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Disrupted sleep has a profound adverse impact on lives of Parkinsons disease (PD) patients and their caregivers. Sleep disturbances are exceedingly common in PD, with substantial heterogeneity in type, timing, and severity. Among the most common sleep-related symptoms reported by PD patients are insomnia, excessive daytime sleepiness, and sleep fragmentation, characterized by interruptions and decreased continuity of sleep. Alterations in brain wave activity, as measured on the electroencephalogram (EEG), also occur in PD, with changes in the pattern and relative contributions of different frequency bands of the EEG spectrum to overall EEG activity in different vigilance states consistently observed. The mechanisms underlying these PD-associated sleep-wake abnormalities are poorly understood, and they are ineffectively treated by conventional PD therapies. To help fill this gap in knowledge, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. These sleep-wake abnormalities resemble those identified in PD patients. Thus, this model may help elucidate the circuit mechanisms underlying sleep disruption in PD and identify targets for novel therapeutic approaches.

BOUT++ turbulence simulations were performed to investigate the impact of turbulence spreading on the edge localized mode (ELM) size and divertor heat flux width $({\lambda _q})$ broadening in small ELM regimes. This study is motivated by EAST experiments. BOUT++ linear simulations of a pedestal radial electric field (Er) scan show that the dominant toroidal number mode (n) shifts from high-n to low-n, with a narrow mode spectrum, and the maximum linear growth rate increases as the pedestal Er well deepens. The nonlinear simulations show that as the net E × B pedestal flow increases, the pressure fluctuation level and its inward penetration beyond the top of the pedestal both increase. This leads to a transition from small ELMs to large ELMs. Both inward and outward turbulence spreading are sensitive to the scrape-off-layer (SOL) plasma profiles. The inward turbulence spreading increases for the steep SOL profiles, leading to increasing pedestal energy loss in the small ELM regime. The SOL width $({\lambda _q})$ is significantly broadened progressing from the ELM-free to small ELM regime, due to the onset of strong radial turbulent transport. The extent of the SOL width $({\lambda _q})$ broadening depends strongly on outward turbulence spreading. The fluctuation energy intensity flux ${\varGamma _\varepsilon }$ at the separatrix can be enhanced by increasing either pedestal Er flow shear or local SOL pressure gradient. The ${\lambda _q}$ is broadened as the fluctuation energy intensity flux ${\varGamma _\varepsilon }$ at the last close flux surface (LCFS) increases. Local SOL E × B flow shear will restrain outward turbulence spreading and the associated heat flux width broadening. Operating in H-mode with small ELMs has the potential to solve two critical problems: reducing the ELM size and broadening the SOL width.

Weimin Cai,1,* Xiao Wu,1,* Kun Guo,2 Yongxian Chen,3 Yubo Shi,4 Xinran Lin1 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Chest Cancer, Xiamen Second People’s Hospital, Xiamen, 36100, People’s Republic of China; 4Department of Pulmonary, Yueqing People’s Hospital, Wenzhou, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinran Lin, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86 18857838243, Fax +86 0576 87755312, Email lxr190910@163.comBackground: Accurate prediction of treatment response in Crohn’s disease (CD) patients undergoing infliximab (IFX) therapy is essential for clinical decision-making. Our goal was to compare the performance of the clinical characteristics, radiomics and deep learning model from computed tomography enterography (CTE) for identifying individuals at high risk of IFX treatment failure.Methods: This retrospective study enrolled 263 CD patients from three medical centers between 2017 and 2023 patients received CTE examinations within 1 month before IFX commencement. A training cohort was recruited from center 1 (n=166), while test cohort from centers 2 and 3 (n=97). The deep learning model and radiomics were constructed based on CTE images of lesion. The clinical model was developed using clinical characteristics. Two fusion methods were used to create fusion model: the feature-based early fusion model and the decision-based late fusion model. The performances of the predictive models were evaluated.Results: The early fusion model achieved the highest area under characteristics curve (AUC) (0.85– 0.91) among all patient cohorts, significantly outperforming deep learning model (AUC=0.72– 0.82, p=0.06– 0.03, Delong test) and radiomics model (AUC=0.72– 0.78, p=0.06– 0.01). Compared to early fusion model, the AUC values for the clinical and late fusion models were 0.71– 0.91 (p=0.01– 0.41), and 0.81– 0.88 (p=0.49– 0.37) in the test and training set, respectively. Moreover, the early fusion had the lowest value of Brier’s score 0.15– 0.12 in all patient set.Conclusion: The early fusion model, which integrates deep learning, radiomics, and clinical data, can be utilized to predict the response to IFX treatment in CD patients and illustrated clinical decision-making utility.Keywords: deep-learning, radiomics, Crohn’s disease, infliximab, prediction

