Search

Li Ye,1 Xiwei Sun,2 Yiping Li,1 Yali Zeng,1 Lacuo Zhuoma,1 Dinglun Zhou,2 Qinying He,3 Ju Wang,4 Wei Yang,1 Hang Yu,1 Yihui Yang,1 Shu Liang,1 Dan Yuan1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 2West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 4Center for AIDS/STD Control and Prevention, Liangshan Center for Disease Control and Prevention, Xichang, Sichuan, People’s Republic of ChinaCorrespondence: Dan Yuan; Shu Liang, Email ydtv1130@163.com; liangshu523@163.comBackground: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART.Methods: A retrospective cohort study was conducted on PLWH who had received ART≥ 6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤ 0.05 considered statistically significant.Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54– 0.65), homosexual transmission (HR=0.43, 95% CI: 0.33– 0.55), and baseline BMI≥ 24 (HR=0.81, 95% CI: 0.72– 0.90). Higher mortality risks were associated with age≥ 50 years at diagnosis (HR=3.21, 95% CI: 2.94– 3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11– 1.37), living separately (HR=1.32, 95% CI: 1.22– 1.43), baseline BMI < 18.5 (HR=1.27, 95% CI: 1.13– 1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15– 1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09– 1.47), and a diagnosis-to-treatment interval > 12 months (HR=1.27, 95% CI: 1.15– 1.41). Compared to those with CD4(+) T cell count of 200– 350cells/μL, 350– 500cells/μL, and > 500cells/μL at baseline, individuals with < 200cells/μL had higher mortality risks (HR=0.73, 95% CI: 0.67– 0.79; HR=0.57, 95% CI: 0.51– 0.64; and HR=0.58, 95% CI: 0.51– 0.66, respectively).Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell < 200cells/μL, baseline WHO stage IV, and a diagnosis-to-treatment interval > 12 months were risk factors for the survival of PLWH.Keywords: PLWH, antiretroviral therapy, survival analysis

Ming Li,&ast; Xinrui Zhang,&ast; Yujie Zhou, Yuteng Chu, Jie Shen, Yue Cai, Xuanrong Sun Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanrong Sun, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China, Email sunxr@zjut.edu.cnIntroduction: Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.Methods: We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.Results: Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects.Conclusion: This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.Keywords: biomimetic macrophage membrane, drug delivery, synergistic treatment, glioma inhibition, near infrared-activatable

Haijie Tan,1,&ast; Yi Chen,2,&ast; Yan Jiang,1 Xiaojing Sun,1 Wei Ye,1 Xuefang Zhu,1 Xiangsheng Xiong1 1Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangsheng Xiong, Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China, Email 158193942@qq.comBackground: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery.Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery.Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582– 0.628) and 0.054 (95% CI: 0.053– 0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576– 1.226) and 0.055 (95% CI: 0.047– 0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1.Conclusion: The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.Keywords: ED90, phenylephrine, norepinephrine, spinal anesthesia-induced hypotension, preeclampsia, cesarean delivery

Shiyuan Huang, Zesen Wang, Xudong Sun, Kuanxin Li The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui Province, 233044, People’s Republic of ChinaCorrespondence: Kuanxin Li, The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, Anhui Province, 233044, People’s Republic of China, Email kuanxinli@126.comBackground: Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration.Methods: Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models.Results: The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups.Conclusion: Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.Keywords: composite hydrogel, nanohydroxyapatite, BMP7, bone regeneration, BTE

Wanjun Bai,1 Xue Sun,1 Bo Qiu,1 Caihui Guo,1 Haojing Song,1 Yiting Hu,1 Xueyuan Zhang,2 Peihua Yin,3 Xiaoru Wang,3 Zhanjun Dong1 1Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei, People’s Republic of China; 2Center for Clinical Pharmacology, Shanghai Innovstone Therapeutics Limited, Shanghai, People’s Republic of China; 3Center for Clinical Pharmacology, CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, People’s Republic of ChinaCorrespondence: Zhanjun Dong, Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, No. 348 Heping West Road, Xinhua District, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China, Tel +86 311 85988604, Email 13313213656@126.comObjective: This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.Methods: A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (Cmax), the areas under the plasma concentration–time curve (AUC0-t, AUC0-∞), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.Results: Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09– 103.44% for Cmax, 94.05– 103.51% for AUC0-t, and 94.56– 103.86% for AUC0-∞ under fasting conditions, and 99.18– 112.48% for Cmax, 98.79– 106.02% for AUC0-t, and 98.95– 105.89% for AUC0-∞ under postprandial conditions, all of which were within the bioequivalence range of 80.00– 125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.Conclusion: The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).Keywords: apremilast, psoriasis, pharmacokinetics, bioequivalence, safety

