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Wenrui Ji,1,* Xiaomin Xie,1,* 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*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

Zhengzheng Fu,1,* Jingwen Zou,1,* Jing Zhong,1 Jipang Zhan,1 Lian Zhang,1 Xiaoru Xie,1 Lai Zhang,1,2 Wenqiang Li,3 Renliang He1 1Department of Dermatologic Surgery and Dermatologic Oncology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510000, People’s Republic of China; 2Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, 510006, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, Guangdong Province, 510500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenqiang Li; Renliang He, Department of Dermatologic Surgery and Dermatologic Oncology, Dermatology Hospital of Southern Medical University, Guangdong Provincial Dermatology Hospital, 2 Lujing Road, Yuexiu District, Guangzhou, Guangdong Province, 510000, People’s Republic of China, Email liwq@gzsport.edu.cn; zshrl2006@smu.edu.cnBackground: The skin regulates body processes. When damaged, it is prone to breeding bacteria, causing inflammation and impeding wound healing. There is an urgent need for new dressings that can combat bacteria to aid in infectious wound repair.Methods: In this study, a curcumin-loaded nanocomposite hydrogel dressing (GelMA/AHA-Gel@Cur) with antibacterial properties and strong toughness was synthesized, designed to combine the modified gelatin-based hydrogel (GelMA/AHA) with curcumin-coated gelatin (Gel@Cur) nanoparticles to promote the healing of bacterial infection wounds. Under UV irradiation, methylacrylylated gelatin (GelMA) and aldehyaluronic acid (AHA) formed a composite network hydrogel through radical polymerization and Schiff base reaction. Meanwhile, the residual aldehyde group on the molecular chain of AHA securely locked Gel@Cur nanoparticles in the hydrogel network through Schiff base reaction.Results: The addition of Gel@Cur nanoparticles not only enhanced the hydrogel’s mechanical strength but also facilitated a sustained, gradual release of curcumin, endowing the composite hydrogel with robust antimicrobial capabilities. In an animal model of infected wounds, the composite hydrogel significantly improved wound closure, healing, and vascularization compared to the control group. Hemocompatibility tests confirmed the hydrogel’s safety, with a hemolysis ratio of just 0.45%. Histological evaluation following treatment with the composite hydrogel showed improved tissue architecture, increased collagen deposition, and regeneration of dermal gland structures.Conclusion: The GelMA/AHA-Gel@Cur composite hydrogel exhibits excellent mechanical properties, potent antimicrobial activity, and controlled drug release, along with superior cell and hemocompatibility. These characteristics make it a promising material for infected wound repair and a potential candidate for clinical skin regeneration applications. Keywords: Nanocomposite hydrogel dressings, infected wound repair, antibacterial properties, drug delivery

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Jun Cao,1,2 Hao Zhang,2 Xin Xie,3 Wei Wang4 1Department of Oncology, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Wei Wang, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +8613891841656, Email wei.wang@xjtufh.edu.cnBackground: VPS72 is highly expressed in hepatocellular carcinoma and prostate cancer, participating in various cellular processes such as gene transcription, replication, DNA repair, maintenance of genome integrity, and cancer progression. However, its role in colorectal cancer remains unknown.Methods: Bioinformatic methods were used to analyze gene expression, correlation and patient survival. Western blotting, colony formation assays and animal experiments were used to evaluate the function of VPS72 in colon cancer in vivo and in vitro.Results: VPS72 was highly expressed in colon cancer tissues and correlated with poor overall survival (P< 0.05) and relapse free survival (P< 0.01). Furthermore, patients with III/IV clinical stage (P< 0.001), N1 nodal metastasis (P< 0.001) or N2 nodal metastasis (P< 0.05) status had poor overall survival. Further analysis showed that VPS72 is correlated with proliferation and EMT biomarkers. Western blotting, colony formation assays and animal experiments showed that VPS72 overexpression promoted colon cancer proliferation and EMT progress.Conclusion: Our study found that VPS72 was correlated with poor overall survival in colon cancer patients, and high expressed level of VPS72 promoted colon cancer progression, indicating its role as a potential prognosis biomarker.Keywords: VPS72, colon cancer, biomarker, proliferation, epithelial–mesenchymal transformation

Ting Sun,1,2,&ast; Jingfang Liu,3,&ast; Hui Wang,3,&ast; Bing Xiang Yang,3– 5 Zhongchun Liu,3 Jie Liu,6 Zhiying Wan,3 Yinglin Li,1 Xiangying Xie,1 Xiaofen Li,3 Xuan Gong,3 Zhongxiang Cai1 1Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Health Science Center, Yangtze University, Jingzhou, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China; 5Population and Health Research Center, Wuhan University, Wuhan, People’s Republic of China; 6Anesthesiology, Virginia Commonwealth University Health System, Richmond, VA, USA&ast;These authors contributed equally to this workCorrespondence: Zhongxiang Cai, Department of Nursing, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email tg20201228@163.com Xuan Gong, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email 12048387@qq.comBackground: Non-suicidal self-injury (NSSI) is a significant social issue, especially among adolescents with major depressive disorder (MDD). This study aimed to construct a risk prediction model using machine learning (ML) algorithms, such as XGBoost and random forest, to identify interventions for healthcare professionals working with adolescents with MDD.Methods: This study investigated 488 adolescents with MDD. Adolescents was randomly divided into 75% training set and 25% test set to testify the predictive value of risk prediction model. The prediction model was constructed using XGBoost and random forest algorithms. We evaluated the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, recall, F Score of the two models for comparing the performance of the two models.Results: There were 161 (33.00%) participants having NSSI. Compared without NSSI, there were statistically significant differences in gender (P=0.035), age (P=0.036), depressive symptoms (P=0.042), sleep quality (P=0.030), dysfunctional attitudes (P=0.048), childhood trauma (P=0.046), interpersonal problems (P=0.047), psychoticism (P) (P=0.049), neuroticism (N) (P=0.044), punishing and Severe (F2) (P=0.045) and Overly-intervening and Protecting (M2) (P=0.047) with NSSI. The AUC values for random forest and XGBoost were 0.780 and 0.807, respectively. The top five most important risk predictors identified by both machine learning methods were dysfunctional attitude, childhood trauma, depressive symptoms, F2 and M2.Conclusion: The study demonstrates the suitability of prediction models for predicting NSSI behavior in Chinese adolescents with MDD based on ML. This model improves the assessment of NSSI in adolescents with MDD by health care professionals working. This provides a foundation for focused prevention and interventions by health care professionals working with these adolescents.Keywords: non-suicidal self-injury, adolescents, major depressive disorder, risk prediction model

Bo Jiang,1 Dong Lu,2 Jiaying Dai,3 Kunfeng Li,4 Qianqian Du,1 Bo Xie,5 Jun Xie,6 Xianhai Zhu,2 Xiang Xie1 1Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences & Medicine, University of Science & Technology of China, Hefei, 230001, People’s Republic of China; 3Department of Interventional Radiology, Anqing Municipal Hospital, Anqing, Anhui, 246000, People’s Republic of China; 4Department of Radiology, Tongling People’s Hospital, Tongling, Anhui, 244300, People’s Republic of China; 5Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 6Department of Radiology, Fuyang People’s Hospital, Fuyang, Anhui, 236600, People’s Republic of ChinaCorrespondence: Xiang Xie, Department of Interventional Ultrasound, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email 15956922618@163.comObjective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems.Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0– 4 points), medium-risk (DTH-B, 5– 6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73± 0.62 months, 12.73± 0.10 months, and 6.93± 0.19 months, respectively (p< 0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems.Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, prognosis prediction model

Huan Wang,1,&ast; Xing Xie,2,&ast; Zuowei Li,3 Lian Xue,4 Qiaoling Liao5 1The First Department of Psychosomatic Diseases, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, People’s Republic of China; 2Mental Health Center of West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Nursing Department, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, People’s Republic of China; 4The Second Department of Psychosomatic Diseases, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, People’s Republic of China; 5The Second Department of Severe Psychiatric, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaoling Liao, The second department of severe Psychiatric, the Third Hospital of Mianyang, Sichuan Mental Health Center, No. 190, Jiannan Road, Youxian District, Mianyang, Sichuan Province, 621000, People’s Republic of China, Email qqliao2009@163.comPurpose: This study aims to investigate the status of family functioning and dissatisfaction of family function from the perception of adolescents with affective disorders and explore associated factors.Methods: This was a multicentric cross-sectional study conducted from April 2022 to February 2023. Adolescents with affective disorders were surveyed in representative samples drawn from three hospitals in Sichuan province, China. Data were obtained from 235 participants regarding their demographic characteristics, family characteristics, disease-related characteristics, and family functioning.Results: The study found family functioning and its’ dissatisfaction both lower than national norms from the perspectives of adolescents. Younger age, single-parent family, and reconstituted family were predictors of not close of cohesion. Younger age, lower educational level of father, and reconstituted family were associated with less change of flexibility. Less times of hospitalizations, higher educational level of father, stem family were more satisfy with cohesion. Higher educational level of father, and stem family were also associated with greater satisfaction with flexibility.Conclusion: The study demonstrated that the family function of adolescents of affective disorders was poor, more attention should be paid to it. Age, family structure, number of hospitalizations and the educational level of father were influencing factors of family functioning. Therefore, it is important for medical worker to assess demographic and family characteristics of adolescents with affective disorders. Younger children, children of reconstituted family and single-parent family, children with repeated hospitalizations and fathers of lower level of education should be given emphasized in implementation of interventions. Based on the evaluation results, personalized family therapy has been proved to be an affective measure and could be used in clinical work.Keywords: affective disorders, adolescent, family functioning

Xiping Liao,1,2,&ast; Ji Liu,3,&ast; Xiaolong Guo,1 Ruiping Meng,1 Wei Zhang,1 Jianyun Zhou,1 Xia Xie,1,2 Hongli Zhou1 1Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Xie, Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email xiexia0128@163.com Hongli Zhou, Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email zhouhli7@mail2.sysu.edu.cnAbstract: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (M&phis;s) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease’s progression. On the other hand, their differentiated offsprings, namely moM&phis;s and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes’ origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD’s course. Through this lens, we aspire to furnish novel perspectives into IBD’s etiology and potential therapeutic strategies.Keywords: IBD, monocytes, inflammatory response

