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Wenguang Lai,1,&ast; Xiaoli Zhao,2,&ast; Zhiyong Gao,1 Haozhang Huang,3,4 Donghui Huang,1 Yang Zhou,3,4 Guoxiao Liang,3,4 Shiqun Chen,3,4 Jin Liu,3 Yong Liu3 1Department of Pharmacy, Heyuan People’s Hospital; Guangdong Provincial People’s Hospital, Heyuan Hospital, Heyuan, 517001, People’s Republic of China; 2Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +86 02083827812-10528, Fax +86 02083851483, Email liuyong@gdph.org.cn; ljaw397017568@163.comPurpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF.Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively.Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01– 1.35], 1.31[1.13– 1.52], 1.51[1.30– 1.76], respectively; P for trend < 0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99– 1.51], 1.50[1.20– 1.86], 1.73[1.37– 2.18], respectively; P for trend < 0.001).Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.Keywords: heart failure with preserved ejection fraction, systemic inflammatory response index, all-cause death, cardiovascular death

Abstract [Objective] The study aims to explore the expression and function of the RIN gene, encoding a MADS-box, and analyze its impact on the metabolism of carotenoids in pepper. [Methods] Based on the fruit development transcriptome of pepper, the full-length CDS of the MADS-box transcription factor Ca- RIN gene related to chili ripening was cloned. The bioinformatics, expression pattern, subcellular localization, and transcriptional activation activity were examined, and the effects of VIGS-induced CaRIN gene silencing on carotenoid metabolism were investigated. [Results] (1) The CDS of CaRIN gene was 732 bp in length. CaRIN gene encoded a protein containing 243 amino acids with a molecular mass of 27.95 kD and an isoelectric point (pI) of 7.06. CaRIN protein had a typical MEF2_ like MADS domain, belonging to the MICK type transcription factor. (2) CaRIN gene was mainly expressed in flowers and fruits with tissue specificity. CaRIN was located in the nucleus and had transcriptional activation activity. (3) The promoter of CaRIN gene had several hormone response elements such as ABRE, and exogenous ABA and ethephon accelerated the fruit to turn red and induced the high expression of CaRIN and related genes. (4) After VIGS-induced gene silencing of CaRIN , the expression level of PSY1, CCS, PDS, CRTZ, LCYB, and NCED1, genes involved in carotenoid metabolic pathway, was decreased by 0.27-0.59 times, and the total carotenoid content in fruits (0.379 mg/g) was decreased compared with the control (0.650 mg/g). [Conclusion] CaRIN may be an important regulatory factor of carotenoid metabolism in capsicum fruits.

The accuracy of blood glucose measurement in clinical laboratories is vital for diabetes diagnosis. Trueness Verification Plan was carried out and analyzed for evaluating the standardization of serum glucose among clinical laboratories.

Objective Due to the characteristics of strong permeability and high water content in water-rich sand layer, the poor muck improvement can easily cause accidents such as spout spilling of screw conveyor and mud cake formation on the cutter plate during shield tunneling, thus affecting shield construction efficiency. So it is necessary to study the muck improvement of earth pressure balance shied tunnel in water-rich sand layer. Method Based on the typical water-rich sand layer working conditions in Qili Station-Minyuan Road West Station interval on Nanchang Metro Line 4, an indoor muck improvement experiment is carried out. The self-made shield soil chamber model device is used to implement soil chamber model experiments on different improved mucks. Based on muck pressure transfer characteristics, the correlations among slump, permeability coefficient and earth pressure transfer coefficient K0 of different improved mucks are established, and the improvement effect of muck under different K0 is studied. Result & Conclusion When foam is used alone to improve the muck, the transfer coefficient K0 of muck is positively correlated with slump, but negatively correlated with permeability coefficient of the muck. When the slump of the muck exceeds 200 mm, K0 decreases gradually. In order to achieve the ideal requirements of muck improvement for earth pressure balance shield in water-rich sand layer, the matched ratio of conditioners is suggested as follows: 25% of foam injection, or 10% injection rate of added bentonite mud. Laboratory and soil chamber model experiments show that the greater K0 is, the better the improvement effect of muck will be. In actual projects, the ideal K0 value of improved muck by using foam alone is 0.60-0.65. While foam and bentonite slurry are combined to improve the muck, the ideal K0 of improved muck is about 0.85.

The open field subsequent filling method in segmented drilling stage is an efficient mining method for inclined medium thick ore bodies.However, blasting, filling and stope stability show complex relationships, causing surface subsidence, roof and floor collapse, and high mining loss rate.This study adopts engineering analogy and industrial experiments to optimize the process of the sublevel drilling and stage open-stoping with backfill of inclined medium thick ore bodies in the aspects of mining sequence, cutting method, and bottom structure layout, and propose a layout method without leaving pillars in the stope.This method directly connects the side walls of the filling body to the chamber after one-step of filling, and improves the strength of the filling body and the recovery rate of the ore block through extrusion blasting.As the key to this method lies in the implementation time, numerical simulation using ANSYS/LS-DYNA shows that medium-depth hole extrusion blasting is used to form cutting grooves, it should be carried out between 7~9 d after filling and curing of the filling body in the stope.Engineering practice has proved the feasibility of this method, which provides technical support for mining production.

Xu Huang,&ast; Feihan Gu,&ast; Mingyu Zhao, Wenkai Huang, Wenjia Han, Ran Chen, Yuanyin Wang College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Chen; Yuanyin Wang, College & Hospital of Stomatology, Anhui Medical University, Key Laboratory. of Oral Diseases Research of Anhui Province, No. 81, Meishan Road, Shushan District, Hefei City, 230032, People’s Republic of China, Email ahmuchenran@163.com; wyy1970548@sohu.comAbstract: Ameloblastoma (AB) is a common odontogenic tumor that develops in the mouth. Despite its benign nature, AB exhibits significant invasiveness leading to tumor metastasis and high postoperative recurrence rates. Studies have shown a relationship between the occurrence and development of various tumors and non-coding RNA (ncRNA). NcRNA, transcribed from the genomes of mammals and other complex organisms, are often products of alternative splicing and processing into smaller products. MicroRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) are the main types of ncRNA. NcRNA play increasingly significant roles in the pathogenesis of human cancers, regulating their occurrence and progression as oncogenes or tumor suppressors. They are involved in tumor development and progression through alternative splicing of pre-mRNA, transcriptional regulation, mRNA stability, protein translation, and chromatin remodeling and modification. The importance of ncRNA in AB has received significant attention in recent years. However, the biological functions and mechanisms of ncRNA in AB remain largely unknown. In this review, we not only explore the functions and roles of ncRNA in AB, but also describe and envision their potential functional roles as biomarkers in AB diagnosis. In particular, we highlight the potential of miR-29a as a molecular marker for diagnosis and therapy. As promising novel therapeutic targets, the biological functions of ncRNA need further study, which is indispensable.Keywords: ameloblastoma, miRNA, biomarker, therapy