Fu-Xing-Zi Li,1 Feng Xu,1 Chang-Chun Li,1 Li-Min Lei,1 Su-Kang Shan,1 Ming-Hui Zheng,1 Xiao Lin,2 Bei Guo,1 Ke-Xin Tang,1 Jia-Yue Duan,1 Yun-Yun Wu,1 Ye-Chi Cao,1 Jun-Jie Liu,3 Ling-Qing Yuan1 1Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Periodontal Division, Hunan Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ling-Qing Yuan, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email allenylq@csu.edu.cnPurpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4– 8°C) likely influences the organism’s blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM.Methods: The effects of CT (4– 8°C) or room temperature (RT, 22– 25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot.Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect.Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.Keywords: cold exposure, plasma-derived extracellular vesicles, type 2 diabetes, insulin sensitivity, β‑cell destruction

Jingling Lan, Xia Lin, Li Liu Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui City, Zhejiang Province, 323000, People’s Republic of ChinaCorrespondence: Li Liu, Department of Cardiothoracic surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, No. 289 Kuocang Road, Liandu District, Lishui City, Zhejiang Province, People’s Republic of China, Email longndj34@163.comObjective: This study aims to explore the influencing factors of cough after pulmonary resection (CAP) after thoracoscopic lung resection in lung cancer patients and to develop a predictive model.Methods: A total of 374 lung cancer patients who underwent lung resection in our hospital from March 2020 to October 2023 were randomly divided into a modeling group (n=262) and a validation group (n=112). Based on the occurrence of CAP in the modeling group, the patients were divided into a CAP group (n=85) and a non-CAP group (n=177). Multivariate Logistic regression analysis was used to identify the influencing factors of CAP in lung cancer patients. A nomogram model for predicting the risk of CAP was constructed using R4.3.1. The consistency of the model’s predictions was evaluated, and a clinical decision curve (DCA) was drawn to assess the clinical utility of the nomogram. The predictive performance of the model was evaluated using ROC curves and the Hosmer-Lemeshow test.Results: Multivariate Logistic regression analysis showed that smoking history (OR=6.285, 95% CI: 3.031– 13.036), preoperative respiratory function training (OR=20.293, 95% CI: 7.518– 54.779), surgical scope (OR=20.667, 95% CI: 7.734– 55.228), and peribronchial lymph node dissection (OR=5.883, 95% CI: 2.829– 12.235) were significant influencing factors of CAP in lung cancer patients (P< 0.05). ROC curves indicated good discriminatory power of the model, and the Hosmer-Lemeshow test showed a high degree of agreement between predicted and actual probabilities. The DCA curve revealed that the nomogram model had high clinical value when the high-risk threshold was between 0.08 and 0.98.Conclusion: The nomogram model based on smoking history, preoperative respiratory function training, surgical scope, and peribronchial lymph node dissection has high predictive performance for CAP in lung cancer patients. It is useful for clinical prediction, guiding preoperative preparation, and postoperative care.Keywords: lung cancer, thoracoscopic resection, persistent cough, influencing factors, prediction model