Jing Zhang,1,&ast; Le Wu,1,&ast; Chenchen Wang,2,&ast; Xin Xie,1 Yuying Han1– 3 1Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Critical Care Medicine, the 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, People’s Republic of China; 3Science and Education Department, Xi’an No. 5 Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuying Han; Xin Xie, Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, 229 Taibai North Road, Xi’an, Shaanxi, 710069, People’s Republic of China, Email hanyuying@nwu.edu.cn; xiexin@nwu.edu.cnAbstract: In the past few decades, chemotherapy has been one of the most effective cancer treatment options. Drug resistance is currently one of the greatest obstacles to effective cancer treatment. Even though drug resistance mechanisms have been extensively investigated, they have not been fully elucidated. Recent genome-wide investigations have revealed the existence of a substantial quantity of long non-coding RNAs (lncRNAs) transcribed from the human genome, which actively participate in numerous biological processes, such as transcription, splicing, epigenetics, the cell cycle, cell differentiation, development, pluripotency, immune microenvironment. The abnormal expression of lncRNA is considered a contributing factor to the drug resistance. Furthermore, drug resistance may be influenced by genetic and epigenetic variations, as well as individual differences in patient treatment response, attributable to polymorphisms in metabolic enzyme genes. This review focuses on the mechanism of lncRNAs resistance to target drugs in the study of tumors with high mortality, aiming to establish a theoretical foundation for targeted therapy.Keywords: lncRNA, drug resistance, chemotherapy, tumor, immune escape

Zhenjie Teng,1– 3 Jing Feng,4 Xiaohua Xie,2 Jing Xu,2 Xin Jiang,2 Peiyuan Lv1– 3 1Department of Neurology, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, People’s Republic of China; 4Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel/Fax +86 31185988906, Email peiyuanlu2@163.comBackground: Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI.Objective: To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM.Methods: A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness.Results: The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit.Conclusions: The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.Keywords: vascular cognitive impairment, mild cognitive impairment, cerebral small vessel disease, type 2 diabetes mellitus, nomogram

Mingzheng Yao,1 Dan Liang,2 Xiuli Zeng,1 Xiaomei Xie,1 Jiali Gao,1 Li’an Huang1 1Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 2Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Li’an Huang, Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China, Email huanglian1306@126.comPurpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance.Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes.Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P < 0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P < 0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score.Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.Plain Language Summary: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. However, relevant clinical studies are less at present. In this study, we found that an increase in the plasma Galectin-3 levels had significant values in death, poor prognosis, and early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy at various times.Keywords: ischemic stroke, Galectin-3, endovascular therapy, inflammation, dynamic change, outcome

Qingchen Li,1– 3,&ast; Xiaolin Xie,1,2,&ast; Jiasong Yang,1,2,4 Peng Gao,5 Wensheng Li1,2,4 1Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 2Shanghai Aier Eye Institute, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 3Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People’s Republic of China; 4Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, People’s Republic of China; 5Department of Ophthalmology, Shanghai Tenth People’s Hospital of Tongji University, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, No. 83 Wuzhong Road, Xuhui District, Shanghai, 201103, People’s Republic of China, Email drlws@qq.comPurpose: To observe the outcome of bilateral femtosecond laser-assisted clear lens extraction with trifocal intraocular lens (IOL) implantation for presbyopia correction and evaluate its feasibility in early presbyopic adults.Methods: Prospective case series of eyes with clear crystalline lenses that underwent femtosecond laser-assisted lens extraction and trifocal IOL (Acrysof IQ PanOptix, Model TFNT00, Alcon) implantation between 2021 and 2023 were followed up for at least 3 months after surgery. Outcome measures included monocular uncorrected visual acuity at near (UNVA, 40 cm), intermediate (UIVA, 60 cm), and distance (UDVA, 5 m), monocular manifest refraction, corrected distance visual acuity (CDVA), defocus curve assessment, and spectacle independence at both near and distance.Results: A total of 60 eyes from 30 consecutive patients were included, and their mean age was 50.4± 6.5 years. After surgery, the mean UNVA (LogMAR) increased from 0.28± 0.16 to 0.08± 0.07, UIVA increased from 0.25± 0.12 to 0.09± 0.06, and UDVA increased from 0.27± 0.21 to 0.01± 0.08. The enhancements of UNVA, UIVA and UDVA were all significant (P < 0.05). The optometric results showed that the mean postoperative spherical equivalent (SE) was − 0.21± 0.24 D, and the mean postoperative CDVA (LogMAR) was − 0.00± 0.06. The preoperative spectacle independences at near and distance were 46.7% (14/30) and 56.7% (17/30), respectively, and both increased to 100% at 3 months after surgery.Conclusion: Satisfactory visual outcomes and safe surgical procedures were observed in this study, which demonstrate that bilateral femtosecond laser-assisted clear lens extraction with PanOptix IOL implantation could be a feasible approach for presbyopia correction in working-age Chinese patients.Keywords: presbyopia-correcting, clear lens extraction, refractive lens exchange, trifocal intraocular lens, refractive surgery

Mingjuan Wu,&ast; Xin Xie,&ast; Qianying Jiang Department of Gynaecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianying Jiang, Department of Gynaecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University, No. 48, Huaishu Road, Wuxi, 214002, People’s Republic of China, Email jqy1727@163.comBackground: Ovarian cysts are common diseases among women. They might affect reproductive function in severe cases, and thus, patients with ovarian cysts often have negative emotions.Purpose: In this study, we elucidated the risk factors for negative emotions in patients with ovarian cysts during the perioperative period and their impact on prognosis.Methods: From August 2019 to August 2021, we retrospectively included 330 female patients with pathologically diagnosed benign ovarian cysts as potential participants in this study. Based on the established inclusion and exclusion criteria, 308 patients were finally included. We performed the t-test and Chi-squared test to analyze the relationship between the negative emotions of the patients and prognosis. Binary logistic regression and linear regression were used to assess independent risk factors for negative patient mood and prognosis.Based on SAS and SDS scores, patients with anxiety and/or depression are considered to combined negative emotions.Results: In total, 47 patients (15.3%) had negative emotions during the perioperative period. The results of the binary logistic regression analysis showed that the menstrual status (OR = 3.099, P = 0.028), intraoperative blood loss (OR = 1.043, P = 0.029), recurrence (OR = 3.691, P = 0.047), and several other factors were independent risk factors for negative emotions. The results of the linear regression analysis showed that the presence of combined negative affect (P = 0.000), recurrence (P = 0.010), postoperative IL-2 (P = 0.035), and several other factors were independent risk factors for patient prognosis.Conclusion: In clinical work, identifying the independent risk factors for negative emotions and enhancing their behavioral awareness and self-efficacy is necessary to improve their quality of life after surgery. Meanwhile, we will continue our exploration of the causes of negative emotions in patients in the future.Keywords: benign ovarian cyst, negative emotions, prognosis, anxiety, depression

HongKui Chen,1,2,&ast; Xianwei Xie,2,3,&ast; Huazhen Xiao,1,2,&ast; Wenjia Liang,1,2 Zhi-Jie Lin,1,2 Biting Lin,2,3 Kai-Yang Lin,2,3 Chun Chen,4 Yansong Guo1,2 1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350000, People’s Republic of China; 2Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases, Fuzhou, Fujian Province, 350000, People’s Republic of China; 3Fujian Heart Failure Center Al liance, Fuzhou, Fujian Province, 350000, People’s Republic of China; 4School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yansong Guo; Chun Chen, Email ysguo1234@126.com; chenchun-0428@163.comBackground: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis’s function in AS.Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR).Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers.Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.Keywords: atherosclerosis, PANoptosis, macrophage, subtypes

Junxian Xu,1 Suhong Xiao,2 Xiaoyun Xie,1 Yunqin Kang,2 Donghong Peng,2 Yanhong Lu2 1College of Medicine, Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Zhejiang Veteran Hospital, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Junxian Xu, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +86-13511357431, Email xujunxian_2022@163.comIntroduction: Hypoglycemia is an acute complication that can appear in people with type 2 diabetes treated with drugs which are associated with a risk of hypoglycemia, and it may lead to individual’s fear of hypoglycemia (FoH). FoH adversely affects diabetic self-management, psychological well-being, and quality of life, and it is associated with sleep quality. Nevertheless, this problem is often underestimated. The purpose of this study was to explore the heterogeneous characteristics of FoH in middle-aged and elderly hospitalized patients with type 2 diabetes and assess its relationship with the sleeping quality.Patients and Methods: A cross-sectional study was performed on 263 middle-aged and elderly patients with type 2 diabetes hospitalized at the Zhejiang Veteran Hospital in Jiaxing, China, from May to August 2022, selected by a convenient sampling method. A questionnaire containing general information, fear of hypoglycemia scale-15 (FH-15) and the Pittsburgh sleep quality index (PSQI) was provided to the participants. Latent profile analysis was performed to examine the potential latent groups in the distribution of answers on the individual FoH items.Results: The results identified three latent classes: Class 1 – Low FoH group (33%); Class 2 – No FoH group (61%); Class 3 – High FoH group (6%). The latent FoH class was the influencing factor of sleep quality, which was better in the No FoH group than in the Low FoH group, while the sleep quality of the Low FoH group was better than that in the High FoH group.Conclusion: A heterogeneity was found in the FoH of middle-aged and elderly hospitalized patients with type 2 diabetes. Health-care providers should pay more attention to these patients with high FoH and develop intervention strategies to mitigate it and improve their sleep quality.Keywords: fear of hypoglycemia, sleeping quality, middle-aged and older adults, type 2 diabetes, latent profile analysis

Xiangying Xie,1,2,&ast; Jingfang Liu,3,&ast; Xuan Gong,3,&ast; Ting Sun,1 Yinglin Li,1 Zhongchun Liu,3 Bing Xiang Yang,3,4 Lili Zhang,1 Kaimei Zhu,1 Zhongxiang Cai1 1Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2School of Medicine, Yangtze University, Jingzhou, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongxiang Cai; Lili Zhang, Department of Nursing, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86-18627932929 ; +86-13971907706, Email tg20201228@163.com; llzhang0301@163.comPurpose: Nonsuicidal self-injury (NSSI) is related to childhood trauma, negative life events, and coping style, but the interaction among these factors and the mechanism by which they interact in adolescents with depressive disorder remain unclear. This paper explores how these factors interact to influence NSSI and provides evidence to develop prevention efforts and interventions for adolescents with depressive disorder with NSSI.Patients and Methods: A cross-sectional design and convenient sampling method were used in this study. The Childhood Trauma Questionnaire, Adolescent Self-Rating Life Events Checklist, Trait Coping Style Questionnaire, and Adolescent Nonsuicidal Self-injury Assessment Questionnaire were completed by 540 adolescents with depressive disorder. Descriptive analysis, chi-square tests, t-tests, Pearson correlations, and serial mediation analyses were used in the data analysis.Results: A total of 398 (79.442%) adolescents with depressive disorders reported experiences of NSSI. The results of serial mediation analyses determined that childhood trauma has a direct (estimate = 0.209, 95% CI: 0.063, 0.334) and indirect (estimate = 0.271, 95% CI: 0.199, 0.371) impact on NSSI. The indirect impact of childhood trauma on NSSI through negative life events alone (estimate = 0.096, 95% CI: 0.007, 0.169), coping styles alone (estimate = 0.088, 95% CI: 0.034, 0.183), and negative life events on coping styles (estimate = 0.086, 95% CI: 0.042, 0.162) was significant.Conclusion: This study demonstrates that screening for childhood trauma should be considered when preventing and treating NSSI behavior in adolescents with depressive disorder. Managing negative life events and coping style may mitigate the negative impact of childhood trauma on NSSI behavior in adolescents with depressive disorder.Keywords: childhood trauma, NSSI, negative life event, coping styles, depressive disorder