Yu Huang,&ast; Ying Huang,&ast; Chaoyong Xiao, Qingling Huang, Xue Chai Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Chai, Department of Radiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email 20600412@163.comObjective: This study aims to evaluate the effectiveness of Magnetic Resonance Virtual Endoscopy combined with 3D-FIESTA-c and 3D-TOF-MRA in preoperative assessment of MVD for PTN, with a focus on accurately detecting neuromuscular contact.Methods: We retrospectively analyzed clinical and imaging data from 240 patients with unilateral primary trigeminal neuralgia undergoing MVD surgery between April 2016 and July 2023. Preoperative scans with 3D-FIESTA-c and 3D-TOF-MRA were performed, and MRVE images were obtained to analyze the relationship between the trigeminal nerve and adjacent vessels. Using the findings during microvascular decompression (MVD) surgery as the gold standard, the diagnostic results of 3D-TOF-MRA + 3D-FIESTA-c were considered as group I, while the combined use of MRVE, 3D-TOF-MRA + 3D-FIESTA-c was considered as group II.Results: In 240 cases, group I had a positive rate of 96.25% and an accuracy rate of 86.25% for identifying responsible blood vessels, while group II had a positive rate of 98.3% and an accuracy rate of 94.17%. There were no statistically significant differences in positive rates between group I and group II, group I and MVD, or group II and MVD (P > 0.05). However, there were statistically significant differences in accuracy rates (P < 0.05). The accuracy for single and multiple arteries with group I was 99.38% and 80.0%, respectively, while with group II, it was 100% and 95.0%. No statistically significant difference was found in accuracy for single or multiple arteries (P> 0.05). The accuracy of evaluating responsibility veins with or without other vessels was 52.73% and 80.0%, respectively, with a statistically significant difference (P< 0.05).Conclusion: MRVE combined with 3D-TOF-MRA + 3D-FIESTA-c significantly improves the accuracy of identifying responsibility vessels, especially veins, in preoperative assessment for MVD. This has important clinical implications for preoperative decision-making and surgical planning. Keywords: primary trigeminal neuralgia, magnetic resonance imaging, magnetic resonance virtual endoscopy, microvascular decompression

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

ObjectiveThis study aims at establishing a teaching catalog and content for breast rare diseases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning (CBL+PBL+RBL).MethodsBy conducting bibliometrics co-occurrence analysis, we collected 6291 articles on breast rare disease published from January, 1975 to June, 2024. Additionally, we retrieved the Textbook on Rare Diseases, the Catalog of Chinese Rare Disease, and Second Batch of Rare Disease Catalog and then decided the teaching content.ResultsFrom 16, 387 keywords, 1000 (6.1%) keywords were identified through co-occurrence analysis, including 50(0.3%) candidate diseases. These were classified into three categories: rare primary breast diseases, rare genetic mutation-related diseases associated with breast cancer, and rare systemic multi-system diseases involving the breast. From the candidate list, 20(0.1%) rare primary breast diseases were further selected for their notable clinical teaching significance, and significant multi-systemic diseases affecting the breast, whether related to gene mutations or not. Teaching plans were drafted using a diversified parallel teaching approaches, taking into account the characteristics of different diseases and the focus of different teaching methods.ConclusionsThis study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Qianxia Huang,&ast; Yingcong Ren,&ast; Ping Yuan,&ast; Ma Huang, Guoyue Liu, Yuanzhi Shi, Guiyang Jia, Miao Chen Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Gui Zhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miao Chen, Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi City, Gui Zhou, People’s Republic of China, Tel +13595248166, Email chenmiao64@163.comAbstract: ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It is primarily characterized by oxidative stress and affects the integrity of the pulmonary barrier. In severe cases, ALI can progress to ARDS(acute respiratory distress syndrome), a condition that poses a serious threat to the lives of affected patients. To date, the etiological mechanisms underlying ALI remain elusive, and available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine protein kinase, performs a pivotal function in the regulation of cellular energy levels and cellular regulatory mechanisms, including the detection of redox signals and mitigating oxidative stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related factor 2), a critical transcription factor, alleviates inflammation and oxidative responses by interacting with multiple signaling pathways and contributing to the modulation of oxidative enzymes associated with inflammation and programmed cell death. Indeed, AMPK induces the dissociation of Nrf2 from Keap1(kelch-like ECH-associated protein-1) and facilitates its translocation into the nucleus to trigger the transcription of downstream antioxidant genes, ultimately suppressing the expression of inflammatory cells in the lungs. Given their roles, AMPK and Nrf2 hold promise as novel treatment targets for ALI. This study aimed to summarise the current status of research on the AMPK/Nrf2 signaling pathway in ALI, encompassing recently reported natural compounds and drugs that can activate the AMPK/Nrf2 signaling pathway to alleviate lung injury, and provide a theoretical reference for early intervention in lung injury and future research on lung protection.Keywords: acute lung injury, AMPK, Nrf2, inflammatory response, oxidative stress

Yuncheng Ni,1,&ast; Ranglang Huang,2,&ast; Shuang Yang,3 Xiao Yan Yang,3 Shan Zeng,3 An Yao,3 Jie Huang,3 Guoping Yang3,4 1Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 3Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Huang; Guoping Yang, Email cellahuang1988@163.com; ygp9880@126.comBackground: Oliceridine is a novel G protein‐biased ligand μ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain.Methods: Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs).Results: 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC0-t and half-life (t1/2) increased more than proportionally with dosage (1.85– 2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed.Conclusion: Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg.Trial Registration: The trial is registered at chictr.org.cn (ChiCTR2100047180).Keywords: pharmacokinetics, oliceridine, chronic pain, G-protein-biased ligand, phase I trial

Shanshan Li,1,2 Le Zhang,3 Boyi Yang,3 Yi Huang,3 Yuqi Guan,3 Nanbo Huang,1 Yingnan Wu,1 Wenshuo Wang,1 Qing Wang,1 Haochen Cai,1 Yong Sun,1 Zijun Xu,1 Qin Wu1,2 1Medical College, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 2Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Qin Wu, Medical College, Jiangsu Vocational College of Medicine, No. 283, South Jiefang Road, Yancheng, 224005, People’s Republic of China, Tel +86-515-88159750, Email hhwuq@163.comBackground: In elderly diabetic patients, depression is often overlooked because professional evaluation requires psychiatrists, but such specialists are lacking in the community. Therefore, we aimed to create a simple depression screening model that allows earlier detection of depressive disorders in elderly diabetic patients by community health workers.Methods: The prediction model was developed in a primary cohort that consisted of 210 patients with diabetes, and data were gathered from December 2022 to February 2023. The independent validation cohort included 99 consecutive patients from February 2023 to March 2023. Multivariable logistic regression analysis was used to develop the predictive model. We incorporated common demographic characteristics, diabetes–specific factors, family structure characteristics, the self–perceived burden scale (SPBS) score, and the family APGAR (adaptation, partnership, growth, affection, resolution) score. The performance of the nomogram was assessed with respect to its calibration (calibration curve, the Hosmer–Lemeshow test), discrimination (the area under the curve (AUC)), and clinical usefulness (Decision curve analysis (DCA)).Results: The prediction nomogram incorporated 5 crucial factors such as glucose monitoring status, exercise status, monthly income, sleep disorder status, and the SPBS score. The model demonstrated strong discrimination in the primary cohort, with an AUC of 0.839 (95% CI, 0.781– 0.897). This discriminative ability was further validated in the validation cohort, with an AUC of 0.857 (95% CI, 0.779– 0.935). Moreover, the nomogram exhibited satisfactory calibration. DCA suggested that the prediction of depression in elderly patients with diabetes mellitus was of great clinical value.Conclusion: The prediction model provides precise and user–friendly guidance for community health workers in preliminary screenings for depression among elderly patients with diabetes.Keywords: prediction model, depression, elderly, diabetes, community–based

