Search

Jing Guan,1 Yue Wang,1 Changjun Dong,1 Yuwen Chen,1 Bingqing Li,1 Yilu Zhou,1 Fanke Huang,1 Peiyuan Sun,1,2 Xue Tian,1,2 Feng Ran,1,2 Jianfeng Lv2 1ChinaThree Gorges University, Yichang, People’s Republic of China; 2Department of Cardiology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, People’s Republic of ChinaCorrespondence: Jianfeng Lv, Department of Cardiology, Affiliated Renhe Hospital of China Three Gorges University, No. 410 Yiling Avenue, Yichang, Hubei Province, People’s Republic of China, Tel +86-18745290427, Fax +86 0717-6558362, Email ljfzxm@163.comBackground: Depression is common among patients with coronary atherosclerotic heart disease and is a prevalent mental health issue, particularly among those with cardiovascular diseases. Depression is commonly associated with elevated blood glucose and lipid levels. The triglyceride-glucose index is a novel indicator reflecting insulin resistance, which has been proven in numerous studies to be associated with cardiovascular diseases.Purpose: Study on the impact of the triglyceride-glucose index (TyG index) on the development of depression in patients with coronary atherosclerotic heart disease (CHD).Patients and methods: Using the Patient Health Questionnaire-9 (PHQ-9), 197 CHD patients were classified into a non-depressed group (n = 44, PHQ-9 < 5) and a depressed group (n = 153, PHQ-9 ≥ 5). Fasting blood glucose (GLU), HDL, total cholesterol (TC), LDL, triglycerides (TG), and TyG index were compared between groups. Depression risk factors were identified via logistic regression, and the predictive value of TyG index was evaluated using ROC analysis.Results: In depressed patients, TyG index, TG, TC, LDL, and GLU were significantly higher, while HDL was lower than in the non-depressed group (p < 0.05). Logistic regression identified TyG index, LDL, GLU, TG, TC, HDL, female sex, smoking, alcohol consumption, and older age as independent risk factors for depression in CHD patients (p < 0.05). ROC analysis showed the TyG index had an AUC of 0.76 (95% CI 0.687– 0.829, p < 0.001) for predicting depression, with a cutoff of 1.613, sensitivity of 45.1%, and specificity of 97.7%. Endpoint events were more frequent in the depression group (χ² = 8.015, p = 0.005).Conclusion: The TyG index is an independent risk factor for depression in patients with CHD, indicating a significant predictive value. Depressed patients have a higher rate of readmission, and managing depression effectively contributes to better prognosis.Keywords: depression, coronary atherosclerotic cardiopathy, triglyceride-glucose index

Xueyun Fu,&ast; Xue Tian,&ast; Jing Lin, Qian Wang, Lingwen Gu, Ziyi Wang, Menghui Chi, Bing Yu, Zhuhui Feng, Wenyao Liu, Lina Zhang, Cui Li, Guiqiu Zhao Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cui Li; Guiqiu Zhao, Department of Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Email yankelicui@126.com; zhaoguiqiu_good@126.comBackground: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro.Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.Keywords: fungal keratitis, MOFs, antifungal, anti-inflammatory, ZIF-8

Xiaotong Tian,1,2 Jing Lin,1,2 Menglan Zhou,3,4 Ying Ge,1 Taisheng Li,1 Li Zhang,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of ChinaCorrespondence: Zhengyin Liu; Li Zhang, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China, Email liuzhy@pumch.cn; zhangli36@pumch.cnPurpose: To evaluate the clinical outcomes and safety of tigecycline (TGC) plus cefoperazone/sulbactam (CPS) or TGC monotherapy in patients with hospital-acquired pneumonia (HAP) caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB).Methods: This was a retrospective analysis of multicenter data from 62 Chinese hospitals with CRAB HAP. Risk factors for receiving TGC with CPS therapy and predictors of mortality were assessed using multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacy and safety of antimicrobial regimens.Results: A total of the 180 patients were included, with 95 receiving TGC monotherapy and 85 receiving combination therapy. Multivariate logistic regression analysis revealed that older age (P = 0.011), and intensive care unit (ICU) admission (P = 0.007) were significant risk factors for combination therapy. Multivariate Cox regression demonstrated that combination therapy was associated with a significantly higher risk of 90-day mortality (P = 0.031). Patients in the standard-dose TGC (SDT) plus CPS subgroup had significantly higher rates of SOFA scores ≥ 7 (P = 0.009) and MV used (P = 0.028), as well as higher 30-/90-day mortality compared to high-dose TGC (HDT) plus CPS group. TGC plus CPS significantly reduced CRP levels (P = 0.009), while the variations in ALT, TBIL, Cr, Hb, and PLT levels did not differ between different antimicrobial regimens after PSM.Conclusion: HDT and CPS combination therapy was more effective in patients with advanced age and more severe condition. Safety profiles of different antimicrobial regimens were similar with liver, kidneys, and coagulation functions.Keywords: carbapenem-resistant Acinetobacter baumannii, hospital acquired pneumonia, tigecycline, cefoperazone/sulbactam, risk factors