Xianyu Xie,1,&ast; Zijun Zhao,2,&ast; Qinde Wu3,&ast; 1Department of Medical Administration, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2School of Public Administration & Law, Fujian Agriculture and Forestry University, Fuzhou, Fujian, People’s Republic of China; 3Department of Education Administration, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinde Wu, Department of Education Administration, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +0086-13365917369, Fax +0086-0591-83325046, Email qdwu88@126.comPurpose: This study aimed to analyze first-choice medical institutions for middle-aged and older adults in Fujian Province to promote the development of hierarchical diagnosis and treatment for them.Patients and Methods: Single factor analysis, disordered multi-classification logistic regression, and multiple correspondence classification were used to analyze the influencing factors of first-choice medical institutions for middle-aged and older adults. A total of 486 valid questionnaires were obtained. The questionnaire was based on Health Service Integration Theory and the behavioral model of Andersen.Results: Age, education level, living area, monthly income, nearest medical institution to home, and integrated health service system understanding significantly influenced respondents’ preference of first medical institution. Middle-aged and older adults were more inclined to visit county and municipal hospitals first. The treatment center’s proximity was also an important determinant of their first-choice selection of medical care.Conclusion: To realize high-quality hierarchical diagnosis and treatment and integrated health service system construction, it is important to improve the service capacity of primary medical institutions, increase the training of family doctors, implement the contract coverage of family doctors, optimize the allocation and geographical layout of primary medical institutions, ensure adequate income levels, and promote township hospital staff.Keywords: hierarchical diagnosis, middle-aged adult, older adult, first medical institution, influencing factors

Jing Feng,1– 3 Xiaohua Xie,4 Zhenjie Teng,4,5 Wenjie Fei,1,2 Yunfeng Zhen,2 Jingzhen Liu,2 Liqun Yang,2 Shuchun Chen1– 3 1Department of Endocrinology, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 4Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 5Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comObjective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM.Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001).Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.Keywords: diabetic kidney disease, type 2 diabetes mellitus, retinal venules, retinal arterioles, diameter

Mingxun Wang,1,&ast; Xinfei Yao,2,&ast; Zhiyuan Bo,3,4,&ast; Jiuyi Zheng,3 Haitao Yu,3 Xiaozai Xie,3 Zixia Lin,3 Yi Wang,5 Gang Chen,3,4 Lijun Wu3 1Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The First Clinical College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijun Wu; Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Fuxue Road, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 577 55579-453, Fax +86 577 55579-555, Email wumolijun@163.com; chen.gang@wmu.edu.cnPurpose: The current study aimed to evaluate the synergistic efficacy of lenvatinib and FOLFOX (infusional fluorouracil (FU), folinic acid, and oxaliplatin) in hepatocellular carcinoma (HCC) using patient-derived xenograft (PDX) and PDX-derived organotypic spheroid (XDOTS) models in vivo and in vitro.Methods: PDX and matched XDOTS models originating from three patients with HCC were established. All models were divided into four groups and treated with drugs alone or in combination. Tumor growth in the PDX models was measured and recorded, and angiogenesis and phosphorylation of the vascular endothelial growth factor receptor (VEGFR2), rearranged during transfection (RET), and extracellular signal-regulated kinase (ERK) were detected using immunohistochemistry and Western blot assays. The proliferative ability of XDOTS was evaluated through active staining and immunofluorescence staining, and the effect of the combined medication was evaluated using the Celltiter-Glo luminescent cell viability assay.Results: Three PDX models with genetic characteristics similar to those of the original tumors were successfully established. Combining lenvatinib with FOLFOX led to a higher tumor growth inhibition rate than individual therapies (P < 0.01). Immunohistochemical analysis demonstrated that the combined treatment significantly inhibited the proliferation and angiogenesis of PDX tissues (P < 0.05), and Western blot analysis showed that the combined treatment significantly inhibited the phosphorylation of VEGFR2, RET, and ERK compared with single-agent treatment. Additionally, all three matched XDOTS models were successfully cultured with satisfactory activity and proliferation, and the combined therapies led to better suppression of XDOTS growth compared with individual therapy (P < 0.05).Conclusion: Lenvatinib combined with FOLFOX had a synergistic antitumor effect in HCC PDX and XDOTS models by inhibiting the phosphorylation of VEGFR, RET, and ERK.Keywords: hepatocellular carcinoma, lenvatinib, chemotherapy, patient-derived xenografts, angiogenesis

Qianqian Pan,1,2 Mingjing Wei,1,3,4 Mengyi Lu,5 Yaping Xu,6 Xing Xie,1,3,4 Xiao Li1,3,4 1Department of Gynecologic Oncology, Women’s Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Zhejiang Financial College, Hangzhou, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou, Zhejiang, 310006, People’s Republic of China; 4Zhejiang University Cancer Center, Hangzhou, Zhejiang, 310058, People’s Republic of China; 5Wenzhou Central Hospital, Wenzhou, Zhejiang, People’s Republic of China; 6Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Xiao Li, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, Zhejiang, People’s Republic of China, 310006, Tel +86-0571-89998891, Fax +86-0571-89998891, Email 5198008@zju.edu.cnBackground: Increasing epidemiological evidence supported that chronic inflammatory factors might be involved in the carcinogenesis and progression of various cancers. The present study tried to investigate the prognostic value of perioperative C-reactive protein (CRP) in prognosis of patients with epithelial ovarian carcinoma (EOC) from a tertiary university teaching hospital.Methods: The cutoff value of CRP was calculated according to receiver operating characteristic (ROC) curve. Variables were compared using Chi-square test. Progress-free survival (PFS) and overall survival (OS) time were assessed by Kaplan–Meier (KM) survival analysis and Log rank test based on serum CRP level. Univariate and multivariate Cox regression analyses were applied for assessing the relationship between clinicopathological parameters and survival.Results: Higher perioperative CRP levels (preoperative ≥ 5.15 mg/L and postoperative ≥ 72.45 mg/L) were significantly associated with serous tumor, high-grade, advanced stage, elevated preoperative CA125, suboptimal surgery, chemotherapy resistance, recurrence and death in EOC (P < 0.01). KM analysis suggested patients with elevated preoperative, postoperative and perioperative CRP had shorter survival (P < 0.01). Elevated perioperative CRP was an independent risk factor for PFS (HR 1.510, 95% CI 1.124– 2.028; P = 0.006) and OS (HR 1.580, 95% CI 1.109– 2.251; P = 0.011). Similar results were obtained for elevated preoperative CRP. Subgroup analysis further suggested that elevated perioperative CRP was also an independent risk factor for prognosis in advanced stage and serous EOC.Conclusion: Elevated perioperative CRP was an independent risk factor for poorer prognosis of EOC, particularly in advanced stage and serous patients.Keywords: epithelial ovarian carcinoma, perioperative C-reactive protein, prognosis

Yining Xiao,1– 3 Zhenjie Teng,1– 3 Jing Xu,2,3 Qianqian Qi,2 Tianyuan Guan,1,2 Xin Jiang,2,3 Huifang Chen,2 Xiaohua Xie,2 Yanhong Dong,2,3 Peiyuan Lv1– 3 1Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email peiyuanlu2@163.comObjective: This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment.Methods: We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment.Results: After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577– 6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342– 5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = − 0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359– 5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315– 24.145) for cognitive impairment and 4.945 (2.063– 11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden.Conclusion: Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.Keywords: systemic immune-inflammation index, inflammation, cognitive impairment, cerebral small vessel disease, total burden

Jingmou Yu,1,2 Xin Xie,2 Liangliang Wang,3 Wenbo Liu,4 Huifeng Xu,4 Xiangmei Lu,4 Xiaofan Li,4 Jin Ren,2,4 Weidong Li2,5 1Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Jiangxi Provincial Key Laboratory of System Biomedicine, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 3Affiliated Hospital of Jiujiang University, Jiujiang, 332000, People’s Republic of China; 4School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, 332000, People’s Republic of China; 5Jiujiang NO.1 People’s Hospital & Water of Life Hospital, Jiujiang, 332000, People’s Republic of ChinaCorrespondence: Jin Ren; Weidong Li, Email yanjiushengrj@126.com; 346880908@qq.comIntroduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis.Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice.Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity.Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.Graphical Abstract: Keywords: metastasis, dual-targeting, breast cancer therapy, reduction-sensitive micelles, drug delivery

Xiachuan Qin,1,2,&ast; Linlin Xia,1,&ast; Chao Zhu,3 Xiaomin Hu,2 Weihan Xiao,2 Xisheng Xie,4 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical university, Hefei, Anhui, People’s Republic of China; 4Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zcxay@163.com Xisheng Xie, Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China, Email xishengx@163.comIntroduction: To explore whether ultrasonic radiomics extracted by machine learning method can noninvasively evaluate lupus nephritis (LN) activity.Materials and Methods: This retrospective study included 149 patients with LN diagnosed by renal biopsy. They were divided into a training cohort (n=104) and a test cohort (n=45). Ultrasonic radiomics features were extracted from the ultrasound images, and the radiomics features were constructed. Furthermore, five machine learning algorithms were compared to evaluate LN activity. The performance of the binary classification model was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: The average AUC of the five machine learning models was 79.4, of which the MLP model was the best. The AUC of the training group was 89.1, with an accuracy of 81.7%, a sensitivity of 83%, a specificity of 80.7%, a negative predictive value of 85.2%, and a positive predictive value of 78%. The AUC of the test group was 82.2, the accuracy was 73.3%, the sensitivity was 78.9%, the specificity was 69.2%, the negative predictive value was 81.8%, and the positive predictive value was 65.2%.Conclusion: Machine learning classifier based on ultrasonic radiomics has high accuracy for LN activity. The model can be used to noninvasively detect the activity of LN and can be an effective tool to assist the clinical decision-making process.Keywords: systemic lupus erythematosus, lupus nephritis, activity, ultrasound, machine learning

During the continuous casting process, the residual oxygen in the tundish can be significantly reduced by argon blowing from the tundish cover (ABTC). As a result, the effect of protective casting can be obviously improved, which helps to reduce the reoxidation of molten steel in the tundish. In the present work, numerical models for the ABTC of a six-strand continuous casting machine were established and verified by the measured oxygen mass fraction in the tundish during the ABTC. The results indicate that the best conditions for ABTC are to install the argon pipes on either side of the tundish cover holes, seal the baking holes, and keep the stopper rod holes open. The argon flow rate should be ≥120 m3/h during the period of empty tundish and ≥60 m3/h during the period of normal casting. Based on the calculation results, industrial testsof ABTC were carried out. The results indicated that the increased nitrogen content in steel(Δw[N]) decreased by 21.5% from 8.78×10- 6 to 6.89×10-6 , from the end of RH to tundish, and the amount of inclusions except for MnS in bloom (scanned size: 8 mm × 8 mm) decreased by 21.3% from 13.43 to 10.57, and the average size of inclusions decreased by 19.0% from 9.27 μm to 7.51 μm.