Shih-Ching Chin,1,&ast; Yun-Hsuan Chang,2– 6,&ast; Chih-Chun Huang,6,7 Ting-Hsi Chou,1 Chieh-Liang Huang,8 Hsiu-Man Lin,9 Marc N Potenza10 1Department of Psychology, Asia University, Taichung, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 5Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan; 7Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 9Department of Child and Adolescent Development and Mental Health, China Medical University Children’s Hospital, Taichung, Taiwan; 10Psychiatry, Child Study and Neuroscience, Center of Excellence in Gambling Research, Yale School of Medicine, New Haven, CT, USA&ast;These authors contributed equally to this workCorrespondence: Yun-Hsuan Chang, Licensed Clinical Psychologist, Institute of Gerontology, College of Medicine; Department of Psychology, National Cheng Kung University, No. 1., University Road, Tainan, Taiwan, Email z11108051@ncku.edu.tw; yh.chang.snoopy@gmail.comIntroduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay.Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing.Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG.Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.Keywords: addictive behaviors, video games, internet addiction, autonomic nervous system, craving, heart rate variability, self-regulation

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Scenarios such as tidal passenger flow, instantaneous large passenger flow, and mixed operation demand an increasing number of autonomous-rail rapid trams (ART) to increase passenger capacity. However, traditional mechanical physical coupling proves too cumbersome for convenient adjustments. This paper proposes a virtual coupling concept and system architecture for autonomous-rail rapid trams as a solution. This study developed a safe braking model and collaborative control model, in addition to establishing a collaborative planning objective function and constraints. Real-time calculations of speeds, accelerations and traction/braking force percentages for the following ART were conducted under the condition of maintaining the minimum safe distance. Simulations and experiments conducted with real trams demonstrated distances between the trams of less than 5 m, arrival time differences of less than 3 s, parking time differences between the leading and following trams of less than 0.5 s, jerks of the following tram not exceeding 0.4 m/ s3, as well as seamless switching between traction and braking during the operation of virtually coupled trams at 45 km/h. These results underscored the effectiveness of the proposed system in facilitating punctual, precise, comfortable and energy-efficient operation of virtually coupled trams. This research lays a solid foundation for potential future applications of virtually coupled ARTs at scale.

ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally， the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group.MethodsThis study was conducted in the Chongming area of Shanghai， China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index（SMI） was measured by bioelectrical impedance analysis（BIA）， and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis， chi-square test， and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass.ResultsIn terms of food intake categories， compared with the long-lived elderly people with normal muscle mass， the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower （P

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting, coagulation, and thermal injury of ex vivo animal tissues, aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia. Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment, respectively. Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s. The effects of layers at powers of 60, 90, 120, 150, and 160 W on tissue injury were observed. Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury. Additionally, in coagulation mode, the effects of 30, 40, and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5, 10, and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue, the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue. However, at a distance of 0.5 cm, the 120 W, 150 W, or 160 W lasers caused slight damage to the bladder tissue. In addition, with the increase in output power, the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased, showing a good linear correlation between vaporization volume and total energy consumption (P0.05). Moreover, when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2, the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power (P0.05). Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation, cutting, and coagulation effect on ex vivo tissues, with a good linear correlation between the effect and the output energy.

In CH3COONa-HCl buffer solution, ClO2- oxidizes excess I- to generate I3-, and I3- forms complex particles with positively charged methylene blue under electrostatic attraction, which enhances the resonance scattering intensity of the system. Based on this principle, a new method for the determination of trace NaClO2 in water by resonance scattering spectroscopy was established.The measurement conditions of this method were optimized to improve the resonance scattering intensity. The optimal dosage of CH3COONa-HCl buffer solution, KI solution, and methylene blue solution, as well as the optimal reaction time and measurement wavelength, were obtained during the measurement. Under the optimal conditions, the resonance scattering intensity increased with the increase of ClO2- mass concentration in the range of 0.018 2-0.364 0 mg/L, which showed a good linear relationship with a detection limit of 0.004 8 mg/L. When this method was used to determine the content of chlorite in groundwater, the relative standard deviation of the measurement results was 1.5%-2.9%, and the recovery rate was 96%-99%.

Xin Tang,1,&ast; Qifu Li,1,&ast; Gaoyangzi Huang,1 Ziwen Chen,2 Ya Huang,1 Xianmei Pei,1 Siwen Zhao,1 Zili Liu,1 Taipin Guo,1 Fanrong Liang2 1School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Kunming, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email acuresearch@126.comPurpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS.Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ2 test or Fisher’s exact test.Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.Keywords: acute lumbar sprain, immediate efficacy, contralateral acupuncture, active exercise, randomized controlled trial

Liuyi Huang,&ast; Xi Li,&ast; Wei Zhou, Haiqing Zhu, Yuehong Lao, Xiaoxia Huang, Zhenjia Deng, Yuting Tang, Jian Wang Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wang, Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email wangjian0771@163.comObjective: There are no studies examining the role of the neutrophil-to-lymphocyte ratio (NLR), the C-reactive protein-to-albumin ratio (CAR), the systemic inflammatory index (SII), and the systemic inflammatory response index (SIRI) in anti-synthetase syndrome (ASS). We aim to compare NLR, CAR, SII, and SIRI in ASS and dermatomyositis/polymyositis (DM/PM), as well as to examine potential correlations between NLR, CAR, SII, and SIRI and clinical features and laboratory parameters in ASS.Methods: Retrospective collection of data from 111 patients with ASS and 175 patients with DM/PM. A Spearman rank correlation analysis was utilized to analyze the correlation between NLR, CAR, SII, and SIRI and inflammatory indexes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value. Univariate logistic regression analysis was performed to assess risk factors for interstitial lung disease (ILD).Results: Compared with DM/PM, NLR, CAR, SII, and SIRI were significantly greater in ASS patients (p < 0.05). NLR, CAR, SII, and SIRI were correlated with albumin, lactic dehydrogenase (LDH), C-reactive protein (CRP), ferritin, white blood cell (WBC), platelets, and myositis disease activity assessment visual analog scales (MYOACT) score (p < 0.05). The ROC curves analysis showed that NLR, SII, and SIRI were all highly predictive of the occurrence of ASS. Comparisons based on clinical characteristics showed elevated levels of NLR, CAR, SII, and SIRI in ASS patients with ILD, fever, and infection (p < 0.05). Univariate logistic regression analysis revealed that NLR, CAR, and SII were significant risk factors for ASS-ILD (p < 0.05).Conclusion: The levels of NLR, CAR, SII, and SIRI were higher in ASS than in DM/PM and correlated with disease activity and specific clinical features. NLR, CAR, SII, and SIRI may be an aid in differentiating ASS from DM/PM and maybe promising biomarkers for ASS.Keywords: the neutrophil-to-lymphocyte ratio, the C-reactive protein-to-albumin ratio, the systemic immune inflammation index, the systemic inflammation response index, anti-synthase syndrome

