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Yan Wang,1– 4,* He Zhao,2– 4,* Kun Zhao,1– 4,* Huhuifen He,1– 4,* Xinyu Li,5 Jingjing Qiu,2– 4 Limei Cui,2– 4 Liang Chen,2– 4 Wenjing Shang,6,7 Yan Sun2– 4 1The Second Medical College, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Otolaryngology and Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China; 5The First Medical College, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 6Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 7Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Sun; Wenjing Shang, Email entsunyan@126.com; wenjshang@bzmc.edu.cnIntroduction: Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality.Methods: Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL.Results: Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL.Discussion: This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research.Keywords: CRP, TNF-α, chronic inflammation, age-related hearing loss, Mendelian randomization

Qingpeng Xie,1,2,* Jiawen Gu,1,2,* Yujia Sun,3 Jinjia Hong,1,2 Jia Wang,1,2 Na Li,1,2 Yuan Zhang,1,2 Meixian Liu,1,2 Xiaoxuan Zhang,1,2 Xiangyu Zhao,1,2 Xiaohang Chen,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China; 3Nursing College of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohang Chen; Xing Wang, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China, Tel +8618834896163 ; +8613934224604, Email kqyx__cxh@163.com; wangxing@sxmu.edu.cnPurpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state. Keywords: ginger exosome-like nanoparticles, periodontitis, tissue repair, oxidative stress, periodontal ligament fibroblasts

Fanfan Wang,1,2 Jian Liu,1,2 Yanyan Fang,1,3 Yue Sun,2 Mingyu He1,2 1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Department of Rheumatism Immunity, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Department of Clinical Data Center, The first Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Jian Liu, The first Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China, Email liujianahzy@126.comObjective: The present study aimed to investigate the potential association between the treatment with Xinfeng Capsule (XFC) and the risk of readmission among patients with rheumatoid arthritis (RA).Methods: Through a retrospective approach, data were collected from all hospitalized patients diagnosed with RA at the First Affiliated Hospital of Anhui University of Chinese Medicine between 2013 and 2021. To mitigate selection bias and confounding factors, patients were stratified into an XFC group and a Non-XFC (Non-XFC) group based on their treatment status using propensity score matching with a 1:2 ratio. Variables such as age, gender, and baseline medications were adjusted. Subsequently, the Cox proportional hazards model was employed to calculate the hazard ratio (HR) for readmission among RA patients, while Kaplan-Meier curves were utilized to depict the incidence of readmission.Results: A total of 9987 RA patients were included in this study. Following rigorous inclusion/exclusion criteria and propensity score matching, the XFC group comprised 2036 patients, while the Non-XFC group contained 4072 patients. The Cox proportional hazards model analysis revealed that XFC acted as a protective factor, significantly reducing the risk of readmission among RA patients. Further examination of Kaplan-Meier curves demonstrated that XFC use not only effectively lowered the frequency of readmissions but also exhibited a more pronounced effect in diminishing the risk of readmission with extended usage durations (beyond 12 months). Additionally, association rule analysis underscored the strong link between XFC and freedom from readmission, as well as the robust correlation between XFC usage and significant improvements in multiple laboratory indicators, including C3, C4, CRP, ESR, and others.Conclusion: This study underscores a robust and long-term association between XFC usage and lower readmission rates among RA patients. As a protective factor against readmission risk in these patients, the clinical value of XFC merits further promotion and investigation.Keywords: rheumatoid arthritis, readmission, cohort study, xinfeng capsule

Yu Sun,1 Zhaoyong Li,1 Jiahao Duan,1 Enxu Liu,1 Fei Sun,1 Lei Yang,2 Long Chen,2 Shaofeng Yang2 1Graduate School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Shaofeng Yang, Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, No. 300 Xue-Shi Road, Yuelu District, Changsha, 410007, Hunan, People’s Republic of China, Tel +86 18391076233, Email a18391076233@163.comAbstract: The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.Keywords: intervertebral disc degeneration, microbiome, inflammation, immunity, metabolism

Yihong Tian,1,2,&ast; Yanyue Tan,3,&ast; Ming Yang,1 Xiayang Lv,3 Yunhao Zheng,1 Qiang Zhang,4 Yanyu Sun,1 Jun Wang,1,2 Xin Xiong1,2 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Orthodontics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Email wangjunv@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aimed to thoroughly explore the relationship between individual oral behavior and the differing numbers of temporomandibular disorder (TMD) symptom in the general population.Methods: A total of 565 participants were recruited and completed a questionnaire containing demographic characteristics, eight specific oral behaviors, and five major TMD symptoms (5Ts) checklist. Multivariate linear regression analysis was performed to assess the relationship between individual oral behavior and the number of TMD symptoms, after controlling for confounders.Results: The prevalence of TMD symptoms was up to 38.2% in the general population, with 64.6% of the participants engaging in one or more oral behaviors. Female participants showed a stronger positive association with most oral behaviors than males. Moreover, wake oral behaviors exhibited a higher correlation coefficient value with TMD symptom number than sleep oral behaviors. Among the eight oral behaviors, bruxism in sleep exhibited no significant correlation with the of TMD symptom number (P> 0.05). Seven other specific oral behaviors were significantly correlated with the number of TMD symptoms by multivariate linear regression analysis (P< 0.01). The associations between the seven oral behaviors and TMD symptom number remained significant in sleep posture pressuring jaw (β: 0.165, 95% CI: 0.080– 0.250), bruxism in awake (β: 0.341, 95% CI: 0.132– 0.550), teeth clenching (β: 0.422, 95% CI: 0.264– 0.580), pressing, holding, or touching teeth together (β: 0.282, 95% CI: 0.169– 0.395), holding or tightening muscles without clenching (β: 0.447, 95% CI0.304– 0.589), holding jaw forward or to the side (β: 0.694, 95% CI0.526– 0.861), and holding jaw in rigid or tense position (β: 0.571, 95% CI0.418, 0.724) after adjustment for demographic factors (P< 0.01).Conclusion: There was a positive association between seven specific oral behaviors and TMD symptom number. Individuals with higher frequency of specific oral behaviors are more likely to suffer from more TMD symptoms. Sleep bruxism exhibited no association with TMD symptoms and symptom number.Keywords: oral behaviors, temporomandibular disorders, TMD symptom number, cross-sectional study

Ying Zhang,1,&ast; Ziyun Shi,2,&ast; Haixia Liang,1 Meixia Chen,1 Yan Sun,1 Fujun Shang,3 Yi Wan4 1Department of Obstetrics and Gynecology, Xijing 986 hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Obstetrics, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Cardiology, Xi’an Gem Flower Changqing Hospital, Xi’an, Shaanxi, People’s Republic of China; 4Department of Health Service, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wan, Department of Health Service, Fourth Military Medical University, No. 169 Changle Xilu, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84712676, Email wanyi@fmmu.edu.cn Fujun Shang, Department of Cardiology, Xi’an Gem Flower Changqing Hospital, Xi’an, Shaanxi, 710201, People’s Republic of China, Tel/Fax +86-29-86022756, Email shangfujun4@163.comObjective: Validation of blood pressure (BP) monitors in pregnant women are needed to ensure the accurate measurement of BP in pregnancy. Therefore the study aimed to evaluate the measurement accuracy of the G.LAB MD41A0 oscillometric automatic upper-arm blood pressure monitor in pregnancy and pre-eclampsia women according to the AAMI/ESH/ISO Universal Standard (ISO 81060– 2:2018).Methods: A total of 45 pregnant women were included in the cross-sectional validation study. The same left-arm sequential method was used for blood pressure measurement, and the blood pressure differences between the test device and the mercury standard reference were assessed according to the AAMI/ESH/ISO Universal Standard.Results: The participants included 15 normotensives, 15 gestational hypertension and 15 pre-eclampsia. The average (mean ± SD) differences between the device and mercury standard was − 0.84± 3.88 mmHg and − 0.58± 3.35 mmHg for systolic and diastolic blood pressure, respectively, for the validation Criterion 1. The SD of the averaged differences between the device and reference readings per participant was 2.92 mmHg and 2.28 mmHg for systolic and diastolic blood pressure, respectively, for the Criterion 2 of the universal standard.Conclusion: The G.LAB MD41A0 automatic upper-arm blood pressure monitor fulfills the criteria of the AAMI/ESH/ISO Universal Standard and can be recommended for clinical use and self-measurement in pregnancy and pre-eclampsia.Keywords: blood pressure monitor, validation, universal standard, pregnancy, pre-eclampsia

Xiaosu Guo,1– 4,&ast; Huimin Shi,1,2,&ast; Yuteng Sun,1 Yuan Xing,1– 3 Xin Guo,1– 3 Zhiyuan Shen,1– 3 Mengyi Zheng,1 Yaxin Zhang,1 Yicun Jia,1 Ye Li,1 Junqiang Bao,1,2 Shujuan Tian1– 3 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei Hospital, Xuanwu Hospital, Capital Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 4Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shujuan Tian; Junqiang Bao, Department of Neurology, The First hospital of Hebei Medical University, Shijiazhuang, Hebei, 050030, People’s Republic of China, Tel +86-0311-87156309, Email 57203005@hebmu.edu.cn; 57903004@hebmu.edu.cnPurpose: To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features.Patients and Methods: We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals.Results: Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients.Conclusion: Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.Keywords: anti-LGI1 antibody encephalitis, epilepsy, electroencephalogram, brain network functional connectivity, immunotherapy