Jianbao Zheng,1,2,&ast; Zepeng Dong,1,&ast; Xianzhen Jin,1 Jing Li,2 Yuanwu Zou,2 Guanghong Bai,2 Qianhong Wu,2 Shenghang Xu,3 Zifeng Wang,3 Xuejun Sun,1 Dingxin Liu,3 Li Guo3 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Tuberculosis Prevention and Treatment Hospital in Shaanxi Province, Xi’an, 710100, People’s Republic of China; 3Center for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianhong Wu; Li Guo, Email 15902969531@126.com; guoli35@mail.xjtu.edu.cnPurpose: This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb).Methods: We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10− 2 and 10− 4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal–Wallis test was used to analyze the differences in grouping factors at representative time points.Results: The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10− 2 and SM with bacterial suspension concentration of 10− 4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference.Conclusion: The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.Keywords: plasma-activated saline, mycobacterium tuberculosis, antibacterial effect, antibiotic sensitivity

Hongmei Sun,1,2 Chao Lv,2,3 Xiaoxue Zhang,1,2 Xuan Sun,1,3,4 Siyu Chen,1,3,4 Ke Li,3,4 Yazhuo Hu,2,3 Yuxin Feng,1,2 Tong Yin,2,3 Jianjun Jia2,3 1Medical School, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Institute of Geriatrics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Geriatric Neurology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianjun Jia; Tong Yin, Institute of Geriatrics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, Haidian District, 100853, People’s Republic of China, Email jiajianjun301@126.com; yintong301@163.comBackground: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer’s disease continuum (ADC).Objective: This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC.Material and Methods: According to 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) standard, amyloid β-protein positive (Aβ+) and negative (Aβ-) patients were recruited according to the Aβ-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aβ+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aβ+ and 73 Aβ– patients using a logistic regression analysis.Results: The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64– 28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28– 4.95).Conclusion: The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.Keywords: Alzheimer’s disease, pharmacogenomics, variant, gene, donepezil

Zirui Bian,1,&ast; Tianzhe Bao,2,&ast; Xuequan Sun,3,4 Ning Wang,1 Qian Mu,5 Ting Jiang,6 Zhongxiang Yu,6 Junhang Ding,2 Ting Wang,7 Qihui Zhou2 1Department of Bone, Huangdao District Central Hospital, Qingdao, People’s Republic of China; 2Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 3Weifang Eye Institute, Weifang Eye Hospital, Zhengda Guangming Eye Group, Weifang, People’s Republic of China; 4Zhengda Guangming International Eye Research Center, Qingdao Zhengda Guangming Eye Hospital, Qingdao University, Qingdao, People’s Republic of China; 5Department of Biomaterials, LongScience Biological (Qingdao) Co, LTD, Qingdao, People’s Republic of China; 6Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao University, Qingdao, People’s Republic of China; 7Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qihui Zhou; Junhang Ding, Tel +86-17660670299, Email qihuizhou@uor.edu.cn; dingjunhang@uor.edu.cnIntroduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species.Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools.Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, &epsiv;-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction.Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation. Keywords: carbon dots, machine learning, antibacterial, minimum inhibitory concentration, classification algorithms

Zichen Wang,1– 3,&ast; Wen Wang,1– 3,&ast; Mingqi Wang,1– 3 Qiao He,1– 3 Jiayue Xu,1– 3 Kang Zou,1– 3 Yan Kang,4 Xin Sun1– 3 1Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center and Cochrane China Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, People’s Republic of China; 3Sichuan Center of Technology Innovation for Real World Data, Chengdu, People’s Republic of China; 4Intensive Care Unit, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Kang; Xin Sun, Email kangyan@scu.edu.cn; sunxin@wchscu.cnObjective: To identify subclasses of acute pancreatitis (AP) patients in the intensive care unit (ICU) by analyzing blood urea nitrogen (BUN) trajectories.Methods: AP patients in West China Hospital System (development cohort) and three public databases in the United States (validation cohort) were included. Latent class trajectory modelling was used to identify subclasses based on BUN trajectories within the first 21 days after ICU admission. Clinical characteristics and outcomes were compared, and results were externally validated.Results: The study comprised 2971 and 930 patients in the development and validation cohorts, respectively, with five subclasses: Class 1 (“Moderate-azotemia, slow decreasing”), Class 2 (“Non-azotemia”), Class 3 (“Severe-azotemia, slow decreasing”), Class 4 (“Moderate-azotemia, rapid increasing”), and Class 5 (‘Moderate-azotemia, slow increasing) identified. Azotemia patients showed significantly higher 30-day mortality risk in development and validation cohorts. Specifically, Class 4 patients exhibited notably highest mortality risk in both the development cohort (HR 5.32, 95% CI 2.62– 10.82) and validation cohort (HR 6.23, 95% CI 2.93– 13.22). Regarding clinical characteristics, AP patients in Class 4 showed lower mean arterial pressure and a higher proportion of renal disease. We also created an online early classification model to further identify Class 4 patients among all patients with moderate azotemia at baseline.Conclusion: This multinational study uncovers heterogeneity in BUN trajectories among AP patients. Patients with “Moderate-azotemia, rapid increasing” trajectory, had a higher mortality risk than patients with severe azotemia at baseline. This finding complements studies that solely rely on baseline BUN for risk stratification and enhanced our understanding of longitudinal progression of AP.Keywords: acute pancreatitis, BUN, trajectories analysis, ICU

