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Dan Kuai,1,2 Mengying Li,1,2 Ling He,1,2 Xiaoyan Li,1,2 Ying He,1,2 Shiqi Liu,1,2 Jiayu Wei,1,2 Xia Ji,3 Yingmei Wang,1,2 Wenyan Tian,1,2 Huiying Zhang1,2 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 2Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 3Baogang Hospital of Aerospace Medicine of Inner Mongolia, Baotou, 014000, People’s Republic of ChinaCorrespondence: Yingmei Wang, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email wangyingmei1978@126.com Huiying Zhang, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154, Anshan Road, He Ping District, Tianjin, 300052, People’s Republic of China, Tel +86-022-60362255, Email huiying_zhang2020@126.comAim: To assess body composition, glucolipid metabolism, and uric acid levels in PCOS (Polycystic Ovary Syndrome) patients to determine their relationship with the risk of endometrial hyperplasia (EH).Methods: A total of 232 patients were included and divided into groups according to whether they had PCOS and endometrial pathology (Group A: non-PCOS and normal endometrium; Group B: PCOS and normal endometrium; Group C: non-PCOS and EH; Group D: PCOS and EH). Body composition differences between groups and correlations between body composition, glucolipid metabolism, and uric acid levels were analyzed.Results: In Group D, the patient’s PSM (Percent Skeletal Muscle) of Trunk, PBF (Percent Body Fat) of Arm, free mass index, FMI (Fat Mass Index), and appendicular skeletal muscle mass index were significantly higher than in Groups A, B, and C. Waist-hip rate, PBF, PBF of Trunk, PSM of Leg, skeletal muscle mass index and visceral fat level were significantly higher than in Groups A and B. FMI was an independent risk factor for EH in PCOS patients, the AUC for FMI prediction of endometrial hyperplasia in PCOS patients was 0.82. FMI had significant positive correlations with fasting glucose, fasting insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), total cholesterol, triglyceride, low-density lipoprotein, triglyceride/high-density lipoprotein, and uric acid levels. FMI was correlated with HOMA-IR and uric acid at 0.602 and 0.649 respectively in PCOS patients.Conclusion: Increased FMI and altered glucolipid metabolism as key factors associated with a higher risk of EH in patients with PCOS. Monitoring body composition and metabolic health in PCOS patients could help identify those at greater risk of EH, guiding preventive interventions.Keywords: polycystic ovary syndrome, endometrial hyperplasia, body composition, glycolipid metabolism, metabolic syndrome

Ran Guo,1 Hanjing Liao,2 Yinuo Meng,3 Xiaoyi Shi,4 Yuting He,4 Zhixiang Zhu,2 Wenzhi Guo1,4 1Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Modern Research Center of Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Department of Faculty of Life Sciences & Medicine, King’s College London, London, UK; 4Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Wenzhi Guo, Henan Key Laboratory of Digestive Organ Transplantation, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, People’s Republic of China, Email fccguowz@zzu.edu.cn Zhixiang Zhu, Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Email zzx@bucm.edu.cnBackground: Fostamatinib is the first spleen tyrosine kinase inhibitor approved for the treatment of chronic adult immune thrombocytopenia via blocking autoantibody-mediated platelet phagocytosis. Nevertheless, the potential of fostamatinib as therapeutic agent against acute inflammatory diseases has not been examined. This study aimed to investigate the effects of fostamatinib on the activation of macrophages and neutrophils and its therapeutic effects on SIRS.Methods: First, RT-qPCR and ELISA were used to detect the effects of fostamatinib on the expression and secretion of inflammatory factors by peritoneal macrophages (PMs) induced with TLR agonists. The activation and ROS release of neutrophils were detected by flow cytometry. Subsequently, the therapeutic effect of fostamatinib on LPS-induced SIRS in mice was examined. Finally, we also explored the underlying mechanisms of fostamatinib exerting pharmacodynamic effects by analyzing its effects on LPS-induced gene expression profile and the activation of signaling pathways in PMs through transcriptome sequencing and Western blot.Results: We found that fostamatinib inhibited the expression and secretion of TNF-α, IL-6, CCL2, CCL3, and CXCL10 (&ast;P < 0.05) in PMs induced by LPS. Fostamatinib also reduced the activation of neutrophils stimulated by LPS, and suppressed the release of ROS by neutrophils. In SIRS mice, fostamatinib diminished the levels of inflammatory factors, and inhibited the excessive consumption of neutrophils in bone marrow. Transcriptome sequencing results showed that fostamatinib significantly inhibited the transcription of Cxcl10, Isg20, Mx1, Rsd2, etc. (&ast;P < 0.05) in PMs induced by LPS. Meanwhile, fostamatinib selectively blocked the phosphorylation of STAT1 and STAT3 in PMs induced by LPS and cytokines (IFN-γ and IL-6).Conclusion: Fostamatinib can significantly inhibit LPS-induced inflammatory response through blocking STAT1/3 signaling pathways and has the potential to be used in the therapy of acute inflammatory diseases, especially SIRS and sepsis, which are resulting from the infection of Gram-negative bacteria.Keywords: fostamatinib, inflammation, macrophages, neutrophils, STAT1/3 signaling pathways, systemic inflammatory response syndrome

Li Wei,1,2,&ast; Xingying Zhao,1,2,&ast; Xiaomei Chen,1 Yuxuan He,1 Jia Liu,1 Jishu Xian,2 Yanni Yang1 1School of Nursing, Army Medical University (Third Military Medical University), Chongqing, 434008, People’s Republic of China; 2Neurosurgery Department, the First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing, 434008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanni Yang, School of Nursing, Army Medical University (Third Military Medical University), No. 30 Gaotanyan Street, Shapingba District, Chongqing, 434008, People’s Republic of China, Email yangyanni@tmmu.edu.cnBackground: Providing informal care for patients with neurocritical diseases is a challenging job, and family caregivers usually experience psychological distress and high caregiver burden. Previous studies have focused on caregiver burden for patients in the home rehabilitation stage, while few studies investigate caregiver burden among informal caregivers of early postoperative inpatients.Objective: This study aimed to investigate caregiver burden for caregivers of patients with neurocritical diseases during hospitalization and to identify predictive factors related to caregiver burden.Methods: From November 2023 to April 2024, a cross-sectional study was conducted using a convenience sampling method to assess patients with neurocritical disease and their family caregivers. The fundamental data regarding patients and caregivers were examined. Family caregivers were requested to complete the Zarit Burden Interview (ZBI), the Coping Adaptation Processing Scale (CAPS-15), the Chinese Auditory Verbal Learning Test of Huashan Version (AVLT-H), the Multifactorial Memory Questionnaire (MMQ), and the Hospital Anxiety and Depression Scale (HADS-A). The variables associated with caregiver burden were identified through the use of multiple linear regression analyses.Results: 300 patients and their family caregivers participated in the study. Predominantly male family caregivers accounted for 55.7%, and the mean age was 46.7 ± 13.1 years. The patients’ average age was 52.8 ± 14.3 years, 151 (50.3%) were men, and 153 (50.3%) had brain tumors. The average caregiver burden was 33.94 ± 17.2. Family caregivers of inpatients with neurocritical diseases experienced a mild to moderate caregiver burden. Patients’ physical function, caregiver’s age, relationship with patients, comorbid chronic disease status, memory function, adaptation level, and anxiety independently predicted caregiver burden, accounting for 66.3% of the total variation.Conclusion: Family caregivers of inpatients with neurocritical diseases experience mild to moderate level of caregiver burden. Tailored early support plans should be developed based on caregivers’ characteristics, including anxiety strategies, memory support, communication optimization, and role adjustment, to reduce their burden.Keywords: caregiver burden, family caregivers, influencing factors, neurocritical disease, hospitalization