Xingxing Zhu,1,&ast; Jialu Chen,2,&ast; Shengjie Wu,3 Jiling Zeng,4 Yahong Sun,1 Xiaohong Wu5 1Department of Pulmonary and Critical Care Medicine, Haining People’s Hospital, Haining, People’s Republic of China; 2Department of Gynaecology, Haining Maternal and Child Health Hospital, Haining, People’s Republic of China; 3Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Wu, Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310000, People’s Republic of China, Tel +86 13588706901, Email 3192018@zju.edu.cnBackground: The incidence of community-acquired empyema caused by the Streptococcus anginosus group (SAG) has been on the rise in the 2020s. To the best of our knowledge, while empyema caused individually by either strain has been reported, there are no reports on empyema caused by concurrent infection with these two strains. Here, we report for the first time empyema caused by concurrent infection with Streptococcus intermedius and Streptococcus constellatus (both SAG species) in a postoperative patient who had been treated for floor of the mouth carcinoma.Case Presentation: A 61-year-old male patient who had undergone surgical treatment for floor of the mouth carcinoma 2 year earlier suddenly presented with left-sided chest pain. Chest computed tomography (CT) revealed encapsulated pleural effusion on the left side, which was diagnosed as empyema. Metagenomic next-generation sequencing(mNGS) of the pleural fluid sample indicated mixed infection caused by Streptococcus intermedius and Streptococcus constellatus. The patient’s condition improved about 5 weeks after treatment with thoracic fluid drainage and cephalosporin antibiotics.Conclusion: This case highlights the possibility of concurrent infection with two SAG strains in patients with empyema. Currently, it is unclear whether there is a definitive relationship between a surgical history of carcinoma of the floor of the mouth and empyema caused by infection with SAG strains. This case could, perhaps, serve as a reference for future related research on the topic.Keywords: Streptococcus intermedius, Streptococcus constellatus, oral carcinoma, pleural effusion, carcinoma of the floor of the mouth, empyema

Yaxin Wang,1 Ziyang Wang,2 Yin Sun,1 Lin Yang,2 Liangkun Ma,1 Jiao Li,2 Suhan Zhang,1 Xuanjin Yang1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, PUMC Hospital, CAMS and PUMC, Beijing, People’s Republic of China; 2Institute of Medical Information/Medical Library, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100020, People’s Republic of ChinaCorrespondence: Yin Sun, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Email sunyin@pumch.cnObjective: The study aimed to obtain more evidence on the association of gestational weight gain and pre-pregnancy body mass index (BMI) with macrosomia.Methods: The data on 5409 live births delivered at Peking Union Medical College Hospital from July 2020 to June 2022 were collected. Group analyses were performed according to the presence or absence of macrosomia. Multivariable binary logistic regression and incidence heatmaps was used to analyze the related factors of macrosomia.Results: The following variables were significantly associated with macrosomia: overweight (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.62– 3.10), obesity (OR: 4.56, 95% CI: 2.93– 6.98), excessive gestational weight gain (OR: 2.39, 95% CI: 1.67– 3.43), gestational age at delivery at 39– 41 weeks (OR: 3.83, 95% CI: 2.56– 5.95), gestational age at delivery over 41 weeks (OR: 7.88, 95% CI: 4.37– 14.19), education level of junior college or below (OR: 1.95, 95% CI: 1.19– 3.09), and multipara (OR: 1.62, 95% CI: 1.09– 2.42). “v” represents the mean weekly weight gain during the second and third trimesters. A higher v value increased the risk of macrosomia by 2.6-fold (95% CI: 1.37– 4.89, P = 0.003). Compared to normal weight women, after adjustment for different pre-pregnancy BMI subgroups, overweight pregnant women had higher weekly weight gain in the second and third trimesters (OR: 4.57, 95% CI: 2.27– 9.10, P < 0.001). Obese pregnant women had higher average weekly weight gain during the second and third trimesters, and the OR value for macrosomia was 11.33 (95% CI: 4.95– 25.18, P < 0.001). To reduce the incidence of macrosomia in overweight pregnant women, v = 0.32 could be considered the critical threshold of average weekly weight gain in these women in the second and third trimesters of pregnancy.Conclusion: Pre-pregnancy BMI and weight gain during pregnancy are closely related to macrosomia. The introduction of average weekly weight gain values in the second and third trimesters of pregnancy probably help pregnant women minimizing adverse pregnancy-related outcomes.Plain Language Summary: What is already known about this topic?Pre-pregnancy BMI and GWG are both risk factors for macrosomia. It is very important to develop effective interventions based on pathogenic factors to promote the health of mothers and children. However, the threshold for maternal weight control in the second and third trimesters of pregnancy is unclear.What is added by this report?Our data suggest that the critical threshold of average weekly weight gain in overweight pregnant women during the second and third trimesters 0.32kg per week is beneficial to reduce the incidence of macrosomia.What are the implications for public health practice?The results of this study highlight the importance of weight management in women in the second and third trimesters, especially those who are overweight, and reasonable control of weight gain will contribute to maternal and fetal health.Keywords: pregnancy, pre-pregnancy BMI, gestational weight gain, macrosomia, critical threshold of weight gain

Tiansu Lv,1,2,&ast; Jie Tian,1,3,&ast; Yaohuan Sun,1,3 Yujuan Zhang,1,2 Fang Qi,1,2 Liulan Xiang,1,2 Yutian Cao,1,2 Wenhui Zhang,1,2 Jiaxuan Huai,1,2 Yinfeng Dong,4 Xiqiao Zhou1,2 1Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiqiao Zhou; Yinfeng Dong, Email zhouxiqiao@njucm.edu.cn; dongyf@njucm.edu.cnBackground: Metabolic Associated Fatty Liver Disease (MAFLD) poses a significant threat to human health, as it can result in hepatic fibrosis and potentially progress to cirrhosis, in addition to causing a range of extrahepatic complications. The early detection of MAFLD is crucial, particularly during the initial stages when the condition may be amenable to reversal and the body composition could be vital importance.Methods: Data from participants at the Jiangsu Province Hospital of Traditional Chinese Medicine, covering the period from January 1 to December 31, 2022, were collected and subsequently randomized into training and validation cohorts. Independent risk factors for MAFLD were identified using statistical methodologies in conjunction with clinical relevance, and these factors were ultimately utilized to develop the nomogram.Results: In the training cohort, there were 356 cases of MAFLD out of a total of 513 patients, representing 71.2%, while in the validation cohort, 161 cases of MAFLD were identified out of 220 patients, accounting for 73.2%. In terms of statistical outcomes and clinical relevance, we identified a total of 12 closely related or significant variables. To enhance our understanding of the critical role of body composition parameters in predicting the incidence of MAFLD, we developed two distinct nomograms, one of which included body composition data. Notably, the nomogram that incorporated body composition demonstrated superior predictive performance, as evidenced by a well-fitted calibration curve and a C-index of 0.893 (with a range of 0.8625 to 0.9242). Furthermore, the decision curve analysis indicated that utilizing the nomogram that included body composition would yield greater benefits.Conclusion: The nomogram serves as an effective tool for predicting MAFLD. Its utility in early risk identification of MAFLD is of significant importance, as it facilitates timely intervention and treatment for patients affected by this condition.Keywords: Metabolic Associated Fatty Liver Disease, Body Composition, Nomogram

Qiang Guo,1,&ast; Yang Xiao,2,&ast; Jing Chu,3 Yu Sun,2 Shaomei Li,3 Shihai Zhang1 1Department of Clinical Laboratory, Anhui Children’s Hospital, Hefei, People’s Republic of China; 2Xuhzou Medical University, Jiangsu, People’s Republic of China; 3Department of Pathology, Anhui Children’s Hospital, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihai Zhang, Department of Clinical Laboratory, Anhui Children’s Hospital, Wangjiang Road 39, Hefei, People’s Republic of China, Tel +86– 13856048692, Email zhangshihai888@126.comObjective: This study aims to identify differentially expressed genes (DEGs) in neuroblastoma (NB) through comprehensive bioinformatics analysis and machine learning techniques. We seek to elucidate these DEGs’ biological functions and associated signaling pathways. Furthermore, our objective extends to predicting upstream microRNAs (miRNAs) and relevant transcription factors of pivotal genes, with the ultimate goal of guiding clinical diagnostics and informing future treatment strategies for Neuroblastoma.Methods: In this study, we sourced datasets GSE49710 and TARGET from the GEO and UCSC-XENA databases, respectively. Differentially expressed genes (DEGs) were identified using the R language “limma” package. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs were conducted using the “clusterProfiler” package. We employed Weighted Gene Co-expression Network Analysis (WGCNA) to isolate the most significant modules associated with death and MYCN amplification, specifically MEpink and MEbrown modules. These modules were then cross-referenced with the DEGs for further GO and KEGG pathway analyses. LASSO regression analysis, facilitated by the “glmnet” package, was utilized to pinpoint three hub genes. We performed differential analysis on these genes and constructed Receiver Operating Characteristic (ROC) curves for disease diagnosis purposes. Immune infiltration analysis was conducted using the “GSVA” package’s ssGSEA function. Additionally, single-gene Gene Set Enrichment Analysis (GSEA) on the hub gene was carried out based on Reactome and KEGG databases. Upstream miRNA and transcription factors associated with the hub gene were predicted using RegNetwork, with visual representations created in Cytoscape. Furthermore, to validate the three identified markers in neuroblastoma tissues, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis was conducted.Results: We identified 483 differentially expressed genes (DEGs) in neuroblastoma. These genes predominantly function in protein translation, membrane composition, and RNA transcription regulation, and are implicated in multiple signaling pathways relevant to neurodegenerative diseases. Utilizing LASSO regression analysis, we pinpointed three hub genes: VGF, DGKD, and C19orf52. The Receiver Operating Characteristic (ROC) curve analysis yielded Area Under Curve (AUC) values of 0.751 and 0.722 for VGF, 0.79 and 0.656 for DGKD, and 0.8 and 0.753 for C19orf52, respectively. Our immune infiltration analysis revealed significant correlations among monocytes, follicular helper T cells, and CD4+ T cells. Notably, in the death group, we observed heightened infiltration levels of activated CD4+ T cells, macrophages, and Th2 cells. C19orf52 exhibited a close association with the infiltration of monocytes, CD4+ T cells, and Th2 cells, with P-values less than 0.05. Furthermore, qRT-PCR analysis corroborated the upregulation of VGF in neuroblastoma tissues, further validating our findings.Conclusion: The hub genes (VGF, DGKD, and C19orf52) of neuroblastoma are screened. VGF, one of the hub genes, may have a high diagnostic value and is involved in the immune cell infiltration in neuroblastoma tissue, which may be used as a biomarker for the diagnosis of neuroblastoma and provides a new direction for clinical prognosis prediction and management improvement. Keywords: neuroblastoma, WGCNA, LASSO regression, bioinformatics analysis