Jing Liu,1,&ast; Zeyi Liang,1,&ast; Maocao Zhongla,2 Hongsheng Wang,3 Xu Sun,4 Juanshan Zheng,1 Xuezhi Ding,1 Feng Yang1 1Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, People’s Republic of China; 2Gannan Animal Disease Prevention and Control Center, Hezuo, People’s Republic of China; 3Xiangyang Vocational and Technical College, Xiangyang, People’s Republic of China; 4College of Life Sciences and Engineering, Lanzhou University of Technology, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of enterococcal isolates (Enterococcus faecalis, Enterococcus faecium and Enterococcus hirae) isolated from clinical bovine mastitis cases in Ningxia, China.Patients and Methods: The enterococci were identified by 16S rRNA amplification and sequencing. Antimicrobial resistance was determined by disc diffusion method. Virulence and antimicrobial resistance genes were detected by PCR assays.Results: Overall, 198 enterococcal isolates were identified from 2897 mastitis samples, including 137 (4.7%) E. faecalis, 50 (1.7%) E. faecium and 11 (0.4%) E. hirae. E. faecalis, E. faecium and E. hirae isolates showed high resistance to tetracycline (92.7%, 68.0%, 90.9%), followed by erythromycin (86.9%, 76.0%, 72.7%). The multidrug-resistant strains of E. faecalis and E. faecium were 29 (21.2%) and 13 (26.0%), respectively. The resistance of E. faecalis, E. faecium and E. hirae isolates to tetracycline is mainly attributed to the presence of tetL (alone or combined with tetM and/or tetK), the erythromycin resistance to ermB (alone or combined with ermC and/or ermA). Moreover, cpd (94.2%), gelE (77.4%), efaAfs (93.4%), and esp (79.6%) were the most common virulence genes in E. faecalis. In E. faecium, except for the gene efaAfs (82.0%), other virulence genes are rarely found. Only two strains of E. hirae carrying asa1 gene were detected.Conclusion: The results of this study can provide a reference for the prevention and treatment of bovine mastitis caused by enterococci.Keywords: bovine mastitis, enterococci, antimicrobial resistance, virulence

Ke Li,1,2,&ast; Lupeng Qiu,1,2,&ast; Yang Zhao,3,&ast; Xiaohui Sun,1,2 Jiakang Shao,1 Chang He,1,2 Boyu Qin,4 Shunchang Jiao4 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Vascular Intervention, Special Medical Center for Strategic Support Forces, Beijing, 100101, People’s Republic of China; 4Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunchang Jiao; Boyu Qin, Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, 8 Dongdajie Street, Fengtai District, Beijing, 100071, People’s Republic of China, Email jiaosc@vip.sina.com; qpm2017@126.comPurpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients.Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan–Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation.Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867– 0.970), 0.908 (95% CI: 0.860– 0.956) and 0.878 (95% CI: 0.798– 0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736– 0.892), 0.819 (95% CI: 0.749– 0.889) and 0.809 (95% CI: 0.678– 0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort.Conclusion: Based on the patients’ treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort.Keywords: small cell lung cancer, treatment response, patient prognosis, nomogram prognostic model

Wei Wei,1,2,&ast; Haili Cao,2,&ast; Di Shen,2 Xiyu Sun,2 Zhenzhen Jia,1 Mingzhen Zhang1 1School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Xi’an No.1 Hospital, Shaanxi Institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, First Affiliated Hospital of Northwestern University, Xi’an, Shaanxi, 710002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenzhen Jia; Mingzhen Zhang, Email jzz324716@stu.xjtu.edu.cn; mzhang21@xjtu.edu.cnPurpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment.Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED.Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells.Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.Keywords: dry eye disease, carbon dots nanozyme, thermosensitive in situ gel, composite ocular drug delivery system