Ruyu Han,1,&ast; Leijuan Gan,1,&ast; Liyu Sun,1 Mengran Lang,2 Xindi Tian,1 Kangwei Zhu,1 Lu Chen,1 Guangtao Li,1 Tianqiang Song1 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 2Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-22-23340123, Fax +86-22-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data.Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently.Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.Keywords: hepatocellular carcinoma, conversion therapy, recurrence-free survival, hepatic resection

Xu Tian,1,&ast; Fangrong Liu,2,&ast; Feili Li,3 Yi Ren,4 Hongcai Shang5 1Chongqing Center for Evidence-Based Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 2Outpatient Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 4Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Ren, Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 6 of 7th Branch of Panxi Road, Jiangbei District, Chongqing, People’s Republic of China, Tel/Fax +86 023 67776180, Email cqszyyrenyi@163.com Hongcai Shang, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 of Haiyuncang, Dongcheng District, Beijing, People’s Republic of China, Tel/Fax +86 010 84013276, Email yxtx880919@163.comPurpose: While the benefits of exercises for chronic obstructive pulmonary disease (COPD) are well-established, the relative effectiveness of different exercise types for stable COPD remains unclear. This network meta-analysis aims to investigate the comparative effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in stable COPD.Methods: Electronic searches were performed in PubMed, Embase, and the Cochrane library to identify relevant randomized controlled trials (RCTs) investigating the effects of exercises on 6-minute walk test distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC), and St. George’s Respiratory Questionnaire (SGRQ) score. Two authors screened the retrieved articles, extracted relevant data, and assessed the risk of bias. Network meta-analysis was conducted using Stata 14.0.Results: This study included a total of 19 studies involving 951 patients with stable COPD. HIIT emerged as the most favorable exercise type for enhancing 6MWD, with a probability of 82.9%. RT exhibited the greatest efficacy in reducing SGRQ scores, with probability of 49.8%. Notably, ET demonstrated superiority in improving FEV1 and FVC, with probabilities of being most effective at 78.1% and 42.0%, respectively.Conclusion: This study suggests that HIIT may be a viable intervention for improving exercise capacity in stable COPD patients, compared to AE, RR, and ET. RT may hold promise for improving quality of life, and ET may demonstrate superiority in improving pulmonary function. However, variation in response likely depends on patient characteristics, program parameters, and delivery context. Future research should explore the synergistic effects of combining RT with ET/HIIT, focusing on patient subgroups, optimal dosing, and settings, as current guidelines indicate this combination may offer the most significant benefits.Keywords: COPD, exercise, pulmonary function, quality of life, network meta-analysis

Bing Yu,1,&ast; Zhimei Xing,2,&ast; Xiaoxuan Tian,2 Rui Feng1 1Department of Breast Surgery, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, People’s Republic of China; 2State Key Laboratory of Component‑Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Feng, Department of Breast Surgery, Tianjin Central Hospital of Obstetrics and Gynecology, No. 156 of Nankai SAN Road, Nankai District, Tianjin, 300100, People’s Republic of China, Tel +86 022-58287167, Email dr.fr@126.comBackground: Triple-negative breast cancer (TNBC) is recognized as the most aggressive molecular subtype of breast cancer. Recent studies have highlighted the complex role of autophagy in the pathogenesis of TNBC.Methods: In this study, we evaluated 18,330 genes, including 1111 autophagy-related genes, (ARGs), across 579 TNBC samples from online databases. Differentially expressed ARGs in TNBC were identified using high-throughput RNA-seq data from the Cancer Genome Atlas (TCGA). Prognostic factors were examined through Cox regression and multivariate Cox analyses, with predictive efficacy assessed using receiver operating characteristic (ROC) curves. A nomogram integrating the risk signature with clinicopathological factors, such as TNM stage, was developed. Immunohistochemical analysis of clinical samples was also conducted.Results: EIF4EBP1 and NPAS3 were significantly correlated with prognostic outcomes in patients with TNBC. Multivariate Cox regression analysis demonstrated that the expression levels of these two genes were accurate predictors of disease progression in TNBC samples from TCGA and the GSE31519 dataset. The efficacy of this predictive model was validated using ROC curve analysis and calibration plots, confirming its ability to accurately estimate the 1-, 2-, and 3-year survival rates for individuals with TNBC. Additionally, EIF4EBP1 and NPAS3 expression influenced drug sensitivity in TNBC cell lines, with notably lower NPAS3 expression in TNBC tissues, particularly in Stage III cases. This study is the first to report NPAS3 expression in patients with TNBC.Conclusion: The autophagy-related genes EIF4EBP1 and NPAS3 may serve as independent prognostic factors for individuals with TNBC.Keywords: autophagy, nomogram, prognosis, risk signature, triple-negative breast cancer