Ling Ding,1 Xuelian Ren,2 Yamei Sun,3 Chengjuan Yu,1 Ge Li,1 Chenggang Wang1 1School of Health, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Office of Academic Affairs, Heze University, Heze, Shandong, People’s Republic of China; 3Center for Mental Health Education, Heze University, Heze, Shandong, People’s Republic of ChinaCorrespondence: Chenggang Wang, Email wangchg1268@163.comObjective: Exploring the core and bridge nodes in problematic social network use and alexithymia among freshmen to provide a basis for understanding the relationship and interventions.Methods: A total of 4057 first-year students from four universities in Shandong Province were chosen and surveyed with the Problematic Mobile Social Media Use Assessment Questionnaire and the Toronto Alexithymia Scale (TAS). Network analysis was performed using R to estimate the connections between nodes. Centrality and predictability indicators were used to identify key nodes, with accuracy and stability validation techniques applied. Gender and residence differences in the network structure were also examined.Results: In the problematic social network use network, the nodes with the highest expected influence were P16 (excessive swiping) and P14 (lack of control over phone usage). In the problematic social network use-alexithymia network, cognitive failure had the highest strength (strength = 1.155) and centrality. Difficulty identifying feelings (bridgestrength = 0.32), externally oriented thoughts (bridgestrength = 0.24), and cognitive failure (bridgestrength = 0.19) were key bridge nodes. No significant differences were found in the network structure across gender and residence, though the network was tightly connected.Conclusion: Cognitive failure plays a central role in problematic social network use among freshmen. Difficulty identifying feelings, externally oriented thoughts, and cognitive failure are critical in linking problematic social network use with alexithymia. Plain Language Summary: In a study with over 4000 freshmen from four universities in Shandong Province, researchers examined the link between problematic social media use and alexithymia. The study used the method of network analysis to analyze data. The key findings were that “cognitive failure”—reduced mental processing due to excessive mobile use—is central to problematic social network use. The most significant issues identified were difficulty identifying feelings, engaging in externally oriented thinking, and cognitive failures. These factors are consistent across different genders and residences, indicating a common pattern among freshmen. The results suggest that interventions to reduce excessive social media use and improve emotional awareness should focus on these areas to help alleviate alexithymia symptoms and enhance student well-being.Keywords: problematic social network use, alexithymia, freshmen, network analysis

Yuyan Sun,1 Bing Lu,1 Yuanwen Hu,2 Yingqi Lv,3 Shao Zhong1 1Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 2Department of Gastroenterology, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 3Division of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.comAbstract: In recent years, pancreatogenic diabetes mellitus has garnered significant attention due to its high incidence, complications, and mortality rates. Glycemic variability (GV) can increase the risk of pancreatogenic diabetes mellitus and its associated complications; however, the precise mechanism remains unclear. The effective control of GV is crucial for preventing the onset of pancreatic diabetes mellitus and improving prognosis. Both diet and antidiabetic medications have substantial effects on GV. However, many patients are prescribed suboptimal or even harmful drugs. Therefore, to provide a comprehensive treatment basis for clinicians to prevent and treat pancreatogenic diabetes mellitus, this study aimed to elucidate the relationship between GV and pancreatogenic diabetes mellitus; investigate the potential mechanisms (such as oxidative stress, inflammatory response, insulin resistance, and lipid metabolism disorders); provide lifestyle guidance; and recommend drug selections to reduce the GV in patients with pancreatogenic diabetes mellitus. Keywords: pancreatogenic diabetes, glucose fluctuation, glycemic variability, therapy, antihyperglycemic drug

Yao Sun, Huiying Zhao, Youzhong An Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Huiying Zhao; Youzhong An, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email zhaohuiying109@sina.com; 2211110449@stu.pku.edu.cnAbstract: Guillain-Barré syndrome (GBS) stands out as the most prevalent and severe acute immune-mediated paralytic neuropathy. Approximately 30% of patients experience respiratory failure necessitating admission to the intensive care unit (ICU) and invasive mechanical ventilation. The management of diseases concomitant with acute respiratory distress syndrome (ARDS) poses significant challenges. This case report illustrates the swift development of ARDS in a patient with GBS, explores the utility of the biomarker neurofilament light chain, and highlights the unexpected advantages of proactive ARDS intervention.Keywords: Guillain-Barré syndrome, severe acute respiratory distress syndrome, case, ventilation

Zhihan Jiang,1,&ast; Yingying Dai,2,&ast; Jing Chang,2 Pingchao Xiang,3 Zhenyu Liang,4 Yan Yin,5 Yongchun Shen,6 Ruiying Wang,7 Bianba Qiongda,8 Hongling Chu,9 Nan Li,9 Xiaoyan Gai,1,10 Ying Liang,1,10 Yongchang Sun1,10 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, GuangZhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 9Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 10Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 13810964766 ; +86 13910979132, Fax +86 108 226 6989, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation.Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred.Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.Keywords: chronic obstructive pulmonary disease, COPD, pulmonary tuberculosis, tuberculosis-associated COPD, protocol

Juan Qiao,1,2 Shiwan Tao,2 Yurong Sun,3,4 Jiabo Shi,2,5 Yu Chen,2,5 Shui Tian,3,4 Zhijian Yao,2,5 Qing Lu3,4 1Department of Psychology, Xuzhou East Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 4Key Laboratory of Child Development and Learning Science, Ministry of Education, Nanjing, People’s Republic of China; 5Nanjing Brain Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhijian Yao, Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email zjyao@njmu.edu.cn Qing Lu, Email luq@seu.edu.cnBackground: γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC.Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features.Results: Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD.Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.Keywords: anxious depression, GABAA receptor, multi-locus genetic profile scores, dorsolateral prefrontal cortex, amygdala subregion

Guo-Hong Zhao,1 Jin-Da Wang,1 Mei-Rui Liu,2,3 Li-Jun Zhang,4 Yan Sun,5 Kai Cao6 1Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pulmonary Rehabilitation, Emergency General Hospital, Beijing, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, Hebei, People’s Republic of China; 4Department of Obstetrics and Gynecology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 5Department of Ophthalmology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 6Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Kai Cao, Email crcteam@163.comObjective: To explore the distribution and influence factors of non-invasive tear film break-up time (NIBUT) in children.Methods: This is a hospital-based cross-sectional study. Spherical equivalent error (SER) was measured with cycloplegia. NIBUT was measured by an ocular surface integrated analyzer.Results: A total of 1269 children (1269 eyes) were included in this study. Participants’ median age was 11 (range 6– 18) years. 47.1% (598/1269) of participants were boys. The median NIBUT of myopic children and non-myopic children were 9.9 seconds (s) (Inter-quartile range, IQR: 6.4 to 16.1) and 10.9 s (IQR: 8.8 to 17.9), respectively, which was statistically significant (p = 0.004). In myopic children, 49.9% (573/1148) were able to achieve NIBUT of 10 s or more, compared to 67.8% (82/121) in non-myopic children, which was statistically significant (p < 0.001). There were 41 (3.57%) children in the myopic group and none (0%) in the non-myopic group with dry eye disease (p = 0.028). There was a positive correlation between NIBUT and age: NIBUT = 9.256 + 0.352&ast;Age. 71.8% (824/1148) of myopic children used electronic products almost every day, compared to 37.2% (45/121) of non-myopic children, which was statistically significant (p < 0.001).Conclusion: The NIBUT of myopic children was significantly shorter than that of non-myopic children. Children with myopia are more likely to have dry eyes. NIBUT increases with age. High frequency of electronic product use may be an important cause to NIBUT shortening in children.Keywords: Tear film break-up time, dry eye, Myopia, ocular surface, children

Fang Fang,1,&ast; Yun Yan Chen,1,&ast; Xin-Ming Zhang,2 Jin Tang,1 Yu-Hao Liu,1 Chen-Shuo Peng,1 Yu Sun1,3 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2School of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241002, People’s Republic of China; 3Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932026, Email whsunyu@163.comBackground: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy. Keywords: Chemo-photothermal therapy, Targeted cancer therapy, Nanoparticles, Cetuximab, Indocyanine green

Jing Han Yang,1,&ast; Ye Sun,1,&ast; Yi Ran Yang,1 Ling Na Qi,1 Wan Yao Li,1 Xiang Zheng Qin2 1School of Medicine, Yanbian University, Yanji City, Jilin Province, 136200, People’s Republic of China; 2Department of Human Histology and Anatomy, Yanbian University, Yanji City, Jilin Province, 136200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Zheng Qin, Department of Human Histology and Anatomy, Yanbian University, Park Street, Yanji City, Jilin Province, 136200, People’s Republic of China, Email 0000003978@ybu.edu.cnAbstract: Now, the erector spinae plane block (ESPB) is widely used in various thoracolumbar surgeries. It has unique advantages: simple and convenient operation, low safety risks, and reduced opioid use. The ESPB is used in thoracic surgery, abdominal surgery, and spinal surgery. There are also relevant research reports on postoperative analgesia during general anesthesia surgery. This article searches the PubMed and Web of Science databases to find and screen relevant studies on ESPB since 2019 and retrospectively summarizes the current indications of ESPB. The methodological quality of the included studies was assessed using the Cochrane bias risk tool. The results showed that the current research on ESPB generally provides low-level clinical evidence. The complex anatomy of the erector spinae muscles is both responsible for its unique advantages and restricts its development. Few anatomical studies have clearly and completely demonstrated the diffusion relationship of local anesthetics among the anatomical structures of the erector spinal muscles. The uncontrollability of the diffusion plane prevents ESPB from being applied on a wider scale with a high level of evidence. To further clarify the scope of application of ESPB and achieve the best analgesic effect, in the future, we should focus on the unique anatomical course and distribution of the erector spinal muscles and their fascia and nerves. It is necessary to combine anatomical, imaging, and histological methods to obtain high-quality evidence to guide clinical application.Keywords: erector spinae plane block, fascial plane block, anatomy, regional anesthesia, pain, nerve block