Shuo Li,1,2 Tingyu Zhang,1,2 Xin Sun,1,2 Xiaoke Li1,2 1Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Xiaoke Li, Beijing University of Chinese Medicine, Haiyuncang 5, Dongcheng District, Beijing, People’s Republic of China, Tel +86 010-84015503, Email lixiaoke@vip.163.comPurpose: Immunogenic cell death (ICD) is a type of regulated cell death that modifies the immune response by releasing DAMPs or danger signals. Herein, we aimed to develop an ICD-related predictive model for patients with hepatocellular carcinoma (HCC) and investigate its applicability for predicting prognostic outcomes and immunotherapeutic responses.Methods: Differentially expressed genes of ICD were identified in the HCC and normal liver samples. A prognostic risk model and a nomogram containing clinicopathological features were created. To validate the effectiveness of the model, an external dataset was used. Clinical characteristics, prognosis, tumor mutation burden, immune microenvironments, biological function and chemotherapeutic drug sensitivity were evaluated for different genetic subtypes and risk groups.Results: A total of 35 ICD-related genes (ICDRGs) were identified between HCC and normal samples, 11 of which were significantly associated with overall survival (OS) in HCC patients. Four different genetic subtypes were formed and eight ICDRGs were selected to develop a risk prognostic model. The risk scores were shown to be an independent prognostic factor for HCC and positively correlated with pathological severity. Patients in the high-risk group had a higher frequency of TP53 mutations, increased expression of immune checkpoints and human leukocyte antigen genes. The inhibitory concentrations of chemotherapeutic drugs differed in different populations.Conclusion: In this study, we developed an ICDRG risk model and demonstrated its applicability in predicting survival outcomes, immune and chemotherapeutic responses in HCC patients. ICDRGs are expected to be used as novel biomarkers in the medical decision-making of HCC.Keywords: immunogenic cell death-related genes, hepatocellular carcinoma, prognosis, immune microenvironments, drug sensitivity

Xulei Sui,1 Peipei Feng,1 Xiaoyuan Sun,1 Peng Liang,1 Ying Liu,2 Guowei Zhang3 1Department of Radiology, Yantaishan Hospital, Yantai City, 264001, People’s Republic of China; 2Department of Pathology, Yantaishan Hospital (East Courtyard), Yantai City, 264003, People’s Republic of China; 3Department of Radiology, Yantaishan Hospital (East Courtyard), Yantai City, 264003, People’s Republic of ChinaCorrespondence: Guowei Zhang, Department of Radiology, Yantaishan Hospital (East Courtyard), No. 10087 Keji Avenue, Laishan District, Yantai City, 264003, People’s Republic of China, Tel +86-0535-6602048, Email zhangguoweiyt@163.comPurpose: This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features.Patients Methods: Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups.Results: Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (< 45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients.Conclusion: PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was < 2 cm in diameter. PIMPC mainly occurs in middle-aged women 45– 59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index > 30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.Keywords: pure invasive micropapillary breast carcinoma, digital mammography, ultrasonography, breast cancer, pathologic features

Han Wu,1,&ast; Hui Wang,2,&ast; Lixia Sun,3,&ast; Mengchen Liu,1 Haoran Wang,1 Xianchang Sun,4 Wenjuan Zhang1 1Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People’s Republic of China; 2Gynecological Minimally Invasive Surgery Center, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 3Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Zhang, Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, 366 Taishan Street, Taian, 271000, People’s Republic of China, Email wenjuanzhang1119@163.com Xianchang Sun, Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan, 250117, People’s Republic of China, Email hotsss@163.comPurpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS).Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups.Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype.Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.Keywords: angiopoietin-like protein 8, insulin resistance, metabolic disorder, obesity, polycystic ovary syndrome, single nucleotide polymorphism

Lanlang Zhang,1 Lixia Huang,2 Shanshan Liu,3 Xiaofeng Sun4 1Department of Haemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 2Department of Gastrology, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 3Nursing Department, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 4Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of ChinaCorrespondence: Xiaofeng Sun, Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of China, Tel +86-13723457417, Email 350787457@qq.comAbstract: This study aimed to optimize bowel preparation efficacy for colonoscopy in elderly constipation patients. A 71-year-old patient with chronic constipation and a history of poor bowel preparation. To address these challenges, we implemented a personalized strategy combining of PEG administration and walking exercise. The PEG was administered according to a protocol, with intermittent exercise breaks of 10 minute. Bowel cleanliness was assessed using the Boston Bowel Preparation Scale (BBPS). Adverse reactions and tolerance were closely monitored throughout the intervention. The patient’s BBPS score improved from 3 to 8 post-intervention. The exercise intervention was well-tolerated (rating I), and mild nausea was observed only after the first PEG dose. No severe adverse reactions occurred. Subsequent Follow-up revealed symptom relief. The personalized approach combining (PEG and exercise intervention) successfully improved bowel preparation quality in the elderly constipation patient undergoing colonoscopy. This approach considers age-related changes in gastrointestinal function and activity level, offering an effective strategy to improve patient tolerance and reduce adverse reactions during bowel preparation. The findings underscore the importance of tailoring interventions for elderly constipation patients to optimize the colonoscopy experience.Keywords: compound polyethylene glycol electrolyte powder, exercise intervention plan, bowel preparation, colonoscopy, elderly, constipation