Yi Zheng,1,2 Xinyu Wang,1 Yang He,1 Shuo Chen,1 Linhai He,1,3,&ast; Yi Zhang1,&ast; 1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 2Department of Stomatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3First Clinical Division, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai He; Yi Zhang, Email helinhai07@126.com; zhangyi2000@263.netPurpose: Exosomes from mesenchymal stromal cells (MSCs) can prevent the development of medication-related osteonecrosis of the jaw (MRONJ) by promoting tooth socket wound healing; however, the exact mechanism remains to be clarified. In this study, our aim was to explore the mechanisms of exosomes derived from adipose-derived mesenchymal stromal cells (ADSCs) in preventing MRONJ by focusing on macrophage M1 polarization and pyroptosis.Methods: The MRONJ model was established by the administration of zoledronate and tooth extraction. Exosomes isolated from the supernatant of ADSCs were mixed with hydrogel and locally injected into the extraction site after tooth extraction. Stereoscope observations, micro computed tomography (microCT), and histological analysis were used to assess tooth socket wound healing.Results: The results showed that exosomes could effectively avoid MRONJ via accelerating gingival wound healing and tooth socket bone regeneration. Mechanistically, zoledronate triggered the NF-κB signaling pathway and promoted p65 transferring into the nucleus in macrophages, resulting in macrophage M1 polarization and pyroptosis-mediated tissue inflammation, while exosomes could reduce macrophage pyroptosis and pro-inflammation cytokines release by suppressing the NF-κB/NLRP3/IL-1β axis. Additionally, IL-1RA derived from exosomes plays a key role in preventing MRONJ. Pyroptosis-related and inflammatory-related processes were upregulated in MRONJ patients further confirmed by assessing MRONJ gingival samples and healthy gingival tissues.Conclusion: ADSCs-derived exosomes could effectively promote tooth socket healing and prevent MRONJ by inhibiting M1 macrophage activation and pyroptosis by blocking the NF-κB/NLRP3/IL-1β axis.Keywords: Medication-related osteonecrosis of the jaw, exosomes, macrophage M1 polarization and pyroptosis, primary wound healing, NF-κB/NLRP3/IL-1β axis

Jiale Wu,1,2 Kaihong Shi,1,2 Wei Chao,1,2 Zeyu Qin,1,2 Youhui Hu,1,2 Yihua Yang,1,2 Yuan He,1,2 Yabing Hua,1,2 Ziming Zhao1,2 1Department of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Yabing Hua; Ziming Zhao, Department of Pharmacy, Xuzhou Medical University, Xuzhou, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China, Email huayabing@xzhmu.edu.cn; zmzhao@xzhmu.edu.cnBackground: The immunotherapeutic approach utilizing Natural Killer (NK) cells for cancer treatment has garnered significant interest owing to its inherent cytotoxicity, immunomodulatory properties, demonstrated safety in in vivo studies. However, multiple immunosuppressive mechanisms in the tumor microenvironment (TME) suppress the anticancer effect of NK cells in the treatment of solid tumors. Herein, a smart NK cell drug delivery system (DDS) with photo-responsive and TME-responsive properties was designed.Methods: The NK cell DDS consists of two parts: the carrier is living NK cell with pH-low (abbreviated as NKpH) insertion peptide on its surface, the cargo is reductive-responsive nanogel (NG) encapsulated siRNA and photosensitizer (abbreviated as SP-NG), the final carrier was abbreviated as SP-NG@ NKpH. Firstly, pHLip helped artificially modified NK cell target and anchor onto cancer and exert the efficacy of cellular immunotherapy. Then, the strategy of combining photoactivation and bioreduction responsiveness achieved the precise release of cargos in cancer cells. Finally, the DDS combined the effect of the immunotherapy of NK cell, the gene therapy of siRNA, and the photodynamic therapy of photosensitizer.Results: Under near-infrared laser irradiation, SP-NG@NKpH induced an increase in reactive oxygen species (ROS) within cells, exacerbated cell membrane permeability, and allowed for rapid drug release. Within the tumor microenvironment (TME), NG exhibits highly sensitive reducibility for drug release. The SP-NG released from NK cells can be uptaken by tumor cells. When exposed to near-infrared laser irradiation, SP-NG@NKpH demonstrates significant tumor-targeting specificity and cytotoxicity.Discussion: The combined effect of the immunotherapy of NK cell, the gene therapy of siRNA, and the photodynamic therapy of photosensitizer obtained a stronger cancer killing effect in vitro and in vivo. Therefore, this versatile NK cell DDS exhibits a good clinical application prospect. Keywords: natural killer cells, photo-responsive, TME-responsive, anticancer, cellular immunotherapy, nanogel

Yin Tang,1– 5,&ast; Yuzhe He,1– 4,&ast; Lidong Wu1– 4 1Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Orthopedic Surgery, Ningbo No.2 hospital, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lidong Wu, Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-057187783777, Email wulidong777@sina.comBackground: Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS.Methods: Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC50) values. RNA immunoprecipitation and pull-down, as well as reporter assays, investigated interactions between hsa_circ_0078767, miR-188-3p, and GPX4 within OS cells exhibiting DOX resistance.Results: OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4.Conclusion: Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.Keywords: GPX4, hsa_circ_0078767, doxorubicin, miR-188-3p, osteosarcoma

Chao Wang,1,&ast; Mei Zhao,2,&ast; Yuanyuan Yue,3 Chao Hu,2 Chunqiu Zhou,2 Zhongyi Zhang,2 Yunliang He,4 Yaqi Luo,4 Tao Shen,2 Sijie Dang,4 Yang Yang,4 Yong Zhang2,4 1Traditional Chinese Medicine Department, Qitai Hospital of the Sixth Division, Xinjiang, 831899, People’s Republic of China; 2College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Department of Ultrasound, Chengdu First People’s Hospital, Chengdu, 610095, People’s Republic of China; 4Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Zhang; Yang Yang, Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, People’s Republic of China, Email 18692213920@163.com; 18721326@qq.comBackground: Modified Suanmei-Tang (MST) comprises four plants common to both traditional Chinese medicine and culinary applications, and it can potentially alleviate metabolic-associated fatty liver disease (MAFLD) triggered by a high-fat diet (HFD).Purpose: This research aims to investigate the impact and underlying mechanisms of MST in ameliorating MAFLD caused by an HFD.Methods: UHPLC-Q-Orbitrap-MS/MS was used to determine the constituents of MST and to evaluate its effects on MAFLD mouse models. Transcriptomics, network pharmacology, and bioinformatics analysis (including Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis) were utilized to further clarify the mechanisms by which MST acts on MAFLD. The experimental methods included ELISA, real time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, molecular docking, and metabolomics. Transcriptomics was integrated with metabolomics to find correlations between differentially expressed genes and metabolites, and crucial genes were validated through RT-qPCR.Results: A total of 23 components of MST were identified. The formulation was found to alleviate metabolic disorders, obesity, insulin resistance, inflammation, and oxidative stress in mice with MAFLD. The findings indicate that MST promoted autophagy by suppressing phosphorylation in the PI3K/AKT/mTOR pathway and enhancing lipid management in the livers of MAFLD mice.Conclusion: MST could effectively improve lipid metabolism disorders and liver lipid deposition in MAFLD mice, and its mechanism might be related to regulating the PI3K/AKT/mTOR pathway to improve autophagy. Keywords: modified Suanmei-Tang, MAFLD, transcriptomics, network pharmacology, metabolomics

Hao Yang,1 Yayun Lu,2 Lina Zhao,3 Yufeng He,1 Yuecheng He,4 Dong Chen5,6 1Department of Stomatology, Health Examination Center of Shanghai Health and Medical Center, Huadong Sanatorium, Wuxi, People’s Republic of China; 2Nursing Department, Health Examination Center of Shanghai Health and Medical Center, Huadong Sanatorium, Wuxi, People’s Republic of China; 3Department of Stomatology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Department of Oral and Maxillofacial Implantology, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China; 5Department of Endodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, People’s Republic of China; 6Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Dong Chen, Department of Endodontics, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, 356 East Beijing Road, Shanghai, 200001, People’s Republic of China, Email chendong@fudan.edu.cn Yufeng He, Department of Stomatology, Health Examination Center of Shanghai Health and Medical Center, Huadong Sanatorium, Wuxi, 214065, People’s Republic of China, Email 1721671899@qq.comAim: The research examined the correlation between the weight-adjusted waist index (WWI) and periodontal disease, as well as the intermediary influence of triglyceride glucose (TyG) index-related indicators, utilizing a health examination dataset.Methods: This cross-sectional study included 39,522 subjects from health check-up database of Shanghai Health and Medical Center. The WWI was determined by applying a formula that includes dividing the waist circumference (WC) by the body weight’s square root. Periodontitis diagnosis followed the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. The correlation between the WWI and periodontitis was investigated through multivariate logistic regression and smoothing curve fitting. Subgroup analysis and interaction tests were also performed to verify the stability of the results. A mediation analysis was conducted to quantify the direct and indirect influences mediated by the TyG-related indicators [TyG, TyG -body mass index (TyG-BMI), TyG -waist-to-height ratio (TyG-WHtR), and TyG-waist circumference (TyG-WC)].Results: Multivariable logistic regression analysis revealed the positive association of WWI and periodontitis (OR=1.37, 95% CI: 1.30– 1.43). Compared to those in the lowest quartile of WWI, participants in the highest quartile exhibited a 82% higher likelihood of periodontitis (OR=1.82, 95% CI: 1.69– 1.96). Subgroup analysis and interaction tests revealed that this positive correlation was consistent in gender, BMI, WC, smoking, drinking, hypertension, and dyslipidemia (P for interaction > 0.05), with some variations noted by age and diabetes status (P for interaction< 0.05). Mediation analysis showed that the proportions mediated by TyG, TyG-BMI, TyG-WC, and TyG-WHtR on the association of WWI and periodontitis risk were 13.13%, 6.30%, 16.46% and 19.79%, respectively.Conclusion: A higher WWI in Chinese adults was linked to an increased likelihood of periodontitis, and this correlation could be partially explained by elevated levels of TyG index-related indicators.Keywords: weight-adjusted waist index, periodontitis, triglyceride glucose index, mediating effect