Ting-Ting Wu,&ast; Ying Pan,&ast; Ying-Ying Zheng, Yi Yang, Xian-Geng Hou, Chang-Jiang Deng, Yi-Tong Ma, Xiang Xie Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-Tong Ma; Xiang Xie, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of China, Tel/Fax +86-991-4366893, Email myt_xj@sina.com; xiangxie999@sina.comBackground: Given that age, international normalized ratio (INR), total bilirubin, and creatinine are reported to be independent risk factors for predicting outcome in patients with coronary artery disease (CAD), it is possible that the age–bilirubin–INR–creatinine (ABIC) score might be a potential prognostic model for patients with CAD.Methods: A total of 6046 CAD patients after percutaneous coronary intervention (PCI) from the retrospective cohort study (Identifier: ChiCTR-ORC-16010153) were evaluated finally. The primary outcome long-term mortality and secondary endpoints mainly major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded. Multivariate Cox regression models were used to determine risk factors for mortality and MACCEs.Results: The ABIC score was significantly higher in the death group than in the survival group. After adjusting for other CAD risk factors, the ABIC score was identified to be an independent risk factor for long-term mortality by multivariate Cox analysis. When in the high ABIC group, the incidence of all-cause mortality would increased 1.7 times (adjusted HR=1.729 (1.347– 2.218), P< 0.001), and 1.5 times for cardiac death (adjusted HR=1.482 (1.126– 1.951), P=0.005).Conclusion: The present study indicated that ABIC score≥ 7.985 predicts high long-term mortality and cardiac death risk for PCI patients. The ABIC score might be a potential prognostic model for patients with PCI.Keywords: age–bilirubin–international normalized ratio–creatinine score, ABIC score, coronary artery disease, mortality, prognosis

Shu-xian Xu,1,&ast; Xin-hui Xie,1,&ast; Lihua Yao,1 Li-chang Chen,2 Qirong Wan,1 Zhen-hua Chen,1 Zhongchun Liu1,3 1Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongchun Liu, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan, Hubei, ZIP 430060, People’s Republic of China, Tel +86-8804191181399, Email zcliu6@whu.edu.cnObjective: Little is known about the effectiveness and cognitive side-effects of electroconvulsive therapy (ECT) in young adults with treatment-resistant depression (TRD). The primary aim of this prospective longitudinal observational trial was to examine the clinical features and cognitive outcomes of young adults with TRD undergoing ECT.Methods: Changes in depressive symptoms and objective and subjective cognitive function were assessed using repeated evaluation at baseline, after each ECT session, and at one-month follow-up using the Montgomery-Äsberg Depression Rating Scale (MADRS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Forward Digital Span Test (FDST), and part of the Columbia Subjective Side Effects Schedule.Results: Of 41 inpatients, 35 (85.4%) and 12 (29.3%) met the criteria for response and remission after ECT, respectively. The greatest clinical improvements occurred during the first 3– 4 ECT sessions. While 34 patients reported subjective cognitive impairment increased with ECT, immediate and delayed memory (RBANS) significantly increased after ECT, consistent with FDST results. Objective cognition significantly improved during follow-up, but subjective cognition remained impaired.Conclusion: ECT is effective in young adults with TRD. Although subjective cognitive impairment increased during treatment, objective cognitive impairments were not observed.Keywords: electroconvulsive therapy, young adults, cognitive function, treatment-resistant depression

Jingmou Yu,1– 3 Liangliang Wang,4 Xin Xie,2 Wenjing Zhu,3 Zhineng Lei,3 Linghui Lv,3 Hongling Yu,3 Jing Xu,4 Jin Ren2,3 1Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, People’s Republic of China; 2Jiangxi Provincial Laboratory Laboratory of System Biomedicine, Jiujiang University, Jiujiang, People’s Republic of China; 3School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, People’s Republic of China; 4Affiliated Hospital of Jiujiang University, Jiujiang, People’s Republic of ChinaCorrespondence: Jingmou Yu; Jin Ren, Email yjm1016@hotmail.com; yanjiushengrj@126.comBackground: Multifunctional stimuli-responsive nanoparticles with photothermal-chemotherapy provided a powerful tool for improving the accuracy and efficiency in the treatment of malignant tumors.Methods: Herein, photosensitizer indocyanine green (ICG)-loaded amorphous calcium-carbonate (ICG@) nanoparticle was prepared by a gas diffusion reaction. Doxorubicin (DOX) and ICG@ were simultaneously encapsulated into poly(lactic-co-glycolic acid)-ss-chondroitin sulfate A (PSC) nanoparticles by a film hydration method. The obtained PSC/ICG@+DOX hybrid nanoparticles were characterized and evaluated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The cellular uptake and cytotoxicity of PSC/ICG@+DOX nanoparticles were analyzed by confocal laser scanning microscopy (CLSM) and MTT assay in 4T1 cells. In vivo antitumor activity of the nanoparticles was evaluated in 4T1-bearing Balb/c mice.Results: PSC/ICG@+DOX nanoparticles were nearly spherical in shape by TEM observation, and the diameter was 407 nm determined by DLS. Owing to calcium carbonate and disulfide bond linked copolymer, PSC/ICG@+DOX nanoparticles exhibited pH and reduction-sensitive drug release. Further, PSC/ICG@+DOX nanoparticles showed an effective photothermal effect under near-infrared (NIR) laser irradiation, and improved cellular uptake and cytotoxicity in breast cancer 4T1 cells. Importantly, PSC/ICG@+DOX nanoparticles demonstrated the most effective suppression of tumor growth in orthotopic 4T1-bearing mice among the treatment groups. In contrast with single chemotherapy or photothermal therapy, chemo-photothermal treatment by PSC/ICG@+DOX nanoparticles synergistically inhibited the growth of 4T1 cells.Conclusion: This study demonstrated that PSC/ICG@+DOX nanoparticles with active targeting and stimuli-sensitivity would be a promising strategy to enhance chemo-photothermal cancer therapy.Graphical Abstract: Keywords: chemo-photothermal treatment, amorphous calcium carbonate, nanoparticles, stimuli-sensitivity, drug delivery, cancer therapy

Chenlu Huang,1,&ast; Weixia Li,2,&ast; Chong Chen,2,&ast; Wei Xu,1 Ling Fei,1 Shuai Tao,3 Qiankun Hu,1 Xudong Xie,1 Xiongyue Cao,1 Xiao-Yu Zhang,1,4 Liang Chen,1 Qiang Li,1 Yuxian Huang1 1Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 3Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 4Section of Education, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxian Huang; Qiang Li, Email yxhuang@fudan.edu.cn; liqiang66601@163.comAim: The early prognosis evaluation of acute-on-chronic liver failure (ACLF) is important to decrease its mortality. We aimed to develop a new score to accurately predict the outcome of patients with ACLF.Methods: A derivation set of 408 patients with hepatitis B virus-related ACLF (HBV-ACLF) based on the Asian Pacific Association for the Study of the Liver criteria is used to develop a prognostic score that was validated in 209 patients with HBV-ACLF and 195 patients with non-HBV-ACLF.Results: Seven factors were significantly related to the 28-day mortality and constituted a new score (CHINAT-CD4 = 0.320 × ln (creatinine) + 0.668 × hepatic encephalopathy score + 0.745 × ln (international normalized ratio) + 0.476 × ln (neutrophil) + 0.251 × ln (aspartate aminotransferase) + 0.411 × ln (total bilirubin) - 0.605 × ln (CD4+ T cells count)). The C-indices of the new score for the 28-/90-day mortality (0.810/0.806) outperformed those of the other seven scores (p≤ 0.05). The results were confirmed in a validation set (0.798/793 for HBV-ACLF; 0.790/0.788 for non-HBV-ACLF). The novel score based on CD4+ T cell count showed high predictive performance for the 28-/90-day mortality of ACLF.Conclusion: The novel score based on CD4+ T cell count can accurately predict the 28-/90-day mortality for patients with ACLF.Keywords: liver failure, chronic liver disease, prognostic score, risk stratification, inflammatory markers

Tingting Zheng,1,&ast; Wenjuan Hu,1,&ast; Hao Wang,1 Xiaoli Xie,2 Lang Tang,3 Weiyan Liu,4 Pu-Yeh Wu,5 Jingjing Xu,1,&ast; Bin Song1,&ast; 1Department of Radiology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Song; Jingjing Xu, Department of Radiology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, 201199, People’s Republic of China, Email songbin@fudan.edu.cn; sb72778@189.cnPurpose: BRAF V600E mutation can compensate for the low detection rate by fine-needle aspiration (FNA) and is related to aggressiveness and lymph node metastasis. This study aimed to investigate the relationship between texture analysis features based on magnetic resonance imaging (MRI) and mutations.Methods: Retrospective analysis was performed on patients with postoperative pathology confirmed papillary thyroid carcinoma (PTC) from 2017 to 2021. One thousand one hundred and thirty-two texture features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) separately by outlining the tumor volume of interest (VOI). Univariate, minimum redundancy maximum relevance (mRMR), and multivariate analyses were used for feature selection to construct 3 models (T2WI, CE-T1WI, and combined model) to predict mutation. The reproducibility between observers was evaluated by intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was used to assess the performance of models. The diagnostic performance of the optimal cut-off value of models were calculated and validated by 10-fold cross-validation.Results: A total of 80 PTCs (22 BRAF V600E wild-type and 58 BRAF V600E mutant) were included in our study. Good interobserver agreement was found on texture features we selected (all ICCs > 0.75). The area under the ROC curves (AUCs) for the T2WI model, CE-T1WI model, and combined model were 0.83 (95% CI: 0.75– 0.91), 0.83 (95% CI: 0.73– 0.90), and 0.88 (95% CI: 0.81– 0.94), respectively. The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420.Conclusion: MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.Keywords: magnetic resonance imaging, texture analysis, radiomics, papillary thyroid carcinoma, BRAF V600E

