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Jiakang Chen,1,* Kasim Allel,2– 4,* Chuyue Zhuo,1,* Wenwei Luo,5 Nanhao He,1 Xu Yang,1 Yingyi Guo,1 Jiong Wang,1 Likang Yao,1 Jiahui Li,1 Yexin Lin,1 Ruiyang Tu,6 Laith Yakob,2,3 Chao Zhuo1 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Disease Control, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; 3Antimicrobial Resistance Centre, London School of Hygiene & Tropical Medicine, London, UK; 4Institute for Global Health, University College London, London, UK; 5Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Science and Technology Studies, University College London, London, UK*These authors contributed equally to this workCorrespondence: Chao Zhuo, State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of China, Email chaosheep@gzhmu.edu.cnIntroduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified.Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related.Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US$2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay.Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.Keywords: Escherichia coli, Klebsiella pneumoniae, bacteremia, ESBL, risk factors, medical costs

Zhongyue Huang,1,&ast; Gaoqiong Yao,2,&ast; Chengzhi Zhang,2 Xin Zhou,2 Guanyang Zou,3,&ast; Chao Zhuo4,&ast; 1Institute of Medical Information/Medical Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanyang Zou, No. 232, Waihuan East Road, Panyu District, Guangzhou, Guangdong Province, 510006, People’s Republic of China, Email zgy1021@hotmail.com Chao Zhuo, 195 Dongfeng West Road, Yuexiu District, Guangzhou, Guangdong Province, 510030, People’s Republic of China, Email chaosheep@gzhmu.edu.cnPurpose: With the increasing frequency and intensity of carbapenem consumption, carbapenem-resistant organisms (CRO) have become a focus of anti-infection research. This study aimed to evaluate the rationality of the clinical use of carbapenems among inpatients in the surgical departments of a tertiary hospital in southwest China.Patients and methods: A point-score system was established for evaluation based on the clinical practices in surgical departments and selected carbapenem prescriptions from June 2020 to June 2021 for hepatobiliary surgery, gastrointestinal surgery, and neurosurgery in the study hospital. Prescriptions with a total score ≥ 270 were defined as rational. Descriptive statistics were used to describe the characteristics and rationality of the prescriptions. The chi-square test, Mann–Whitney U-test, and Kruskal–Wallis H-test were used to compare characteristics between rational and irrational prescriptions. Linear regression analysis was used to determine the factors affecting the rationality of carbapenem prescriptions.Results: According to 192 carbapenem prescription records, the median age of patients was 62 years [IQR, 48.0– 73.0], and 20% of patients had abdominal infections, 10% had lung infections, 14% had intracranial infections, and 3% had urinary tract infections. 56% of carbapenem prescriptions were irrational. Compared with rational carbapenem prescriptions, irrational prescriptions had a higher proportion of those with inappropriate indications (49% vs 0%, p < 0.05), incorrect variety selection (15% vs 0%, p< 0.05), and unreasonable assessment of etiology and efficacy (46% vs 8%, p < 0.05). Linear regression analysis suggested that the diagnosis of cholecystitis (standardized regression coefficient=0.183, p< 0.05) and replaced medication (standardized regression coefficient = 0.154, p< 0.05) influenced the rationality of carbapenem prescriptions.Conclusion: Our study shows that the irrational use of carbapenems deserves attention, especially in surgical departments. Interventions for carbapenem use that are based on evaluation criteria should be developed to reduce the emergence and spread of carbapenem-resistant bacteria.Keywords: carbapenem, prescription review, surgery

Heng Chen,1,&ast; Xingang Sun,1,&ast; Chengui Zhuo,2 Jianqiang Zhao,3 Aohan Zu,1 Qiqi Wang,1 Liangrong Zheng1 1Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Cardiology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, People’s Republic of China; 3Department of Cardiology, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangrong Zheng; Qiqi Wang, Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email 1191066@zju.edu.cn; 1508036@zju.edu.cnPurpose: Cardiac troponin I (cTnI) is a well-established biomarker for stroke prediction, especially in patients with heart diseases. However, the causal effect of circulating cTnI on stroke remains unclear.Methods: We employed Mendelian Randomization (MR) analysis to determine the associations between genetically predicted circulating cTnI levels and stroke and its subtypes. Summary-level data for exposure and outcomes were generated from different genome-wide association studies. Single-nucleotide polymorphisms (SNPs) associated with circulating cTnI at genome-wide significance level (P < 5 × 10− 8) were employed as instrumental variables (IVs). We used fixed-effect inverse-variance weighted (IVW) as the main method for pooling MR estimates. Sensitivity analyses and multivariable MR analyses were carried out to assess the robustness of the results.Results: Using the fixed-effects IVW method, we found that genetically elevated plasma cTnI levels may have a causal effect on the risk of cardioembolic stroke (CES) (odds ratio (OR), 1.58; 95% confidence interval (CI), 1.17– 2.13; P = 0.003). Additional analyses including multiplicative random-effects (mre) IVW, weighted median, MR-Egger and MR-PRESSO yielded similar results, but with broader CIs that span 1.0. The total effect of cTnI on CES was attenuated by adjusting for the effect of atrial fibrillation (OR,1.26; 95% CI, 0.76– 2.11; P = 0.371) and smoking (OR,1.53; 95% CI, 0.87– 2.66; P = 0.137). In addition, we found no causal effect of cTnI on the risk of any stroke and other stroke subtypes, including any ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, and intracerebral hemorrhage. These results were consistent across sensitivity analyses.Conclusion: This study provides little evidence that increased serum cTnI levels lead to a higher risk of stroke.Keywords: Mendelian randomization, cardiac troponin I, stroke, causation, genome-wide association studies