Xingyuan Gao,1,2 Man Yu,3 Yuyang Sun,3 Tiansi Zhang,1 Xin Li,1,3,4 Lingli Zhang,5 Changqing Wang1 1School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China; 2Simcere Zaiming Pharmaceutical Co., Ltd., Nanjing, People’s Republic of China; 3School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 4Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, People’s Republic of ChinaCorrespondence: Changqing Wang, School of Health Policy and Management, Nanjing Medical University, Jiangning District, Nanjing, 211166, People’s Republic of China, Email cqwang@njmu.edu.cn Lingli Zhang, School of International Pharmaceutical Business, China Pharmaceutical University, Jiangning District, Nanjing, 211198, People’s Republic of China, Email zhanglingli@cpu.edu.cnPurpose: The increasing global burden of cancer has become a significant challenge for public health. The Chinese government introduced the National Drug Price Negotiation (NDPN) policy with the goal of lowering the prices of innovative drugs and enhancing their accessibility. This study aims to evaluate the impact of the 2021 NDPN policy on the availability, utilization, and cost of anticancer medicines in China.Methods: Data was gathered from 1519 hospitals between April 2021 and December 2022, with a focus on eight anticancer drugs affected by the 2021 NDPN policy. The availability, Defined Daily Doses (DDDs), and cost per Defined Daily Dose (DDDc) before and after the intervention were evaluated through interrupted time series analysis.Results: The NDPN policy resulted in a substantial 5.10% increase in the availability of anticancer drugs (p < 0.001). Utilization also experienced a significant surge, with an immediate increase of 11,254.36 DDDs (p < 0.001) and a monthly increase of 1208.28 DDDs (p < 0.001) following policy implementation. The DDDc decreased by US&dollar; 111.00 (p < 0.001) immediately after the policy. Disparities in regional drug utilization were evident, with higher usage in the eastern region.Conclusion: The 2021 NDPN policy has notably enhanced the availability and utilization of anticancer medications in China while reducing their cost, in line with the policy’s objectives. However, continuous monitoring is essential to ensure sustained access and to tackle regional disparities in drug utilization.Keywords: anticancer medicines, national drug price negotiation, China, availability, utilization, cost, interrupted time series analysis

Xinlai Ma,1 Yang Zhang,2 Yuxiao Sun,1 Hongyu Mou,1 Wei Zhang2 1The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, People’s Republic of ChinaCorrespondence: Wei Zhang, Department of Pulmonary and Critical Care Medicine, Shandong University of Traditional Chinese Medicine Affiliated Hospital, No. 42, West Culture Road, Lixia District, Jinan, Shandong, 250011, People’s Republic of China, Email huxzhijia@126.comBackground: In the past few years, there has been a growing fascination with the connection between mental well-being and respiratory conditions. However, the causal relationship between personality traits and respiratory diseases remains largely unknown. This study aimed to investigate the link between genetically predicted emotional instability and eight respiratory conditions using a two-sample Mendelian randomization (MR) analysis.Methods: In a GWAS dataset from the UK Biobank, SNPs linked to emotional instability were discovered among 204,412 participants of European descent. Genetic information for lung cancer, pulmonary fibrosis, pneumonia, and bronchiectasis was obtained from the European Bioinformatics Institute (EBI). While data for chronic obstructive pulmonary disease (COPD), pulmonary embolism, chronic cough, and asthma was collected from the UK BioBank. An MR study was carried out to investigate how specific single nucleotide polymorphisms (SNPs) impact the likelihood of developing the eight respiratory conditions listed. Our main approach for the initial screening was the utilization of inverse variance weighting (IVW). Multiplicity was assessed using the MR-Egger regression test, while heterogeneity was evaluated with Cochran’s Q test. To ensure the reliability of the findings, a leave-one-out analysis was conducted.Results: IVW found evidence that emotional instability had a significant causal effect on the increased risk of COPD (OR = 1.009; 95% CI = 1.001– 1.017; P = 0.022), pneumonia (OR = 1.648; 95% CI = 1.036– 2.622; P = 0.035), chronic cough (OR = 1.077; 95% CI = 1.013– 1.145; P = 0.017) and increased risk of asthma (OR = 1.073; 95% CI = 1.026– 1.123; P = 0.002) had a significant causal relationship. This association remained strong in the case of potential confounders, including smoking. Additionally, the instrumental variable weighted method in this study did not find any indication of a causal link between emotional instability and lung cancer, pulmonary embolism, pulmonary fibrosis, and bronchiectasis (all P > 0.05).Conclusion: The research discovered a link between emotional instability and a higher likelihood of developing COPD, pneumonia, chronic cough, and asthma. This study also found that emotional instability was not causally associated with lung cancer, pulmonary embolism, pulmonary fibrosis, and bronchiectasis.Keywords: emotional instability, respiratory diseases, Mendelian randomization

Qianhan Lin,1 Jiajia Li,1 Zulimire Abudousalamu,1 Yating Sun,1 Mengyang Xue,1 Liangqing Yao,2 Mo Chen1 1Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecologic Oncology, Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liangqing Yao; Mo Chen, Email yaoliangqing@163.com; chenmo_nicy@163.comAbstract: Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.Keywords: targeted drug delivery, ovarian cancer, drug conjugates, nanoparticle, hydrogel

Haoming Luo,1,2,&ast; Miao Guo,3,4,&ast; Mingxing Li,1 Yueshui Zhao,1 Jing Shen,1 Fukuan Du,1 Yu Chen,1 Shuai Deng,1 Yuhong Sun,1 Li Gu,1 Wanping Li,1 Xiaobing Li,1 Meijuan Chen,1 Zhangang Xiao,1,5,6 Shengpeng Wang,3,4 Xu Wu1,7 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2Department of Pharmacy, Three Gorges University Hospital of Traditional Chinese Medicine & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443003, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 4Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 5Department of Pharmacy, Gulin County Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, 646500, People’s Republic of China; 6School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 7Department of Paediatric Care, Luzhou People’s Hospital, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China, Email swang@um.edu.mo Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@swmu.edu.cnIntroduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy. Keywords: rosavin, colitis, inflammatory bowel disease, organoid, intestinal stem cell

Yiping Wang,1 Zhiqing Hu,2,3 Yueming Ding,2,3 Yanjun Sun,2,3 Rui Meng,1 Yuan He1– 3 1School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China; 2Institute of Medical Humanities, Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Marxism, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yuan He, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China, Email heyuan@njmu.edu.cnObjective: Our study aimed to examine the association between delay discounting (DD) and body mass index (BMI) in individuals with hypertension. Additionally, we sought to explore and compare the potential mediating effects of self-efficacy, physical activity and sedentary behavior in this association.Methods: A cross-sectional survey was conducted in two cities in the Jiangsu province of China, specifically Nanjing and Yangzhou, from March to June 2023. A total of 972 hypertensive patients completed the questionnaire (Mage = 64.7 years, SDage = 8.2 years, 54.2% female). Participants engaged in a money choice experiment on computers, provided their height and weight, and completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and General Self-Efficacy Scale (GSES). The experimental program was generated using the programming software E-Prime version 2.0. Multiple hierarchical regression analysis was conducted to identify potential covariates. Two serial mediation models were conducted using PROCESS macro 4.1 in SPSS 27.0. Physical activity and sedentary behavior were designated as M2 to investigate and contrast their respective mediating effects in the association between delay discounting and body mass index.Results: Self-efficacy, physical activity, and sedentary behavior served as mediators in the relationship between delay discounting and BMI. Self-efficacy accounted for 14.9% and 14.3% of the total effect in Models 1 and 2, respectively, while physical activity and sedentary behavior each accounted for 14.9% and 9.5% of the total effect, respectively. The serial mediation effects of self-efficacy and physical activity, as well as self-efficacy and sedentary behavior, were significant (B = 0.01, 95% CI [0.01, 0.02]; B = 0.01, 95% CI [0.002, 0.01]), collectively contributing 2.1% and 2.4% of the total effect. Sedentary behavior played a smaller mediating role compared to physical activity in this association.Conclusion: The results indicated that self-efficacy, physical activity and sedentary behavior could act as mediators in the association between delay discounting and BMI, thus potentially mitigating the risk of obesity in hypertensive individuals.Keywords: delay discounting, obesity, physical activity, sedentary behavior, self-efficacy, hypertension