Yuting Wang,&ast; Yan Liu,&ast; Kan Liu, Yuan He, Hui Ding Department of Pulmonary and Critical Care Medicine, Yixing People’s Hospital Affiliated to Jiangsu University, Yixing, Jiangsu Province, 214200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Ding, Email dh1350519@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is one of the most common clinical respiratory illnesses, defined by permanent pathological deterioration that leads to respiratory failure. Regarding COPD treatment, oxygen therapy is very important. Non-invasive positive pressure ventilation (NPPV) is a technique for non-invasive mechanical ventilation that enables patients to get positive pressure support without the need of an artificial airway. Instead, it merely employs the mask by covering the mouth and nose, or simply the nose of patients. NPPV has been shown to be beneficial for COPD patients experiencing respiratory failure. High-flow nasal cannula (HFNC) oxygen therapy shows some advantages, including the reduction of anatomical dead space, the prompt correction of low oxygen levels as well as the improvement of patients’ tolerance. Owing to its continuous progress, ventilation technology strongly improves COPD treatment. In this study, the authors analyze the application of NPPV and HFNC in COPD so as to provide recommendations for mechanical ventilation treatment.Keywords: chronic obstructive pulmonary disease, high flow nasal cannula, non-invasive positive pressure ventilation, respiratory failure

Dan Kuai,1,2 Jiayu Wei,1,2 Mengying Li,1,2 Lu Chen,3 Dongcan Zhang,1,2 Xiaoyan Li,1,2 Ying He,1,2 Shiqi Liu,1,2 Huiying Zhang,1,2 Wenyan Tian,1,2 Yingmei Wang1,2 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 2Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 3Department of Gynecology and Obstetrics, The First People’s Hospital of Datong City, Datong, Shanxi, 037000, People’s Republic of ChinaCorrespondence: Wenyan Tian; Yingmei Wang, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154, Anshan Road, He Ping District, Tianjin, People’s Republic of China, 300052, Tel +86 60362277; 86-022-60362255, Email tianwenyan1108@163.com; wangyingmei1978@126.comObjective: To evaluate the therapeutic outcomes of weight loss and metformin use in patients with endometrial hyperplasia (EH), and to identify the factors influencing treatment efficacy.Methods: This study included data from patients diagnosed with either EH or endometrial atypical hyperplasia (EAH). Patients selected a progestin treatment regimen based on their diagnosis. Those with concurrent obesity or insulin resistance received additional weight management support and metformin therapy. Follow-up assessments were conducted every 3– 6 months.Results: A total of 202 patients were included. The metformin group exhibited significantly greater improvement in abnormal uterine bleeding (91.5% vs 57.1%, p < 0.001) and in ultrasound findings (91.5% vs 66.7%, p < 0.001) than the non-metformin group. Patients who achieved > 3% weight loss and those using metformin showed a significantly higher rate of disease reversal than those with ≤ 3% weight loss (91.2% vs 77.6%, p = 0.034) and the non-metformin group (93.2% vs 52.4%, p < 0.001). At follow-up durations exceeding 12 months, metformin use was associated with a significantly higher disease reversal rate (82.1% vs 42.9%, p = 0.048) and a lower recurrence rate (12.8% vs 28.6%, p = 0.048). Weight loss of > 3% (odds ratio: 0.041, 95% confidence interval: 0.004– 0.437, p = 0.008) and metformin use (odds ratio: 0.059, 95% confidence interval: 0.011– 0.311, p = 0.001) were both independently associated with improved reversal rates in patients with EH/EAH.Conclusion: Combining progestin therapy with weight loss and metformin is more effective in reversing EH than progestin alone. Regular metformin use, alongside weight loss, serves as a protective factor in EH management, with the protective effect of metformin increasing with longer use.Keywords: endometrial hyperplasia without atypia, comprehensive management, weight management, metformin

Chong Zhang, Jianqing Xu, Ming Wang, Yue He, Yumei Wu Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yumei Wu, Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, 17 Qihelou St, Dongcheng District, Beijing, 100006, People’s Republic of China, Email wym597118@ccmu.edu.cnPurpose: The aim of this study was to explore the immune subtypes of endometrial cancer (EC) and its characteristics by immunogenes from the perspective of multidimensional genomics (multi-omics).Patients and Methods: Immune subtypes were carried out using an unsupervised non-negative matrix factorization clustering (NMF) method and their characteristics were analysed. Key genes were identified using random forest analysis. A predictive model for immune subtypes and their clinical prognosis were constructed. The relationship between immune subtypes and molecular subtypes was investigated.Results: Two immune subtypes C1 and C2 were available. C2 patients were younger, less graded, had significantly higher immune cell infiltration, immune checkpoint expression, tumor neoantigens, tumor mutation load than C1 (P< 005). S100A9, CD3D, CD3E, HLA-DRB1 and IL2RB were the key genes with significant survival outcomes. S100A9 expression was lower in C2 than C1, and IL2RB, HLA-DRB1, CD3E and CD3D expression was higher than C1 (P< 0.05). The predictive accuracy of five key genes for immune subtypes was good, with a Receiver operating characteristic of 0.941. The incidence of TP53abn type in C2 was significantly lower than that of C1, and the incidence of POLE type was significantly higher than that of C1 (P< 0.0001).Conclusion: EC can be divided into two immune subtypes based on immunogenes. Low expression of S100A9 and high expression of IL2RB, HLA-DRB1, CD3E, and CD3D suggest sensitivity to immunotherapy and a good prognosis.Keywords: endometrial cancer, immune subtype, immunotherapy, multidimensional genomic, tumor immune microenvironment

Yuping He,1,2,&ast; Minghao Xu,2,3,&ast; Chenhao Zhou,2,3 Qiongzhu Dong,2,4 Zhiqiu Hu,2,4,5 Ning Ren2– 4 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People’s Republic of China; 3Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China; 4Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Ren, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86 21 64041990, Email ren.ning@zs-hospital.sh.cn Zhiqiu Hu, Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, People’s Republic of China, Tel +86 21 64923400, Email huzq@fudan.edu.cnPurpose: Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker.Patients and Methods: This study collected tumor and peritumoral archived specimens from 180 HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV.Results: In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC.Conclusion: CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.Keywords: Cathepsin V, HCC, biomarker, immune infiltrating cells, PD-1 inhibitor

Yaojie Fu,1,&ast; Yujing He,2,&ast; Caixia Zheng,3 Jianyong Zeng,3 Hongjie Ou3 1Emergency Department, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Intense Care Unit, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongjie Ou, Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, No. 10, Shanggu Road, Xiamen, Fujian, 361001, People’s Republic of China, Email ouhongjie@sina.com Yujing He, Intense Care Unit, The First Affiliated Hospital of Xiamen University, No. 10, Shanggu Road, Xiamen, Fujian, 361001, People’s Republic of China, Email heyujing1988@126.comIntroduction: Sepsis remains a significant global health challenge due to its high morbidity and mortality rates. Disseminated Intravascular Coagulopathy (DIC) represents a critical complication of sepsis, contributing to increased mortality and economic burden. Despite various prognostic scoring systems, there is a lack of a specific model for DIC prediction in sepsis patients.Methods: This observational study included 336 sepsis patients. Clinical and laboratory data were collected, and prognoses were defined according to established criteria.Results: We enrolled 336 patients, with 304 in the non-DIC group and 32 in the DIC group. Patients with DIC had notably lower platelet (PLT) and higher levels of prothrombin time (PT), lactate (LAC), and procalcitonin (PCT) compared to those without DIC. Univariate and multivariate analyses identified risk factors associated with the DIC, showing that PLT (OR = 0.985, 95% CI 0.978– 0.993, p < 0.001), PT level (OR = 1.140, 95% CI 1.004– 1.295, p = 0.044), and LAC (OR = 1.101, 95% CI 0.989– 1.226, p = 0.078) were related factors. A risk model was established, and its sensitivity and specificity in predicting DIC among sepsis patients were assessed by comparing it to the SOFA score. The area under the ROC curve for the model was 0.850, while the SOFA score was 0.813. With a model score >− 2.12, the sensitivity for predicting DIC was 84.4%, and the specificity was 75.0%.Conclusion: Our study introduces a predictive model for DIC detection in sepsis patients, emphasizing the need for clinicians to focus on patients with high model scores for timely intervention.Keywords: sepsis, risk model, disseminated intravascular coagulopathy, platelet, mortality