Chao Zhuo,1 Yijiang Huang,2 Wenyuan Liu,3 Jin-Fu Xu,4 Wei Yun Zhu,5 Gregory G Stone,6 Jean Li Yan,7 Naglaa Mohamed8 1State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Respiratory Clinical Medical Center, Hainan Cancer Hospital, Hainan, People’s Republic of China; 3Respiratory Department, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Medical Department, Pfizer Investment Co. Ltd., Beijing, People’s Republic of China; 6Biopharmaceuticals Group, Pfizer Inc., Groton, CT, USA; 7Biopharmaceuticals Group, Pfizer Inc., Cambridge, MA, USA; 8Biopharmaceuticals Group, Pfizer Inc., New York, NY, USACorrespondence: Chao Zhuo, Email chaosheep@sina.comBackground: Ceftaroline fosamil has demonstrated superior clinical efficacy versus ceftriaxone for hospitalized adults with moderate-to-severe community-acquired pneumonia (CAP) in a Phase 3 trial in Asia and in a meta-analysis of three trials in Asia, North America, and Europe. Efficacy and safety outcomes for the subset of patients in China in the ASIA CAP trial were analyzed to determine if the same conclusions hold in the China subpopulation.Methods: Hospitalized adults with Pneumonia Outcomes Research Team risk class III–IV CAP were randomized (1:1) to receive either intravenous ceftaroline fosamil 600 mg every 12 h or ceftriaxone 2 g every 24 h for 5– 7 days. The primary efficacy variable was clinical response at test-of-cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included microbiological responses and safety.Results: Of 302 patients randomized in China, 205 were included in the CE population. Clinical cure rates at TOC were 80/105 (76.2%) for ceftaroline fosamil and 61/100 (61.0%) for ceftriaxone (difference 15.2%, 95% CI 2.5, 27.6), thereby meeting predefined non-inferiority and superiority criteria for the overall study. Subgroup analyses of the primary endpoint demonstrated consistency of favourable efficacy of ceftaroline fosamil across age groups, Pneumonia Outcomes Research Team risk classes and CURB-65 scores. Microbiological responses were presumed from clinical outcomes. Adverse events were consistent with the study treatments’ known safety profiles.Conclusion: The China subset results are consistent with the overall study population, despite the smaller sample size. Ceftaroline fosamil was both non-inferior and superior to ceftriaxone for empiric treatment of Chinese patients with moderate-to-severe CAP.Trial Registration: ClinicalTrials.gov identifier NCT01371838.Keywords: ceftriaxone, CURB-65, treatment outcomes, clinical trial