Jiahua Wu, Xihua Lin, Xueyao Yin, Zhiye Xu, Nan Wu, Ziyi Zhang, Jiaqiang Zhou,&ast; Hong Li&ast; Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Jiaqiang Zhou, Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of China, Email srrshnfm@zju.edu.cn; zjq8866@zju.edu.cnPurpose: Metabolic syndrome (MetS) is an increasingly prevalent issue in China’s public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province.Methods: This cohort study included 359 adults aged 40– 65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression.Results: In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals.Conclusion: The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.Keywords: metabolic syndrome, normal weight, overweight, WHtR, BMI, TyG

Ling Wang,1– 3,&ast; Fangqing Cai,3,&ast; Yixuan Li,3,&ast; Xiaolan Lin,3 Yuting Wang,3 Weijie Liang,3 Caiyu Liu,4 Cunze Wang,3 Junshan Ruan1– 3 1School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Molecular Biology Laboratory of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junshan Ruan, School of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, 134 Dongjie, Fuzhou, 350001, People’s Republic of China, Tel +86 591-88216343, Fax +86 591-87532356, Email ruanjunshan@163.comPurpose: Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC.Methods: In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEG-PBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic–hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated.Results: TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 μg/mL to more than 5 mg/mL. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity.Conclusion: In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.Keywords: renal cell carcinoma, drug delivery, pH-responsive, mPEG-PBAE, nanomicelles

Yunze Feng,1,&ast; Wencan Zhang,1,&ast; Kunpeng Li,1 Xiangyu Lin,1 Chen Liu,1 Chongyi Wang,1 Bingtao Hu,1 Kaibin Wang,1 Wanlong Xu,1 Haipeng Si1,2 1Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 2Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong, 266035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haipeng Si, Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong Universityl, Qingdao, Shandong, 266035, People’s Republic of China, Email sihaipeng1978@email.sdu.edu.cn Wanlong Xu, Department of Orthopedics Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email xuwanlong20082008@163.comPurpose: One-hole Split Endoscopy (OSE) is a newer surgical modality that can be applied to posterior cervical foraminotomy (PCF), lumbar discectomy, laminectomy, and decompression. It incorporates intervertebral foraminotomy, open surgery, and other lumboendoscopic techniques with a wide observation field, free space, and compatibility with various spinal surgical techniques and instruments. This study investigated the clinical efficacy of minimally invasive posterior cervical nucleus pulposus removal for cervical spondylotic radiculopathy (CSR) by OSE-Keyhole technique.Patients and Methods: This was a retrospective study of 63 patients treated with OSE keyhole treatment for CSR between May 2021 and September 2023 at Qilu Hospital of Shandong University, Qilu Hospital of Shandong University (Qingdao, China), and Second Hospital of Shandong University, respectively. Clinical outcomes included patients’ preoperative and postoperative visual analogue scale (VAS) - arm and neck, Japanese Orthopaedic Association Assessment Treatment Score (JOA) - cervical spine, which were collected at baseline, two days postoperatively, one month postoperatively, and three months postoperatively after the last follow-up visit for evaluation, and perioperative indicators, including intraoperative bleeding, length of hospital stay, postoperative complications, and reoperations, which were also collected.Results: Statistical analyses were performed for the baseline data and follow-up results of 63 patients. Compared to the preoperative baseline values, the follow-up results two days, one month and three months after surgery showed significant improvements in vas-arm, neck and JOA scores in the operated patients (P< 0.05) as well as a reduction in all perioperative-related indices.Conclusion: In the treatment of cervical pain and disability due to radiculopathy, OSE keyhole removal of the posterior cervical nucleus pulposus is a better clinical option as it is less invasive and recovers better postoperatively.Keywords: nerve root type cervical spondylosis, unilateral cervical disc herniation, posterior cervical laminectomy, single-channel endoscopy