Ruijing Su,&ast; Yue Yang,&ast; Haiyan Wu, Bo Liu, Xinyuan Tian, Chaoyu Zhou, Yanxin Hu, Tianlong Liu Laboratory of Veterinary Pathology and Nanopathology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianlong Liu; Yanxin Hu, Email liutianlong@cau.edu.cn; huyx@cau.edu.cnBackground: A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT).Materials and Methods: In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy.Results: MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response.Conclusion: The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors. Keywords: zeolitic imidazolate framework-8, photothermal agent polydopamine, 1-methyl-D-tryptophan, photoluminescence, camptothecin

Xiang Li,1 Mengtian Pan,1 Xinjuan Tian,1 Lele Zixin Yang,2 Jingjing Zhang,1 Dongmei Yan,3 Baohui Xu,4 Li Zhao,1 Weirong Fang1 1Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2The Pennsylvania State University, Eberly College of Science, State College, PA, USA; 3Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Surgery, Stanford University School of Medicine, Stanford, CA, USACorrespondence: Li Zhao; Weirong Fang, Email zhaoli@cpu.edu.cn; weirongfang@cpu.edu.cnBackground: Tripartite motif containing 59 (TRIM59) is a ubiquitin ligase and is involved in the pathogenesis of various diseases, including cancers, sepsis, and other immune-related diseases. However, it has not been defined whether TRIM59 plays a role in ischemic stroke in mice.Methods: This study determined the influence of Trim59 deficiency on experimental stroke outcomes and the cerebral proteomic profile using myeloid cell Trim59 conditional knockout (Trim59-cKO) mice and a label-free quantitative proteomic profiling technique. The possible mechanisms by which TRIM59 affected stroke onset were elucidated by in vivo and in vitro experiments.Results: Immunofluorescence staining results showed that TRIM59 expression was up-regulated after cerebral ischemia and co-localized with macrophages. Myeloid cell Trim59 deficiency exacerbated ischemic injury on day 3 after experimental stroke. In proteomic analysis, 23 differentially expressed proteins were identified in ischemic brain of Trim59-cKO mice as compared to Trim59flox/flox mice. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed proteins were enriched in complement and coagulation cascades. Protein–protein interaction analysis suggested the central role of clusterin in the interaction network. ELISA and Western blot assays confirmed the reduced levels of clusterin protein in the ischemic brains of Trim59-cKO mice. Further experimental results showed that clusterin was expressed in neurons. Conditional co-culture experiments of primary neurons and bone marrow-derived macrophages demonstrated that LPS stimulated macrophages to secrete complement C3. In addition, TRIM59 may affect the changes in clusterin expression in an indirect manner by influencing the secretion of complement C3 in macrophages. In vivo experiments also proved a significant increase in C3 levels in the brains of Trim59-cKO mice after ischemia.Conclusion: Myeloid cell Trim59 deficiency aggravated ischemic stroke outcomes in conjunction with a distinct cerebral proteomic profile, and the underlying mechanism may be related to the regulation of macrophage C3 expression by TRIM59.Keywords: Trim59, ischemic stroke, proteomic profile, complement and coagulation cascades, C3