Xiaochen Ma, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Yang Xie, Caixia Li, Kai Zhang Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Kai Zhang, Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China, Email zhangkai@qiluhospital.comAim: This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs).Materials and Methods: A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed.Results: The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE.Conclusion: The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.Keywords: hepatocellular carcinoma, immunotherapy, soluble programmed cell death protein 1, drug-eluting beads transarterial chemoembolization

Kun Cao,1,2,&ast; Zehui Wang,1,3,5,6,&ast; Xiaojiao Sun,3– 6,&ast; Di Yan,1– 3 Yanwen Liu,3 Ting Ma,3 Xiaojuan Sun1,2 1Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 4Animal Experiment Center of Ningxia Medical University, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 5Stem Cell Institute, General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 6Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zehui Wang, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email wangzehui364@163.com Xiaojuan Sun, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email ms_sunxiaojuan@126.comIntroduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3β/β-catenin signaling axis and toxicological effects.Methods: The structural and morphological changes of BM were analyzed using scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). In vivo, wound healing of BM was assessed in SD rats through dynamic monitoring and calculation of wound healing rate. Immunohistofluorescence (IHF), H&E, and Masson staining were utilized; in vitro, primary cell culture, and a variety of assays including CCK-8, Transwell, Scratch, Immunocytofluorescence (ICF), and Western blot (WB) were performed, both for morphology and molecular analysis.Results and Discussion: Preparation of BM involved attaching NMBG to RGD-exposed collagen while avoiding the use of toxic chemical reagents. BM exhibited a distinctive superficial morphology with increased Si content, indicating successful NMBG attachment. In vivo studies on SD rats demonstrated the superior wound healing capability of BM, as evidenced by accelerated wound closure, thicker epithelial layers, and enhanced collagen deposition compared to the NC group. Additionally, BM promoted skin fibroblast migration and proliferation, possibly through activation of the GSK-3β/β-catenin signaling axis, which was crucial for tissue regeneration. This study underscored the potential of BM as an effective wound-healing dressing.Conclusion: A new method for synthesizing ECM-like membranes has been developed using nano-mesoporous bioactive glass and collagen-derived peptides. This approach enhances the bioactivity of biomaterials through surface functionalization and growth factor-free therapy.Keywords: NMBG, proliferation, RGD, migration, wound healing, GSK-3β/β-catenin signaling axis

Jiao Chen, Danmei Luo, Chengxia Sun, Xiaolan Sun, Changmao Dai, Xiaohong Hu, Liangqing Wu, Haiyan Lei, Fang Ding, Wei Chen, Xueping Li Geriatric Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Xueping Li, Chengdu University of Traditional Chinese Medicine, No. 37, Shier Bridge Road, Chengdu, Sichuan, People’s Republic of China, Tel +86-18380251086, Email 3173907@qq.comPurpose: Building and validating a clinical prediction model for novel coronavirus (COVID-19) re-positive cases in malnourished older adults.Patients and Methods: Malnourished older adults from January to May 2023 were retrospectively collected from the Department of Geriatrics of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. They were divided into a “non-re-positive” group and a “re-positive” group based on the number of COVID-19 infections, and into a training set and a validation set at a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify predictive factors for COVID-19 re-positivity in malnourished older adults, and a nomogram was constructed. Independent influencing factors were screened by multivariate logistic regression. The model’s goodness-of-fit, discrimination, calibration, and clinical impact were assessed by Hosmer-Lemeshow test, area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CIC), respectively.Results: We included 347 cases, 243 in the training set, and 104 in the validation set. We screened 10 variables as factors influencing the outcome. By multivariate logistic regression analysis, preliminary identified protective factors, risk factors, and independent influencing factors that affect the re-positive outcome. We constructed a clinical prediction model for COVID-19 re-positivity in malnourished older adults. The Hosmer-Lemeshow test yielded χ2 =5.916, P =0.657; the AUC was 0.881; when the threshold probability was > 8%, using this model to predict whether malnourished older adults were re-positive for COVID-19 was more beneficial than implementing intervention programs for all patients; when the threshold was > 80%, the positive estimated value was closer to the actual number of cases.Conclusion: This model can help identify the risk of COVID-19 re-positivity in malnourished older adults early, facilitate early clinical decision-making and intervention, and have important implications for improving patient outcomes. We also expect more large-scale, multicenter studies to further validate, refine, and update this model.Keywords: malnutrition, COVID-19, re-positive, clinical prediction model