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune

Xinying Chen,1,* Ce Chen,2,* Feng Ji,3,* Yong Xu,4 Wenqiang Wang,5 Xiaodong Lin,2 Deguo Jiang,2 Xueqin Song,6 Xiangyang Gao,7 Hongjun Tian,8 Chuanjun Zhuo,8 Jingliang Zhang9 1Psychiatric-Neuroimaging-Genetics-Comorbidity Laboratory (PNGC_Lab), Tianjin Mental Health Centre, Mental Health Teaching Hospital of Tianjin Medical University, Tianjin Anding Hospital, Tianjin 300222, People’s Republic of China; 2Psychiatric-Neuroimaging-Genetics Laboratory, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 3Department of Psychiatry, School of Mental Health, Jining Medical University, Jining 272119, Shandong Province, People’s Republic of China; 4Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, MDT Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 5Co-Collaboration Laboratory of China and Canada, Xiamen Xianyue Hospital and University of Alberta, Xiamen 361000, People’s Republic of China; 6The First Affiliated Hospital/Zhengzhou University, Biological Psychiatry International Joint Laboratory of Henan/Zhengzhou University, Henan Psychiatric Transformation Research Key Laboratory/Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 7Health Management Institute, Center for Statistical Analysis of Medical Data, Medical Big Data Analysis Center, Chinese PLA General Hospital, Beijing 100191, People’s Republic of China; 8Department of Neurology and Psychiatry Biological Imaging Laboratory (NPBI_Lab), Tianjin Fourth Center Hospital, Tianjin 200024, People’s Republic of China; 9Department of Psychiatry, Wenzhou Kangning Hospital, Wenzhou, Zhejiang Province 325007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuanjun ZhuoDepartment of Neurology and Psychiatry Biological Imaging Laboratory (NPBI_Lab), Tianjin Fourth Center Hospital, Tianjin 200024, People’s Republic of ChinaTel/Fax +86-22-24394542Email chuanjunzhuotjmh@ieee.orgJingliang ZhangDepartment of Psychiatry, Wenzhou Kangning Hospital, Wenzhou, Zhejiang Province 325007, People’s Republic of ChinaEmail zhangjl12141029@sina.comPurpose: Although visual deficits can be observed at any stage of schizophrenia, few studies have focused on visual cortex alterations in individuals at high risk of schizophrenia. This study aimed to investigate the pathological changes of the primary visual cortex in a prenatal mouse model of MK801-induced high-risk schizophrenia.Methods: The high-risk schizophrenia model was generated by MK801 injection into pregnant mice. The male offspring without schizophrenia-like behaviors in early adulthood were defined as the high-risk mouse model of schizophrenia (HRMMS) and divided into two groups. One HRMMS group received the antipsychotic agent risperidone beginning at postnatal week 4 and another group did not receive any treatment. After treatment for 4 weeks, in vivo two-photon calcium imaging was performed to characterize the primary visual cortex activity. The novel object recognition test and the prepulse inhibition apparatus test were also implemented to assess the cognitive and behavioral performance, respectively.Results: Both groups of HRMMS mice, with or without antipsychotic treatment, had decreased neuronal calcium activity, demonstrating primary visual cortex impairment. More notably, antipsychotic treatment did not normalize the impaired neuronal activities in the primary visual cortex. Correspondingly, the treatment did not improve the cognitive or behavioral impairment.Conclusion: Visual cortex impairment might be a prominent feature of individuals at high risk of schizophrenia that cannot be normalized by early treatment with antipsychotic medication, indicating the presence of independent regulatory pathways for visual perception disturbance in schizophrenia. Thus, visual system impairment in schizophrenic patients must be further studied.Keywords: schizophrenia, animal model, primary visual cortex, antipsychotics

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

Abstract Triple negative breast cancer is the most malignant subtype of breast cancer and current treatment options are limited. Radiotherapy is one of the primary therapeutic options for patients with TNBC. In this study, we discovered that the E3 ubiquitin ligase, HECTD3, promoted TNBC cell survival after irradiation. HECTD3 collaborated with UbcH5b to promote p62 ubiquitination and autophagy while HECTD3 deletion led to p62 accumulation in the nucleus in response to irradiation, thus inhibiting RNF168 mediated DNA damage repair. Furthermore, the HECTD3/UbcH5b inhibitor, PC3-15, increased the radiosensitivity of TNBC cells by inhibiting DNA damage repair. Taken together, we conclude that HECTD3 promotes autophagy and DNA damage repair in response to irradiation in a p62-denpendent manner, and that inhibition of the HECTD3-p62 axis could be a potential therapeutic strategy for patients with TNBC in addition to radiotherapy.

Abstract Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.

Abstract Accurate prediction of drug-target interactions (DTIs) is crucial for advancing drug discovery and repurposing. Computational methods have significantly improved the efficiency of experimental predictions for drug-target interactions in Western medicine. However, accurately predicting the complex relationships between Chinese medicine ingredients and targets remains a formidable challenge due to the vast number and high heterogeneity of these ingredients. In this study, we introduce the CWI-DTI method, which achieves high-accuracy prediction of DTIs using a large dataset of interactive relationships of drug ingredients or candidate targets. Moreover, we present a novel dataset to evaluate the prediction accuracy of both Chinese and Western medicine. Through meticulous collection and preprocessing of data on ingredients and targets, we employ an innovative autoencoder framework to fuse multiple drug (target) topological similarity matrices. Additionally, we employ denoising blocks, sparse blocks, and stacked blocks to extract crucial features from the similarity matrix, reducing noise and enhancing accuracy across diverse datasets. Our results indicate that the CWI-DTI model shows improved performance compared to several existing state-of-the-art methods on the datasets tested in both Western and Chinese medicine databases. The findings of this study hold immense promise for advancing DTI prediction in Chinese and Western medicine, thus fostering more efficient drug discovery and repurposing endeavors. Our model is available at https://github.com/WANG-BIN-LAB/CWIDTI .

