quantitative polymerase chain reaction(PCR) were used to analyze the expression pattern of the UGT gene in flowers and leaves of Ch. indicum. Quasi-targeted metabolomics was used to analyze the differential metabolites in flowers and leaves. The results showed that a total of 279 UGT genes were identified in the Ch. indicum genome. Phylogenetic analysis showed that these UGT genes were divided into 8 subfamilies. Members of the same subfamily were distributed in clusters on the chromosomes. Tandem duplications were the main driver of the expansion of the UGT gene family from Ch. indicum. Structural domain analysis showed that 262 UGT genes had complete plant secondary metabolism signal sequences(PSPG box). The analysis of cis-acting elements indicated that light-responsive elements were the most ubiquitous elements in the promoter regions of UGT gene family members. Quasi-targeted metabolome analysis of floral and leaf tissue revealed that most of the flavonoid metabolites, including luteolin-7-O-glucoside and kaempferol-7-O-glucoside, had higher accumulation in flowers. Comparative transcriptome analysis of flower and leaf tissue showed that there were 72 differentially expressed UGT genes, of which 29 genes were up-regulated in flowers, and 43 genes were up-regulated in leaves. Correlation network and phylogenetic analysis showed that CindChr9G00614970.1, CindChr2G00092510.1, and CindChr2G00092490.1 may be involved in the synthesis of 7-O-flavonoid glycosides in Ch. indicum, and real-time fluorescence quantitative PCR analysis further confirmed the reliability of transcriptome data. The results of this study are helpful to understand the function of the UGT gene family from Ch. indicum and provide data reference and theoretical basis for further study on the molecular regulation mechanism of flavonoid glycosides synthesis in Ch. indicum.