Qianfeng Liu,&ast; Kangbi Wu, Xiaofang Lin, Kali Xiang,&ast; Jing Wang&ast; Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kali Xiang; Jing Wang, Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Avenue, Enshi City, Hubei, 445000, People’s Republic of China, Email xkl18963926688@163.com; 366413620@qq.comBackGround: Considerable studies have demonstrated a significant association between red blood cell distribution width (RDW) and clinical adverse events in cardiovascular or respiratory diseases, infections, and pulmonary embolism. However, there are limited data on prognostic predictions for patients suffering from chronic obstructive pulmonary disease (COPD).Methods: This study conducted a retrospective cohort analysis using data gathered from patients who diagnosed with COPD in the respiratory department of The Central hospital of Enshi Tujia and Miao Autonomous Prefecture between 2018 and 2021. Specifically, the RDW was recorded on their first admission. Multivariate logistic regression analysis were employed to examine the correlation between RDW and deterioration of COPD within one-year period.Results: The cohort of 1799 patients in the study comprised 74.7% male and had an average age of 68.9 ± 9.9 years. The fully adjusted model revealed that, the RDW-middle group (≤ 13.7,> 12.8; OR 1.5, 95% CI 1.0– 2.3, p=0.055) and the RDW-high group (> 13.7; OR 1.7, 95% CI 1.1– 2.6, p=0.013) had a 50% and 70% increased risk of deterioration within 1 year, respectively, in comparison with the RDW-low group (≤ 12.8). Subgroup analysis indicated that this trend was more significant in patients with hypertension (p for interaction = 0.016), and the probability of deterioration within 1 year in the RDW-high group was 3.3 times higher compared to the RDW-low group (OR 3.3, 95% CI 1.4– 7.9, p=0.008).Conclusion: A significant association was observed between the increase in RDW and the heightened risk of deterioration within a year in patients diagnosed with COPD. Most importantly, our findings suggested the importance of RDW in enhancing the risk stratification and prevention of deterioration of COPD.Keywords: red blood cell distribution width, COPD, prognosis, deterioration, risk stratification

Ran Zhang,1,2 Ya-Jie Lei,1,2 Sheng-Yue Wen,1,2 Jian Pang,1,2 Yue-Long Cao,1,2 Min Zhang,1,2 Hong-Sheng Zhan,1,2 Xun Lin,3 Bo Chen1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Orthopedics and Traumatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bo Chen; Xun Lin, Tel +86-21-20256519, Email cbm818@shutcm.edu.cn; linxund@163.comPurpose: To prove more accurately that Chinese herbal bath therapy may be a safe, effective, simple alternative treatment modality for knee OA, we designed a randomized, double-blind, placebo-controlled trial to explore the effectiveness of SSBD for the relief of pain, daily activities, and quality of life in patients with knee OA.Patients and Methods: A single-center, 52-week, randomized controlled trial of SSBD versus placebo is being performed. A total of 200 patients with symptomatic knee OA will be randomly allocated to the SSBD treatment or placebo intervention group for 4 weeks. The two groups of patients are allowed to steam and bathe their knees once every other day, using one packet of SSBD each time, for 30 minutes, 3 times a week, for a total of 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at 4 weeks is the primary outcome measure, and the secondary outcomes include WOMAC stiffness and function scores, the Lysholm knee scale score, quality of life, the Brief Pain Inventory score, the Patient’s Global Impressions of Improvement Scale score and the Clinical Global Impressions of Severity scale score. The safety of the herbal medications will also be evaluated.Conclusion: We will discuss whether SSBD has greater advantages in terms of efficacy, safety, and patient overall perception than does placebo control in middle-aged and elderly patients with knee OA. The findings may provide new and valuable information about the efficacy and safety of Chinese herbal bath therapy in the treatment of knee osteoarthritis.Keywords: balneotherapy, traditional Chinese medicine, complementary and integrative medicine, randomized placebo-controlled trial, knee osteoarthritis