In the process of mining coal resources, a large amount of coal gangue, fly ash and other by-products are produced, which cause a series of secondary disasters and environmental problems. In order to solve a series of disasters caused by the accumulation of coal gangue hills, based on the distribution of coal gangue hills in important mining areas in China, the main disasters were analyzed, the treatment experiences and results were studied, the ecological treatment methods for the stability of coal gangue hills were explored, and the shortcomings of the existing treatment of coal gangue hills were discussed. It combined with the new technology of coal gangue utilization and green treatment at home and abroad, a zero-carbon treatment method of pile-soil collaborative slope protection is proposed, which can provide reference for the resource utilization and ecological environment protection of coal gangue hills in China.

Abstract Aims To retrospectively compare the long‐term outcomes following atrial fibrillation (AF) ablation between heart failure (HF) with preserved ejection fraction (EF) (HFpEF) and reduced/mildly reduced EF (HFr‐mrEF) patients, and to identify novel predictors of adverse clinical events. Methods In total, 1402 AF patients with HF who underwent successful ablation were consecutively enrolled. Adverse clinical events including all‐cause death, HF hospitalization, and stroke were followed up. Cox proportional hazards models were used to assess the associations between clinical factors and events. Kaplan–Meier analysis was performed to estimate the cumulative incidences of these events. A receiver operating characteristic curve was used to test the ability of these predictors. Results During a follow‐up period of 42 ± 15 months, 265 (18.9%) patients experienced adverse clinical events after ablation. The cumulative incidence of adverse clinical events was significantly higher in HFr‐mrEF than in HFpEF (25.4% vs. 15.7%, P

Abstract Colorectal cancer (CRC) is a common malignant tumor with the third and second highest incidence and mortality rates among various malignant tumors. Despite significant advancements in the present therapy for CRC, the majority of CRC cases feature proficient mismatch repair/microsatellite stability and have no response to immunotherapy. Therefore, the search for new treatment options holds immense importance in the diagnosis and treatment of CRC. In recent years, clinical research on immunotherapy combined with epigenetic therapy has gradually increased, which may bring hope for these patients. This review explores the role of epigenetic regulation in exerting antitumor effects through its action on immune cell function and highlights the potential of certain epigenetic genes that can be used as markers of immunotherapy to predict therapeutic efficacy. We also discuss the application of epigenetic drug sensitization immunotherapy to develop new treatment options combining epigenetic therapy and immunotherapy.

Abstract Probabilistic machine learning utilizes controllable sources of randomness to encode uncertainty and enable statistical modeling. Harnessing the pure randomness of quantum vacuum noise, which stems from fluctuating electromagnetic fields, has shown promise for high speed and energy-efficient stochastic photonic elements. Nevertheless, photonic computing hardware which can control these stochastic elements to program probabilistic machine learning algorithms has been limited. Here, we implement a photonic probabilistic computer consisting of a controllable stochastic photonic element – a photonic probabilistic neuron (PPN). Our PPN is implemented in a bistable optical parametric oscillator (OPO) with vacuum-level injected bias fields. We then program a measurement-and-feedback loop for time-multiplexed PPNs with electronic processors (FPGA or GPU) to solve certain probabilistic machine learning tasks. We showcase probabilistic inference and image generation of MNIST-handwritten digits, which are representative examples of discriminative and generative models. In both implementations, quantum vacuum noise is used as a random seed to encode classification uncertainty or probabilistic generation of samples. In addition, we propose a path towards an all-optical probabilistic computing platform, with an estimated sampling rate of ~1 Gbps and energy consumption of ~5 fJ/MAC. Our work paves the way for scalable, ultrafast, and energy-efficient probabilistic machine learning hardware.

Nowadays, high-strength press-hardened steels (PHS) have gained wide applications in automotive body-in-white owing to excellent mechanical properties. Nevertheless, the fatigue properties of high-strength PHS and associated failure mechanisms have not been clearly revealed, which restricts their potential applications in other parts of automobiles involving fluctuating and repetitive stresses, such as wheels or beams. In this work, the fatigue behavior of 1900 and 2000 MPa grade PHS is systematically studied, with the main focus on the associated deformation and fatigue cracking mechanisms. The fatigue behavior of these two steels is similar, and the ratio of fatigue strength to tensile strength is around 0.5. The fatigue damage mechanism of high-strength PHS is dominated by surface cracking, as the fine martensite structures reduce the stress concentration and cracking at small-sized inclusions. This work can provide guidance for the application of high-strength PHS in alternating loads scenarios.

Current analysis of fragile bronzes mainly relies on the research of two-dimensional aspects such as sample cross-sections and surfaces while typically utilizing optical and electronic microscopy, Raman spectroscopy, and X-ray fluorescence spectroscopy (XRF). As a fast and nondestructive testing method, computer tomography (CT) can be used to characterize and detect the internal structures, corrosion conditions, and corrosion distribution of bronzes. This study used the CT imaging results of fragile bronzes to analyze, locate, and measure corrosion in fragile bronzes quickly and accurately, thus providing strong support for corrosion evaluation and protection research of fragile bronzes. The results verified the value and application prospects of CT technology in the protection of cultural relics.