Rui-Gui Zhang,1– 3 Yu-Mei Liu,2– 4 Zhi-Ye Yao,2,3 Jing-Xuan Fang,4 Yuan Li,2– 4 Man-Li Zheng,2,3 Xin Sun,2,3 Shu-Sheng Wen,4,5 Xi-Meng Wang,4,6 Jian Zhuang,4 Dan-Dong Luo,4 Shao-Ru He1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510260, People’s Republic of China; 2Department of Neonatal Pediatrics, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Department of Pediatrics, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 6Global Health Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Shao-Ru He, Department of NICU, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences, No. 106 of Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Tel +8620-83827812, Email Hshru_rsh@163.comBackground: Studies of chylothorax after congenital heart disease in infants are rare. Chylothorax has a higher incidence in infancy, but its risk factors are not well understood.Objective: The purpose of this study is to investigate the risk factors of chylothorax after congenital heart surgery in infants.Methods: This retrospective study included 176 infants who underwent congenital heart disease surgery at the Guangdong Cardiovascular Institute, China, between 2016 and 2020. According to the occurrence of chylothorax, the patients were divided into a control group (n = 88) and a case group (n = 88). Univariate and multivariate logistic regression were performed to analyse the incidence and influencing factors of chylothorax after congenital heart surgery in infants.Results: Between 2016 and 2020, the annual incidence rate fluctuated between 1.55% and 3.17%, and the total incidence of chylothorax was 2.02%. Multivariate logistic regression analysis showed that postoperative albumin (p = 0.041; odds ratio [OR] = 0.095), preoperative mechanical ventilation (p = 0.001; OR = 1.053) and preterm birth (p = 0.002; OR = 5.783) were risk factors for postoperative chylothorax in infants with congenital heart disease.Conclusion: The total incidence of chylothorax was 2.02% and the annual incidence rate fluctuated between 1.55% and 3.17% between 2016 and 2020. Premature infants, longer preoperative mechanical ventilation and lower albumin after congenital heart surgery may be risk factors for chylothorax. In addition, infants with chylothorax are inclined to be infected, need more respiratory support, use a chest drainage tube for longer and remain longer in hospital.Keywords: congenital heart surgery, congenital heart disease, postoperative chylothorax, infant, risk factor

Yuting Feng, Xue Bao, Jinxuan Zhao, Lina Kang, Xuan Sun, Biao Xu Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Xuan Sun; Biao Xu, Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email sunxuan891119@163.com; xubiao62@nju.edu.cnIntroduction: Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury.Methods: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro.Results: MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also could attenuate the activation of NLRP3 inflammasome both in vivo and in vitro. At the same time, the infarction size and MVO following I/R injury were reduced by MSC-Exo. Moreover, systemic depletion of neutrophils partly negated the therapeutic effects of MSC-Exo. Up-regulation of miR-199 in neutrophils has been shown to decrease the expression of NETs formation after stimulation.Discussion: Our results demonstrated that MSC-Exo mitigated myocardial I/R injury in mice by modulating neutrophil infiltration and NETs formation. This study provides novel insights into the potential therapeutic application of MSC-Exo for myocardial ischemia/reperfusion injury. Keywords: myocardial ischemia/reperfusion injury, mesenchymal stromal cells, exosomes, neutrophil extracellular traps, mir-199

Mengqi Wang,1,&ast; Shuting Lan,1,&ast; Wenqi Zhang,1,&ast; Qin Jin,2 Hua Du,3 Xiaomei Sun,1 Lijun He,1 Xiangyun Meng,1 Liya Su,1 Gang Liu1 1Key Laboratory of Medical Cell Biology, Department of Achievement Transformation, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Liu, Email 20190043@immu.edu.cnIntroduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations.Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells.Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway.Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.Keywords: copper, carbon quantum dots, breast cancer, oxidative stress, MAPK signaling pathway