Chi Zhou,1,&ast; Xu Li,1,&ast; Wenli Shen,2 Qunfang Huang,1 Xiaoling Lin,1 Gaofeng Zhang,3 Yin Dong3,4 1Department of Health Management, School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Health Development, Hangzhou Xixi Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3The People’s Hospital of Yuhuan, Taizhou, Zhejiang, People’s Republic of China; 4Vanke School of Public Health, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yin Dong, The People’s Hospital of Yuhuan, No. 18 Changle Road, Yucheng Street, Yuhuan, Taizhou, 317600, People’s Republic of China, Tel +86-18957678008, Email 9597082@qq.comBackground: The responsiveness of community health centers can reflect the soft capacity of medical institutions and is related to the improvement of health outcome indicators. This study is aimed at assessing the level and distribution of community health centers’ responsiveness and its associated factors among outpatients under the health-oriented integrated healthcare system in China.Methods: A total of 634 outpatients were recruited from six community health centers in Zhejiang Province, China, in July 2022. SPSS software was used to conduct the analysis (version 23.0). Health system responsiveness was used as a measure of outpatient responsiveness to health care services through a self-administered questionnaire. Determinants of community health centers’ responsiveness were determined by using a multiple linear regression model at a p-value < 0.05.Results: The total score of community health centers responsiveness was 8.25± 1.01, and the Gini coefficient is 0.027. Within these domains, social support and dignity received the highest scores, while choice of providers and autonomy scored the lowest. Age group between 60– 74 years (β: 0.129; 95% CI: 0.042– 0.529), ≥ 75 years (β: 0.095; 95% CI: 0.006– 0.707), monthly income with 8000 RMB and above (β: 0.098; 95% CI: 0.035– 0.653), having a family doctor (β: 0.124; 95% CI: 0.096– 0.410), and satisficing with community health service (β: 0.298; 95% CI: 0.848– 1.428) were significant predictors of community health centers’ responsiveness.Conclusion: The Chinese community health centers show high responsiveness, indicating that the construction of a health-oriented integrated healthcare system has been effective. The family doctor contract service is important and should continually enhance both technical proficiency and health promotion capabilities. Encourage residents to actively participate in their treatment process is also essential.Keywords: responsiveness, community health center, outpatient

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

Ruijie Zhang,1,&ast; Xinran Dong,2,&ast; Lu Zhang,1,&ast; Xinao Lin,1 Xuefeng Wang,1 Yan Xu,3 Chuyan Wu,4 Feng Jiang,1 Jimei Wang1 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Center for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Neurology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jimei Wang; Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email wjm821920@163.com; dxyjiang@163.comBackground: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age.Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37– 42 weeks, within 1– 7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age.Results: The alpha frequency band’s spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency’s spectral_diff_C4 was the most effective, whereas the delta frequency’s spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA).Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.Keywords: quantitative EEG, neonates, sleep, postmenstrual age