Wenrui Ji,1,&ast; Xiaomin Xie,1,&ast; Guirong Bai,1 Yalei Fan,2 Yanting He,1 Li Zhang,1 Haiyan Zhou,1 Ling Li,1 Dan Qiang,1 Huan Li1 1Department of Endocrinology, the First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China; 2The Second Clinical Medical School of Ningxia Medical University, Yinchuan, 750001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomin Xie, Department of Endocrinology, the First People’s Hospital of Yinchuan, Liqun West Street No. 2, Xingqing District, Yinchuan, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Tel +8613895189599, Email xxm2324@126.comPurpose: COVID-19 viral infection results in dysregulation of the complement system and a decrease in cortisol and adrenocorticotropin hormone (ACTH) levels. This study aimed to explore the complement system, as well as cortisol and ACTH responses in patients with post-COVID-19 conditions (PCC) and type 2 diabetes mellitus (T2DM).Patients and Methods: This study recruited 31 patients with PCC and T2DM (PCC-T2DM), 19 patients with PCC (PCC), 10 patients with T2DM (T2DM), and 10 healthy participants (control). Cortisol and ACTH in the PCC and PCC-T2DM groups were assessed using the insulin tolerance test. In the fasting state, serum samples were collected for proteomic analyses. Spearman correlation analysis was performed between proteins and cortisol, as well as between proteins and ACTH.Results: Cortisol and ACTH levels were consistently decreased in the PCC and PCC-T2DM groups. Proteomic analyses revealed that most of the differentially abundant proteins (DAPs) in the PCC vs control and PCC-T2DM vs T2DM were involved in the coagulation and complement cascade, and the essential complement C3 was significantly upregulated in the PCC and PCC-T2DM groups when compared to their controls. Additionally, complement-related DAPs in the PCC vs control and PCC-T2DM vs T2DM were significantly correlated with cortisol and ACTH levels. In comparing PCC-T2DM samples with PCC samples, we found that upregulated DAPs were linked to the complement system and other immune system, and most DAPs were negatively correlated with cortisol and ACTH.Conclusion: Our study revealed that T2DM exacerbated dysregulation of the complement system in patients with PCC, and significant correlations were present between complement protein levels and those of cortisol and ACTH. These results provide novel insights into the dysregulation of complement and endocrine hormones in patients with PCC and T2DM.Keywords: post-COVID-19 condition, type 2 diabetes mellitus, complement, cortisol, adrenocorticotropin hormone

Weijun Wan,1,2,&ast; Yunjing Pan,1,2,&ast; Jinshu Pang,1,2 Xiumei Bai,1,2 Lipeng Li,1,2 Tong Kang,1,2 Jiamin Chen,1,2 Rong Wen,1 Dongyue Wen,1 Hong Yang,1– 3 Yun He1,2 1Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor/Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun He; Hong Yang, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email heyun@stu.gxmu.edu.cn; yanghong@gxmu.edu.cnPurpose: The explosive progression of residual hepatocellular carcinoma (HCC) following incomplete thermal ablation is challenging, and the underlying mechanisms require further exploration. We investigated the mechanism by which Forkhead box P4 (FOXP4) promotes the malignant transformation of residual HCC cells through N-deacetylase and N-sulfotransferase 2 (NDST2) after incomplete thermal ablation.Methods: The clinical significance of FOXP4 and NDST2 in HCC was evaluated using big data analysis. FOXP4 expression was detected in clinical samples of HCC. The gene expression levels in an in vitro heat-stressed HCC cell model were determined using quantitative real-time PCR (RT-qPCR) and Western blotting. The effects of the genes on heat-stressed HCC cells were investigated using Cell Counting Kit-8 (CCK-8), scratch, Transwell migration, and invasion assays. Additionally, the regulatory relationship between FOXP4 and NDST2 was validated using the Cleavage Under Targets and Tagmentation (CUT&Tag) experiments and phenotypic assays.Results: High FOXP4 expression was correlated with liver cancer occurrence and development. In the heat-stressed HCC cell model, downregulating FOXP4 inhibited cancer cell progression. Besides, there was a positive association between FOXP4 and NDST2 in liver cancer. Suppressing FOXP4 reduced NDST2 expression in the heat-stressed HCC cells. Furthermore, reducing NDST2 expression weakened the biological behavior of heat-stressed HCC cells.Conclusion: FOXP4 and NDST2 are crucial in the incomplete thermal ablation of residual cancer. FOXP4 might regulate the biological progression of residual HCC after incomplete thermal ablation through NDST2.Keywords: ablation therapy, gene expression regulation, cancer inhibition, hepatocellular carcinoma

Mengyao Shi,1,&ast; Xueyu Mao,2,&ast; Xuechun Wu,2 Min Chu,2 Huicong Niu,2 Lulu Sun,1 Xinyue Chang,1 Yu He,1 Yi Liu,1 Daoxia Guo,3 Yonghong Zhang,1 Zhengbao Zhu,1 Jing Zhao2,4 1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 4Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China, Email zhao_jing@fudan.edu.cn Zhengbao Zhu, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, People’s Republic of China, Email zbzhu@suda.edu.cnBackground: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.Keywords: prealbumin, ischemic stroke, prognosis, cohort study

Yuxia He,1,2,&ast; Yuling Mao,1,2,&ast; Yaoming Chen,3,&ast; Ling Tang,1 Haiyu Hou,1 Chenyun Sun,1 Yaqi Shang,1 Na-Na Tan,4 Lei Li1,2 1Department of Obstetrics and Gynecology, Center for Reproductive Medicine; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Health Management; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Li; Na-Na Tan, Email lileigo@foxmail.com; tannana0212@126.comPurpose: This study investigated the incidence and microbial etiology of embryo contamination in assisted reproductive technology (ART), and its influence on embryo development, pregnancy and neonatal outcomes.Methods: A retrospective analysis was conducted on embryo contamination at the Reproductive Centre of the Third Affiliated Hospital of Guangzhou Medical University, between 2018 and 2021.Results: In the period from 2018 to 2021, the average incidence of embryo contamination was 0.12%. Bacterial growth was observed in 39 cases, with a preponderance of Escherichia coli (20, 51.28%), Streptococcus agalactiae (7, 17.95%). The fertilization rate of contaminated embryos was 18.18% (Klebsiella pneumoniae) to 94.79% (S. agalactiae), the cleavage rate was 9.09% (Enterobacter cloacae) to 98.90% (S. agalactiae), and the available embryo rate of Day 3 was 0 (Klebsiella pneumoniae, Enterobacter cloacae) to 63.33% (S. agalactiae). Blastocyst formation rate was 3.23% (Proteus mirabilis) to 64.29% (Streptococcus mitis). E. coli contamination occurred mostly on Day 1, and S. agalactiae on Days 3 and 5. After rinsing and rescuing treatment, six healthy male babies were born.Conclusion: E. coli and S. agalactiae were the most common bacterial embryo contaminants. Most microbial contamination can significantly decrease the fertilization rate. Embryo transfer after rinsing and continuing culture had no negative effect on neonatal outcomes, but there was an increased risk of early abortion due to E. coli contamination.Keywords: in vitro fertilization, microbial contamination, remedial treatment, pregnancy outcome, neonatal outcomes

Xixuan Zhao,1– 4 Yining He,5 Juzhao Zhang,1– 3 Senlin Lin,1– 3 Haidong Zou,1– 4 Yingyan Ma1– 4 1Shanghai Eye Diseases Prevention & Treatment Center/ Shanghai Eye Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2National Clinical Research Center for Eye Diseases, Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Biostatistics Office of Clinical Research Unit, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Yingyan Ma; Haidong Zou, Email mYy_29@163.com; zouhaidong@sjtu.edu.cnAbstract: Myopia is increasingly prevalent in children. Its association with insufficient sleep has been studied, yielding inconsistent findings. This review aims to assess the association of insufficient sleep with myopia and myopia-related refractive parameters in children. A total of 657 articles were identified, of which 40 were included in the systematic review and 33 were included in the meta-analysis. Results showed that insufficient sleep was significantly associated with an increased prevalence of myopia (odds ratio [OR] = 1.59; 95% confidence interval [CI] = 1.31, 1.95; I2 = 99%), and an increased prevalence of high myopia (OR = 3.36; 95% CI = 1.26, 9.00; I2 = 96%). Shorter sleep duration was significantly linked to faster changes in axial length (AL) (β = 0.05; 95% CI = 0.02, 0.08; I2 = 0%). However, correlation between insufficient sleep and the incidence of myopia, spherical equivalent refraction, corneal curvature radius (CR) and AL/CR were insignificant. Moreover, the effect of insufficient sleep on premyopia and astigmatism was not well-studied. The results of this study suggest that insufficient sleep may be an important risk factor for the development of myopia in school-aged children. Therefore, in addition to ensuring sufficient outdoor activities and reducing near work, it is necessary to inform children and parents about the importance of adequate sleep to mitigate the risk of myopia.Keywords: insufficient sleep, myopia, children, axial length, refractive parameters