Chao Zeng,1,&ast; Lu Li,1,&ast; Mengrui Wang,2,&ast; Jun Xiong,1 Wenjuan Pang,1 Haiyan Yu,1 Jiadi He,1 Xuguang Wang,1 Yingying Chen,1 Yanyan Sun1 1Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Sun; Jun Xiong, Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China, Email b2008194@126.com; xiongjun107@hotmail.comObjective: Ciprofol is a novel anesthetic agent, its efficacy and safety had been verified and its clinical implementation has been expanded. However, the knowledge about ciprofol in children is meager. The aim of study is to evaluate the safety and effectiveness of ciprofol in general anesthesia in children undergoing adenoidectomy and adenotonsillectomy, compared with propofol.Materials: We retrospectively analyzed data of children who underwent adenoidectomy or adenotonsillectomy with general anesthesia from June to August 2023 to evaluate the safety and effectiveness of ciprofol. The primary outcomes included hemodynamic changes during induction and postoperative complications in post-anesthesia care unit. The secondary outcomes were extubation time, pediatric anesthesia emergence delirium (PAED) score. Meanwhile, subgroup analysis was performed based on age.Results: 301 children met the inclusion criteria, 157 received ciprofol induction and 144 received propofol. Patient demographics and operation-related information were similar in the two groups. However, the dosage of dexmedetomidine in the propofol group was significantly higher than that of the ciprofol group (p=0.001). The trends of hemodynamic shift during induction and intubation were the same in the two groups. The PAED scores on post-extubation 10min and 20min were significantly reduced in the ciprofol group (p< 0.001 and p=0.046). Moreover, in the ≤ 72 months and the > 72 months subgroups, the scores were also significantly lower in the ciprofol group on post-extubation 10min. With the score of > 10, the incidence of emergence delirium of the ciprofol group was significantly lower on post-extubation 10min and 20min in the population and the ≤ 72 months subgroups (p=0.03 and p=0.02). There were no obvious postoperative complications in both groups.Conclusion: Ciprofol exhibited advantageous characteristics in the induction of children, such as stable hemodynamics, a relatively lower incidence of postoperative delirium without apparent post-anesthesia complications. Ciprofol may emerge as a novel option for general anesthesia in pediatric patients.Keywords: ciprofol, propofol, adenoidectomy, child, general anesthesia, delirium

Jinfeng Ai,1 Yihan Sun,2 Minrong Yan,1 Maolin Liu,1 Dongjun Zhong,1 Wei He,2 Xu Kang,2 Xinsheng Chen2 1The Second Clinical Medical College, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Dermatology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Xu Kang; Xinsheng Chen, Email Kangxuwf@163.com; xinshengchen@souhu.comAbstract: Follicular atresia triad, also known as paradoxical acne (FOT), is a rare and serious clinical syndrome in dermatology, mainly manifested by coalescing acne, purulent perifolliculitis of the head, and suppurative sweating inflammation, and FOT combined with necrotising fasciitis of the lower limbs and squamous cell carcinoma is rare both at home and abroad. In this article, we share the clinical data and treatment of a patient with follicular atresia triad and necrotising fasciitis and squamous cell carcinoma of the left lower limb for your reference.Keywords: follicular atresia triad, necrotising fasciitis, squamous cell carcinoma

Yueming Ding,1 Huiying Zhang,1 Zhiqing Hu,1 Yanjun Sun,1 Yiping Wang,2 Baolong Ding,3 Guofeng Yue,4 Yuan He1,5 1Institute of Medical Humanities, School of Marxism, Nanjing Medical University, Nanjing, People’s Republic of China; 2School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 4School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China; 5Research Center for Social Risk Management of Major Public Health Events (Key Research Base of Philosophy and Social Sciences of Universities in Jiangsu), Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yuan He, Institute of Medical Humanities, School of Marxism, School of Nursing, Research Center for Social Risk Management of Major Public Health Events (Key Research Base of Philosophy and Social Sciences of Universities in Jiangsu), Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email heyuan@njmu.edu.cn Guofeng Yue, School of Health Policy and Management, Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email gfyue@njmu.edu.cnBackground: Improving health-related quality of life (HRQoL) among hypertensive individuals has emerged as a significant public health issue. However, current research has ignored the individual heterogeneity of perceived social support (PSS) among hypertensive patients. The potential mechanism of delay discounting (DD), living alone, and PSS on HRQoL remains unclear, and further exploration is required.Aim: This study aimed to ascertain PSS profiles among hypertensive patients and examine the hypotheses that DD mediates the relationship between PSS and HRQoL and that this mediating process is moderated by living alone in hypertensive patients.Methods: A cross-sectional study was carried out in Jiangsu, China. In total, 1815 hypertensive patients completed socio-demographic and HRQoL questionnaires, a PSS scale, and a DD task. Data analyses included a latent profile analysis, χ2-test, Spearman correlation analysis, and PROCESS macro for regression analysis.Results: Four potential PSS profiles were identified: lowest (3.2%), moderate–low (26.6%), moderate–high (42.4%), and highest (27.8%). DD mediated the association between PSS and HRQoL. The first half of this mediating process was moderated by living alone.Conclusion: Our findings indicated that PSS, DD, and living alone significantly influence the HRQoL of individuals with hypertension. Healthcare professionals should consider variations in PSS among hypertensive patients and implement interventions to reduce DD by enhancing PSS, in order to improve the HRQoL of this population.Keywords: perceived social support, delay discounting, health-related quality of life, living alone, hypertensive patients, latent profile analysis

Changjin Wang,1,&ast; Bangyuan Yang,1,&ast; Songyuan Luo,1 Shengneng Zheng,2 Yinghao Sun,1 Jiaohua Chen,1 Ruixin Fan,3 Jianfang Luo,1,&ast; Jie Li1,&ast; 1Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li; Jianfang Luo, Email leomoku1981@163.com; jianfangluo@sina.comBackground: The relationship between pulmonary hypertension (PH) and outcomes after transcatheter aortic valve replacement (TAVR) has been shown to be unfavorable. The impact of gender on TAVR outcomes remains controversial. There have been no studies evaluating the simultaneous effects of both factors on TAVR outcomes.Methods: We retrospectively analyzed a prospective cohort of patients who underwent TAVR between January 2016 and December 2022. The patients were stratified by gender and the presence of PH. The primary outcome of the study was all-cause mortality. Secondary outcome was a composite of all-cause mortality and heart failure hospitalization.Results: We identified a total of 133 female patients without PH, 179 males without PH, 87 females with PH, and 122 males with PH. The median follow-up period was 18 months. Female patients without PH demonstrated a lower cumulative mortality rate compared to those with male gender and/or PH. Adjusted multivariate Cox proportional hazard analyses revealed that male gender and PH status, either individually or in combination, were independently associated with long-term mortality when compared to female patients without PH. Specifically, females with PH (HR 6.80, 95% confidence interval (CI): 1.49– 31.12, P=0.013), males without PH (HR 6.45, 95% CI: 1.47– 28.22, P=0.013), and males with PH (HR 7.2, 95% CI: 1.63– 31.81, P=0.009) demonstrated significantly higher risk for mortality.Conclusion: Patients who were male or had PH status had a higher risk of mortality. However, there was no synergistic effect between being male and having PH on the prognosis after TAVR.Keywords: transcatheter aortic valve replacement, gender, pulmonary hypertension, outcome

Ying Yang,1– 3,&ast; Bixia Zhou,1,2,&ast; Min Li,4 Yishuai Sun,1,2 Xulei Jiang,1,2 Xinxin Zhou,1,2 Chengjun Hu,1,2 Dou Zhang,3 Hang Luo,3 Wuyuan Tan,1,2 Xinghua Yang,1,2 Shaorong Lei1,2 1Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, People’s Republic of China; 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Oncology, Changsha Central Hospital, University of South China, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaorong Lei, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email leishaorong@csu.edu.cn Xinghua Yang, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email yxhua8805@sina.comPurpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect.Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.Results: We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing.Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios. Keywords: nanomaterials, hybrid hydrogel, bone scaffolds, craniofacial bone defects, bone regeneration

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

Jianghao Xiao, Dengkai Chen, Suihuai Yu, Hui Wang, Yiwei Sun, Hanyu Wang, Zhiming Gou, Jingping Wang Key Laboratory of Industrial Design and Ergonomics, Ministry of Industry and Information Technology, Northwestern Polytechnical University, Xi’an, 710072, People’s Republic of ChinaCorrespondence: Jianghao Xiao, Key Laboratory of Industrial Design and Ergonomics, Ministry of Industry and Information Technology, Northwestern Polytechnical University, 127 Youyi West Road, Xi’an, 710072, People’s Republic of China, Tel +86 15528076860, Email xiaojianghao@mail.nwpu.edu.cnPurpose: Exposure to artificial light influences human performance, which is essential for maintaining healthy work and sleep. However, existing research has not explored the intrinsic links between sleep performance and human states over time under prebedtime light exposure interventions (LEIs).Methods: To investigate the time-dependent effects of altered prebedtime light exposure, four LEI groupings (&num;L1 - &num;L4) and a Time factor (D8, D9, and D10) were chosen for sleep experiments in enclosed spaces. Forty-eight young adults recruited were available for data analysis. Subjective alertness (SA), negative affect (NA), subjective sleep, and objective sleep were measured via the Karolinska Sleepiness Scale, Positive and Negative Affect Schedule, Next-day Self-assessment Sleep Quality, and joint assessment of wrist actigraphy and sleep diaries, respectively. Statistical analysis was used for the effects of light exposure on the human states (corresponding to the SA and NA) and sleep performance, while the process model helped construct the associations between the two.Results: The statistical effects revealed that the Time had a significant main effect on subjective sleep and changes in prebedtime alertness; the LEI had a significant main effect only on sleep onset latency (SOL). After undergoing altered prebedtime light exposure, the mean SA increased at prebedtime of D9 (p = 0.022) and D10 (p = 0.044); No significant effect on the NA was observed; Mean subjective sleep had a significant increase from D8 to D10. Moreover, five actigraphy-estimated sleep parameters were interrelated. In light of this, a chained pathway relationship was identified. The SOL played a mediating predictor between prebedtime state and objective sleep, which was linked to the awakening state through subjective sleep.Conclusion: Our study suggests that time-dependent effects of altered prebedtime light exposure on sleep performance are associated with human states at prebedtime and awakening, with implications for its prediction of sleep health.Keywords: prebedtime light exposure, sleep performance, non-visual effects, alertness, negative affect, sleep onset latency