– OBJECTIVE: The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy. MATERIALS AND METHODS: A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals. RESULTS: A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain. CONCLUSIONS: Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis. [ABSTRACT FROM AUTHOR]

Abstract Background Traditional ecological knowledge (TEK) and practice associated with wild edible plants (WEPs) is an important part of local culture of the Yao people in Jianghua Yao Autonomous County, which possesses the biggest population of Yao ethnic group in China. Economic development, urbanization, and transition of lifestyle and changing interests of the younger generations risk loss of such valuable knowledge. However, no record had been reported about WEPs from the Yao communities of Jianghua County. It is urgent to assemble data on the major WEPs and their uses in Jianghua. This can be used to educate and stimulate new interest in these WEPs, to aid inheritance and improvement of cultural identity and confidence, to enhance local resilience to various changes and to suggest pathways for novel and value-added applications to create new local business opportunities. Methods To record WEPs associated with TEK and practice, we conducted field surveys in 2018, 2019 and 2023. The ethnobotanical methods such as free-listing, participatory observation, semi-structured interview, and market survey were adopted in the field investigations. Information about WEPs including vernacular names, parts used, ways of use, and collection time were recorded. Voucher specimens were collected, identified, and deposited in the herbarium at Minzu University of China, in Beijing. Results Totally, 81 Yao people from 12 villages were interviewed. WEPs traditionally play a crucial role in Yao peoples’ daily lives. A total of 130 plant species from 89 genera and 49 families were recorded. The plants collected showed great diversity and reflected unique local culture. Most (54.5%) WEPs were also used as medicines. Baba can be defined as a cultural identity food, and WEPs are commonly used as tea substitutes for their health benefits. Conclusions We conclude that WEPs use is facing great challenges in a rapidly changing era. Preservation of WEPs related practice and knowledge is not only important for conserving local biocultural diversity, but also valuable in providing potential functional and healthy materials for food security and future economic development. Cultivation of young generations’ interest in nature and biodiversity, combined with local policy to enhance public awareness are recommended.

Abstract Synthetic membrane nanopores made of DNA are promising systems to sense and control molecular transport in biosensing, sequencing, and synthetic cells. Lumen-tunable nanopore like the natural ion channels and systematically increasing the lumen size have become long-standing desires in developing nanopores. Here, we design a triangular DNA nanopore with a large tunable lumen. It allows in-situ transition from expanded state to contracted state without changing its stable triangular shape, and vice versa, in which specific DNA bindings as stimuli mechanically pinch and release the three corners of the triangular frame. Transmission electron microscopy images and molecular dynamics simulations illustrate the stable architectures and the high shape retention. Single-channel current recordings and fluorescence influx studies demonstrate the low-noise repeatable readouts and the controllable cross-membrane macromolecular transport. We envision that the proposed DNA nanopores could offer powerful tools in molecular sensing, drug delivery, and the creation of synthetic cells.

Abstract Background Alzheimer’s disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. Methods The differentiated human neural cells were induced by Aβ1–42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aβ1–42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. Results The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. Conclusions Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aβ-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Abstract To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.

Multiphase microfluidic has emerged as a powerful platform to produce novel materials with tailor-designed functionalities, as microfluidic fabrication provides precise controls over the size, component, and structure of resultant materials. Recently, functional materials with well-defined micro-/nanostructures fabricated by microfluidics find important applications as environmental and energy materials. This review first illustrated in detail how different structures or shapes of droplet and jet templates are formed by typical configurations of microfluidic channel networks and multiphase flow systems. Subsequently, recent progresses on several representative energy and environmental applications, such as water purification, water collecting and energy storage, were overviewed. Finally, it is envisioned that integrating microfluidics and other novel materials will play increasing important role in contributing environmental remediation and energy storage in near future.

Based on morphological and plastid data, we have described and confirmed that Coptis austrogaoligongensis distributed in Tongbiguan Provincial Nature Reserve, Yingjiang County, Yunnan Province, is a new species of Coptis. It is distinctly different from C. teeta subsp. teeta and C. teeta subsp. lohitensis with differences mainly reflected in the following features: former leaf segment lobes contiguous to each other, and lateral segments equal to central one; plants without developed stolons; inflorescences with only 1–3 flowers; petals have short claws. Phylogenetic analysis indicated that C. austrogaoligongensis is a sister to C. teeta subsp. teeta and C. teeta subsp. lohitensis.