Juan Du,1,&ast; Li-Li Shi,2,&ast; Wei-Wei Jiang,3 Xue-Ai Liu,3 Xin-Hong Wu,3 Xiang-Xiang Huang,3 Ming-Wei Huo,3 Ling-Zhi Shi,3 Jingjian Dong,2 Xiaohong Jiang,2 Renyu Huang,4 Qing-Ri Cao,3 Wenzhou Zhang1 1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China; 4College of Social Science, Soochow University, Institute of Culture and Tourism Development, Soochow University, Suzhou, 215123, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhou Zhang, Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China, Email hnzzzwzx@sina.com Qing-Ri Cao, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Jiangsu, 215123, People’s Republic of China, Email qrcao@suda.edu.cnBackground: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations. Keywords: DTX-BSA nanoparticles, thermal-driven self-assembly, microfluidic technology, in-vitro release, pharmacokinetics

Abstract Documenting tangible cultural heritage using 3D modeling techniques is gradually becoming an indispensable component of archaeological practice. The 3D modeling techniques based on photogrammetry and LiDAR scanning enable high-accuracy and high-realistic reconstruction of archaeological sites, and have been proven a powerful tool for documenting archaeological excavations. However, dynamically documenting an ongoing excavation using these techniques is still considered tedious, time-consuming, expensive, and dependent on expertise. Moreover, the application of 3D modeling techniques in archaeological excavations still faces some technical challenges, such as modeling with multi-source and multi-scale data, fusing local models at different times into a whole, achieving fast modeling while GPU workstations are not available in the field, and evaluating the quality of 3D models. As a result, there are still very few archaeological teams deeply engaged in dynamic documentation with 3D modeling techniques, and traditional drawing sketches and taking photographs still dominate. In these senses, documenting the archaeological excavation at the Yunxian Man site (located in Hubei, China) is an invaluable opportunity for exploration and practice. Archaeologists determined to conduct dynamically documenting at the beginning of the 6th excavation project for the site, and established a rotation system to reconcile physical excavation with digital preservation. Through repeated practice and communication, we proposed a workflow and pursued several new methods to enhance the feasibility of dynamically documenting, and obtained 4D models of the ongoing archaeological excavations. In 2022, the Yunxian Man site unearthed the most intact fossil of hominin cranium from about one million years ago in the Eurasian continent, preserving important and scarce anatomical features of early humans in Asia. As the original taphonomic context of the fossil corroded away during physical excavations, the digital documentation consisting of 4D models serves as permanent original data source in subsequent archaeological research. Moreover, we obtained cross-scale 3D models from geographical environment to archaeological site, excavation area, and cultural remains, and all of these 3D models are in an actual, unified coordinate framework. Thus, we can contribute to multidisciplinary cross-collaborative research through data sharing. Considering that digital documentations serve a great value in archaeological research, this paper focuses on sharing the workflow and methods to facilitate digital preservation for more archaeological projects.

Pancreatic regenerating (REG) protein belongs to the calcium-dependent lectin superfamily, and is encoded by regenerating gene. As secreted growth factors with multiple functions, REG protein family plays a regulatory role in nutrient metabolism, anti-apoptosis, anti-fibrosis, anti-inflammation and antibacterial. Since 1979, REG protein family has been found to be associated with various diseases, such as diabetes, inflammation and cancer. Several subtypes of REG proteins are involved in different pathogenesis of diabetes. The purpose of this study is to review the origin, structural characteristics, distribution patterns of REG protein family and its pathogenesis and therapeutic regulation in different types of diabetes, and to explore the potential application value of REG protein family in the early warning，diagnosis, treatment and prognosis of diabetes, with a view to its wider application in the fields of therapeutic targets and biomarkers in the future.

Abstract Background Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that has been found to be associated with dysregulation of gastrointestinal functions and gut microbial homeostasis (the so-called “gut-brain axis”). ASD is often accompanied by poor performances in social interaction and repetitive behaviors. Studies on the gut-brain axis provide novel insights and candidate targets for ASD therapeutics and diagnosis. Based on the ASD mice model, this work aims to reveal the mechanisms behind the interaction of intestinal barrier function and probiotics in ASD mouse models. Results We found an altered intestinal barrier in both BTBR T+ Itpr3tf/J (BTBR) and valproic acid (VPA) mice, including increased intestinal permeability, decreased expression of intestinal tight junction proteins (claudin1, claudin3, and occludin), and increased levels of IL-6, TNF-α, and IFN-γ. Based on intestinal microbial alternation, C. butyricum can drive reduced expression of histone deacetylases 1 (HDAC1) and enhanced intestinal barrier function, significantly promoting behavioral abnormalities of ASD in BTBR mice. In parallel, we confirmed that C. butyricum was involved in the regulation of intestinal function by the Trek1 channel, indicating that it is a target of C. butyricum/butyric acid to improve intestinal barrier function in ASD mice. Conclusions Our finding provides solid evidence for the gut microbiota involved in ASD through the brain-gut axis. In addition, the probiotics C. butyricum hold promise to improve gut health and ameliorate behavioral abnormalities associated with ASD.

Introduction: Gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) are prevalent in Taiwan. Few studies have investigated the associations between obesity indices with GERD and PUD simultaneously. This study aimed to investigate the correlations among obesity indices with GERD and PUD in a large cohort of participants, around 120,000, in the Taiwan Biobank (TWB). Methods: A total of 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) were included to analyze the associations among obesity indices, including body mass index (BMI), waist-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose index (TyG index), with GERD and PUD. Self-reported GERD and PUD were obtained by questionnaires. Multivariate logistic regression analysis was employed to analyze the relationship between obesity indices with GERD and PUD. Results: The prevalence of GERD and PUD was 13.7% and 14.6%, respectively. After multivariable analysis, high WHR (odds ratio [OR] = 1.009, p < 0.001), WHtR (OR = 1.005, p = 0.003), BRI (OR = 1.022, p = 0.005), AVI (OR = 1.013, p < 0.001), LAP (OR = 1.001, p < 0.001), TyG index (OR = 1.068, p < 0.001), and VAI (OR = 1.013, p = 0.002) were significantly associated with GERD, except BMI (p = 0.384). On the other hand, low BMI (OR = 0.984; p < 0.001) and AVI (OR = 0.994; p = 0.036) were significantly associated with PUD. However, the values of WHR (p = 0.151), WHtR (p = 0.304), BRI (p = 0.452), LAP (p = 0.799), VAI (p = 0.347), and TyG index (p = 0.642) were not. Conclusion: This study found that high obesity indices are associated with GERD, but low obesity indices are associated with PUD in a large Taiwanese population study. Our findings may alert physicians to notice that different obesity index may be associated with different gastrointestinal disorder.