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

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

Mingyuan Ren,1,2,&ast; Yijia He,1,&ast; Jianzhong Zhang,3 Jinfang Zhang,1,2 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Technical Innovation Center for Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfang Zhang; Guoqiang Zhang, Email 58303110@hebmu.edu.cn; 57702800@hebmu.edu.cnAbstract: Tjalma’s syndrome is a benign combination of ascites, pleural effusion, and elevated CA-125 occurring in patients with systemic lupus erythematosus. Reports of Tjalma’s syndrome are scarce. An elevated CA-125 level often suggests the possibility of the presence of a malignant tumor. We report a case of generalised erythema and blisters with pruritus, massive unilateral pleural effusion and elevated CA-125. This patient was finally diagnosed with bullous systemic lupus erythematosus after exclusion of tumour and other maculopapular disorders. We hope that this particular case may provide a more comprehensive and novel diagnostic idea of systemic lupus erythematosus and pleural effusion, avoiding unnecessary anxiety, laboratory tests and surgical interventions.Keywords: systemic lupus erythematosus, bullous systemic lupus erythematosus, pleural effusion, Tjalma’s syndrome, CA-125

Jingfei Weng,1,2,&ast; Yuyao Xiao,1,&ast; Jing Liu,3,&ast; Xiaohua Liu,4 Yuqing He,2 Fei Wu,1 Xiaoyan Ni,1 Chun Yang1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang; Xiaoyan Ni, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 18702135336 ; +86 15201803582, Email dryangchun@hotmail.com; nixiaoyan1103@126.comPurpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student’s t test, χ 2 test, and multivariable regression analysis.Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson–Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.Keywords: liver neoplasms, magnetic resonance imaging, P53-mutated

Yue He,1,&ast; Qianhan Liu,1,&ast; Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Yuru He,1,2 Xing Wang,1,2 Zuowei Wang,3,4 Ping Zhang,5 Xiaojia Huang,3,4 Meihong Yu,5 Jill K Murphy,6 Erin E Michalak,6 Jing Liu,6 Tao Yang,1,2 Xiaorui Yang,7 Yiru Fang,1,8,9 Raymond W Lam,6 Jun Chen1,2 1Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 3Division of Mood Disorders, Shanghai Hongkou Mental Health Center, Shanghai, People’s Republic of China; 4Clinical Research Center for Mental Health, School of Medicine, Shanghai University, Shanghai, People’s Republic of China; 5Fengxian District Mental Health Center, Shanghai, People’s Republic of China; 6Department of Psychiatry, University of British Columbia, Vancouver, Canada; 7Department of Psychology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 8Department of Psychiatry & Affective Disorders Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 9CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Jun Chen, Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China, Tel +86 21-34773367, Email doctorcj2010@gmail.com Raymond W Lam, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada, Tel +1 604-822-7325, Email r.lam@ubc.caPurpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder.Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points.Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up.Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.Keywords: major depressive disorder, measurement-based care, enhanced measurement-based care, smartphone-based intervention

Yuting Xiang,1,2,&ast; Li Tang,1,&ast; Hua Pang,3 Han Xu,1,2 Yiman He,1,2 Yuyue Feng,3 Linjun Ju,3 Liang Zhang,1 Dong Wang1 1Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Zhang; Dong Wang, Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email zhangliang338@cqmu.edu.cn; wang57554@163.comBackground: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration.Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments.Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice.Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.Keywords: ultrasound, thermal effect, vasodilatation, drug delivery, tumor microenvironment

Robin Schmidt,1,2 Charlie Alexander Hamm,1,3 Christopher Rueger,1 Han Xu,1 Yubei He,1,2 Luzie Alexandra Gottwald,4 Bernhard Gebauer,1 Lynn Jeanette Savic1– 3 1Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiology, Berlin, 13353, Germany; 2Experimental Clinical Research Center (ECRC) at Charité - Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, 13125, Germany; 3Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, 10117, Germany; 4Vivantes Humboldt-Klinikum, Berlin, 13509, GermanyCorrespondence: Lynn Jeanette Savic, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Radiologie, Augustenburger Platz 1, Berlin, D-13353, Germany, Email lynn-jeanette.savic@charite.dePurpose: Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE).Patients and Methods: Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher’s exact and t-test, Kaplan–Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson’s correlation.Results: OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed.Conclusion: The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.Keywords: cancer imaging, hepatocellular carcinoma, microvascular invasion, magnetic resonance tomography, predictive imaging biomarkers

Yangshuo Li,1,&ast; Zhihao Zhou,1,2,&ast; Xiaolan Liang,1,&ast; Jie Ding,1 Yalun He,1 Shuai Sun,1 Wen Cheng,1 Zhexin Ni,1,3 Chaoqin Yu1 1Department of Traditional Chinese Gynecology, the First Affiliated Hospital of Naval Military Medical University (Changhai Hospital), Shanghai, People’s Republic of China; 2Traditional Chinese Medicine Department, No. 929 Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhexin Ni, Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, People’s Republic of China, Email nizxzg@163.com Chaoqin Yu, Department of Traditional Chinese Gynecology, the First Affiliated Hospital of Naval Military Medical University (Changhai Hospital), 168 Changhai Road, Shanghai, 200433, People’s Republic of China, Email cqyu@smmu.edu.cnIntroduction: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.Methods: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.Results: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.Discussion: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential. Keywords: endometriosis, single-cell sequencing, interleukin-17, gut microbiota, bile acids, myeloid cell

Yingzi He,&ast; Jingjing Wang,&ast; Jianan Wang, Ruojun Qiu, Shuo Wang, Ting Jin, Hong Li, Fenping Zheng Department of Endocrinology, the Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fenping Zheng, Department of Endocrinology, the Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Zhejiang, 310016, People’s Republic of China, Email 3407004@zju.edu.cnObjective: This study assessed possible associations among physical activity (PA), sitting time (ST), metabolic syndrome (MetS), and the individual components thereof. We analyzed the entire study sample and subpopulations stratified by visceral fat area (VFA). We hypothesized that individuals with elevated VFA might respond differently to modifiers of metabolic health, including PA and ST.Methods: This cross-sectional study, conducted between March and May 2010, enrolled 957 adults with abdominal magnetic resonance imaging (MRI) aged 40– 65 years living in the urban communities in Hangzhou, China. PA and ST were recorded using the standard International Physical Activity Questionnaire (IPAQ) and categorized into three levels. The ethnicity-specific cutoff for central obesity was VFA ≥ 80 cm2 on MRI according to Chinese population-based research. Multiple logistic regression models were used to analyze the associations between PA, ST, MetS and its components.Results: In the total subject population, participants reporting high level of PA were at a lower risk of MetS (OR = 0.46, 95% CI: 0.25, 0.86) than those declaring low PA. In the subgroup population with VFA ≥ 80 cm2 (ie, with central obesity), moderate-to-high PA levels were associated with a lower risk of MetS (p for trend < 0.05) and a lower risk of decreased high-density lipoprotein cholesterol (HDL-C) concentrations (p for trend < 0.05). In addition, ST > 3 h/day was a risk factor for both MetS (p for trend < 0.05) and hypertriglyceridemia (p for trend < 0.05) in the total subject population. While in the central obesity subgroup, ST > 3 h/day was found a stronger risk factor.Conclusion: Our study suggests that moderate-to-high levels of PA may have a role in prevention of MetS, and ST > 3 h/day was associated with a higher risk of MetS, particularly in individuals with central obesity.Keywords: metabolic syndrome, physical activity, sitting time, central obesity, visceral fat area

Qing Zhu,1,2,&ast; Yijia He,1,2,&ast; Sijia Chen,1,2 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Provincial Innovation Center of Dermatology and Medical Cosmetology Technology, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqiang Zhang, Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Email 57702800@hebmu.edu.cnAbstract: Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.Keywords: hypertrophic discoid lupus erythematosus, lupus erythematosus, vitiligo, association

Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality

Mengjuan Sun,1,&ast; Jun Wei,1,&ast; Yanhui Su,1,&ast; Yangjingwan He,1 Liang Ge,1 Yan Shen,1 Bohui Xu,2 Yanlong Bi,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, People’s Republic of China; 3Pediatric Intensive Care Unit, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Zheng; Yanlong Bi, Email zhengchunli@cpu.edu.cn; pulong123@163.comPurpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.Keywords: acute lung injury, simvastatin, respiratory distress syndrome, pH response