Qingyan Jiao,1,&ast; Yeqing Dong,2,&ast; Xiaojuan Ma,3 Shiyi Suzy Ji,4 Xinyu Liu,1 Jian Zhang,1 Xia Sun,1 Dazhi Li,1 Xingguang Luo,5 Yong Zhang1 1Unit of Bipolar Disorder, Tianjin Anding Hospital, Tianjin, 300222, People’s Republic of China; 2Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, People’s Republic of China; 3Tianjin Medical College, Tianjin, 300222, People’s Republic of China; 4Teachers College, Columbia University, New York, NY, USA; 5Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA&ast;These authors contributed equally to this workCorrespondence: Yong Zhang, Unit of Bipolar Disorder, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel/Fax +86 22 8818 8258, Email zhangyong@tjmhc.comPurpose: Major depressive disorder (MDD) is associated with worse cognitive functioning. We aim to examine the association between baseline cognitive functioning and the reduction rate in HDRS-17 total scores and to highlight the predictors of the reduction rate in HDRS-17 total scores in MDD with first-episode, drug-naïve (FED) patients.Patients and Methods: Ninety FED patients were recruited consecutively and evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Functioning Assessment Short Test (FAST) and the MATRICS Consensus Cognitive Battery (MCCB) at baseline and again at week 8.Results: Eighty-four FED patients completed the study. Comparison showed that response group had significantly higher T scores in TMT-A, BACS-SC, WMS-III, BVMT-R, MSCEI and CPT-IP, but showed significantly lower scores in FAST total scores including autonomy, occupational functioning, cognitive functioning, interpersonal relationship than non- response group (all p’s< 0.05). Partial correlation analysis also found that the reduction rate in HDRS-17 total scores could be negatively associated with autonomy, cognitive functioning and interpersonal relationship domains as well as total FAST scores, also was further positively associated with T-scores of BACS-SC, CPT-IP and MSCEI in MCCB, even when accounting for potential confounders. Furthermore, the levels of cognitive function domain, autonomy domain in FAST, and BACS-SC, CPT-IP in MCCB may predict the reduction rate in HDRS-17 total scores in FED patients (all p’s< 0.05).Conclusion: Our findings underscore significant correlations between baseline functioning and the reduction rate in HDRS-17 total scores in FED patients. Moreover, better baseline cognitive function, autonomy, speed of processing and attention/vigilance are more likely to predict patients’ response to antidepressant treatment, indicating pre-treatment better cognitive functioning may be predictors to treatment response in FED.Keywords: FED, FAST, MCCB, treatment response, the reduction rate in HDRS-17 total scores

Jianli Ge,1 Huazhang Li,2 Guangwei Ren,3 Xiaoming Sun,1,4 Hua Jiang1 1Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 2Department of Science and Education, Shanghai Guangming Traditional Chinese Medicine Hospital, Shanghai, 201399, People’s Republic of China; 3Department of Science and Education, Sanlin Community Health Service Center, Shanghai, 200124, People’s Republic of China; 4School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Hua Jiang; Xiaoming Sun, Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China, Email Huajiang2013@tongji.edu.cn; xm_sun2003@aliyun.comBackground: Age-related hearing loss (ARHL) is experiencing a continuously rising in prevalence among the elderly worldwide. General practitioners (GPs) may have a unique position in its community detection and management.Objective: This study aims to assess the KAP of GPs regarding ARHL through questionnaire, to investigate the role of them in the management and to propose strategies for the hearing screening within the community.Methods: An online survey was administered to 1173 GPs, selected from 56 community health centers (CHCs) in Shanghai during April to June 2022. A scale endorsed by a panel of multidisciplinary experts was used to assess knowledge (7 items), attitudes (12 items), and practice (10 items). A mean score was computed and converted into a scale ranging from 0 to 100. Odds ratios (ORs) were calculated for potential predictors of higher levels of KAP scores (with mean value as a cutoff point) through logistic modelling.Results: A total of 1022 GPs completed the questionnaire with response rate 87.13%. The average scores are 69.90 ± 32.27, 66.09 ± 7.15, and 59.89 ± 21.99 for Knowledge, attitude, and practice, respectively. 24.3% of participants achieve a complete score of knowledge, whereas 5.48% receive zero. 11.6% consider ARHL as not a disease. Above 30.0% are not familiar with the screening tool. 10.8% refuse to undergo hearing screening. Higher levels of compliance in practice are found in the participants with higher levels of knowledge (OR=1.409, p=0.000) and more favorable attitude (OR=1.028, p=0.000). Male (OR=0.708, p=0.036) is associated with lower levels of attitudes.Conclusion: GPs have a low level of ARHL knowledge, a lack of positive attitude towards the detection and management of it, and lower awareness in practice. Further research is required to gain a more comprehensive understanding of the attitudes held by GPs and explore more accessibility strategies.Keywords: age-related hearing loss, KAP, general practitioners