Abstract Background Clinical repair of critical-sized bone defects (CBDs) in the tibial diaphysis presents numerous challenges, including inadequate soft tissue coverage, limited blood supply, high load-bearing demands, and potential deformities. This study aimed to investigate the clinical feasibility and efficacy of employing 3D-printed prostheses for repairing CBDs exceeding 10 cm in the tibial diaphysis. Methods This retrospective study included 14 patients (11 males and 3 females) with an average age of 46.0 years. The etiologies of CBDs comprised chronic osteomyelitis (10 cases) and aseptic non-union (4 cases), with an average defect length of 16.9 cm. All patients underwent a two-stage surgical approach: (1) debridement, osteotomy, and cement spacer implantation; and (2) insertion of 3D-printed prostheses. The interval between the two stages ranged from 8 to 12 weeks, during which the 3D-printed prostheses and induced membranes were meticulously prepared. Subsequent to surgery, patients engaged in weight-bearing and functional exercises under specialized supervision. Follow-up assessments, including gross observation, imaging examinations, and administration of the Lower Extremity Functional Scale (LEFS), were conducted at 3, 6, and 12 months postoperatively, followed by annual evaluations thereafter. Results The mean postoperative follow-up duration was 28.4 months, with an average waiting period between prosthesis implantation and weight-bearing of 10.4 days. At the latest follow-up, all patients demonstrated autonomous ambulation without assistance, and their LEFS scores exhibited a significant improvement compared to preoperative values (30.7 vs. 53.1, P

There exists a significant risk of water blooms during the utilization of recycled water in landscape environments. The nitrogen and phosphorus discharge standards of sewage treatment plants are very low. Controlling hydraulic retention time (HRT) is currently the most effective means to control water bloom. This article proposes a new method for determining the HRT threshold based on water transparency as a control indicator. The following results were obtained: (1) with the nitrogen and phosphorus concentrations of 15 and 0.5 mg/L, respectively, the threshold for HRT under high temperature and strong light is 4.6 days, while the threshold under low temperature and low light is 11.5 days. (2) With the nitrogen and phosphorus concentrations of 10 and 0.3 mg/L, respectively, the threshold for HRT under high temperature and strong light is 5 days, while the threshold under low temperature and low light conditions is 12.3 days. (3) The HRT threshold obtained under high temperature and strong light is lower than that obtained under low temperature and low light conditions. (4) The higher the concentrations of nitrogen and phosphorus, the smaller the HRT threshold obtained. (5) Blue algae have stronger adaptability than green algae and diatoms. HIGHLIGHTS A new method for determining the hydraulic retention time (HRT) threshold based on water transparency was proposed.; Cyanobacteria have stronger adaptability than green algae and diatoms.; Light and temperature have a significant impact on the determination of the HRT threshold.; The higher the concentrations of nitrogen and phosphorus, the smaller the threshold value of HRT obtained.;

Abstract The inductive logic of grounded theory and the principle of avoiding theoretical preconceptions are significantly different from the deductive logic and hypothesis testing of traditional quantitative research. Based on the limitations of theory production in quantitative research, this paper proposes a Computing Grounded Theory (CGT) approach that directly quantitatively assists theories. With the help of machine learning and attribution algorithms, CGT identifies variables that have not been the focus of previous studies based on the predictive power of the independent variables to propose new theoretical hypotheses, following the principle that causality is a sufficient and unnecessary condition for predictability. This paper systematically discusses CGT’s basic idea, logical premise, and methodological foundation while providing an empirical example. This method bridges the gap in the theoretical production of quantitative research and is of great value in theory, discipline, knowledge systems and social governance.

Abstract Globally, but especially in the Chinese Loess Plateau, landslides are considered to be one of the most severe and significant geological hazards. The purpose of this study is to design two ensemble machine learning methods, which are denoted as ADTree-Dagging and SVM-Dagging, for modeling landslide susceptibility in Lanzhou City (China). For this aim, the slope units extracted by the curvature watersheds method are used to construct landslide susceptibility modeling, and ten landslide conditioning factors are included in the landslide susceptibility evaluation (altitude, slope angle, slope aspect, cutting depth, surface roughness, relief amplitude, gully density, rainfall, distance to roads, and lithology). The conditioning factors selection and spatial correlation analysis were implemented by using the correlation attribute evaluation method and the frequency ratio model. The comprehensive performance of the models was tested using the receiver operating characteristic (ROC), area under the ROC curve (AUC), the root mean square error (RMSE), and several other performance metrics. For the training dataset, the results show that the SVM-Dagging model acquire the largest AUC value (0.953), lowest RMSE (0.3125), highest positive predictive value (96.0%), highest negative predictive value (91.2%), highest sensitivity (91.6%), highest specificity (95.8%), highest accuracy (93.6%), and highest Kappa (0.873). Similar results are observed in the validation dataset. Results demonstrated that the Dagging technique has improved significantly the prediction ability of SVM and ADTree models. The Dagging method can combine different models by leveraging the strengths of each model to create methods with higher flexibility than traditional machine learning methods. Therefore, in this study, the proposed new models can be applied for land-use planning and management of landslide susceptibility in the study area and in other areas containing similar geological conditions.