Chunmei Liu,1 Yuzheng He,2 Jianmin Luo3 1Department of Radiation Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Jianmin Luo, Department of Hematology, The Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86 1348368527, Email luojm31555@163.comPurpose: In situations where pathological acquisition is difficult, there is a lack of consensus on distinguishing between adenocarcinoma and squamous cell carcinoma from imaging images, and each doctor can only make judgments based on their own experience. This study aims to extract imaging features of chest CT, extract sensitive factors through logistic univariate and multivariate analysis, and model to distinguish between lung squamous cell carcinoma and lung adenocarcinoma.Methods: We downloaded chest CT scans with clear diagnosis of adenocarcinoma and squamous cell carcinoma from The Cancer Imaging Archive (TCIA), extracted 19 imaging features by a radiologist and a thoracic surgeon, including location, spicule, lobulation, cavity, vacuolar sign, necrosis, pleural traction sign, vascular bundle sign, air bronchogram sign, calcification, enhancement degree, distance from pulmonary hilum, atelectasis, pulmonary hilum and bronchial lymph nodes, mediastinal lymph nodes, interlobular septal thickening, pulmonary metastasis, adjacent structures invasion, pleural effusion. Firstly, we apply the glm function of R language to perform logistic univariate analysis on all variables to select variables with P < 0.1. Then, perform logistic multivariate analysis on the selected variables to obtain a predictive model. Next, use the roc function in R language to calculate the AUC value and draw the ROC curve, use the val.prob function in R language to draw the Calibrat curve, and use the rmda package in R language to draw the DCA curve and clinical impact curve. At the same time, 45 patients diagnosed with lung squamous cell carcinoma and lung adenocarcinoma through surgery or biopsy in the Radiotherapy Department and Thoracic Surgery Department of our hospital from 2023 to 2024 were included in the validation group. The chest CT features were jointly determined and recorded by the two doctors mentioned above and included in the validation group. The included image feature data are complete and does not require preprocessing, so directly entering statistical calculations. Perform ROC curves, calibration curves, DCA, and clinical impact curves in the validation group to further validate the predictive model. If the predictive model performs well in the validation group, further draw a nomogram to demonstrate.Results: This study extracted 19 imaging features from the chest CT scans of 75 patients downloaded from TCIA and finally selected 18 complete data for analysis. First, univariate analysis and multivariate analysis were performed, and a total of 5 variables were obtained: spicule, necrosis, air bronchogram Sign, atelectasis, pulmonary hilum and bronchial lymph nodes. After conducting modeling analysis with AUC = 0.887, a validation group was established using clinical cases from our hospital, Draw ROC curve with AUC = 0.865 in the validation group, evaluate the accuracy of the model through Calibrate calibration curve, evaluate the reliability of the model in clinical practice through DCA curve, and further evaluate the practicality of the model in clinical practice through clinical impact curve.Conclusion: It is possible to extract influential features from ordinary chest CT scans to determine lung adenocarcinoma and squamous cell carcinoma. The model we have set up performs well in terms of discrimination, accuracy, reliability, and practicality.Keywords: lung cancer, LUAD, LSCC, image features, predict

Guixing Zeng,1 Yujie Lin,2 Peirui Xie,3 Jiarong Lin,4 Yaxing He,5 Junping Wei1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 5School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, People’s Republic of ChinaCorrespondence: Junping Wei, Email weijunping@126.comBackground: To investigate the association between the NLR and the risk of all-cause and cardiovascular mortality in US adults with diabetic kidney disease (DKD).Methods: The data utilized for this analysis were sourced from ten National Health and Nutrition Examination Survey cycles (1999– 2018) with mortality data (up to 31 December 2019) via linkage to the National Death Index. The optimum NLR threshold for predicting survival outcomes was determined through the maximally selected rank statistics. Restricted cubic spline (RCS), weighted Cox proportional hazard regression, stratified analyses, and time-dependent receiver-operating characteristic curve (ROC) were employed to delineate the prospective correlations of the NLR with both all-cause and cardiovascular mortality.Results: In this investigation, a cohort comprising 2581 patients diagnosed with DKD was examined, encompassing 624 individuals with a higher NLR (≥ 3.07) and 1957 subjects with a lower NLR (< 3.07). Over a median follow-up of 79 months (interquartile range, 44– 128 months), 1103 deaths occurred, including 397 from cardiovascular causes and 706 from non-cardiovascular causes. The RCS analysis elucidated the positive linear correlation (both nonlinear P > 0.05). In the multivariable analyses, each one-unit increase in the NLR value was correlated with a 51% increased risk of all-cause mortality (1.51(1.28, 1.77)) and a 71% increased risk of cardiovascular mortality (1.71(1.32, 2.21)). The results were largely consistent across stratified analyses encompassing variables such as age, sex, race/ethnicity, marital status, family income, education levels, BMI, drinking status, smoking status, hypertension, CVD, and anti-infective drugs (P for interaction > 0.05 for all). Time-dependent ROC analyses underscored the NLR’s credible predictive efficacy for both short-term and extended durations in forecasting both all-cause and cardiovascular mortality.Conclusion: The findings emphasize the promising use of the NLR in stratifying and prognosticating the risk of mortality in DKD in clinical practice.Keywords: neutrophil–lymphocyte ratio, diabetic kidney disease, predictor, mortality, cohort study

JiuLing Deng,1,&ast; Jing Liu,1,&ast; WanSheng Chen,2,3,&ast; Qing Liang,1 YuQiong He,2,3 GuangChun Sun1 1Department of Pharmacy, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China; 2Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: GuangChun Sun, Department of Pharmacy, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 21 24289464, Email sunguangchun@5thhospital.com YuQiong He, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Tel +86 21 81886182, Email yuqionghe1993@163.comAbstract: With ever-increasing intensive studies of idiopathic pulmonary fibrosis (IPF), significant progresses have been made. Endoplasmic reticulum stress (ERS)/unfolded protein reaction (UPR) is associated with the development and progression of IPF, and targeting ERS/UPR may be beneficial in the treatment of IPF. Natural product is a tremendous source of new drug discovery, and accumulating studies have reported that many natural products show potential therapeutic effects for IPF via modulating one or more branches of the ERS signaling pathway. Therefore, this review focuses on critical roles of ERS in IPF development, and summarizes herbal preparations and bioactive compounds which protect against IPF through regulating ERS.Keywords: idiopathic pulmonary fibrosis, endoplasmic reticulum stress, natural products, mechanisms

Jingli Yang,1– 4 Yu He,1– 5 Qing Ai,1– 4 Chan Liu,1– 4 Qiqi Ruan,1– 4 Yuan Shi1– 4 1Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Neonatology, Jiangxi Hospital Affiliated to Children’s Hospital of Chongqing Medical University, Jiangxi, People’s Republic of ChinaCorrespondence: Yuan Shi, Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Email shiyuan@hospital.cqmu.edu.cnPurpose: Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets.Patients and Methods: Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups.Results: Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. Proteobacteria and Bacteroidota were increased in the lungs of NARDS neonates, whereas Firmicutes, Streptococcus, and Rothia were reduced. Lactobacillus in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma.Conclusion: Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.Keywords: Neonatal acute respiratory distress syndrome, NARDS, lung microbiota, gut microbiota, tryptophan metabolites, correlation analysis, predictive diagnosis

Wanying Wu,1,2,&ast; Congzhuo Jia,1,2,&ast; Xiayan Xu,1– 3 Yibo He,1,2 Yun Xie,1,2,4 Yang Zhou,1,2 Hongyu Lu,1,2 Jin Liu,1,2 Jiyan Chen,1,2 Yong Liu1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyan Chen; Yong Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.com; liuyong@gdph.org.cnBackground: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status.Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality.Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06– 1.18; HR 1.21, 95% CI 1.14– 1.29; HR 1.43, 95% CI 1.34– 1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08– 1.30; HR 1.58, 95% CI 1.44– 1.74; HR 1.89, 95% CI 1.72– 2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P < 0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity > 0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets.Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group.Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.Keywords: platelet-to-HDL-cholesterol ratio, coronary artery disease, diabetes, all-cause mortality, cardiovascular mortality