Xingqiang Wang,1,2,&ast; Xianna Yang,3,&ast; Shiqi Wang,3,&ast; Xiaofang Tian,1 Jianmei Yin,3 Nian Liu,3 Pengtao Di,1 Jipeng Qi,3 Ya Li,3 Jimin Chen,3,4 Yang Wu,1 Jingjin Wu,1,2 Weiqing Zhao,5 Jiangyun Peng,1,2 Ling Zhang,1,2 Lingli Gu1 1Department of Rheumatology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 2Yunnan Provincial Clinical Medicine Research Center of Rheumatism in TCM, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 3The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 4Department of Integrative Internal Medicine, The Lijiang Hospital of Traditional Chinese Medicine, Lijiang, Yunnan, 674100, People’s Republic of China; 5Department of Rheumatology and Immunology, The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang; Lingli Gu, Email zebaiyuan@126.com; guyuxin82@126.comAbstract: Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).Keywords: rheumatoid arthritis, glucocorticoids tapering, clinical trial, traditional Chinese medicine, Yupingfeng Guizhi Decoction, Juanbi Decoction

Pingyang Ke,1,&ast; Jing Liu,1,2,&ast; Chengzhi Chen,3,&ast; Sen Luo,3,&ast; Huiwen Gu,3,&ast; Juan Gu,4 Yan Liu,1 Yuanlin Ma,1 Yuan Meng,1 Liqin Hu,1 Xin Tian,1 Fei Xiao1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, People’s Republic of China; 2Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Xiao; Xin Tian, Email feixiao81@126.com; xintian@cqmu.edu.cnBackground: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy.Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK-242).Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK-242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis.Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances.Keywords: zinc oxide nanoparticles, epilepsy, excitation/inhibition balance, autophage

Ruyu Han,&ast; Leijuan Gan,&ast; Mengran Lang,&ast; Guangtao Li, Lu Chen, Xindi Tian, Kangwei Zhu, Liyu Sun, Tianqiang Song Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-022-23340123, Fax +86-022-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease.Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19– 9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients’ RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91).Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.Keywords: nomogram, Barcelona clinic Liver cancer system, recurrence-free survival, hepatic resection, radiofrequency ablation

In order to solve the problem of insufficient hardness and friction wear performance of Ni-based coatings under certain extreme working conditions, this paper designs experiments from a process perspective to study the effects of laser scanning method and overlap rate on the microstructure and properties of laser clad Ni60-WC composite coatings. Unlike previous studies, this study considers the comprehensive effects of laser scanning method and overlap rate on coating performance for specific laser clad layers, rather than just one of them. The results show that the performance of the coating after fusion is the best in the single line scanning mode and the overlap rate is within the range of 30 to 35%. The maximum hardness of the laser clad coating can reach 1216 HV, which is 1.08 to 1.43 times the 850 to 1150 HV hardness of the Ni-WC coating reported so far. The wear resistance of the laser clad coating has also been improved to some extent. The results confirm the phenomenon of interactive influence between scanning mode and overlap rate in the laser cladding process, which will provide a new 4knowledge for optimizing laser cladding in the future. [ABSTRACT FROM AUTHOR]

Calcium-based thermochemical energy storage (TCES) provides a realizable solution to address the challenges of intermittence and volatility in the large-scale utilization of clean energy. Although modified CaCO3/CaO systems have shown promise for stable cyclic performances, the modification mechanism of different additives remains unclear, and a unified theoretical framework for selecting modified elements is needed. This work systematically explores the effects of 34 metal elements on the cyclic stability, heat release capacity, and thermal conductivity of a CaCO3/CaO TCES material using density functional theory (DFT) calculations and experimental tests. The surface energy of the modified CaO surfaces is proportional to the atomic radius for non-transition metal atoms or the ionization energy for transition metal atoms. Trends in Ca4O4 adsorption energy are generally opposite to those of surface energy. Both low surface energy and high Ca4O4 adsorption energy indicate surface stability. Furthermore, the heat release capacity of the modified CaO surfaces is investigated by studying the CO2 adsorption process. Al, Zr, and Ce modifications enhance the stability and affinity for CO2 of the surfaces, but competition with the original CaO for CO2 adsorption may reduce heat release. Additionally, phonon calculations indicate metal substitution can hinder heat transfer by strengthening the coupling between optical and acoustic branches. Finally, the microstructure, cyclic stability, heat release capacity, and thermal conductivity are studied by experiments, and the reliability of the computational predictions is verified. This work uncovers the modification rules of different metal elements on the TCES performances of CaCO3/CaO pairs at the atomic scale. The findings provide a theoretical reference for material modification, and can serve as a basis for higher-scale study to offer more reliable guidance for material modification and facilitate future applications. [ABSTRACT FROM AUTHOR]