Yicheng Wen,1,&ast; Xiaofang Xie,1,&ast; Ping Xu,2,&ast; Chengcheng Yang,1 Zhichen Zhu,1 Jie Zhu,1 Jingnan Lv,1 Haifang Zhang,1 Liang Chen,3,4 Hong Du1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 3Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA; 4Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA&ast;These authors contributed equally to this workCorrespondence: Hong Du, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People’s Republic of China, Email hong_du@126.comBackground: Shewanella genus, as an important carrier of resistance genes, has the potential to transmit resistance to many antimicrobials in many circumstances, especially in aquatic environment. The aim of the study was to describe the risk of Shewanella xiamenensis in hospital environment through analysis of genomic comparison and resistance status.Methods: Seven S. xiamenensis strains were isolated from hospital wastewater. PCR and Sanger sequencing were carried out for detection of common carbapenemase genes. Antimicrobial susceptibility testing was performed to determine the antimicrobial profile. Whole genome sequencing was applied, and sequences were further used for genomic analysis.Results: Seven Shewanella xiamenensis were all positive for blaNDM and blaOXA-48. Antimicrobial susceptibility testing showed all Shewanella xiamenensis were resistant to cefotaxime, ceftazidime, imipenem, meropenem, gentamycin and trimethoprim-sulfamethoxazole. Whole genome sequencing and phylogenetic analysis demonstrated the diversity of Shewanella xiamenensis despite isolating from one wastewater pool.Conclusion: To the best of our knowledge, this is the first report of detection of three types blaOXA-48-like genes in one hospital in China. And we have detected multi-drug resistant S. xiamenensis from hospital wastewater. This emphasizes that the presence of naturally existing carbapenemases in the environment may be significantly overlooked and that the blaOXA-48-like genes in China may originate through the horizontal gene transfer from S. xiamenensis to Enterobacterales rather than import from other countries.Keywords: OXA-48, NDM, Shewanella xiamenensis, hospital wastewater, reservoir, horizontal transmission, surveillance, New Delhi metallo-β-Lactamase

Dong Xu,1 Xu Zhu,2 Junyu Huo,2 Xupin Xie,1 Changpin Huang,1 Xin Fang,1 Ting Yin3 1Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University, First Affiliated Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ting Yin, Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13777879077, Fax +86 56005600, Email ameliyt@163.com Xin Fang, Department of Vascular, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13867478324, Fax +86 56005600, Email fangxin324@hotmail.comPurpose: Peripheral arterial disease (PAD) presenting with underlying hypertension (HTN) poses a higher risk of bilateral lower limb amputation than PAD patients without HTN. While the role of HTN management of PAD patients has received limited attention. We analyzed the clinical characteristics of PAD in adults with HTN and explored risk factors for PAD to construct a nomogram for evaluating critical limb ischemia (CLI) and lesion severity.Methods Patients and Methods: Between January 2014 and December 2019, we retrospectively evaluated 1886 patients with peripheral artery disease with coexisting HTN. Patients were randomly divided into training (n = 1320, 70%) and validation cohorts (n = 566, 30%), and according to the subjective experience of PAD [Fontaine classification (I–II vs III–IV)], patients were further classified into intermittent claudication (IC) and CLI groups. LASSO regression and multivariate Cox proportional hazard analyses were used to construct a nomogram using variables defined in the training cohort, which was validated in the validation cohort. The evaluation of the predictive discriminative, accuracy and clinical application are further analyzed.Results: In the training cohort, optimal independent factors included age, male sex, body mass index, diabetes mellitus, heart rate, triglyceride, and uric acid (AM-BDHTU), which were included in the nomogram predicting the CLI risk (all P < 0.05). The C-index values for CLI risk in PAD with HTN patients were 0.729 (95% CI: 0.704– 0.807) and 0.728 (95% CI: 0.652– 0.744) in the training and validation sets, respectively. Calibration curves indicated good consistency between predicted and actual outcomes. DCA confirmed the clinical utility of the diagnostic model.Conclusion: The AM-BDHTU nomogram, constructed and validated using simple to obtain clinical variables, when combined with the Fontaine classification, effectively predicts the risk of CLI among PAD patients with HTN.Keywords: peripheral arterial disease, hypertension, vascular-related complications, LASSO regression, nomogram, predictive diagnosis

Lijuan Zhuang,&ast; Xiaoyan Xie,&ast; Lihua Wang, Xiulan Weng, Yingling Xiu, Dabin Liu, Liying Zhong Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liying Zhong; Dabin Liu, Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, People’s Republic of China, Tel +86-13860610354 ; +86-13489997701, Fax +86-591-87551247, Email zhongliying@fjmu.edu.cn; 15968250@qq.comBackground: The characteristics of high-risk human papillomavirus (HR-HPV) infection in different pathological types of cervical cancer in China are unclear. The aim of this study was to evaluate HR-HPV genotypes and age stratification with cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC) in China.Materials and Methods: Patients diagnosed with cervical cancer by histopathology in Fujian Maternity and Child Health Hospital from January 1, 2014, to December 31, 2017, were included in this study. The HR-HPV genotype was analyzed in cervical specimens. Logistic regression was used to calculate odds ratios (ORs). All tests of statistical significance were two-sided, and the P value< 0.05.Results: A total of 1,590,476 women were screened for cervical cancer, and 688 cervical cancers were detected, including 554 SCC and 93 ADC. The overall HR-HPV infection rate in SCC was higher than that in ADC (91.2% vs 81.7%, P=0.005). HPV-16 was the most prevalent genotype in SCC (70.0%) but was only 31.2% in ADC (P< 0.001). However, the prevalence of HPV-18 in ADC was significantly higher than that in SCC (45.2% vs 7.0%; P< 0.001). In SCC, the prevalence of HPV-16 was consistently much higher than that of HPV-18 regardless of age group. Among ADC, the prevalence of HPV-18 was higher than that of HPV-16 in women aged ≥ 45 years. Interestingly, in those aged < 35 years, the highest prevalence was observed for HPV-16. HPV-18 infection has the highest risk of ADC (OR= 12.109; P< 0.001), and HPV-45 and HPV-51 were also found to be associated with the occurrence of ADC. However, HPV-16 infection greatly increased the risk of having histological SCC.Conclusion: HPV-16 and HPV-18 infections are key risk factors for SCC and ADC. The use of HR-HPV genotyping tests in cervical cancer screening and vaccination against major HPV genotypes could reduce the incidence of cervical cancer.Keywords: cervical squamous cell carcinoma, cervical adenocarcinoma, high-risk human papillomavirus

Ling Zhang1 &ast;, Xinhua Xie2 &ast;, Yangyan Sun1 &ast;, Futao Zhou1 1School of Basic Medicine, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futao Zhou, School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Email zhft522@163.comObjective: Hyperhomocysteinemia (HHcy), as an important risk factor for Alzheimer’s disease (AD), would aggravate cognitive dysfunction. This study aimed to investigate whether and to what degree the homocysteine (Hcy) levels in blood and cerebrospinal fluid (CSF) were elevated in AD patients compared with healthy controls and to explore the factors related to the elevated Hcy levels in AD patients.Methods: PubMed and Embase databases were searched to identify eligible studies, and study quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Ratio of mean (RoM) Hcy concentrations was used as a measure of fold-change between AD patients and healthy control subjects.Results: We identified 35 eligible studies, consisting a total of 2172 patients with AD and 2289 healthy controls. The pooled results showed that patients with AD had a significantly higher blood level of Hcy (RoM, 1.32; 95% CI, 1.25– 1.40; p< 0.001) than controls did, with large heterogeneity across studies (I2=81.4%, p< 0.001). Hcy level in CSF did not differ significantly between patients with AD than controls (RoM, 1.12; 95% CI, 0.90– 1.39, p=0.293; I2=69.4%, p=0.02). A random effects meta-regression analysis revealed that there was an inverse correlation between the blood levels of Hcy and folate (p=0.006). There was no link found between the blood levels of vitamin B12, or the Mini-Mental Status Examination scores reflecting the degree of cognitive impairment, and blood levels of Hcy.Conclusion: Regardless of dementia severity, there is an approximate one-third increase in blood Hcy in AD patients, which is robustly associated with a decreased level of blood folate in AD, but not with that of blood vitamin B12 nor the degree of dementia. Future investigation on the cause-and-effect link between Hcy and folate is warranted to clarify this issue.Keywords: homocysteine, Alzheimer’s disease, meta-regression

Lijuan Zhuang &ast;, Xiulan Weng &ast;, Lihua Wang, Xiaoyan Xie, Liying Zhong, Dabin Liu, Yingling Xiu Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingling Xiu; Dabin Liu, Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, People’s Republic of China, Tel +86-13860610354 ; +86-13489997701, Fax +86-591-87551247, Email xiuyingling@fjmu.edu.cn; xiuyingling1985@163.com; 15968250@qq.comPurpose: A high-risk human papillomavirus E6/E7 mRNA (HR-HPV mRNA) assay is widely used in cervical cancer screening in China. However, it is still unclear whether stand-alone HR-HPV mRNA testing is sufficient for primary screening. The purpose of this study was to investigate the feasibility of a stand-alone HR-HPV mRNA assay for primary screening of cervical cancer.Methods: Women aged 21 and older were recruited in Fujian Province, China, from January 2020 to January 2022. Cervical exfoliated cells were collected for cervical cytology and HR-HPV mRNA assays, and women with positive results on either assay were referred for colposcopy. The screening effectiveness of the assay was calculated based on the cervical histology. When comparing the efficacy of the different screening strategies, only women aged 25 and older were included.Results: A total of 9927 women were recruited. This study identified 217 cases of high-grade squamous intraepithelial disease or worse (HSIL+). The overall age-specific HR-HPV infection rate showed a U-shaped distribution. The sensitivity of the HR-HPV mRNA assay to identify CIN2+ and CIN3+ was 97.2% and 97.9%, respectively, which was significantly higher than that of cytology (82.9% and 88.6%, P< 0.001 and 0.002). The sensitivity of the HR-HPV mRNA primary screening strategy to identify CIN2+ and CIN3+ was 92.2% and 94.3%, respectively, which was similar to the co-testing strategy (P=0.336 and 0.394) and higher than the cytology primary screening (P=0.002 and 0.048). In addition, the HR-HPV primary screening strategy had a lower referral rate for colposcopy than cytology primary screening (5.4% vs 6.6%, P< 0.001), and the screening cost was lower than co-testing (&dollar;29,594.3 per 1000 screened women vs &dollar;55,140 per 1000 screened women, P< 0.001).Conclusion: In conclusion, the detection of CIN2+/CIN3+ by HR-HPV mRNA is both specific and sensitive. It may be suitable for primary screening of cervical cancer in China.Keywords: cervical cancer, HR-HPV, E6/E7 mRNA, primary screening, cervical intraepithelial neoplasia