AIM: To investigate the biomechanical properties and practical application of absorbable materials in orbital fracture repair. METHODS: The three-dimensional (3D) model of orbital blowout fractures was reconstructed using Mimics21.0 software. The repair guide plate model for inferior orbital wall fracture was designed using 3-matic13.0 and Geomagic wrap 21.0 software. The finite element model of orbital blowout fracture and absorbable repair plate was established using 3-matic13.0 and ANSYS Workbench 21.0 software. The mechanical response of absorbable plates, with thicknesses of 0.6 and 1.2 mm, was modeled after their placement in the orbit. Two patients with inferior orbital wall fractures volunteered to receive single-layer and double-layer absorbable plates combined with 3D printing technology to facilitate surgical treatment of orbital wall fractures. RESULTS: The finite element models of orbital blowout fracture and absorbable plate were successfully established. Finite element analysis (FEA) showed that when the Young's modulus of the absorbable plate decreases to 3.15 MPa, the repair material with a thickness of 0.6 mm was influenced by the gravitational forces of the orbital contents, resulting in a maximum total deformation of approximately 3.3 mm. Conversely, when the absorbable plate was 1.2 mm thick, the overall maximum total deformation was around 0.4 mm. The half-year follow-up results of the clinical cases confirmed that the absorbable plate with a thickness of 1.2 mm had smaller maximum total deformation and better clinical efficacy. CONCLUSION: The biomechanical analysis observations in this study are largely consistent with the clinical situation. The use of double-layer absorbable plates in conjunction with 3D printing technology is recommended to support surgical treatment of infraorbital wall blowout fractures.

In recent years, with rising concerns over food quality and safety, computer vision technology has gradually attracted attention and begun to be widely used in the field of food quality evaluation. Machine learning technologies such as artificial neural networks (ANN), convolutional neural networks (CNN), and support vector machines (SVM) allow automatic assessment and monitoring of food quality by training on large amounts of food images and related data. Particularly, with the development of deep learning, the computer is now able to more accurately recognize food features such as appearance, shape, and color, thereby allowing food classification, prediction and quality monitoring. In addition to its conventional application in food quality assessment, learning technologies also find application in more complex tasks such as defect detection, foreign object detection, and freshness assessment. These technologies not only improve the efficiency of food production and processing but also reduce errors caused by human factors, thereby ensuring food quality and safety. However, despite the significant progress in the application of learning technologies in food quality assessment, there are still challenges that need to be overcome. For instance, the high cost of acquiring and annotating food image datasets, as well as insufficient data quality and quantity, may affect the performance and generalization ability of models. Furthermore, the interpretability and transparency of models are important issues, especially when explaining or making decisions on food quality assessment results. Therefore, further research is needed to explore how to improve the quality and scale of datasets, optimize the robustness and interpretability of models, and develop more efficient and sustainable food quality assessment systems.

Objective: Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy. Methods: We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (n = 20,583) and the internal validation set (n = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (n = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values. Results: The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872–2.774, P < 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089–16.293, P < 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617–2.437, P < 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568–14.194, P < 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338–1.935, P < 0.001). Conclusion: Survival Quilts could allow accurate prediction of 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS in gastric cancer patients following gastrectomy.

Abstract Background Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response. Methods We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT). Results We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1–4 BCs (66.7% vs. 15.9%, p

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Maoliang Tian,1,&ast; Wenqiang Li,1,&ast; Xiaoyu He,2 Qian He,3 Qian Huang,4 Zhiping Deng1 1Zigong First People’s Hospital, Zigong City, Sichuan Province, 643000, People’s Republic of China; 2North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China; 3West China Second Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China; 4Dazhou Dachuan District People’s Hospital (Dazhou Third People’s Hospital), Dazhou, Sichuan Province, 635000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Huang, Dazhou Dachuan District People’s Hospital (Dazhou Third People’s Hospital), Dazhou, Sichuan Province, 635000, People’s Republic of China, Email hq15196767955@163.com Zhiping Deng, Zigong First People’s Hospital, Zigong City, Sichuan Province, 643000, People’s Republic of China, Email dengzp1016@163.comBackground: In human health, vitamins play a vital role in various metabolic and regulatory processes and in the proper functioning of cells. Currently, the effect of Vitamin E (VE) intake on multiple causes of death in Chronic obstructive pulmonary disease (COPD) patients is unclear. Therefore, this paper aims to investigate the relationship between VE and multiple causes of death in COPD patients, to guide the rationalization of dietary structure and reduce the risk of COPD death.Methods: This study screened patients with COPD aged ≥ 40 years from the National Health and Nutrition Examination Survey (NHANES) database 2008– 2018. Weighted COX regression was used to analyze the association between VE intake and multiple causes of death in COPD. The restricted cubic spline(RCS) is drawn to show their relationship. Finally, we conducted a subgroup analysis for further verification.Results: A total of 1261 participants were included in this study. After adjustment for multiple covariates, VE intake was associated with all-cause death in COPD patients, and chronic lower respiratory disease (CLRD) deaths were linearly associated with cardiovascular disease (CVD) deaths there was no such correlation. Subgroup analyses showed no interaction between subgroups, further validating the robustness of the relationship.Conclusion: In COPD patients, VE intake was negatively associated with all-cause mortality and CLRD death. Higher VE intake reduces the risk of all-cause mortality and CLRD death in COPD patients.Keywords: vitamin E, COPD, CVD, CLRD, COX regression analyses

Asami Shimokawa, Aya Ikeda, Kazuhiro Harada, Rie Takahashi, Jane Huang, Tomoko Tsukahara-Kawamura, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpPurpose: Vernal keratoconjunctivitis (VKC) is a refractory ocular allergic disorder that mainly affects boys. Long-term follow-up has been rarely reported for VKC. We investigated the long-term clinical outcome of VKC to identify relevant clinical features of prognostic value based on follow-up for a median of 70 months.Methods: In total, 45 consecutive patients clinically diagnosed with VKC aged 4 to 12 years at onset at the Department of Ophthalmology of Fukuoka University Hospital were included. Patients were treated with immunosuppressive eye drops without simultaneous corticosteroid eye drops, except for the occurrence of exacerbations. Collated variables were gender, age at onset, clinical score of ocular lesions (conjunctival giant papillae, limbal edema and corneal epithelial lesions) at the first visit, and clinical score of atopic dermatitis (AD) at baseline. Cumulative cure rate was estimated using Kaplan–Meier method. A binomial logistic predictive model was used to determine the most reliable clinical predictors of VKC outcome.Results: The observation period ranged from 24 to 188 months, with median of 70 months. Among the 45 cases enrolled, all non-cured cases (14 cases) observed clinically were complicated by AD. Cumulative cure rate was 74.5% and 84.9% at eight- and ten-year follow-up, respectively. Ten-year cumulative cure rates of cases with and without AD were 50.5% and 100%, respectively, and a significant difference was found between these cumulative cure curves. Binomial regression analysis revealed that AD and gender were significantly related to worse outcome, and this binomial regression model had high sensitivity and specificity.Conclusion: This study demonstrated that th eclinical outcomeof VKC might be predicted by several factors that can beobtained in the early clinical phase. Information on the long-term prognosis of VKC patients might play an important role for precision medicine for VKC in childhood.Keywords: vernal keratoconjunctivitis, cumulative cure rate, atopic dermatitis, immunosuppressive eye drops, binomial logistic analysis