Fibre-reinforced cemented paste backfill (F-CPB; a mixture of tailings, fibre, cement, and water) is exposed to non-isothermal curing environments in the field. However, no investigations have been conducted on the impact of non-isothermal curing environments on F-CPB compressive strength, shear characteristics and stress–strain behaviour, although these are important design parameters for F-CPB structures. Therefore, a series of mechanical and microstructural tests were performed on samples with and without fibres exposed to isothermal and non-isothermal conditions. It was found that the non-isothermal curing condition substantially enhances the F-CPB compressive strength and strength gain ratio. The shear strength, cohesion and internal friction angle of the F-CPB samples cured under non-isothermal conditions were higher than those cured under isothermal conditions. These impacts of non-isothermal curing on the compressive and shear characteristics of F-CPBs are related to the temperature-induced change in the microstructure of these samples. The F-CPBs cured under non-isothermal conditions had more hydration products than those cured under isothermal conditions. Moreover, mercury instrusion porosimetry (MIP) tests showed that the F-CPBs subjected to non-isothermal conditions had a finer pore structure than those exposed to isothermal conditions, which contributed to an enhancement of the mechanical characteristics of the F-CPBs subjected to non-isothermal curing. [ABSTRACT FROM AUTHOR]

Background: This paper aimed to investigate the radiation dosimetry and dose deposition to the surrounded organs at risk (OARs) with different radial and longitudinal margins based on the normal tissue complication probability (NTCP) and dose-volume histogram (DVH) methods. Materials and Methods: Fifteen patients with histologically diagnosed esophageal cancer were retrospectively selected. From the clinical target volume (CTV), eight planning target volumes (PTV) were expanded for each patient, with one group of four radial margins (3mm, 5mm, 7mm, 10mm) and the other group of four longitudinal margins (3mm, 5mm, 7mm, 10mm). Then, eight plans with the prescription dose of 50.4Gy were designed in the tomotherapy system. Within each group, doses for the OARs and NTCP-based risk of pneumonitis and pericardial disease were compared. Results: Almost all the dose parameters in both groups, except for the Dmax (maximum dose) of the spinal cord in the longitudinal direction, showed significant linearly increasing trends with the expansion of margins. For same dose parameters, the increased slopes in the radial direction were larger than those in the longitudinal. Heart V30Gy (the percent volume of receiving 30Gy) grew fastest compared to other clinical constraint indexes in both groups, and the most significant difference in the risk of pneumonitis was observed in the radial group when the margin was expanded from 3 to 10mm. Conclusions: In order to lower the likelihood of radiation-related toxicity, radial margin expansion should be more strictly controlled in the radiotherapy of esophageal cancer with tomotherapy. [ABSTRACT FROM AUTHOR]

To predict the grain protein content of foxtail millet in a timely, effective, and rapid manner, the study used the net photosynthetic rate of leaves as an intermediate parameter. By using hyperspectral reflectance-net photosynthetic rate of leaves-grain protein content and using the 2020 potted plant experiment data, hyperspectral data and its first derivative (1ST) data with different photoperiod treatments, the models were constructed using machine learning algorithms (SVM, PLS and BP) based on net photosynthetic rate. The results revealed that the accuracy of the SVM model was better than that of the PLS model and BP model, and the SVM model based on the first derivative (1ST) spectral reflectivity was better than the original spectral (R) reflectivity, the R2, RMSE, RPD of the modeling set and validation set were 0.988, 0.732, 0.823, 4.061, 8.697, 1.810, respectively The correlation coefficient between net photosynthetic rate and grain protein content was 0.872 and R2 was 0.719 at 10 days after anthesis. The SVM model can be used to accurately monitor the grain protein content of foxtail millet, and provide technical support for hyperspectral techniques in high-yield cultivation and Intensive farming of foxtail millet. [ABSTRACT FROM AUTHOR]

Abstract Background Previous researches found that maternal adverse childhood experiences not only affect the psychological behavior of preschool children, but also have direct or indirect negative effects on the executive functions and cognition of offspring. And, the possible social psychological mechanism between maternal adverse childhood experiences and preschool children’s executive functions is still not clear. Objectives This study mainly tries to understand the association between parenting stress and child maltreatment in maternal adverse childhood experiences and children’s executive functions through longitudinal cohort. Participants and setting Participants were 2160 preschool children and their mothers who finally completed baseline and 3 waves of follow-up. Methods Using a cohort study, a baseline survey of junior kindergartens was carried out in June 2021 and followed up every six months, with a total of 3 follow-ups. Results We found that executive functions in preschoolers were significantly positively correlated with maternal adverse childhood experiences, parenting stress, physical assault, psychological aggression, neglect and nonviolent discipline (r = 0.180, 0.386, 0.274, 0.302, 0.189, 0.148, respectively, P