Jiangpei Shi,1,&ast; Rongguang Zhang,1,&ast; Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Tiantian Tang,1,2,&ast; Yujiao Wang,1,2,&ast; Taotao Li,1,2,&ast; Ding Liu,1,2 Kai Yang,1,2 Jing Sun,1,2 Yajun Shi,1,2 Dongyan Guo,1,2 Junbo Zou,1,2 Fengyun Bai,3 Ying Sun,3 Mei Wang,1,2 Xiaofei Zhang1,2 1Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 3Shaanxi Dongtai Pharmaceutical Co., Ltd., Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Wang; Xiaofei Zhang, Key Laboratory of Basic and New Drug Research in Chinese Medicine; Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, People’s Republic of China, Email wangmei0708@163.com; 2051028@sntcm.edu.cnObjective: To explore the mechanism and active components of the anti-colitis effects of myrrh essential oil (MEO).Methods: In this study, we investigated the anti-inflammatory effects and molecular mechanisms of MEO on dextran sulfate sodium (DSS)-induced colitis with in vitro cell experiments, RNA-seq (RNA Sequencing), Weighted gene co-expression network analysis (WGCNA), combined with “weighting coefficient” network pharmacology, as and in vivo pharmacodynamic experiments. A 3% DSS solution was used to induce colitis in BALB/c mice and MEO was administered orally. We performed gas chromatography-mass spectrometry (GC-MS) analysis of the MEO components. The disease activity index (DAI) was evaluated by observing body weight, fecal characteristics, and blood in the stool of mice. The levels of inflammatory cytokines (TNF-α and IL-1β) in mouse serum were measured using ELISA (Enzyme-linked immunosorbent assay) kits. Additionally, the expression of MAPK-related proteins (JNK, p-JNK, ERK, and p-ERK) in mouse colonic tissues was detected by Western blotting and immunohistochemistry.Results: MEO (0.0625– 0.125μg/g, p.o). significantly inhibited the expression of the inflammatory mediator Nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. After treatment, there was a significant increase in body weight and alleviation of diarrhea and bloody stools in colitis mice. It also reduced inflammatory cell infiltration. Furthermore, it decreased the serum levels of TNF-α and IL-1β, and reduced the activity of p-JNK and p-ERK in the MAPK pathway.Conclusion: MEO relieved DSS-induced colitis by modulating the MAPK pathway. The experimental results indicate that the MAPK pathway might be inhibited by the synergistic effect of gamma-Muurolene, Curzerene, beta-Elemene, and Furanoeudesma 1.3-diene in MEO, which provides a novel idea for subsequent research and development of new anti-colitis drugs. Keywords: colitis, myrrh essential oil, MAPK signaling pathway, RNA sequencing, weighted gene co-expression network analysis

Jing Shang,1,&ast; Qi Xia,1,&ast; Yuji Sun,2 Hongtao Wang,2 Jia Chen,1 Yue Li,1 Feng Gao,2 Peihao Yin,1,3,4 Zeting Yuan1– 4 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China; 2Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Shanghai, 200062, People’s Republic of China; 4The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zeting Yuan; Peihao Yin, Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People’s Republic of China, Email yuan340202@163.com; yinpeihao@shutcm.edu.cnPurpose: Compared with traditional photothermal therapy (PTT, > 50°C), mild PTT (≤ 45°C) is a promising strategy for tumor therapy with fewer adverse effects. Unfortunately, its anti-tumor efficacy is hampered by thermoresistance induced by overexpression of heat shock proteins (HSPs). In our previous study, we found bufalin (BU) is a glycolysis inhibitor that depletes HSPs, which is expected to overcome thermotolerance of tumor cells. In this study, BU-loaded multifunctional nanoparticles (NPs) were developed for enhancing the mild PTT of colorectal cancer (CRC).Methods: Fe3O4 NPs coated with the polydopamine (PDA) shell modified with polyethylene glycol (PEG) and cyclic arginine-glycyl-aspartic peptide (cRGD) for loading BU (Fe3O4@PDA-PEG-cRGD/BU NPs) were developed. The thermal variations in Fe3O4@PDA-PEG-cRGD/BU NPs solution under different conditions were measured. Glycolysis inhibition was evaluated by measuring the glucose uptake, extracellular lactate, and intracellular adenosine triphosphate (ATP) levels. The cellular cytotoxicity of Fe3O4@PDA-PEG-cRGD/BU NPs was analyzed using a cell counting kit-8 assay, Calcein-AM/PI double staining, and flow cytometry in HCT116 cells. The magnetic resonance imaging (MRI) performance and anti-tumor therapeutic efficacy of Fe3O4@PDA-PEG-cRGD/BU NPs were evaluated in HCT116-tumor bearing mice.Results: Fe3O4@PDA-PEG-cRGD/BU NPs had an average diameter of 260.4± 3.5 nm, the zeta potential of – 23.8± 1.6 mV, the drug loading rate of 1.1%, which had good thermal stability, photothermal conversion efficiencies and MRI performance. In addition, the released BU not only killed tumor cells but also interfered with glycolysis by targeting the steroid receptor coactivator 3 (SRC-3)/HIF-1α pathway, preventing intracellular ATP synthesis, and combating HSP-dependent tumor thermoresistance, ultimately strengthening the thermal sensitivity toward mild PTT both in vitro and in vivo.Conclusion: This study provides a highly effective strategy for enhancing the therapeutic effects of mild PTT toward tumors. Keywords: mild photothermal therapy, glycolysis metabolism, bufalin, HIF-1α, SRC-3

Xiaolu Chen,1– 3 Jian Liu,1,2 Guizhen Wang,1,2 Yanqiu Sun,1,2 Xiang Ding,1– 3 Xianheng Zhang1– 3 1Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86 551 62838582, Fax +86 551 62821605, Email liujianahzy@126.comObjective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism.Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of “active component-target-disease” was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP’s delay of immune inflammation in OA.Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway.Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.Keywords: osteoarthritis, chondrocytes, inflammation, LncRNA HOTAIR/APN/PI3K/AKT

Yadong Sun,1 Yanjie Shan,1 Jiaqiong Xie,1 Ke Chen,1 Jia Hu2 1Faculty of Social Sciences, Chongqing University, Chongqing, People’s Republic of China; 2Institute for Advanced Studies in Humanities and Social Science, Chongqing University, Chongqing, People’s Republic of ChinaCorrespondence: Ke Chen; Jia Hu, Chongqing University, Shapingba, Chongqing, People’s Republic of China, 400044, Tel +86-13628362626, Email chenke197729@163.com; hujia827@cqu.edu.cnPurpose: With the development of information technology and various social media, recommendation algorithms have increasingly more influence on users’ social media usage. To date, there has been limited research focused on analyzing the impact of recommendation algorithms on social media use and their corresponding role in the development of problematic behaviors. The present study analyzes the impact of recommendation algorithms on college students’ information sharing and internalizing, externalizing problem behaviors to address the aforementioned shortcomings.Methods: An online questionnaire survey was conducted among 34,752 college students in China. A latent profile analysis was conducted to explore the various behavioral patterns of Chinese college students’ information sharing across the three social media platforms identified for this study. The Bolck–Croon–Hagenaars (BCH) method Regression Mixture Modeling was then used to analyze the differences in internalizing and externalizing problem behaviors among the different subgroups of Chinese college students.Results: The level of information sharing by college students across different social media platforms could be divided into “WeChat Moments low-frequency information sharing”, “middle-frequency comprehensive information sharing”, “TikTok high-frequency information sharing”, and “Sina Weibo high-frequency information sharing”. Significant differences were observed regarding internalizing and externalizing problem behaviors among college students in different information-sharing subgroups.Conclusion: This study identified four subgroups with different information-sharing characteristics using latent profile analysis. Among them, college students who are in subgroup of social media information sharing influenced by recommendation algorithms exhibit higher frequency of information sharing and higher level of internalizing and externalizing problematic behaviors. These results expand our understanding of college students’ social media usage and problem behaviors from a technological perspective. In future, the negative impacts of recommendation algorithms on college students can be reduced by improving their awareness of these algorithms and optimizing the algorithms themselves.Keywords: user-generated content, recommendation algorithms, latent profile analysis, internalizing problem behaviors, externalizing problem behaviors

Yanmeng Sun,1,2,&ast; Zheng Li,1,2,&ast; Yanfang Li,3 Chunyan Zhang,1,2 Mengyuan Wang,1,2 Wenwen Yu,1,2 Guohua Liu,2,3 Shifu Wang1,2 1Department of Microbiology Laboratory, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Microbiology Laboratory, Shandong Provincial Clinical Research Center for Children’s Health and Disease, Jinan, Shandong, People’s Republic of China; 3Department of Neonatology, Children’s Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifu Wang, Email wshfu709@163.comAbstract: Anaerobic bacterial meningitis is a serious infection of the central nervous system (CNS) that leads to severe neurological complications, resulting in high levels of disability and mortality worldwide. However, accurately diagnosing and isolating the responsible pathogens remains challenging due to the difficulty in culturing anaerobic bacteria, as they require harsh anaerobic culture conditions. Anaerobic bacteria have rarely been reported in meningitis, especially in children. This report details the first infant with anaerobic meningitis caused by Prevotella bivia. Additionally, we present a case of infant anaerobic meningitis caused by P. bivia, detected using metagenomics next-generation sequencing (mNGS). Our clinical experience highlights the importance of early identification of Prevotella spp. through mNGS and anaerobic culture, the effectiveness of antimicrobial medications, and the timely implementation of carefully planned precision therapeutic regimens. Furthermore, we have conducted a comprehensive review of 10 cases of Prevotella spp. infection, summarized their clinical and laboratory examination characteristics, and identified their commonalities.Keywords: Prevotella bivia, anaerobic meningitis, infant