Qinzheng Chen,1 Zhen He,1 Yaxin Wang,2 Xuanjin Yang,2 Nana Liu,2 Suhan Zhang,2 Liangkun Ma,2 Xuezhong Shi,1 Xiaocan Jia,1 Yongli Yang,1 Yin Sun,2 Yuan He3 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, People’s Republic of China; 3National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, People’s Republic of ChinaCorrespondence: Yin Sun, Department of Obstetrics and Gynecology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, 100730, People’s Republic of China, Email yinsun_pumch@163.com Yongli Yang, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China, Email ylyang377@zzu.edu.cnPurpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester.Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester.Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (β 0.010, 95% CI 0.001, 0.019) and fetal body weight (β 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively).Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.Keywords: body mass index, fetal growth, adverse neonatal outcomes, fasting plasma glucose, mediation analysis, cohort study

Weijian Zhu,1 Ying He,1 Mufang Huang,1 Shezhu Fu,1 Ziyi Liu,1 Xiaoqi Wang,1 Zhixin Li,1 Xiaoliang Li,1 Jiangming Chen,2 Yangqiu Li3 1Department of Hematology, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuahai, 519050, People’s Republic of China; 2Department of Haematology, Wuzhou Gongren Hospital, Wuzhou, 543001, People’s Republic of China; 3Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 10632, People’s Republic of ChinaCorrespondence: Yangqiu Li, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China, Email yangqiuli@hotmail.comObjective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent β-thalassemia (TDT).Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed.Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P< 0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1– 2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed.Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.Keywords: β-thalassemia, transfusion-dependent, thalassemia, thalidomide, foetal hemoglobin

Yan He,1,&ast; Yulei Tang,1,&ast; Silu Wen,1 Lin Dong,1 Fen Li,1,2 Yuqing Deng,1 Zezhang Tao1 1Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zezhang Tao; Yuqing Deng, Email taozezhang111@163.com; qingerdeng0713@163.comBackground: Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR.Methods: LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot.Results: The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1β axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1β can be reversed by BOB.1 siRNA.Conclusion: This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1β axis, which open up new avenues for studying the pathogenesis of AR. Keywords: allergic rhinitis, allergy, macrophage polarization, LncRNA, LINC00998

Wenlong Nie,&ast; Yun Liu,&ast; Jinshuai Lan, Ting Li, Yitian He, Zhe Li, Tong Zhang, Yue Ding School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tong Zhang; Yue Ding, Email zhangtongshutcm@hotmail.com; Dingyue-2001@hotmail.comBackground: Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD.Methods: N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds.Results: The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of − 5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the Cmax, AUC0-∞, AUC0-t, T1/2 and MRT0-∞ values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats.Conclusion: The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects. Keywords: nanoparticles, enhancing bioavailability, comparative pharmacokinetics, UPLC-MS/MS, Xie-Bai-San decoction

Qiu Huang,&ast; Yue Ge,&ast; Yu He, Jian Wu, Yonghua Tong, Haojie Shang, Xiao Liu, Xiaozhuo Ba, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Chen; Kun Tang, Email zhqchen8366@163.com; tangsk1990@163.comAbstract: Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.Keywords: nanoparticles, cancer therapy, cancer-associated fibroblasts, drug delivery, cancer, nanomedicine

Yi He,1,2 Lejia Zhang,1,2 Siyuan Huang,1,2 Yuquan Tang,3 Yiming Li,1,2 Hongyu Li,1,2 Guanhui Chen,4 Xun Chen,1,2 Xiliu Zhang,1,2 Wei Zhao,1,2 Feilong Deng,1,2 Dongsheng Yu1,2 1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 3Zhujiang Hospital, Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Department of Stomatology, the Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, 518107, People’s Republic of ChinaCorrespondence: Feilong Deng; Dongsheng Yu, Email dengfl@mail.sysu.edu.cn; yudsh@mail.sysu.edu.cnBackground: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects. Keywords: nanomaterials, MGO nanocomposites, craniomaxillofacial bone repair, circular RNAs, circAars

Yanxia He,1,&ast; Zhumei Luo,1,&ast; Haoqing Chen,2,3,&ast; Liqing Ping,2,3 Cheng Huang,2,3 Yan Gao,2,3 Huiqiang Huang2,3 1Department of Oncology, The Third People’s Hospital of Chengdu, Sichuan, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiang Huang; Yan Gao, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China, Email huanghqsysucc@163.com; gaoyan@sysucc.org.cnBackground: Systemic inflammation, immunity, and nutritional status are closely related to patients’ outcomes in several kinds of cancers. This study aimed to establish a new nomogram based on inflammation-immunity-nutrition score (IINS) to predict the prognosis of extranodal natural killer/T-cell lymphoma (ENKTL) patients.Methods: The clinical data of 435 patients with ENTKL were retrospectively reviewed and randomly assigned to training cohort (n=305) and validation cohort (n=131) at a ratio of 7:3. Cox regression analysis was employed to identify independent prognostic factors and develop a nomogram in the training cohort. Harrell’s concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were employed to assess the performance of the nomogram and compare it with traditional prognostic systems (PINK, IPI, KPI). Internal validation was performed using 1000 bootstrap resamples in the validation cohort. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) of patients in different risk groups.Results: In the training cohort, in addition to several classic parameters, IINS was identified as an independent prognostic factor significantly associated with the OS of patients. The nomogram established based on the independent prognostic indicators showed superior survival prediction efficacy, with C-index of 0.733 in the training cohort and 0.759 in the validation cohort compared to the PINK (0.636 and 0.737), IPI (0.81 and 0.707), and KPI (0.693 and 0.639) systems. Furthermore, compared with PINK, IPI, and IPI systems, the nomogram showed relatively superior calibration curves and more powerful prognostic discrimination ability in predicting the OS of patients. DCA curves revealed some advantages in terms of clinical applicability of the nomogram compared to the PINK, IPI, and IPI systems.Conclusion: Compared with traditional prognostic systems, the nomogram showed promising prospects for risk stratification in ENKTL patient prognosis, providing new insights into the personalized treatment.Keywords: inflammation-immunity-nutrition score, extranodal natural killer/T-cell lymphoma, nomogram, prognosis, overall survival

Yinxi He,1 Yanxia Chen2 1Department of Orthopaedic Trauma, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Yanxia Chen, Department of Endocrinology, the Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email chenyx@hebmu.edu.cnAbstract: As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes’ underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management.Keywords: exosomes, extracellular vesicles, osteoporosis, osteoblast function, osteoclast function

Qun Wei, Zilian Wang, Yu He, Xia Hong, Xuling Shen, Songying Zhang Reproductive Medicine Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Songying Zhang, Email zhangsongying@zju.deu.cnObjective: This study aims to investigate the phenomenon of sexual intercourse-related fear among women utilizing assisted reproductive technology due to dyspareunia. The primary objective is to offer insights that can inform the development of targeted nursing interventions.Methods: Employing a purposive sampling approach, a cohort of 23 female patients experiencing dyspareunia and undergoing treatment at the Reproductive Medicine Center of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2022 and December 2022, were selected as participants for this research. Semi-structured, in-depth interviews were conducted to gather qualitative data. The Colaizzi 7-step analysis method was subsequently applied to scrutinize the interview transcripts and identify emergent themes.Results: The analysis yielded five prominent themes: psychological disturbances, incongruent cognitive perceptions, anticipations regarding conception, insufficient adaptive responses, and sexual expectations.Conclusion: It is imperative for medical practitioners to demonstrate reverence for patients’ sexual beliefs and conditions, attune to their apprehensions, and offer efficacious emotional support. Tailored and multifaceted sexual health knowledge should be dispensed based on patients’ individual requirements and their envisioned sexual experiences, thereby fostering spousal and familial harmony. By prioritizing patients’ sexual well-being, cultivating a compassionate medical milieu, and augmenting the quality of assisted reproductive services, comprehensive improvements can be achieved.Keywords: dyspareunia, female, assisted reproductive technology, qualitative research