Gongjie Zhang,1 Xinlyu Huang,1 Hanlin Li,1 Huizi Gong,1 Yabin Zhou,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Yabin Zhou, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10 59616884, Email chouyabin@163.com Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti Nan Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 18611369216, Email roseliufang@qq.comBackground: Hair loss is common in hypothyroidism patients. However, the link with alopecia areata (AA) and androgenetic alopecia (AGA) is unclear. Previous observational studies have presented completely opposite results. This study aims to causally link hypothyroidism with AA and AGA.Methods: A two-sample Mendelian Randomization (MR) study, utilizing data from FinnGen Consortium, investigated the causal link between hypothyroidism and AA and AGA. We employed Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode to assess the risk association.Results: The discovery samples included 13,429 hypothyroidism cases (94,436 controls), 767 alopecia areata cases (394,105 controls), and 220 androgenetic alopecia cases (219,249 controls). MR analysis showed a causal link between hypothyroidism and AA, with significant results from IVW (OR, 1.34; CI, 1.16– 1.56; P = 0.0001), MR-Egger (OR, 1.56; CI, 1.09– 2.23; P = 0.0240), and weighted median (OR, 1.34; CI, 1.06– 1.69; P = 0.0140). However, no clear causal relationship was found between genetically predicted hypothyroidism and AGA risk (p > 0.05).Conclusion: The results show hypothyroidism causally associated with AA onset, but not AGA. These findings address contentious issues in observational studies. Comprehensive thyroid function assessments are crucial for AA patients, emphasizing thorough clinical examinations’ importance.Keywords: hypothyroidism, alopecia areata, androgenetic alopecia, Mendelian randomization study, causality

Xiao-Dong Huang,1,&ast; Jia-Bao Chen,2,&ast; Xiao-Yun Dong,1 Wei-Long Wang,1 Jin Zhou,1 Zhen-Feng Zhou1 1Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medicine College), Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Feng Zhou, Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, 310008, People’s Republic of China, Tel +86-571-56005077, Email zhenfeng9853@163.comPurpose: This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia.Patients and Methods: Sixty female patients aged 65– 80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 μg/kg), while Group R received remimazolam alone. Dosing adjustments (± 2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale.Results: The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845– 5.859) and 8.184 mg (95% CI, 6.636– 13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533– 8.068) and 11.298 mg (95% CI, 9.101– 19.617), respectively.Conclusion: This study provides compelling evidence that the administration of 1 μg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 μg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.Keywords: remimazolam, fentanyl, effective dose, elderly

Shiyu Hu,1,2,&ast; Wenyu Chen,2,&ast; Xiaoli Tan,2,&ast; Ye Zhang,1,2 Jiaye Wang,1,2 Lifang Huang,3 Jianwen Duan4 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Health Management Center, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifang Huang, Health Management Center, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314001, People’s Republic of China, Email jxhuanglifang@126.com Jianwen Duan, Department of Hepatobiliary Surgery, Quzhou People’s Hospital, No. 2, Zhongloudi, Quzhou, Zhejiang, 324000, People’s Republic of China, Email 695377686@qq.comPurpose: The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence.Patients and Methods: This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell’s concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation.Results: In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976– 0.980) for the training set and 0.977 (0.974– 0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all.Conclusion: We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.Keywords: metabolic syndrome, risk factors, nomogram, prediction

Tingting Zhang,1– 3,&ast; Jinglin Mi,1– 3,&ast; Xinling Qin,1– 3,&ast; Zhechen Ouyang,1– 3 Yiru Wang,1– 3 Zhixun Li,1– 3 Siyi He,1– 3 Kai Hu,1– 3 Rensheng Wang,1– 3 Weimei Huang1– 3 1Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimei Huang; Rensheng Wang, Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email huangweimei@gxmu.edu.cn; wangrensheng@gxmuhospital.cnBackground: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved.Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation.Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF.Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.Keywords: rosmarinic acid, exosomes, tRNA, N7-methylguanosine, radiation-induced pulmonary fibrosis

Jiasen Ma,1 Xiuqin Huang,2 Yanping Hu,1 Bing Xu,1 Chunhua Jin1 1Emergency Department, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, People’s Republic of China; 2Department of Plastic and Cosmetic Surgery, The 72nd Group Military Hospital of the People’s Liberation Army of China, Huzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Chunhua Jin, Emergency Department, Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, People’s Republic of China, Email mjsjch@163.comBackground: Secretoneurin is a neuropeptide with several neuroprotective properties. Here, we discuss the importance of serum secretoneurin in assessing severity and predicting delayed cerebral ischemia (DCI) and functional outcomes following aneurysmal subarachnoid hemorrhage (aSAH).Methods: A prospective cohort study of 167 patients with aSAH and 100 controls was performed to determine serum secretoneurin levels. Severity was reflected by the Hunt-Hess and modified Fisher scores. Prognostic parameters included DCI and poor 6-month prognosis (extended Glasgow outcome scale scores of 1– 4). Univariate analysis followed by multivariate analysis was performed to determine the correlation between severity and prognosis.Results: Compared to controls, patients exhibited a marked elevation in serum secretoneurin levels. Serum secretoneurin levels, which were independently correlated with Hunt-Hess scores and modified Fisher scores, independently predicted DCI and bad 6-month prognosis. Serum secretoneurin levels, which were linearly related to the risk of DCI and poor prognosis under a restricted cubic spline, effectively distinguished the risks under the receiver operating characteristic (ROC) curve. Subgroup analysis for prognosis or DCI prediction revealed no substantial interactions between serum secretoneurin levels and other variables, such as age, sex, hypertension, diabetes, alcohol consumption, and cigarette consumption. In addition, the prognosis model, in which serum secretoneurin, Hunt-Hess scale, and modified Fisher scale were merged, was graphically represented by a nomogram and performed well under the calibration, decision, and ROC curves.Conclusion: Serum secretoneurin levels significantly increased after aSAH, which was intimately correlated with disease severity and independently associated with DCI and worse outcomes, indicating that serum secretoneurin may be a potential prognostic biomarker of aSAH.Keywords: aneurysm, subarachnoid hemorrhage, secretoneurin, delayed cerebral ischemia, prognosis, outcome, severity