Kuocheng Yan,1,&ast; Xiaohui Wang,2,&ast; Yao Han,1,&ast; Yuan Tian,1 Mengwei Niu,1 Xue Dong,1 Xiaowei Li,2 Hao Li,1 Yansong Sun1 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 2Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Li, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China, Email lihao88663239@126.com Xiaowei Li, Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China, Email lixwei12@126.comBackground: Infection caused by Helicobacter pylori (H. pylori) affects approximately 50% of the global population. It is a major pathogenic factor for chronic gastritis and gastric cancer. Besides, the resistance to antibiotics such as clarithromycin could reduce the eradication rate. Currently, there is an urgent need for a swift, easy to perform, and highly sensitive detection method for H. pylori and clarithromycin resistance.Methods: We used FAM/Digoxin labeled primers to amplify specific H. pylori 23S rRNA fragments by Recombinase Aided Amplification (RAA), and resistance mutations were distinguished using CRISPR/Cas13a system combined with lateral flow strip. Twenty-eight saliva samples were analyzed using qPCR, gene sequencing and this method to evaluate the detection efficiency.Results: We developed a simultaneous detection method for H. pylori and clarithromycin resistance mutations named sensitive H. pylori easy-read dual detection (SHIELD). The results showed both A2142G and A2143G mutant DNAs causing clarithromycin resistance could be distinguished from the wild type with a concentration of 50 copies/μL, and no cross-reaction with other 5 common gastrointestinal bacteria was observed. For the detection of H. pylori in 28 saliva samples, the positive predictive value of this method was 100% (19/19) in comparison with qPCR. For detecting clarithromycin resistance, the positive predictive value of this method was 84.6% (11/13) compared with gene sequencing.Conclusion: SHIELD assay showed high sensitivity and specificity in detecting H. pylori and clarithromycin resistance mutations. It could be a potential measure in the rapid detection of H. pylori, large-scale screening and guiding clinical medication.Keywords: Helicobacter pylori, clarithromycin resistance mutation, recombinase aided amplification, CRISPR/Cas13a, nucleic acid detection

Hongjuan Jiang, Xiangyu Chi, Yanhong Sun, Hongwen Li Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Hongwen Li, Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Email lihongwen_91@163.comBackground: Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models.Methods: The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis.Results: The serum concentration of VDBP was significantly higher in COVID-19 with ALI (P < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (r=0.329, P = 0.002), c-reaction protein (r = 0.470, P < 0.001), serum amyloid A (r = 0.900, P < 0.001), procalcitonin (r = 0.670, P < 0.001), and interleukin 6 (r = 0.452, P < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001– 1.006, P = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1β and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group (P < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced (P < 0.05).Conclusion: In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.Keywords: Vitamin D binding protein, COVID-19, acute lung injury, pathogenesis

Xinfu Cao,1 Yi Sun,1 Yuqiao Chen,1 Chao Tang,2 Hongwen Yu,3 Xiaolong Li,1 Zhenhua Gu1 1Department of Cardiology, Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People’s Republic of China; 3Department of Cardiology, Gaochun Branch of Nanjing Hospital of Traditional Chinese Medicine, Nanjing City, Jiangsu Province, People’s Republic of ChinaCorrespondence: Zhenhua Gu; Xiaolong Li, Department of Cardiology, Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou City, Jiangsu Province, People’s Republic of China, Email 18101490727@163.com; 15650796727@163.comObjective: To explore the risk factors of atrial fibrillation (AF) in patients with coronary heart disease (CHD), and to construct a risk prediction model.Methods: The participants in this case-control study were from the cardiovascular Department of Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine from June 2016 to June 2023, and they were divided into AF group and non-AF group according to whether AF occurred during hospitalization. The clinical data of the two groups were compared by retrospective analysis. Multivariate Logistic regression analysis was used to investigate the risk factors of AF occurrence in CHD patients. The nomogram model was constructed with R 4.2.6 language “rms” package, and the model’s differentiation, calibration and effectiveness were evaluated by drawing ROC curve, calibration curve and decision curve.Results: A total of 1258 patients with CHD were included, and they were divided into AF group (n=92) and non-AF group (n=1166) according to whether AF was complicated. Logistic regression analysis showed that age, coronary multiple branch lesion, history of heart failure, history of drinking, pulmonary hypertension, left atrial diameter, left ventricular end-diastolic diameter and diabetes mellitus were independent risk factors for the occurrence of AF in CHD patients (P < 0.05). The ROC curve showed that the AUC of this model was 0.956 (95% CI (0.916, 0.995)) and the consistency index was 0.966. The calibration curve of the model is close to the ideal curve. The analysis of decision curve shows that the prediction value of the model is better when the probability threshold of the model is 0.042~0.963.Conclusion: The nomogram model established in this study for predicting the risk of AF in patients with CHD has better predictive performance and has certain reference value for clinical identification of high-risk groups prone to AF in patients with CHD.keywords: coronary heart disease, atrial fibrillation, risk factors, logistic regression analysis, nomogram model

Mingjun Gong,1 Min Sun,1 Yaqi Sun,2 Lijuan Jin,1 Shen Li3 1Sports Training College, Tianjin University of Sport, Tianjin, People’s Republic of China; 2Mental Health Institute, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Shen Li, Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +86-22-88188875, Email lishen@tmu.edu.cnObjective: Using meta-analysis to comprehensively and quantitatively evaluate the impact of acute sleep deprivation on different sports performance of athletes, this study aims to provide scientific guidance for coaches in optimizing and adjusting training and competition arrangements.Methods: Establishing literature inclusion and exclusion criteria, we conducted searches in both Chinese and English databases. Using stata 14.0, we analyzed 75 indicators from 27 included literature, focusing on three aspects: the impact of acute sleep deprivation on overall athletic performance, the impact on sporting performance across various athletic abilities, and the disparities in athletic performance between morning and afternoon following acute sleep deprivation.Results: The effect size of acute sleep deprivation on overall athletic performance was − 0.56 (P< 0.05). Sub-analyses revealed effect sizes of − 0.23 (P< 0.05) for whole night sleep deprivation, − 1.17 (P< 0.05) for partial sleep deprivation at the end of the night, and − 0.25 (P> 0.05) for partial sleep deprivation in the beginning of the night. The effect sizes of acute sleep deprivation on high intensity intermittent exercise, skill control, speed, aerobic endurance, and explosive power indicators were − 1.57, − 1.06, − 0.67, − 0.54, and − 0.39 respectively (P< 0.05). The effect sizes of acute sleep deprivation on the overall athletic performance in the morning and afternoon were − 0.30, and − 1.11, respectively (P< 0.05).Conclusion: Acute sleep deprivation significantly impairs the overall athletic performance of athletes, with a more pronounced negative impact observed with partial sleep deprivation at the end of the night. Various types of exercise performance are adversely affected by acute sleep deprivation, with magnitude of impact ranking high intensity intermittent, skill control, speed, aerobic endurance, and explosive power. Following acute sleep deprivation, athletes’ overall sporting performance in the afternoon is inferior to that in the morning.Keywords: acute sleep deprivation, athletes, athletic ability, sporting performance, meta-analysis

Zhiliang Li,1,2,&ast; Jiali Yang,1,3,&ast; Yang Sun,1 Shuo Han,1 Jietao Gong,1 Yi Zhang,1,3 Zhiyuan Feng,1 Hong Yao,4 Peiying Shi1,5 1College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 2College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 5State and Local Joint Engineering Laboratory of Natural Biotoxins, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yao, Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email hongyao@mail.fjmu.edu.cn Peiying Shi, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China, Email peiyshi@126.comPurpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK.Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP. Keywords: Schisandra chinensis bee pollen extract, HepG2 cells, proteomics, ferroptosis, Wnt-signaling pathway, focal adhesion–signaling pathway

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

Jingyao Dai,1 Yiting Hua,1 Yijie Chen,1 Jiali Huang,1 Xiaoxian Zhang,1 Yiwen Sun,1 Chen Chen,1 Yanyan Chen,2 Kaijing Zhou2 1School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yanyan Chen; Kaijing Zhou, Email cyy@eye.ac.cn; zhoukaijing@wmu.edu.cnPurpose: To explore 1) the level of shared decision-making (SDM) participation in intraocular lens (IOL) selection in cataract patients and the factors that influence this participation and 2) the relationships between preparation for decision-making (PrepDM)and the level of SDM participation and satisfaction with the decision (SWD). Provide guidance for improving SDM in ophthalmology.Patients and Methods: 176 cataract patients were asked to complete the PrepDM scale, the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and the SWD instrument in IOL decision-making process. Multiple linear regression was used to analyze the influencing factors of the level of SDM. The Process program and bootstrap sampling method was used to test whether the level of participation in SDM was a mediating variable among the three.Results: The SDM-Q-9 median score was 77.78 (IQR 31.11– 88.89). Patients with a history of surgery in the operative eye (P=0.022) or PrepDM < 60 points (P< 0.001) had lower SDM-Q-9 scores than patients with no history of surgery in the operative eye or PrepDM ≥ 60 points. Patients with an education level lower than primary school had lower SDM-Q-9 scores than patients with other education levels (P< 0.05). The PrepDM of cataract patients was positively correlated with the level of SDM (r=0.768, P< 0.001) and with the SWD (r=0.727, P< 0.001), and the level of SDM was positively correlated with the SWD (r=0.856, P< 0.001). The level of SDM fully mediated PrepDM and SDW, with a mediating effect value of 0.128 and a mediating effect of 86.66% of the total effect.Conclusion: The SDM of cataract patients involved in IOL selection was in the upper middle range. Education, history of surgery in the operated eye, and PrepDM were factors that influenced the level of SDM. The level of participation in SDM fully mediated the relationship between PrepDM and SWD.Keywords: cataract, intraocular lens, shared decision-making, preparation, satisfaction

Jian Cui,1 Yunliang Sun,2 Haifeng Jing,3 Qiang Chen,1 Zhihao Huang,1 Xin Qi,1 Hao Cui1 1Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, Dongying, Shandong, 257061, People’s Republic of China; 2Department of Respiratory and Sleep Medicine, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256600, People’s Republic of China; 3College of Software and Microelectronics, Peking University, Beijing, 100000, People’s Republic of ChinaCorrespondence: Jian Cui, Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, 271 Bei Er Lu, Dongying City, Shandong Province, 257061, People’s Republic of China, Tel +86-15066073763, Email jian.cui@sdipct.edu.cnPurpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency.Methods: The study involved 50 normal and 100 obstructive sleep apnea–hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM).Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤ 0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%.Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.Keywords: sleep depth value, sleep continuity, EEG features, timing fitness, ANN model