Abstract Background The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. Methods Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. Results The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant–bone interface in 10 patients. Conclusion The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.

Abstract A pressing challenge in spatially resolved transcriptomics (SRT) is to benchmark the computational methods. A widely-used approach involves utilizing simulated data. However, biases exist in terms of the currently available simulated SRT data, which seriously affects the accuracy of method evaluation and validation. Herein, we present scCube ( https://github.com/ZJUFanLab/scCube ), a Python package for independent, reproducible, and technology-diverse simulation of SRT data. scCube not only enables the preservation of spatial expression patterns of genes in reference-based simulations, but also generates simulated data with different spatial variability (covering the spatial pattern type, the resolution, the spot arrangement, the targeted gene type, and the tissue slice dimension, etc.) in reference-free simulations. We comprehensively benchmark scCube with existing single-cell or SRT simulators, and demonstrate the utility of scCube in benchmarking spot deconvolution, gene imputation, and resolution enhancement methods in detail through three applications.

Abstract Metabolic reprogramming has become increasingly important in tumor biology research. The glucose metabolic pathway is a major energy source and is often dysregulated in breast cancer. DAB2IP is widely reported to be a tumor suppressor that acts as a scaffold protein to suppress tumor malignancy in breast cancer. Interestingly, DAB2IP has also been found to be a potential regulator of glucose uptake; however, the exact mechanism remains unclear. In this study, we found that DAB2IP inhibited glucose uptake under hypoxia conditions in breast cancer cells by suppressing HIF-1α signals. Mechanically, DAB2IP interacted with the E3 ubiquitin ligase STUB1 via its PER domain, thus triggering STUB1 mediated HIF-1α ubiquitylation and degradation, and inhibit glucose metabolism and tumor progression. Deleting the PER domain abrogated the DAB2IP-related inhibitory effects on glucose uptake, intracellular ATP production, and lactic acid production in breast cancer cells. These findings elucidate the biological roles of DAB2IP in cancer-related glucose metabolism as well as a novel mechanism by which STUB1-driven HIF-1α ubiquitylated degradation is regulated in breast cancer.

Abstract Background T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. Methods A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. Results A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p

Abstract Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 μg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Abstract Background To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT). Methods Total of 143 EC patients in the authors’ hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated. Results Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively. Conclusion CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.

Current treatments for osteosarcoma, the most common primary bone cancer, including surgery, radiotherapy, and chemotherapy, are largely ineffective against metastatic and chemo-resistant cases, emphasizing the need for novel therapies. In this study, we investigated (20S)-Protopanaxatriol [(20S)-PPT], a natural product from Panax notoginseng, an herb used both as food and medicine, for its ability to enhance osteosarcoma sensitivity to ferroptosis induced by inducers such as RSL3, ML210, and IKE. Specifically, (20S)-PPT increased lipid peroxidation in osteosarcoma cells exposed to RSL3. This effect was mediated by ACSL4 upregulation, as ACSL4 knockdown reversed (20S)-PPT-sensitized ferroptosis. Importantly, (20S)-PPT significantly reduced tumor growth in xenograft models when combined with IKE. Collectively, our study confirms that combining (20S)-PPT with ferroptosis inducers offers a promising novel strategy for treating osteosarcoma.

Pancreatic cancer remains one of the most lethal malignancies, with conventional treatment options providing limited efficacy. Recent advancements in immunotherapy have offered new hope, yet the unique tumor microenvironment (TME) of pancreatic cancer poses significant challenges to its successful application. This review explores the transformative impact of single-cell technology on the understanding and treatment of pancreatic cancer. By enabling high-resolution analysis of cellular heterogeneity within the TME, single-cell approaches have elucidated the complex interplay between various immune and tumor cell populations. These insights have led to the identification of predictive biomarkers and the development of innovative, personalized immunotherapeutic strategies. The review discusses the role of single-cell technology in dissecting the intricate immune landscape of pancreatic cancer, highlighting the discovery of T cell exhaustion profiles and macrophage polarization states that influence treatment response. Moreover, it outlines the potential of single-cell data in guiding the selection of immunotherapy drugs and optimizing treatment plans. The review also addresses the challenges and prospects of translating these single-cell-based innovations into clinical practice, emphasizing the need for interdisciplinary research and the integration of artificial intelligence to overcome current limitations. Ultimately, the review underscores the promise of single-cell technology in driving therapeutic strategy innovation and improving patient outcomes in the battle against pancreatic cancer.

Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P

We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.