Junlin Li,1,2,&ast; Xianhai Xie,1,2,&ast; Jiayong Zhang,3,4,&ast; Po Shen,3,4 Yuan Zhang,3 Chen Chen,2,5 Yanna Si,3 Jianjun Zou2,5 1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Anesthesiology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanna Si; Jianjun Zou, Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China; Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China, Tel +86 13851639332 ; +86 15380998951, Email siyanna@163.com; zoujianjun100@126.comPurpose: Early and accurate prediction of elderly patients at high risk of postoperative cognitive dysfunction (POCD) after non-cardiac surgery will provide favorable evidence for rational perioperative management and long-term postoperative recovery. This study aimed to develop bedside dynamic nomograms to provide accurately an individualized prediction of the risk of POCD at 6-month postoperatively with patients undergoing non-cardiac surgery and to guide clinical decision-making and postoperative management.Patients and Methods: We retrospectively collected patients undergoing surgical treatment at the Nanjing First Hospital between May 2020 and May 2021. We collected the data on preoperative, intraoperative, and postoperative variables. Clinical and laboratory data on admission and intraoperative variables and postoperative variables were used. We measured the performances of the nomograms using sensitivity, specificity of the receiver operating characteristic (ROC), the area under the ROC curves (AUC), the 10-fold cross-validation, and decision curve analysis (DCA).Results: POCD was observed in 23 of 415 patients (5.6%) at 6-month postoperatively. The preoperative and postoperative models obtained 91.6% and 94.0% accuracy rates on the data. Compared to the preoperative model, the postoperative model had an area under the receiver characteristic curve (AUC) of 0.973 vs 0.947, corresponding to a specificity of 0.941 vs 0.918 and a sensitivity of 0.913 vs 0.870. The overall performance of the postoperative model was better than the preoperative model.Conclusion: In this study, we developed novel bedside dynamic nomograms with reasonable clinical utility that can provide individualized prediction of POCD risk at 6-month postoperatively in elderly patients undergoing non-cardiac surgery at different time points based on patient admission and postoperative data. External validations are needed to ensure their value in predicting POCD in elderly patients.Keywords: postoperative cognitive dysfunction, elderly patients, noncardiac surgery, dynamic nomograms, predict, pre- and postoperative models

Qi Tang, Jiafen Liao, Xi Xie Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Xi Xie, Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China, Tel/Fax +86 0731 8529 5255, Email Hsixie1997@csu.edu.cnAbstract: To strengthen the understanding of rheumatic diseases (RDs) as the most common underlying conditions associated with acquired hemophilia (AH), a potentially fatal bleeding condition due to the development of autoantibodies or inhibitors to coagulation factor VIII, and rarely to factor IX, here we presented two cases of RDs associated AH to elucidate the disease progression, treatment, and prognosis. The presented 2 cases showed good responses to glucocorticoid (GC) and immunosuppressive agents. And then, a case-based systematic review was conducted to better understand the clinically practiced diagnosis and treatment of RDs associated AH. A total of 14 articles were included in the final literature review. All the identified 14 patients with underlying RDs and AH presented with bleeding symptoms, increased APTT, decreased FVIII activity, and positive FVIII inhibitors. Twelve of the 14 patients (85.7%) started an eradication of autoantibodies treatment with GC and immunosuppressive agents. Among which six patients achieved partial or complete remission, and four patients (28.6%) switched to Rituximab and responded well. Nine of the 14 patients received hemostasis therapy, including recombinant human FVIIa (rFVIIa). Two patients (14.3%) died due to mass bleeding and key organ failure. AH should be highly suspected in patients with RDs presenting spontaneous mucocutaneous or internal bleeding and an isolated prolonged APTT. Given the high morbidity of AH, it is important to facilitate efficient and proper management.Keywords: acquired hemophilia, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, connective tissue disease

Mengshi Tang,1,&ast; Yan Zeng,2,&ast; Weijun Peng,3 Xi Xie,1 Yongyu Yang,4 Biting Ji,5 Fen Li1 1Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Department of Rheumatology, Yueyang Central Hospital, Yueyang, 414000, People’s Republic of China; 3Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 4Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 5Shanghai Jing’an District Dental Disease Prevention and Control Institute, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fen Li, Department of Rheumatology and Immunology, the Second Xiangya Hospital, Central South University, No. 139, Renmin Middle Road, Changsha, 410011, People’s Republic of China, Email lifen0731@csu.edu.cnAbstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to severe joint damage, disability and mortality. Quercetin (QUE) is a natural flavonoid that is ubiquitous in fruits and vegetables. This article reviews the effect of QUE on articular and extra-articular manifestations of RA in vitro and in vivo. In general, for articular manifestations, QUE inhibited synovial membrane inflammation by reducing inflammatory cytokines and mediators, decreasing oxidative stress, inhibiting proliferation, migration and invasion, and promoting apoptosis of fibroblast-like synoviocytes (FLS), regulated autoimmune response through modulating Th17/Treg imbalance and Th17 cells differentiation, reducing autoantibodies levels and regulating ectonucleoside triphosphate diphosphohydrolase (E-NTPDase)/ectoadenosine deaminase (E-ADA) activities, reduced bony damage via lowering matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa B ligand (RANKL) expression and osteoclasts formation. For extra-articular manifestations, QUE could reverse the neurodegenerative processes of the enteric nervous system (ENS) and exhibited cytoprotective, genoprotective and hepatoprotective effects. In addition, we also summarize some contradictory experimental results and explore the possibility for these differences to form a sound basis for the clinical application of QUE for RA.Keywords: rheumatoid arthritis, quercetin, pharmacological

Liyun Sun,1,&ast; Xinwei Guo,2,&ast; Yeping Qin,3 Ping Li,4 Chunxia Yu,2 Xuesong Gao,2 Xinran Xie,4 Xuying Xu5 1Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Beiyuan Rehabilitation Department, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China; 3Dermatology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 4Beijng Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 5Ulcers Surgical Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuying Xu, Ulcers Surgical Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel +86 1-87906642, Email xxying@126.com.cn Xinran Xie, Beijng Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel +86 1-87906565, Email xiexinran@bjzhongyi.comPurpose: Psoriasis is an immune-mediated chronic inflammatory disease. Metabolic syndrome (MetS) is characterized by central obesity, hypertension, dyslipidemia, diabetes and insulin resistance (IR). Increasing evidence indicates that psoriasis is associated with MetS. This study aimed to explore some metabolite indexes which could evaluate the severity or predict the risk of psoriasis patients associated with MetS.Patients and methods: It was a case-control study conducted in Beijing Hospital of Traditional Chinese Medicine. Sixty healthy volunteers (HC), 100 patients with psoriasis (Ps), 100 patients with MetS (MetS) and 80 patients with both psoriasis and MetS (Ps+MetS) were entered between January 2016 and December 2018. Blood samples were taken after at least 12 hours fasting and the contents of trimethylamine N-oxide (TMAO), carnitine, choline and betaine in serum were measured by Liquid Chromatography Mass Spectrometry (LC-MS/MS). Besides, the serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (CHO), triglyceride (TG), blood glucose (BG), creatinine (Cr), urea nitrogen (BUN), uric acid (UA) were determined.Results: The non-healthy groups had different degrees of dyslipidemia, Ps-MetS> Ps >MetS. Compared with HC, the Ps had a higher level of TG; The MetS had the lowest level of HDL; The Ps+Mets had the highest level of TG and CHO. The Ps and Ps+MetS both had high level of UA, but there was no difference between the two groups. As for intestinal metabolites, the Ps had significant differences in TMAO, carnitine, and betaine in comparison with HC. The MetS had the highest level of TMAO. There was positive correlation between PASI and TMAO and betaine.Conclusions: TMAO and betaine could serve as indexes reflecting the severity of psoriasis. TG, CHO, LDL and UA could serve as risk factors of MetS in psoriatic patients.Keywords: psoriasis, metabolic syndrome, TMAO

Ting Zhang,1– 3,&ast; Xiaohui Xie,2– 4,&ast; Qianqian Li,1– 3,&ast; Lei Zhang,2,3,5,6 Yue Chen,2,4 Gong-Jun Ji,2,3,5 Qiangqiang Hou,2– 4 Tianxia Li,7 Chunyan Zhu,2,3,5,6 Yanghua Tian,4,8,9 Kai Wang2– 5,9 1Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, Anhui Province, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 6Department of Psychiatry, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 7Anhui Mental Health Center, Hefei, Anhui Province, People’s Republic of China; 8Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 9Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Zhu; Yanghua Tian, Email ayswallow@126.com; ayfytyh@126.comPurpose: Insomnia is a recognized feature of generalized anxiety disorder (GAD). The underlying neural substrate of insomnia in GAD is still unclear. Cortical folding is a reliable index and possibly an endophenotype of psychiatric disease. The aim of this study was to explore whether the aberrant cortical morphology was associated with insomnia in GAD.Patients and Methods: We enrolled 73 patients with GAD and 74 matched healthy controls (HCs) to undergo neuropsychiatric assessment and 3.0 T magnetic resonance imaging scanning. Neuropsychiatric batteries included the 14-item Hamilton Anxiety Rating Scale (HAMA) and the Insomnia Severity Index (ISI). Using FreeSurfer7.1.1, we calculated local gyrification index, cortical thickness and surface area and identified group differences in these parameters. Then, we calculated the functional connectivity of these identified regions and determined functional alterations. The relationship between these neuroimaging indicators and clinical measurement was explored.Results: Compared with HCs, the LGI in the bilateral orbitofrontal cortex (OFC), bilateral insula, left middle frontal gyrus, left temporal pole, and left fusiform area was significantly decreased in GAD. GAD patients had concurrent decreased surface area in the left OFC and thicker right OFC. GAD patients also exhibited increased functional connectivity between the left insula and frontoparietal control network. In addition, a negative relationship was observed between decreased LGI in these limbic regions and ISI score.Conclusion: GAD patients presented aberrant cortical folding in limbic network. Cortical morphology is a potential endophenotype in GAD, corresponding to an insomnia phenotype.Keywords: generalized anxiety disorder, cortical morphology, insomnia, limbic network, frontoparietal control network