Yu-Chieh Ho,1,&ast; Chia-Ti Wang,1,&ast; Tzu-Chieh Weng,2 Chung-Han Ho,3,4 Kang-Ting Tsai,5,6 Chien-Chin Hsu,1,7 Hung-Jung Lin,1,7,8 Hsiu-Chin Chen,5,9 Chien-Cheng Huang1,7,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 4Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 5Department of Senior Welfare and Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 6Division of Geriatrics and Gerontology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 7School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; 8Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan; 10Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Cheng Huang, Department of Emergency Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email jasonhuang0803@gmail.com Hsiu-Chin Chen, Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email 300006@mail.chimei.org.twPurpose: The home-based medical integrated program (HMIP) is a novel model for home healthcare (HHC) in Taiwan, initiated in 2016 to enhance care quality. However, the outcomes of this program on health outcomes and medical resource utilization in HHC patients remain unclear. Thus, we conducted this study to clarify it.Patients and Methods: The authors utilized the Taiwan National Health Insurance Research Database to identify HHC patients who received HMIP and those who did not between January 2015 and December 2017. A retrospective cohort study design was used. Convenience sampling was employed to select patients who met the inclusion criteria: being part of the HHC program and having complete data for analysis.Results: A total of 4982 HHC patients in the HMIP group and 10,447 patients in the non-HMIP group were identified for this study. The mean age in the HMIP group and non-HMIP group was 77.6 years and 76.1 years, respectively. Compared with the non-HMIP group, the HMIP group had lower total medical costs for HHC, fewer outpatient department visits and lower medical costs, lower medical costs for emergency department visits, fewer hospitalizations, and a lower mortality rate (34.6% vs 41.2%, p< 0.001).Conclusion: The HMIP is a promising model for improving care quality and reducing medical resource utilization in HHC patients. While this suggests that the non-HMIP model should be replaced, it’s important to note that both non-HMIP and HMIP models currently coexist. The HMIP may serve as an important reference for other nations seeking to improve care quality and reduce medical resource utilization in their own HHC systems.Keywords: home-based medical integrated plan, health outcomes, medical resource utilization, Taiwan

Xiaoyan Huang,1,2 Xiangrong Zhao,1,2 Yaping Li,1,2 Yangmeng Feng,1,2 Guoan Zhang,3 Qiyu Wang,4 Cuixiang Xu1,2 1Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 3Department of Cardiovascular Surgery, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 4Department of Graduate School, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Cuixiang Xu, Email xucuixiang1129@163.comBackground: Dilated cardiomyopathy (DCM) is the second leading cause of heart failure, with intricate pathophysiological underpinnings. In order to shed fresh light on the mechanistic research of DCM, we combined bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data to examine significant cells and genes implicated in the disease.Methods: This analysis employed publicly accessible bulk RNA-seq and scRNA-seq DCM datasets. The scRNA-seq data underwent normalization, principal component, and t-distribution stochastic neighbor embedding analysis. Cell-to-cell communication networks and activity analysis were conducted using CellChat. Utilizing enrichment analysis, the marker genes’ role in the active cells was evaluated. After screening by limma software and weighted gene co-expression network analysis, the differentially expressed genes (DEGs) served as hub genes. Furthermore, these hub genes were subjected to immunological studies, transcription factor expression, and gene set enrichment. Lastly, the expression of the four hub genes and their connection to DCM were verified using the rat models.Results: Fibroblasts and monocytes were chosen as hub cells from among the eight identified cell clusters; their marker genes intersected with DEGs to yield six hub genes. In addition, the six hub genes and the essential module genes intersected to yield four essential genes (ASPN, SFRP4, LUM, and FRZB) that were connected to the Wnt signaling pathway and highly expressed in fibroblast. The four hub DEGs had an expression pattern in the DCM rat model experiment results that was in line with the findings of the bioinformatics study. Additionally, there was a strong correlation between decreased cardiac function and the up-regulation of ASPN, SFRP4, LUM, and FRZB.Conclusion: Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes ASPN, FRZB, LUM, and SFRP4 in fibroblasts may aid in the mechanistic investigation of DCM.Keywords: dilated cardiomyopathy, single cell RNA-seq, bulk RNA-seq, weighted gene co-expression network analysis, wnt signaling pathway, fibroblasts

Allison Maher,1 Michelle Bennett,1 Hsin-Chia Carol Huang,1,2 Philip Gaughwin,1,3 Mary Johnson,1 Madeleine Brady,1 Kacie Patterson,1,3 Tanya Buettikofer,1,3 Jo Morris,1 Veronica Mary Rainbird,3 Imogen Mitchell,1,2 Bernie Bissett1,3 1Rehabilitation and Community Services / Respiratory Medicine, Canberra Health Services, Canberra ACT, Australia; 2College of Health and Medicine, Australian National University, Canberra ACT, Australia; 3Faculty of Health, University of Canberra, Canberra ACT, Bruce, AustraliaCorrespondence: Bernie Bissett, Email Bernie.Bissett@canberra.edu.auObjective: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature.Background: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia’s few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation.Methods: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer’s presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4– 6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual’s progress, at an intensity 4– 6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥ 50% of their maximum inspiratory pressure).Discussion: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts.Conclusion: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual’s symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.Plain Language Summary: Long COVID affects 5-10% of people following COVID infection. There is little specific guidance on how exercise can be safely prescribed in Long COVID. This paper is the first to provide a detailed description of an Australian multidisciplinary Long COVID clinic, including specific tools and guidance about how exercise can be prescribed while minimising post-exertional symptom exacerbation. The tools described could be valuable to other health facilities striving to optimise multidisciplinary care for people with Long COVID, incorporating safe exercise prescription.Keywords: COVID, rehabilitation, multidisciplinary care, physiotherapy, respiratory muscle training

Liying Zhan,1,&ast; Zhihua Lv,2,&ast; Yunjing Zhang,3,&ast; Jingdi Chen,4 Lu Wang,1 Raojuan Huang,5 Yaqi Sun,5 Wei Wu1 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Institute of Translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Orthopedics, the Airborne Military Hospital, Wuhan, Hubei, People’s Republic of China; 5First Clinical College of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, Email weiwu2012@whu.edu.cnPurpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p< 0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.Keywords: metagenomic next-generation sequencing, cerebrospinal fluid, central nervous system infections, diagnosis

Roumei Wang,1,&ast; Shien Fu,2,&ast; Rui Huang,3,&ast; Chengcheng Qiu,1 Yunxia Tang,1 Yaoli Liu1 1Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Public Hygiene of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaoli Liu, Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356706, Email 100youngly@163.comObjective: This study aimed to evaluate the quadriceps femoris in patients with chronic thyrotoxic myopathy (CTM) using musculoskeletal ultrasound and to explore its practical clinical value for the diagnosis of CTM.Methods: A total of 241 subjects recruited from the First Affiliated Hospital of Guangxi Medical University were surveyed for detailed medical history and underwent grip strength tests, fixed-distance walking, and quadriceps femoris ultrasound examinations. Differences in muscle parameters between the CTM, non-CTM, and healthy groups were analyzed. An Receiver operating characteristic (ROC) curve was established to analyze the predictive value of various ultrasound measurements for CTM, and Spearman correlation analysis and binary logistic regression were applied to explore the factors associated CTM.Results: The quadriceps femoris contraction index, muscle thickness, muscle cross-sectional area, and pennation angle in the CTM group were significantly lower than those in the non-CTM and healthy groups (p< 0.01). The ROC curve prediction showed that the pennation angle had the best sensitivity and specificity for diagnosing myogenesis, with an area under the curve of 89%. Moreover, the pennation angle of the CTM group was positively correlated with step speed (r=0.245, p=0.031) and body surface area (r=0.276, p=0.014), but negatively correlated with age (r=− 0.306, p=0.007). Regression analysis showed that the quadriceps femoris contraction index, muscle thickness, pennation angle, and cross-sectional area were factors that related the CTM. After adjusting for potential confounding factors, the association between Muscle Bundle Length and CTM became significant (OR=1.99, 95% CI: 1.22, 3.35, p=0.007). Muscular echo in patients was observed to varying degrees of enhancement.Conclusion: Musculoskeletal ultrasonography in the quantitative analysis of muscle parameters and muscle echo of the quadriceps femoris can provide essential imaging evidence for predicting CTM.Keywords: chronic thyrotoxic myopathy, musculoskeletal ultrasound, muscle echo intensity, Heckmatt Scale