Abstract Background Despite established excellent treatment strategies for Wilms tumor (WT), effective prognostic evaluation methods were lacking. This study aims to examine prognostic factors for WT through real-world peripheral blood cell profiling. Methods Basic data and pre-treatment laboratory indices from WT and non-WT children underwent Wilcoxon test analysis. Chi-square tests assessed the correlation between blood cells and the overall survival (OS) and event-free survival (EFS) of WT. Further the Log-rank test and multivariate Cox were used to identify independent prognostic factors for OS. Traditional accepted factors were included in multi-Cox and the nomogram was constructed to further validate the outcome. Results Blood cells significantly differed between WT and non-WT groups (P

Abstract Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18–90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals’ own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03–0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01–0.16%) (P

[Objective] The purpose of this study is to explore the pollination biology and reproductive characteristics of Rhododendron excellens, providing a theoretical basis for the conservation of small population species. [Methods] In the field, the pollination and reproduction biology of R. excellens were studied by studying the floral characteristics, pollinating insects, flower visiting characteristics, flower odor, and breeding system. [Results] (1) Unlike widespread Rhododendron species, pollen vitality of R. excellens was low whereas stigma vitality was strong, with a longer duration. (2) The main pollinating insect was Apis cerana in the daytime. The main volatile was 1,8-cineole that attracts moths for pollinating at night. (3) Through hand pollination, it was found that R. excellens breeding system was self-compatible with dominant out-crossing. [Conclusion] The flower morphology of R. excellens tends to avoid active self-pollination and have low pollen viability, but sustained strong stigma receptivity may be a strategy to adapt to low pollination efficiency. The main pollinating insect is A . cerana in the daytime, while moth pollination at night cannot be excluded. Its breeding system is self-compatible and is evolving towards a facultatively mixing mating system.

Automatic text summarization (ATS) is a popular research direction in natural language processing, and its main implementation methods are divided into two categories: extractive and abstractive. Extractive summarization directly uses the text content in the source document, and compared with abstractive summarization, it has higher grammatical and factual correctness, and has broad prospects for extractive summarization in domains such as policy interpretation, official document summarization, legal and medicine industry, etc. In recent years, extractive summarization based on deep learning has received extensive attention. This paper mainly reviews the research progress of extractive summarization technology based on deep learning in recent years, and analyzes the relevant research work for the two key steps of extractive summarization: text unit encoding and summary extraction. Firstly, according to the different model frameworks, text unit encoding methods are divided into four categories: hierarchical sequential encoding, encoding based on graph neural networks, fusion encoding, and pre-training-based encoding. Then, according to the different granularity of summary extraction in the summary extraction stage, summary extraction methods are divided into two categories: text unit-level extraction and summary-level extraction. This paper also introduces commonly used public datasets and performance evaluation indicators for extractive summarization tasks. Finally, the future possible research directions and corresponding development trends in this field are predicted and summarized.

Abstract Severe tissue defects present formidable challenges to human health, persisting as major contributors to mortality rates. The complex pathological microenvironment, particularly the disrupted immune landscape within these defects, poses substantial hurdles to existing tissue regeneration strategies. However, the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine, providing encouraging prospects for tissue regeneration and restoration. This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration. We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration. Subsequently, we explore the design and functional properties of immunomodulatory nanosystems. Finally, we address the challenges and prospects of clinical translation in nanomedicine development, aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.

Abstract The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P

This paper studies the finite-time stabilization (FTS) and finite-time contraction stabilization (FTCS) of parameter-uncertain systems subjected to impulsive disturbances by using an event-triggered aperiodic intermittent control (EAPIC) method, which combines aperiodic intermittent control with event-triggered control. By employing the Lyapunov method and linear matrix inequality techniques, sufficient conditions for FTS and FTCS are derived. Additionally, within the finite-time control framework, relationships among impulsive disturbance, intermittent control parameters, and event-triggered mechanism (ETM) thresholds are established under EAPIC to ensure FTS and FTCS. The sequence of impulsive moments is determined by a predetermined ETM, and Zeno phenomena are also excluded. Finally, the effectiveness of the EAPIC approach is demonstrated through two numerical examples.