Wei Cheng, Fen Li, Jing Tian, Xi Xie, Jin-Wei Chen, Xiao-Fei Peng, Qi Tang, Yan Ge Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yan Ge, Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China, Email geyan2003@csu.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by dermatological disorders and osteoarticular inflammatory lesions. This article reviews the application of biologics and other treatments based on the therapeutic target and the size of molecules in SAPHO syndrome. We found that drugs, especially biologics, have different effects on bone, joint, and skin damage. This may relate to the different inflammatory pathways involved in the osteoarticular and cutaneous symptoms in SAPHO patients. In this study, we provide stratified medication recommendations for SAPHO syndrome. Patients with osteoarticular symptoms can consider tumor necrosis factor blockers, JAK inhibitor, interleukin (IL)-1 inhibitor, and IL-17 inhibitor. Patients with cutaneous symptoms should consider IL-17 and JAK inhibitors. Apremilast, Tripterygium wilfordii Hook F, and bisphosphonates are other effective treatments.Keywords: SAPHO, osteoarticular symptoms, cutaneous symptoms, immune pathway pathways, biologics, targeted small molecule compounds

Yao Wang,1,2 Kaiyu Huang,1,2 Sijia Sun,1,2 Yahong Deng,1,3 Xuefeng Xie1,2 1School of Pharmacy, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Hefei, People’s Republic of China; 3Department of Pharmacy, First Affiliated Hospital of Anhui Medical University, Hefei, 230000, Anhui, People’s Republic of ChinaCorrespondence: Xuefeng Xie, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, People’s Republic of China, Tel +8613721098599, Fax +86551-65161040, Email xuefengxie@ahmu.edu.cnBackground: The rational choice of drugs for treating patients with advanced non-small-cell lung cancer (NSCLC) is significantly impacted by changes in modern drug policy, health insurance negotiation, and budget impact analyses. Here, we provide a basis for rational drug use decisions in clinical practice and promote the widespread use of pharmacoeconomic methods in clinical decision-making based on current drug policies in China and real-world data.Methods: A Markov model was developed to evaluate the health and economic outcomes in patients with advanced NSCLC treated with first-line chemotherapy with gefitinib and gefitinib plus chemotherapy. Clinical data, cost, and utility data were extracted from published literature or real-world data; sensitivity analysis was performed to assess the uncertainty in the results. The results were summarized as QALYs and the ICER.Results: The average cost and QALYs associated with gefitinib and gefitinib plus chemotherapy strategies were $62,882.83 and 1.70 and $84,509.30 and 1.93, respectively. The ICER for gefitinib plus chemotherapy versus gefitinib alone was $95,135.50. The one-way sensitivity analysis showed that the utility value of progressive disease (PD) had the greatest impact on the treatment outcome. Probabilistic sensitivity analysis showed that if China’s willingness to pay threshold was $33,300/QALY, the probability of superiority of the gefitinib plus chemotherapy regimen was 0.Conclusion: The study suggests that, from the perspective of the Chinese health system, gefitinib plus chemotherapy is not a cost-effective option for NSCLC patients with EGFR mutations. These findings may help clinicians make the best treatment decisions for patients with NSCLC.Keywords: gefitinib, Markov model, cost effectiveness, NSCLC

Yi Lao,1 Taidong Li,2 Xin Xie,1 Kangbiao Chen,1 Ming Li,1 Lu Huang1 1The Fourth Department of Medical Oncology, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, Zhanjiang, Guangdong, 524002, People’s Republic of China; 2Department of Thoracic Surgery, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, Zhanjiang, Guangdong, 524002, People’s Republic of ChinaCorrespondence: Lu HuangThe Fourth Department of Medical Oncology, Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital, No. 2 Mid Renmin Avenue, Zhanjiang, 524002, Guangdong, People’s Republic of ChinaTel +86-0759-2633696Email luternh@163.comBackground: MicroRNA-195-3p (miR-195-3p) plays an important role in some tumors, but its role in LUAD is unclear. This study explored the expression of miR-195-3p in LUAD and the relationship between the expression of miR-195-3p and the clinical and prognostic characteristics of LUAD patients.Methods: MiR-195-3p expression and clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA). Kruskal–Wallis test, Wilcoxon signed rank test, logistic regression, and Cox regression were used to assess the relationship between the expression level of miR-195-3p and clinical features in LUAD tissues. Kaplan–Meier survival curves were used to analyze the effect of miR-195-3p expression levels on the prognosis of LUAD patients. Target genes of miR-195-3p were predicted by several software. GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and immune infiltration analysis were used to analyze the possible regulatory network of miR-195-3p.Results: Compared with normal lung tissue, miR-195-3p is down expressed in LUAD tissue (P < 0.001). The low miR-195-3p expression in LUAD was significantly associated with N stage (P = 0.046), pathologic stage (P = 0.011), and gender (P = 0.010). Low miR-195-3p expression predicted a poorer overall survival (HR: 0.60; 95% CI: 0.45– 0.81; P = 0.001) and disease-specific survival (HR: 0.55; 95% CI: 0.37– 0.80; P = 0.002). The expression of miR-195-3p (HR: 0.488; 95% CI: 0.304– 0.784; P = 0.003) was independently correlated with OS in LUAD patients. High expression of miR-195-3p genes, including ABCC2, AGMAT, ARNTL2, ATP6V0A4, CDC25A, CDK1, FAM111B, GJB2, GRIP1, HMGA2, HOXA9, KIF14, SYT2, and TFAP2A, were associated with poor OS in LUAD. GO and KEGG analysis suggested that miR-195-3p was related to the phagosome pathway. MiR-195-3p may promote the function of B cells, dendritic cells, eosinophils, immature dendritic cells, macrophages, Mast cells, NK cells, plasmacytoid dendritic cells, and follicular helper T cells.Conclusion: Low miR-195-3p expression is significantly associated with poor survival in LUAD, which may be a promising prognostic biomarker for LUAD.Keywords: lung adenocarcinoma, miR-195-3p, gene expression, prognosis, immune infiltration, biomarker

Weiwei Yang,1,&ast; Qing He,2,&ast; Zhaohui Hu,3 Xiangtao Xie2,4 1Department of Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, People’s Republic of China; 2Department of Orthopedics, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, 545005, People’s Republic of China; 3Department of Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545005, People’s Republic of China; 4Department of Orthopedics, Liuzhou Worker’s Hospital, Liuzhou, Guangxi, 545005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohui HuLiuzhou People’s Hospital, No. 8 Wenchang Road, Liuzhou, Guangxi, 545006, People’s Republic of China, Tel/Fax +867722662676, Email huzhaohui817@163.comXiangtao XieThe Fourth Affiliated Hospital of Guangxi Medical University, No. 156 Heping Road, Liuzhou, Guangxi, 545027, People’s Republic of China, Tel +867723832719Email xiexiangtao813@163.comPurpose: Postmenopausal osteoporosis (PMOP) is a common and debilitating chronic disease, but it has just no cure options. The objective of this study was to identify genes associated with osteoporosis and reveal potential therapeutic targets.Methods: Expression profiles from GSE13850 and GSE56815 datasets were combined for differential expression analysis. Extraction of intersecting genes from the combined datasets and the differentially expressed genes in GSE56814 were performed to construct a multi-scale embedded gene co-expression network analysis (MEGENA) to obtain module genes. Module genes with an area under the receiver operating characteristic curve (AUC) > 0.60 were chosen to construct the least absolute shrinkage and selection operator (LASSO) model to obtain feature genes. A regulated network was constructed using differentially expressed micro-RNAs (miRNAs) in GSE74209 and feature genes. Finally, key genetic pathways and pathways of the Kyoto Encyclopedia of Genes and Genomes were identified and explored.Results: The commonly identified differentially expressed genes involve oxidative phosphorylation and caffeine metabolism. We identified 66 modules with 2354 module genes based on MEGENA. CARD8, FOXO4, IL1R2, MPHOSPH6, MPRIP, MYOM1, PRR5L and YIPF4 were identified as feature genes by the LASSO model. Furthermore, predicted miRNA target genes included 8 genes associated with PMOP. The largest AUC was observed for FOXO4, which was found at the nexus of feature genes and miRNA-regulated genes and which correlated with the upregulation of dendritic cells. Moreover, FOXO4 was found to be involved in ABC transporters, as well as cocaine and nicotine addiction.Conclusion: FOXO4 may serve as potential biomarker and therapeutic target for PMOP.Keywords: postmenopausal osteoporosis, microRNAs, bioinformatics analysis, FOXO4, biomarker

Jian Chen, Shu Li, Yan Ge, Jin Kang, Jia-fen Liao, Jin-feng Du, Jing Tian, Xi Xie, Fen Li Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Fen LiDepartment of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, No. 139 Ren Min Middle Road, Changsha, 410011, People’s Republic of ChinaEmail lifen0731@csu.edu.cnBackground: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study.Methods: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥ 1.2 folds change or ≤ 0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs.Results: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis.Conclusion: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.Keywords: rheumatoid arthritis, proteomics, effectiveness, disease modifying antirheumatic drugs, serotransferrin

Xingming Xie,1,2 Chaochun Chen,1,2 Shu Feng,1,3 Shi Zuo,2 Xueke Zhao,3 Haiyang Li1,2 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Haiyang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People’s Republic of ChinaTel/Fax +86 851-6855119Email lihaiyang@gmc.edu.cnPurpose: Acyl-CoA thioesterase 7(ACOT7) plays an important role in the metabolism of fatty acids. Hepatocellular carcinoma (HCC) has an abnormal lipid profile, and the role of ACOT7 in hepatocellular carcinoma has not been detailedly elucidated. Therefore, we conducted the study to explore the role of ACOT7 in HCC.Materials and Methods: The ACOT7 and Krüppel-like factor 13 (KLF13) mRNA expression levels were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis identified the underlying upstream regulator of ACOT7. Quantitative real-time PCR was used to detect the expression of mRNA, and immunohistochemical staining and Western blotting were used to detect the expression of protein. Cell Counting Kit-8 and EdU assays were employed to assess the proliferation of HCC cells. Wound-healing and Transwell migration assays were utilized to test the migration ability of HCC cells. Dual-luciferase reporter assay and ChIP assay were used to explore the potential mechanism. Gas chromatography-mass spectrometer was used to analyze the content of free fatty acids. Xenograft tumour growth was used to evaluate the effect of ACOT7 in vivo.Results: According to The Cancer Genome Atlas (TCGA) database, ACOT7 mRNA was found to be upregulated and predicted the poor prognosis. Overexpression of ACOT7 enhanced the proliferation, migration and invasion abilities of HCC cells in vitro, as well as the HCC cells proliferation in vivo. Moreover, ACOT7 overexpression increased the yield of the monounsaturated fatty acid Oleic acid (C18:1), which strengthened the proliferation and migration abilities of HCC cells. Mechanistically, KLF13 transcriptionally promoted ACOT7 expression. Further, KLF13 was also overexpressed in HCC tissues and facilitated HCC progression.Conclusion: Acyl-CoA thioesterase 7 is transcriptionally activated by Krüppel-like factor 13 and promotes the progression of hepatocellular carcinoma.Keywords: acyl-CoA thioesterase 7, Krüppel-like factor 13, hepatocellular carcinoma, unsaturated fatty acid, prognosis