Wentao Luo,1 Xiuwen Lin,1 Yuchong Chen,2 Wenfeng Luo,3 Huagen Zhang1 1The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China; 2The Fourth Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000 People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of ChinaCorrespondence: Huagen Zhang, The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China, Tel +8613549175546, Email 672825592@qq.comBackground: Metagenomic next-generation sequencing (mNGS) is a high-throughput sequencing technique that identifies a wide array of pathogens directly from clinical specimens. This study evaluates the diagnostic value of mNGS in Pneumocystis jirovecii pneumonia (PJP) and compares its efficacy with traditional detection methods, including Grocott’s Methenamine Silver (GMS) staining, serum (1– 3)-β-D-Glucan (BDG) testing, and Lactate Dehydrogenase (LDH) testing.Methods: Seventy-eight patients hospitalized between January 2022 and March 2023 with suspected pulmonary infections were included. Patients were eligible for mNGS if they exhibited symptoms such as fever, cough, dyspnea, or progressive hypoxemia, and met specific clinical criteria for PJP. Specimens obtained included bronchoalveolar lavage fluid, sputum, and peripheral blood. Positive rates and pathogen distributions detected by mNGS and traditional methods were compared.Results: In the PJP group, 25%, 37.5%, and 9.38% of patients had solid organ tumors, corticosteroid use, and skin diseases, respectively, significantly higher than in the non-PJP group. The sensitivity and specificity of mNGS were both 100%, significantly higher than those of serum BDG (sensitivity 50%, specificity 81.8%) and LDH (sensitivity 9.3%, specificity 91.3%). Significant differences in microbial composition between the PJP and Non-PJP groups were observed. mNGS detected multiple mixed pathogens in 96.88% of PJP cases, with 68.75% exhibiting mixed bacterial and viral infections. Notably, 71% of patients improved following antibacterial treatment based on mNGS results.Conclusion: mNGS technology shows superior sensitivity and specificity in diagnosing PJP and guides precise treatment for complex pulmonary infections.Keywords: mNGS, Pneumocystis jirovecii pneumonia, pulmonary infections, dominant pathogens, sensitivity

Weimin Cai,1 Xiao Wu,1 Yongxian Chen,2 Junkai Chen,3 Xinran Lin1 1Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Respiratory, Xiamen Second hospital, Xiamen, People’s Republic of China; 3Department of Emergency, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, People’s Republic of ChinaCorrespondence: Xinran Lin, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86 18857838243, Email lxr190910@163.comObjective: This study aimed to identify the risk factors and construct a reliable prediction model of 28-day all-cause mortality in critically ill patients with acute pancreatitis (AP) using machine learning techniques.Methods: A total of 534 patients from three different institutions were included. Thirty-eight possible variables were collected from the Intensive care unit (ICU) admission for investigation. Patients were split into a training cohort (n = 400) and test cohort (n = 134) according to their source of hospital. The synthetic minority oversampling technique (SMOTE) was introduced to handle the inherent class imbalance. Six machine learning algorithms were applied in this study. The optimal machine learning model was chosen after patients in the test cohort were selected to validate the models. SHapley Additive exPlanation (SHAP) analysis was performed to rank the importance of variable. The predictive performance of the models was evaluated by the calibration curve, area under the receiver operating characteristics curves (AUROC), and decision clinical analysis.Results: About 13.5% (72/534) of all patients eventually died of all-cause within 28 days of ICU admission. Eight important variables were screened out, including white blood cell count, platelets, body temperature, age, blood urea nitrogen, red blood cell distribution width, SpO2, and hemoglobin. The support vector machine (SVM) algorithm performed best in predicting 28-d all-cause death. Its AUROC reached 0.877 (95% CI: 0.809 to 0.927, p < 0.001), the Youden index was 0.634 (95% CI: 0.459 to 0.717). Based on the risk stratification system, the difference between the high-risk and low-risk groups was significantly different.Conclusion: In conclusion, this study developed and validated SVM model, which better predicted 28-d all-cause mortality in critically ill patients with AP. In the future, we will continue to include patients from more institutions to conduct validation in different contexts and countries.Keywords: all-cause mortality, machine learning, acute pancreatitis, prognosis, predict

Lan Hong,1,&ast; Huihui Xu,2,&ast; Jiaqi Zheng,2 Xiujian Lin,2 Lijun Wang,2 Chengjia Zhao,3 Xiaolian Tu,4 Jingjing Zhang,5 Ke Zhao,1,6 Guohua Zhang6,7,&ast; 1Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Education, Renmin University of China, Beijing, 100872, People’s Republic of China; 4School of Renji, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5School of Nursing, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Institute Of Aging, Key Laboratory Of Alzheimer’s Disease Of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Zhang, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email zghcnu@wmu.edu.cn Ke Zhao, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China, Email cocozk1986@163.comBackground: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05– 1.12), more depression (OR: 1.17; 95% CI = 1.06– 1.29) and anxiety (OR: 1.16; 95% CI = 1.05– 1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12– 1.19), anxiety (OR: 1.10; 95% CI = 1.06– 1.14), and depression (OR: 1.10; 95% CI = 1.06– 1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.Keywords: bedtime procrastination, latent profile analysis, latent transition analysis, problematic smartphone use, depression, anxiety, self-control