Ferroptosis is a recently identified form of cell death characterized by lipid peroxidation and elevated iron levels. It is closely associated with hematologic malignancies, including leukemia, multiple myeloma (MM), and myelodysplastic syndromes (MDS). Research indicates that ferroptosis could represent a novel therapeutic target for these hematologic malignancies. Furthermore, traditional Chinese medicine (TCM) has been shown to modulate hematologic malignancies through the ferroptosis pathway. This paper aims to elucidate the mechanisms underlying ferroptosis and summarize the current research advancements regarding ferroptosis in hematologic malignancies, as well as the role of traditional Chinese medicine in the prevention and treatment of ferroptosis, with the goal of enhancing treatment efficacy.

Binomials have been relatively understudied compared to other types of multiword expressions (MWEs) in second language research, such as collocations and idioms. This study investigated English as a Foreign Language (EFL) learners’ processing of English binomials and how it is influenced by interlexical factors (L1-L2 congruency and L1-lexicalization) and intralexical factors (word and binomial frequency, binomial reversibility, and binomial predictability). Forty Chinese EFL learners participated in a phrase acceptability judgment task of 64 target binomials (16 congruent L1-lexicalized, 16 congruent L1-nonlexicalized, and 32 incongruent) and 64 non-binomial controls. Results revealed that learners experienced difficulty judging the formulaicity of binomials. They processed binomial stimuli significantly faster than non-binomial baselines, demonstrating a binomial phrase effect. They also processed L1-L2 congruent items faster and more accurately than incongruent items, showing a robust congruency effect. The congruent items which are lexicalized in the L1 showed further processing advantage than the non-lexicalized items, indicating a graded congruency effect. Moreover, binomial reversibility and binomial predictability (measured with cloze probability) also showed significant effects. These findings highlight the need to distinguish and investigate different types of congruency, explore appropriate measures for MWE predictability, and to examine binomials focusing on their unique features.

BackgroundIn China, as people’s standard of living improves and the medical service system becomes more sophisticated, the demand for higher-quality and improved healthcare services is steadily rising. Inequality in health resource allocation (HRA) is more pronounced in ethnic minority areas (EMAs) than in developed regions. However, little research exists on high-quality medical resources (HQMRs) in China’s EMAs. Hence, we examined the spatiotemporal dynamic evolution of HQMRs in China’s EMAs from 2007 to 2021 and identified the main factors affecting their respective HQMR levels.MethodsWe selected tertiary hospitals to represent the quality of healthcare resources. We employed descriptive statistical techniques to analyze changes in the distribution of HQMRs from 2007 to 2021. We used the Dagum Gini coefficient and kernel density approach to analyze the dynamic evolution of HQMRs in China’s EMAs. We utilized the least squares dummy variable coefficient (LSDVC) to identify key factors affecting HQMR.ResultsThe number of HQMRs in each EMA has risen annually. The average number of tertiary hospitals increased from 175 in 2007 to 488 in 2021. The results of the Dagum Gini coefficient revealed that the differences in the HQMR level in China’s EMAs have slowly declined, and intra-regional disparities have now become the primary determining factor influencing overall variations. The kernel density plot indicated that the HQMR level improved significantly during the study period, but bifurcation became increasingly severe. Using the LSDVC for analysis, we found that gross domestic product (GDP) per capita, the size of the resident population, and the number of students enrolled in general higher education exhibited a significant negative correlation with HQMR levels, while GDP and urbanization rate had a significant promoting effect.ConclusionThe HQMR level in EMAs has risen rapidly but remains inadequate. The differences in HQMR between regions have continued to narrow, but serious bifurcation has occurred. Policymakers should consider economic growth, education, and population size rather than simply increasing the number of HQMRs everywhere.

Eukaryotic microorganisms were the key components of marine microecosystems and were involved in biogeochemical cycling processes. Although oceanographers have emphasized their importance in open oceans, the current understanding was not comprehensive enough about the assembly processes and co-occurrence network of different fraction eukaryotic microbial communities in the coastal China sea. We used co–occurrence networks and ecological process model to investigate possible ecological interactions in two fractions (small fraction 0.22–3 μm; large fraction 3–200 μm) of eukaryotes throughout different depths and geographical regions of coastal China sea. We found that environmental distance shapes the diversity of the two fractions eukaryotic microorganisms. Dispersal limitation and homogeneous selection processes were the key drivers of eukaryotic microbial community assembly. Co-occurrence network analysis showed that the networks of the 0.2–3 μm eukaryotes more nodes and edges, with more complex interactions between microorganisms, and higher network stability than that of 3–200 μm eukaryotic microorganisms. Temperature, oxygen, salinity, and nutrients play the crucial role in the abundance of two fractions eukaryotic microorganisms. These results crystallize the knowledge of eukaryotic microbes in the coastal China sea, which was essential for addressing the challenges posed by global change.