Changjuan Li,1,2 Jianwei Mi,1 Fulai Gao,1 Xinying Zhu,1 Miao Su,1 Xiaoli Xie,1 Dongqiang Zhao1 1Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei Province, People’s Republic of China; 2Department of Gastroenterology, The First Hospital of Handan City, Handan, 056002, Hebei Province, People’s Republic of ChinaCorrespondence: Dongqiang ZhaoDepartment of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215, He ping West Road, Xinhua District, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaTel +86 0311 66636179Email hbzdq1998@163.comPurpose: We aimed to compare the histological and/or cytological diagnostic outcomes of EUS-FNA using 19G and 22G needles for solid pancreatic lesions and to evaluate the feasibility and safety of 19G needle.Patients and Methods: Data from patients with solid pancreatic lesions, who underwent EUS-FNA, were retrospectively retrieved from a single tertiary center from June 2017 to January 2021. The sensitivity, specificity, and accuracy of diagnosis, sample adequacy, number and time of punctures, and adverse events, were compared between the 19G and 22G groups. Univariate and multivariate logistic regression analyses were used to identify optimal factors for a correct histological diagnosis.Results: A total of 186 patients (19G group, n = 90; 22G group, n = 96) were analyzed in the study. The higher sensitivity and accuracy were observed in 19G group than those in the 22G group both in histological evaluation (89.3% vs 76%, p = 0.031; 91.1% vs 79.2%, p = 0.023; respectively) and in the combined histological and cytological evaluations (93.3% vs 81.3%, p = 0.027; 94.4% vs 84.3%, p = 0.027, respectively). However, there were no significant differences in specificity, positive predictive value (PPV), and negative predictive value (NPV). The number of needle passes and the puncture time were significantly lower in the 19G group than that in the 22G group (1.66 ± 0.07 vs 2.25 ± 0.08, p < 0.001; 125.4 ± 4.93s vs 169.0 ± 5.6s p < 0.001; respectively). Only 2 cases were failed in the 19G group and no serious complications occurred. Univariate and multivariate logistic analyses suggested that CA199 levels and needle types are related to the accuracy of the EUS-FNA histological diagnosis.Conclusion: EUS-FNA using a 19G needle is effective and safe for solid pancreatic lesions. Compared with the 22G needle, EUS-FNA with a 19G needle can obtain a better histological diagnostic accuracy of solid pancreatic lesions, and with fewer needle passes and in a shorter time.Keywords: sensitivity, specificity, diagnostic accuracy, histology, cytology

Xiao Xie, Fangbao Ding, Haibo Xiao Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Fangbao Ding; Haibo XiaoDepartment of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of ChinaEmail dingfangbao@xinhuamed.com.cn; xiaohaibo@xinhuamed.com.cnBackground: Non-small cell lung cancer (NSCLC) is a subtype of lung cancer which seriously threatens the health of people. Circular RNAs (CircRNAs) are endogenous RNAs which have stable closed structure; they are known to be involved in tumorigenesis of NSCLC. Meanwhile, hsa_circ_0000729 was reported to be upregulated in NSCLC. Nevertheless, the function of hsa_circ_0000729 in NSCLC remains unclear.Methods: Western blot and RT-qPCR were performed to investigate protein and mRNA levels, respectively. CCK-8 assay was performed to test the cell viability and cell death was investigated by flow cytometry. NSCLC cell pyroptosis was observed by electron microscope. In addition, the migration and invasion of NSCLC cells were detected by wound healing and transwell assay. The relation among hsa_circ_0000729, miR-1281 and FOXO3 was explored by dual luciferase reporter assay and RNA pull-down.Results: Hsa_circ_0000729 was found to be upregulated in NSCLC cells, and hsa_circ_0000729 knockdown obviously suppressed the proliferation of NSCLC cells through inducing pyroptosis. In addition, silencing of hsa_circ_0000729 notably inhibited the invasion and migration of NSCLC cells. Meanwhile, hsa_circ_0000729 could bind with miR-1281, and FOXO3 was directly targeted by miR-1281. Moreover, the anti-tumor effect of hsa_circ_0000729 siRNAs on NSCLC was markedly reversed by miR-1281 antagomir. Furthermore, silencing of hsa_circ_0000729 inhibited the tumor growth of NSCLC in vivo.Conclusion: Knockdown of hsa_circ_0000729 inhibits the tumorigenesis of NSCLC through mediation of miR-1281/FOXO3 axis. Thus, hsa_circ_0000729 might be served as a crucial mediator in NSCLC.Keywords: hsa_circ_0000729, miR-1281, FOXO3, pyroptosis

Linjuan Su, Xiaoqing Wu, Na Lin, Xiaorui Xie, Meiying Cai, Meiying Wang, Lin Zheng, Liangpu Xu Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Medical Genetic Diagnosis and Therapy Center, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Liangpu Xu; Lin ZhengFujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Medical Genetic Diagnosis and Therapy Center, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaEmail ipxiu304@126.com; zlin1536@126.comIntroduction: Increased nuchal translucency (NT) is closely related to an increased risk of chromosomal abnormalities. However, the criterion of increased NT for invasive prenatal diagnosis remains controversial, as the cutoff values are inconsistent among countries. This study was conducted to compare the various cutoff values of increased NT and calculate the incidence of chromosomal abnormalities to determine the predictive ability of these cutoff values in conventional chromosome analysis.Methods: A total of 3223 invasive samples with increased nuchal translucency (NT) or other non-ultrasound indications were collected from singleton pregnant women. Samples with isolated increased NT were divided into five groups based on the NT thickness: 909 samples in the NT ≥ 2.5 mm group, 819 samples in the NT ≥ 95th group, 547 samples in the NT ≥ 99th group, 527 samples in the NT ≥ 3.0 mm group, and 253 samples in the NT ≥ 3.5 mm group; 2301 samples with normal NT were considered as the control group. All five groups were karyotyped and the results were compared. The accuracy of the NT cutoff value for the screening of chromosomal abnormalities was assessed using receiver operating characteristic curve analysis.Results: Detection of all chromosomal aberrations and trisomy 21 showed that the sensitivity and false-positive rate decreased sequentially in the NT ≥ 2.5 mm, NT ≥ 95th, NT ≥ 3 mm, NT ≥ 99th, and NT ≥ 3.5 mm groups, whereas the specificity, positive predictive value, and false-negative rates increased sequentially. Comprehensive analysis of various factors, including sensitivity and specificity, revealed values equal to or higher than the calculated 95th percentile of NT distribution, which showed a sensitivity of 49.2% and specificity of 75.67% for detecting all aneuploidies and a sensitivity of 64% and specificity of 75.45% for trisomy 21, exhibiting the highest ability for the screening of chromosomal defects in first-trimester screening.Conclusion: For different thresholds of NT thickness, values equal to or higher than the calculated 95th percentile of the NT distribution showed the highest ability for the screening of chromosomal defects in first-trimester screening.Keywords: nuchal translucency, cutoff value, invasive prenatal diagnosis, chromosomal abnormalities, first-trimester screening, crown-rump length, trisomy 21

Jianyun Long, Xupin Xie, Dong Xu, Changpin Huang, Yongchang Liu, Xiaohu Meng, Xuchao Cai, Xin Fang Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaCorrespondence: Xin FangDepartment of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, ZheJiang University School of Medicine Hangzhou, Zhejiang, 310014, People’s Republic of ChinaTel +86 571-56005600Email hzfhfx@126.comObjective: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in aortic aneurysms. Recent recommendations suggest that combining RDW with other biomarkers could yield better results. We, therefore, propose evaluating the biomarker of vascular aging, albumin with RDW to predict the risk of aortic aneurysms. This study aims to explore whether the combination of RDW with albumin can effectively predict the prognosis of aortic aneurysm patients.Methods: This retrospective cohort study was conducted among adults (age > 18) with aortic aneurysms in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). RAR was measured according to the red blood cell distribution width and albumin. The primary outcome was the 30-day mortality rate, and the secondary outcome was the 90-day and one-year mortality rates. Estimation of hazard ratios (HR) was obtained from Cox regression models for all-cause mortality related to red cell distribution width-to-albumin ratio (RAR) values.Results: In total, 312 patients were involved, with an average age of 74.9 ± 10.9 years and an average RAR value of 5.4 ± 1.6 mL/g. In 30 days for all-cause mortality, the HR (95% CI) in the highest RAR group (> 5.8 mL/g) in tertiles was 2.54 (1.25, 5.14) in the unadjusted model, with a significant difference compared with the reference group (P < 0.05). After adjusting for race, gender and age, there was still a correlation (P < 0.05), and the HR (95% CI) was 2.51 (1.23, 5.10). Further adjustment of possible covariates showed similar correlation in model 3 (P < 0.05), and HR (95% CI) was 2.66 (1.17, 6.01). Multivariable logistic regression shows that RAR is an independent risk factor for the outcome of aortic aneurysms after adjusting the covariates. In the subgroup analysis, we analyzed the patient’s complications, and no significant interaction was observed.Conclusion: RAR is a risk factor for patients with aortic aneurysms. However, more in-depth research is warranted to further analyze and substantiate our findings on the role of RAR in aortic aneurysm patients.Keywords: red blood cell distribution width–albumin ratio, aortic aneurysms, retrospective cohort study, MIMIC-III

Lei Yu,1,&ast; Xiaofang Xie,1,&ast; Xiaoyu Cao,1 Junren Chen,1 Guanru Chen,1 Yan Chen,1 Gangmin Li,1 Junyuan Qin,1 Fu Peng,2 Cheng Peng1 1State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fu PengDepartment of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, People’s Republic of ChinaTel/Fax +86 28-61800018Email fujing126@yeah.netCheng PengState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaTel/Fax +86 28-61800231Email cdtcmpengcheng@126.comAbstract: Cancer is still an insurmountable problem for humans and critically attacking human health. In recent years, natural products have gained increasing attention in the field of anti-tumor due to their extensive sources and minimal side effects. Maslinic acid (MA), a pentacyclic triterpene acid mainly derived from the olive tree (Olea europaea L.) has been confirmed to possess great anti-cancer effects. This paper reviewed the inhibitory effect of MA and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others. MA inhibited the proliferation of various tumor cells and showed lower IC50 values in melanoma 518A2 cells and gastric cancer MKN28 cells compared with other cell lines. A series of semi-synthetic derivatives obtained by modifying MA chemical structure have been shown to have high cytotoxicity to human tumor cell lines, but low cytotoxicity to non-malignant cells, which is conducive to developing its potential as a chemotherapeutic agent. These studies suggest that MA derivatives have broad prospects in the development of antitumor therapeutics in the future and warrant further study.Keywords: maslinic acid, tumor, mechanism, derivatives