Yujun He,1,2,&ast; Furui Miao,2,&ast; Cai He,1 Yushan Fan,2 Fangzhi Zhang,2 Pu Yang,3 Miaodong Wang,3 Jiujie He2 1Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 2Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 3Graduate School of Guangxi University of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cai He, Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, No. 356 Nanmian Street, Xixiangtang District, Nanning City, 530011, People’s Republic of China, Email 578485231@qq.com Yushan Fan, Faculty of acupuncture, moxibustion and tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, 530001, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS) is the most prevalent upper limb compressive neuropathy. A considerable number of clinical trials and meta-analyses have provided evidence supporting the effectiveness of acupuncture in treating CTS. Nevertheless, the ideal choice of acupoints remains ambiguous.Objective: A data mining analysis was conducted with the objective of determining the most effective acupoint combinations and selection for CTS.Methods: A search was conducted across seven Chinese and English electronic bibliographic databases spanning from their inception to March 2023. Selected were clinical trials that evaluated the efficacy of acupuncture therapy for CTS, with or without randomised controlled methods. Data extraction mainly included acupoint prescriptions. Information such as first author, study design and study setting were also extracted. The principal outcomes comprised the clinical manifestations linked to CTS. Statistical descriptions were generated using Excel 2019. The analysis of association rules was conducted using SPSS Modeler 18.0. Using SPSS Statistics 26.0, exploratory factor analysis and cluster analysis were conducted.Results: 142 trials (including 86 RCTs and 56 non RCTs) were identified, and 193 groups of effective prescriptions involving 68 acupoints were extracted. The most frequently used acupoints were Da-ling (PC7), Nei-guan (PC6), He-gu (LI4), Wai-guan (TE5), and Yang-xi (LI5). The most frequently used meridians were the pericardial meridian and the large intestine meridian. The majority of special acupoints used were Five-shu points and Yuan-source points, with acupoints on the upper limbs being the most frequently used. The core acupoint groups were analyzed and 11 groups of association rules, 8 factors, and 5 effective cluster groups were obtained.Conclusion: The evidence-based acupoint selection and combinations of acupuncture therapy for carpal tunnel syndrome were provided by the findings of this study.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Xuqing Zhou,1,2,&ast; Xu Wang,1,2,&ast; Jiaqi Li,3,&ast; Mengxue Zhang,4 Yi Yang,1 Shihui Lei,1 Ying He,3 Hua Yang,3 Desheng Zhou,4 Chun Guo1,2 1Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 2The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, 410128, People’s Republic of China; 4Department of Neurology, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Guo, Email chunguosm@163.comBackground: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating.Aim: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects.Materials and Methods: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments.Results: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3).Conclusion: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins. Keywords: intracerebral hemorrhage, Annao Pingchong decoction, oxidative stress, network pharmacology, vivo experiments, SIRT1

Fei Wang,1,2 Chun Yue Yan,3 Yuan Qin,4 Zheng Ming Wang,1 Dan Liu,1 Ying He,1 Ming Yang,2 Li Wen,1 Dong Zhang1 1Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Medical Imaging, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 3Department of Emergency Medicine, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 4Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing, 404031, People’s Republic of ChinaCorrespondence: Dong Zhang, Department of Radiology, Xin Qiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86-23-68774676, Email hszhangd@tmmu.edu.cnBackground: Currently, it is still confused whether preoperative aminotransferase-to-platelet ratio (APRI) and gamma-glutamyl transferase-to-platelet ratio (GPR) can predict microvascular invasion (MVI) in solitary hepatocellular carcinoma (HCC). We aimed to develop and validate a machine-learning integration model for predicting MVI using APRI, GPR and gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI.Methods: A total of 314 patients from XinQiao Hospital of Army Medical University were divided chronologically into training set (n = 220) and internal validation set (n = 94), and recurrence-free survival was determined to follow up after surgery. Seventy-three patients from Chongqing University Three Gorges Hospital and Luzhou People’s Hospital served as external validation set. Overall, 387 patients with solitary HCC were analyzed as whole dataset set. Least absolute shrinkage and selection operator, tenfold cross-validation and multivariate logistic regression were used to gradually filter features. Six machine-learning models and an ensemble of the all models (ENS) were built. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model’s performance.Results: APRI, GPR, HBPratio3 ([liver SI‒tumor SI]/liver SI), PLT, peritumoral enhancement, non-smooth margin and peritumoral hypointensity were independent risk factors for MVI. Six machine-learning models showed good performance for predicting MVI in training set (AUCs range, 0.793– 0.875), internal validation set (0.715– 0.832), external validation set (0.636– 0.746) and whole dataset set (0.756– 0.850). The ENS achieved the highest AUCs (0.879 vs 0.858 vs 0.839 vs 0.851) in four cohorts with excellent calibration and more net benefit. Subgroup analysis indicated that ENS obtained excellent AUCs (0.900 vs 0.809 vs 0.865 vs 0.908) in HCC > 5cm, ≤ 5cm, ≤ 3cm and ≤ 2cm cohorts. Kaplan‒Meier survival curves indicated that ENS achieved excellent stratification for MVI status.Conclusion: The APRI and GPR may be new potential biomarkers for predicting MVI of HCC. The ENS achieved optimal performance for predicting MVI in different sizes HCC and may aid in the individualized selection of surgical procedures.Keywords: hepatocellular carcinoma, microvascular invasion, inflammatory biomarker, magnetic resonance imaging, machine learning

YuJian He,1,2,&ast; Guang Yang,1,&ast; Pengpeng Wang,1,3 Xu Wang,1,3 Zuying Xiong,1 Yan He,1,&ast; Zibo Xiong1,&ast; 1Renal Division, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Renal Division, PKU-Shenzhen Clinical Institute of Shantou University Medical College, Shenzhen, People’s Republic of China; 3Renal Division, PKU-Shenzhen Clinical Institute of Shenzhen University Medical College, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zibo Xiong, Renal Division, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China, Tel +86-13510880599, Email xiong0301@163.comPurpose: Antibiotic administration leads to alterations in pathogenic organisms and antibiotic resistance, posing a significant risk to peritoneal dialysis patients’ health. This study aimed to investigate changes in the cause-specific peritonitis, pathogen profiles, antibiotic resistance, and the prognostic factors among patients with peritoneal dialysis-associated peritonitis (PDAP) at our center.Patients and Methods: We included 463 PDAP patients who attended Peking University Shenzhen Hospital between 2002 and 2023. We analyzed the effects of empirical treatment regimens with cefazolin and ceftazidime or gentamicin.Results: From 2002 to 2023, we observed that gram-positive staphylococci emerged as the primary causative agents, while the proportion of gram-negative bacillary, enteric peritonitis, and catheter-associated peritonitis decreased significantly. However, the overall cure rate for PDAP and gram-negative bacillary peritonitis declined significantly from 2014 to 2023. Notably, we observed no increase in antibiotic resistance associated with antibiotic drugs use. In addition, reduced lymphocyte counts due to the prevalence of 2019 coronavirus disease (COVID-19) emerged as an independent risk factor for treatment failure in cases of gram-negative bacillary peritonitis.Conclusion: We did not observe elevated antibiotic resistance in our center when employing empirical dosing strategies involving cefazolin, ceftazidime, or gentamicin. Additionally, we found that a decrease in lymphocyte count due to the COVID-19 epidemic was a significant risk factor for treatment failure in cases of gram-negative bacillary peritonitis at our center. This study provides a foundation for developing clinical treatment strategies for PDAP.Keywords: antibiotic resistance, COVID-19, lymphocyte count, peritoneal dialysis, peritonitis, pathogen spectrum

Linli Xu,1,&ast; Yuanchao Li,2,&ast; Yanan He,2,&ast; Mengtong Chen,2 Yuting Zhang,2 Chunlong Liu,2 Li Zhang1 1Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong Province, People’s Republic of China; 2Clinical College of Acupuncture, Moxibustion, and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang, Department of Obstetrics, Guangdong Provincial Maternal and Child Health Care Hospital, Guangzhou, Guangdong Province, People’s Republic of China, Tel +8613432213940, Email 413788598@qq.comBackground: Pregnancy-related Pelvic Girdle Pain (PPGP) is a prevalent condition characterized by various physiological and pathological processes in the female body. The objective of this study is to offer a comprehensive understanding of the current research landscape, key areas of interest, and potential future directions in the field of PPGP.Methods: Using Web of Science, we explored PPGP literature from 2002 to 2022. VOSviewer and CiteSpace facilitated a quantitative analysis, revealing co-authorship patterns, co-occurring themes, citations, and co-citations.Results: We identified, peaking at 99 publications in 2021. The United States led with 138 publications and the highest citation count (3160). The Karolinska Institute boasted the highest tally of publications (n = 21). Regarding the volume of publications, the esteemed journal of BMC Pregnancy and Childbirth attained the foremost position. Notably, Gutke, Annelie emerged as the most prolific and highly cited author. The analysis of keyword co-occurrence and co-citation clustering unveiled an intricate tapestry of PPGP studies, spanning various domains including risk factors, mechanistic intricacies, diagnostic benchmark, treatment modalities, and far-reaching ramifications on one’s quality of life.Conclusion: Research endeavors exploring PPGP have unveiled an enduring trajectory of growth in contemporary times. The existing body of research primarily focuses on delving into the intricate interplay of epidemiological factors and the profound implications of interventions encompassing physical therapy, exercise protocols, and diverse modes of pain management within the domain of PPGP. Multidisciplinary integration encapsulates a prevailing trajectory of progress within this domain, while the focal point of future inquiries into PPGP may revolve around subjects pertaining to standardized outcome reporting.Keywords: pregnancy-related pelvic girdle pain, bibliometric analysis, CiteSpace, VOSviewer, therapeutic