Ecological environmental protection is an important support for China to achieve ecological civilization, but it often encounters challenges in fairly distributing protection responsibilities and development rights between the wider society and local communities living in protected areas. Ecological protection planning is an instrument for reconstructing environmental protection responsibilities and development rights among different social groups: the communities within the protected areas bear the responsibility for ecological protection but may lose some development rights to some extent, whereas the communities outside the protected areas enjoy the benefits of environmental protection without having to fulfill related obligations. This asymmetry of rights and obligations triggers environmental injustice, and is a crucial factor in determining the effectiveness of policy implementation. The changing patterns of environmental (in)justice are shaped by negotiations between governments at different scales and local stakeholders, and involve complex political processes. Therefore, this study introduces a theoretical framework that integrates scale politics and environmental justice to explore the distinctive-scale political processes involved in achieving environmental justice in ecological protection areas under China's segmented and hierarchical political system. First, the pattern of environmental justice is shaped by the highest-scale actors among relevant stakeholders. Second, intermediate-scale actors tend to prioritize compliance with policy directives from higher scales and may use methods such as scale retention or devolution to limit the interest demands of lower scales. Finally, lower-scale actors may seek to enhance their political discourse power through scale escalation when faced with unjust situations created by a top-down decision-making system. Empirically, this research selected a village yet to be reconstructed in an ecological protection zone in the central provincial capital city of China as a case study and analyzed the environmental injustice faced by the villagers and pathways to change the injustice. The empirical findings suggest that, without prior consideration of the development rights of local residents, strict top-down ecological environmental protection methods often aggravate tense relationships among actors at different scales. Specifically, this leads to environmental injustice, in which the development rights of local residents at lower scales are overshadowed by the protection requirements enforced by higher-scale government entities. Environmental (in)justice includes the allocation, institutional, and recognition dimensions. In response, scale reconstruction emerges as an informal strategy for lower-scale residents to seek justice. Through this strategy, lower-scale residents appeal to higher-scale governments to intervene in the development issues of ecological protection areas, and thus strive to achieve equality in development rights and protective responsibilities. This process opens a way to achieve environmental justice. Additionally, the reliance on informal mechanisms underscores the lack of formal mechanisms in China to ensure that lower-scale groups have fair rights to urban ecological environmental protection. To address the challenges, this article integrates theoretical insights with empirical evidence to propose the following policy measures:(1) strengthening the top-down transmission of policies to implement the principle of balancing ecological protection by improving people's livelihoods, (2) establishing mechanisms for achieving environmental justice through the balanced allocation of rights and responsibilities, and (3) enhancing the democratic participation of relevant stakeholders in planning.

During the stage of high-quality development, the orderly promotion of citizenization of the floating population is crucial to ensure the high-quality population development and sustainable socio-economic growth of our country. In this study, dynamic monitoring survey data of China's floating population in 2017 were referenced to categorize the settlement intentions of this population group into three types (viz., short term, long term, and permanent) according to their expected residence duration. Subsequently, the mobility and residential characteristics of this population were analyzed by using a multinomial logistic regression model to examine differences in their demographic and family characteristics, mobility patterns, economic status, and social integration. The findings are as follows: (1) Dongguan and Huizhou, located on the east bank of the Pearl River and primarily driven by manufacturing industries, have a significant proportion of populations with short-term settlement intentions. By contrast, cities with lower living costs or more comprehensive services are more likely to attract long-term residents. (2) The inter-provincial floating population tends to flow into Shenzhen, with individuals migrating a short distance being more predominant. Long-distance inter-provincial migrants have a stronger intention to settle permanently. Within the province, the floating population tends to flow into Guangzhou, displaying a certain degree of geographical proximity in city choices and a tendency to stay long term or permanently. (3) Groups characterized by female sex, older age, higher educational level, marital status, longer inflow time, non-work-related inflow reasons, and higher income level tend to take up long-term or permanent residence at their destination. Conversely, lower levels of these characteristics are associated with shorter stays. Higher degrees of social integration can promote permanent settlement intentions among inter-provincial migrants compared with the effect on their intra-provincial counterparts. (4) Each factor has different effects on groups with the same settlement intention within and outside the province, as reflected in the varying impacts of educational level, marital status, income level, and migration reasons on inter- and intra-provincial floating populations. This study breaks through the traditional binary division model of settlement intentions, enhancing our understanding of floating populations through the "short-term residence–long-term residence–permanent settlement" categorization method. The Pearl River Delta region, one of the areas with the largest concentration of the floating population and the highest degree of economic development in China, serves as a critical case study. Understanding the flow and residence patterns of this population in this region will help government departments implement relevant policies and safeguarding measures tailored to different settlement intentions, thereby improving urban operational efficiency.

To enhance the reliability of Ti2AlNb alloys as an aerospace engine component in marine environments， the hot salt corrosion behavior of Ti2AlNb alloy with nominal compositions of Ti-22Al-23Nb-1Mo-1Zr（atom fraction/%） coated with Na2SO4/NaCl（95/5，mass ratio）at temperatures of 550， 650 ℃ and 750 ℃ was investigated.The corrosion mass gain curves of alloys at different temperatures were drawn. The surface morphologies， cross-section structures， and corrosion products of the alloy after hot salt corrosion were examined and analyzed by X-ray diffraction（XRD）， scanning electron microscopy（SEM）， and energy dispersive X-ray spectroscopy（EDS）. The results show that the corrosion rate at 550 ℃ is lower and the oxide scales are straight， dense and intact， exhibiting excellent resistance to hot salt corrosion. The corrosion mass gain curves of the alloy follow a parabolic law at 650℃ and the oxide scales exhibit small-scale peeling and internal cracks， with a slightly layered structure. The alloy exhibits good resistance to hot salt corrosion at 650 ℃ in general. A significant mass loss is observed during the corrosion process at 750 ℃， with the oxide scales cracking and peeling severely. Furthermore， within the oxide scales emerges a distinct layered structure where two layers of corrosion products alternately exist： the main layer is mainly composed of TiO2 and contains various corrosion products including NbAlO4， while the other layer is mainly composed of NaNbO3. The resistance to hot salt corrosion of the alloy decreases seriously at 750 ℃.