Yuelin Zhang, Xue Lin, Xinxin Chen, Weixiang Fang, Kailing Yu, Wenting Gu, Yinghui Wei, Hangsheng Zheng, Jigang Piao, Fanzhu Li School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Fanzhu Li; Ji-Gang Piao, Email lifanzhu@zcmu.edu.cn; jgpiao@zcmu.edu.cnAbstract: Mesoporous silica nanoparticles (MSNs) have attracted extensive attention as drug delivery systems because of their unique meso-structural features (high specific surface area, large pore volume, and tunable pore structure), easily modified surface, high drug-loading capacity, and sustained-release profiles. However, the enduring and non-specific enrichment of MSNs in healthy tissues may lead to toxicity due to their slow degradability and hinder their clinical application. The emergence of degradable MSNs provided a solution to this problem. The understanding of strategies to regulate degradation and clearance of these MSNs for promoting clinical trials and expanding their biological applications is essential. Here, a diverse variety of degradable MSNs regarding considerations of physiochemical properties and doping strategies of degradation, the biodistribution of MSNs in vivo, internal clearance mechanism, and adjusting physical parameters of clearance are highlighted. Finally, an overview of these degradable and clearable MSNs strategies for biosafety is provided along with an outlook of the encountered challenges. Keywords: mesoporous silica nanoparticles, degradation, clearance, biodistribution, strategies

Qing Lin,1,2,&ast; Yafei Jing,2,3,&ast; Cailing Yan,2 Xinyi Chen,2 Qiong Zhang,2 Xinhua Lin,2,3 Yunlu Xu,2,4 Bing Chen2,3 1Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Pharmacy, Fujian Medical University, Fujian, People’s Republic of China; 3Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Chen, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email BingChen_001@126.com; BingChen_001@fjmu.edu.cn Yunlu Xu, Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email xuyunlu3578@126.comBackground: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.Methods: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.Results: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78± 1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78± 5.93%).Conclusion: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.Keywords: cobra venom cytotoxin, tumor microenvironment, pH-responsive, targeted delivery, liposomes

Yonggui Zhang,1 Xianzhong Lin,2 Chen Ye,2 Peiling Zhang3 1Department of Anesthesiology, The Second Hospital of Longyan, Fujian, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of ChinaCorrespondence: Xianzhong Lin, Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, People’s Republic of China, Email lxzyjs@fjmu.edu.cnBackground: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms.Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment.Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05).Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.Keywords: amnesic mild cognitive impairment, hyperbaric oxygen, apoptosis, learning and memory impairment

Suling Chen,1,&ast; Yuanhui Jiang,1,&ast; Xiaoli Lin,1,&ast; Hongjie Chen,1 Xiaoxuan Wu,2 Zhe Qian,3 Xuwen Xu,1 Huiqun Zhong,1 Jie Peng,1 Shaohang Cai1 1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Communicable and Endemic Disease Control and Prevention, Haizhu District Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 3Second Department of Elderly Respiratory, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqun Zhong; Jie Peng, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email lovely870821@163.com; pjie138@163.comPurpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH.Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS.Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P