Zeyu Wang, Zhaoxin Zhu, Yifan Sun, Ting Wang, Yunlan Lu, Wenliang Che, Weijing Liu, Yawei Xu Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Weijing Liu; Yawei Xu, Tel/Fax + 86- 02166308182, Email liuweijing98@sina.com; xuyawei@tongji.edu.cnBackground: The respiratory rehabilitation technique is a crucial component of early cardiac recovery in geriatric patients with acute myocardial infarction (AMI). This study primarily investigated the effectiveness of a novel respiratory rehabilitation technique, metronomic breathing (MB), on geriatric patients after percutaneous coronary intervention for AMI and compliance with home-based rehabilitation compared to traditional respiratory rehabilitation.Methods: From June 2022 to March 2023, 75 acute myocardial infarction (AMI) patients admitted to the Shanghai Tenth People’s Hospital Cardiovascular Department were consecutively enrolled. Ultimately, 46 patients completed the follow-up in this study— 26 in the MB group and 20 in the control group—who underwent the novel MB technique and conventional abdominal breathing training. The primary endpoint of the study was left ventricular function measured by noninvasive hemodynamics three months after discharge. The secondary endpoints were compliance and quality of life after three months of home rehabilitation.Results: After the intervention, several cardiac functional parameters (SV, SVI, CO, CI, LCW, and LCWI), myocardial contractility parameters (VI), and systemic vascular resistance parameters (SVR and SVRI) were significantly greater in the MB group than in the preintervention group (P < 0.05). Furthermore, post-treatment, the MB group exhibited greater SV, SVI, CO, CI, and VI; lower SVR, SVRI, and SBP; and a lower readmission rate three months later than did the control group. The SF-36 scores after three months of MB intervention, PE, BP, GH, VT, SF, RE, and MH, were all significantly greater than those before treatment (P < 0.05). Moreover, the MB group displayed greater compliance with home-based cardiac rehabilitation (P < 0.05).Conclusion: Compared to conventional respiratory rehabilitation training methods, short-term metronomic respiratory therapy is more effective for reducing systemic vascular resistance, enhancing left ventricular ejection function, enhancing quality of life, and increasing home-based rehabilitation compliance in geriatric patients following AMI with PCI.Keywords: metronomic breathing, MB, acute myocardial infarction, AMI, cardiac rehabilitation, efficacy, gerontal patients

Yu Gao,1 Yuechi Sun2 1School of Psychology, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2School of Economics and Management, China University of Geosciences (Beijing), Beijing, People’s Republic of ChinaCorrespondence: Yu Gao, School of Psychology, Shandong Second Medical University, 7166 Baotong West Street, Weicheng District, Weifang, Shandong, 261053, People’s Republic of China, Email gaoyucugb@163.comBackground: Public health emergencies not only threaten the physical and mental health of the public but also trigger a series of risky behaviors of the public, which in turn lead to the emergence or intensification of risk events, disrupting existing economic and social order.Purpose: Based on construal level theory, cognitive appraisal theory of emotions and mood maintenance hypothesis, the study aims to investigate the collectively effect of risk perception and psychological insecurity in the connection between psychological distance and public risky behavior.Participants and Methods: Cross-sectional data was derived from 257 China urban residents. All participants finished the psychological distance scale, risk perception scale, psychological insecurity scale, and risky behavior scale. The research hypothesis was tested using the PROCESS macro.Results: The direct impact of psychological distance on risky behavior was not significant (β=− 0.018, p> 0.05). The indirect impact of psychological distance on risky behavior was significant. In other words, the impact of psychological distance on risky behavior was serially mediated via risk perception and psychological insecurity (β=0.011, 95% CI= [0.0013, 0.025]).Conclusion: Risk perception and psychological insecurity play serial mediating roles in the relationship between psychological distance and public risky behavior. We conclude that during public health emergencies, public health managers should pay extra attention to the risk perception and psychological insecurity level of the public with closer psychological distance, take measures to reduce their risk perception, enhance their psychological security, and reduce their risky behavior, thereby ensuring the physical and mental health of the public and maintaining the stability of economic and social order.Keywords: public health emergencies, psychological distance, risk perception, psychological insecurity, risky behavior

Xiaoyan Wu,1,2 Yuzhe Sun,2,3 Shuyi Wei,2,3 Huoyou Hu,1 Bin Yang2 1Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 2Department of Dermatology, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 3Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, 510091, People’s Republic of ChinaCorrespondence: Huoyou Hu, Shenzhen Second People’s Hospital, 3002 Sungang West Road, Shenzhen, Guangdong, 518035, People’s Republic of China, Tel +86-13554918106, Email huhuoyou1029@163.com Bin Yang, Jinan University, 601 West Huangpu Avenue, Guangzhou, Guangdong, 510632, People’s Republic of China, Tel +86-13922207231, Email yangbin1@smu.edu.cnBackground: Ferroptosis is a type of cell death characterized by the accumulation of iron-dependent lethal lipid peroxides, which is associated with various pathophysiological processes. Psoriasis is a chronic autoimmune skin disease accompanied by abnormal immune cell infiltration and excessive production of lipid reactive oxygen species (ROS). Currently, its pathogenesis remains elusive, especially the potential role of ferroptosis in its pathophysiological process.Methods: The microarrays GSE13355 (58 psoriatic skin specimens versus 122 healthy skin specimens) and the ferroptosis database were employed to identify the common differentially expressed genes (DEGs) associated with psoriasis and ferroptosis. The functions of common DEGs were investigated through functional enrichment analysis and protein-protein interaction analysis. The potential diagnostic markers for psoriasis among the common DEGs were identified using four machine-learning algorithms. DGIdb was utilized to explore potential therapeutic agents for psoriasis. Additionally, CIBERSORT was employed to investigate immune infiltration in psoriasis.Results: A total of 8 common DEGs associated with psoriasis and ferroptosis were identified, which are involved in intercellular signaling and affect pathways of cell response to stress and stimulation. Four machine-learning algorithms were employed to identify poly (ADP-ribose) polymerase 12 (PARP12), frizzled homolog 7 (FZD7), and arachidonate 15-lipoxygenase (ALOX15B) among the eight common DEGs as potential diagnostic markers for psoriasis. A total of 18 drugs targeting the five common DEGs were identified as potential candidates for treating psoriasis. Additionally, significant changes were observed in the immune microenvironment of patients with psoriasis.Conclusion: This study has contributed to our enhanced comprehension of ferroptosis-related genes as potential biomarkers for psoriasis diagnosis, as well as the alterations in the immune microenvironment associated with psoriasis. Our findings offer valuable insights into the diagnosis and treatment of psoriasis.Keywords: psoriasis, ferroptosis, biomarker, immune

Shulin Wei,1,2,&ast; Mingxing Li,1,2,&ast; Qin Wang,1,2,&ast; Yueshui Zhao,1,2 Fukuan Du,1,2 Yu Chen,1,2 Shuai Deng,1,2 Jing Shen,1,2 Ke Wu,1,2 Jiayue Yang,1,2 Yuhong Sun,1 Li Gu,1 Xiaobing Li,1 Wanping Li,1 Meijuan Chen,1 Xiao Ling,3 Lei Yu,3 Zhangang Xiao,1,2 Lishu Dong,3 Xu Wu1,2 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, 646100, People’s Republic of China; 3Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lishu Dong, Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China, Email 1275607519@qq.com Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@126.comAbstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.Keywords: mesenchymal stem cells, immunomodulation, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cell therapy

Yang Sun,1,2 Bo-Wei Liu,2 Xin Zhang,2 Fu-Zai Yin2 1Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, People’s Republic of ChinaCorrespondence: Fu-Zai Yin, Email yinfuzai62@163.comBackground: Apolipoprotein (Apo) may be associated with sarcopenia in elderly inpatients with type 2 diabetes mellitus (T2DM), but fewer studies are available. In this study, we explored the association of ApoA1, ApoB, and ApoB/ApoA1 with sarcopenia and compared the predictive role of Apo indicators for sarcopenia in an elderly T2DM.Objective: To investigate the relationships between the Apo and sarcopenia in elderly inpatients with T2DM.Methods: This study included 253 inpatients with T2DM (mean age of 70.11± 5.44 years, 32.8% male). The inpatients were divided into the sarcopenic group (n = 100) and non-sarcopenic group (n = 153). The associations among the Apo and sarcopenia were assessed using multivariate analyses.Results: Inpatients in the sarcopenia group showed lower ApoA1 levels than those in the non-sarcopenia group (1.25± 0.21 vs 1.36± 0.20 g/L, P < 0.05) and showed higher ApoB/ApoA1 and ApoB levels than those in the non-sarcopenia group (0.82± 0.27 vs 0.69± 0.19 g/L, P < 0.05;1.00± 0.32 vs 0.93± 0.24 g/L, P < 0.05, respectively). After adjusting for age and BMI, the logistic regression model indicated that ApoA1 was a protective factor for elderly inpatients with T2DM sarcopenia.(OR =0.079,95% CI: 0.021~0.306, P < 0.05);ApoB and AopB/AopA1 were risk factors for elderly inpatients with T2DM sarcopenia.(OR =3.578,95% CI:1.318~9.715, P < 0.05;OR =16.440,95% CI:4.437~60.427, P < 0.05, respectively). AopB/AopA1 provided an AUC value of 0.765 in elderly men.(95% CI: 0.665~0.866, P< 0.05).Conclusion: ApoA1, AopB, and AopB/AopA1 are associated with sarcopenia in elderly inpatients with T2DM, and AopB/AopA1 may be a potential predictor of sarcopenia in elderly men with T2DM.Keywords: type 2 diabetes mellitus, sarcopenia, Apolipoprotein A1, Apolipoprotein B, Apolipoprotein B/A1