Kun Ye,1 Xiang Lin,2 Tai-Zhi Chen,2 Long-Hui Wang,2 Sheng-Xing Liu2 1Department of Orthopaedics, Qiantang Campus of Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310018, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of ChinaCorrespondence: Sheng-Xing Liu, Email liushx6688@163.comPurpose: This study aimed to explore the therapeutic effect and potential mechanism of heparin-binding protein (HBP) reduction on sepsis-related acute lung injury.Methods: We utilized a murine model of sepsis-induced by intraperitoneal injection of lipopolysaccharides (LPS) in C57BL/6J mice divided into four groups: Control, LPS, Anti-HBP, and ceftriaxone (CEF). Following sepsis induction, Anti-HBP or CEF treatments were administered, and survival rates were monitored for 48 h. We then used reverse-transcription quantitative PCR to analyze the expression levels of HBP in lung tissues, immunohistochemistry for protein localization, and Western blotting for protein quantification. Pulmonary inflammation was assessed using enzyme-linked immunosorbent assays of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and interferon-γ). The activation state of the aryl hydrocarbon receptor (AhR) signaling pathway was determined via Western blotting, evaluating both cytoplasmic and nuclear localization of AhR and the expression of cytochrome P450 1A1 protein by its target gene.Results: Anti-HBP specifically reduced HBP levels. The survival rate of mice in the Anti-HBP and CEF groups was much higher than that in the LPS group. The severity of lung injury and pulmonary inflammatory response in the Anti-HBP and CEF groups was significantly lower than that in the LPS group. AhR signaling pathway activation was observed in the Anti-HBP and CEF groups. Additionally, there was no significant difference in the above indices between the Anti-HBP and CEF groups.Conclusion: HBP downregulation in lung tissues significantly improved LPS-induced lung injury and the pulmonary inflammatory response, thereby prolonging the survival of sepsis mice, suggesting activation of the AhR signaling pathway. Moreover, the effect of lowering the HBP level was equivalent to that of the classical antibiotic CEF.Trial Registration: Not applicable.Keywords: sepsis, acute lung injury, heparin-binding protein, aryl hydrocarbon receptor signaling pathway

Guizhong Huang,1,&ast; Pu Xi,1,&ast; Zehui Yao,1,&ast; Chongyu Zhao,2,&ast; Xiaohui Li,1 Zexian Chen,3 Xiaojun Lin1 1Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 3Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Lin, Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Tel +8620-8734-1639, Email linxj@sysucc.org.cnBackground: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection.Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes.Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19– 9 (CA19-9) levels, and postoperative adjuvant therapy.Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.Keywords: locally advanced intrahepatic cholangiocarcinoma, inflammation, nutrition, competing risk analysis, propensity matching analysis

Ruiwei Guo,1,2 Jin Wu,1,2 Yanmin Zheng,1,2 Xiaona Lin,1,2 Zelin Zhuang,1,2 Jingjing Yin,1,2 Zhirong Lin,1 Lei Xie,1,2 Shuhua Ma1,2 1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Laboratory of Medical Molecular Imaging, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Shuhua Ma; Lei Xie, Email shuhua6633@163.com; 13lxie1@stu.edu.cnBackground: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood.Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison.Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT.Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.Keywords: inflammatory bowel disease, graph theory, visuospatial working memory, cognitive impairment, mental rotation task

Jincheng Ma,1– 3,&ast; Jiansong Lin,4,&ast; Xite Lin,1– 3 Yuan Ren,1– 3 Dabin Liu,5 Shuting Tang,1– 3 Leyi Huang,1– 3 Shuxia Xu,4 Xiaodan Mao,1– 3 Pengming Sun1– 3,5 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian Province, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Gynecology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Mao; PengMing Sun, Email maodan1985@fjmu.edu.cn; sunfemy@hotmail.comObjective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation.Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC.Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d.Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.Keywords: endometrial cancer, mismatch repair-deficiency, immune, molecular classification, MutL, MutS

Zetan Chen,1,2 Gang Wu,2 Xiangying Lin,2 Xiaopeng Huang,2 Shuai Zhang,2 Kaihua Chen,1 Zhongguo Liang,1 Xiaodong Zhu1,3,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-13978873616, Email zhuxdonggxmu@126.comPurpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC).Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors.Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis.Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.Keywords: serum sialic acid, nasopharyngeal carcinoma, prognosis, propensity score matching