Yan Ding,1,&ast; Banqin Wang,2,&ast; Yongjun Liu,1 Shengjie Dong,1 Xuri Sun,1 Zhilin Cao,1 Leisheng Wang1 1Department of Orthopedics, Yantaishan Hospital, Yantai, People’s Republic of China; 2Department of Blood Transfusion, Shandong Provincial Qianfoshan Hospital Affiliated with Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leisheng Wang, Department of Orthopedics, Yantaishan Hospital, No. 10087 Keji Road, Yantai, 264003, People’s Republic of China, Tel +86-13792566016 ; +86-0535-6863898, Email 37724148@qq.comPurpose: Percutaneous pedicle screw fixation is a common minimally invasive treatment for traumatic thoracolumbar and lumbar fractures; however, research on hardware removal after successful healing is limited. We aimed to introduce a rapid, safe, minimally invasive, and cost-effective method for percutaneous pedicle screw removal.Patients and Methods: We conducted a retrospective analysis of demographic (age, sex, body mass index, alcohol use, and current smoking), clinical (hypertension and diabetes mellitus), surgical (affected levels, number of screws, time of surgery, and blood loss), and treatment cost characteristics of 92 patients who had undergone percutaneous pedicle screw removal between May 2016 and February 2023. The first 57 patients underwent the conventional method, and the remaining 35 underwent the modified method. Independent-sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the two groups.Results: No significant differences were observed in the demographic parameters, complications, or affected levels between the groups. However, the average surgical time (P=0.000) was significantly shorter, and the average blood loss volume (P=0.002) and total cost (P=0.000) were significantly lower in the modified group than in the conventional group.Conclusion: Compared with the conventional method, our modified method can shorten the surgical time, reduce blood loss, and reduce the total cost of treatment. It is a quick and safe minimally invasive method that does not require additional surgical instruments and is suitable for implementation in primary hospitals.Keywords: bone screw, device, Kirschner wire, surgery, control

Jiaping Shu,1,&ast; Lili Jia,2,&ast; Pei Zhang,2 Ren Wang,2 Meiqiu Wang,2 Xiaoyi Sun,2 Yingchao Peng,2 Peipei Wang,2 Xiaojie Li,2 Zilu Tang,3 Tingting Han,3 Tao Ju,3 Yaqin Wei,4 Wei Pang,5 Chunlin Gao,2 Zhengkun Xia1 1Department of Pediatrics, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 2Department of Pediatrics, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, 210093, People’s Republic of China; 3Department of Pediatrics, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210093, People’s Republic of China; 4Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 5Department of Military Information, Chinese People’s Liberation Army 31102, Nanjing, Jiangsu, 210000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengkun Xia, Department of Pediatrics, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Email njxzk@126.com Chunlin Gao, Department of Pediatrics, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, 210093, People’s Republic of China, Email shuangmu34@163.comIntroduction: The pandemic of SARS-CoV-2 brings great challenge and threats to humans worldwide. Multiple variants of SARS-CoV-2 tend to be epidemic, among which Omicron is highly infectious within China. The aim of this study was to analyze the clinical characteristics of children infected with SARS-CoV-2 variant B.1.1.529 (Omicron) in the Shanghai, China.Methods: We included 9378 pediatric patients diagnosed with Omicron and treated in the Shanghai International Convention and Exhibition Center between April 1, 2022 and May 31, 2022. We recorded and summarized the clinical characteristics, infectious conditions and biological features of the children infected with Omicron.Results: A total of 9355 paediatric patients were treated in isolation since Makeshift became available, including 5564 males (59.48%) and 3791 females (40.52%). More than half (55.56%) of the affected children were identified at premises screening. The number of symptomatic or asymptomatic patients was 4530 (48.42%) and 4825 (51.58%), respectively. Initial signs or symptoms in asymptomatic patients included fatigue (3582, 38.29%), cough (560, 5.99%), fever (242, 2.59%) and other (146, 1.56%). Age and number of vaccinations in paediatric patients were negatively associated with the number of days from positive to negative nucleic acid test results.Conclusion: Age and number of vaccinations were key factors influencing the conversion of nucleic acid test results in paediatric patients. Early childhood vaccination is encouraged to establish a complete immune barrier.Keywords: Omicron variant, COVID-19, child patients, clinical characteristics

Runing Zhou,1 Xiyu Sun,2 Mingyue Guo,1 Huimin Zhang,1 Xuanfu Chen,1 Meixu Wu,1 Haozheng Liang,1 Xiaoyin Bai,1 Gechong Ruan,1 Hong Yang1 1Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hong Yang, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, People’s Republic of China, Tel +86-10-69155014, Email yangh@pumch.cnAim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined.Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval.Results: A total of 516 and 848 patients were confirmed to have Crohn’s disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P< 0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51– 60 years and 12.5 months in UC patients at the age of 41– 50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay.Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.Keywords: inflammatory bowel disease, diagnostic delay, China

Haojing Song, Bo Qiu, Xue Sun, Caihui Guo, Yiting Hu, Wanjun Bai, Zhanjun Dong Department of Medicine, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of ChinaCorrespondence: Wanjun Bai; Zhanjun Dong, Department of Medicine, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China, Tel +86-0311-85988326 ; +86-0311-85988604, Fax +86-0311-85988604, Email baiwanjun0311@163.com; yqlcdzj@163.comBackground: The objective of this study was to evaluate the effect of a high-fat meal on the pharmacokinetics and safety of 80/5 mg valsartan/amlodipine tablets in healthy subjects.Subjects and Methods: These results were derived from a bioequivalence trial where subjects were randomly assigned to take valsartan/amlodipine 80/5mg under fed conditions or after a high-fat meal contained 978.6 kilocalories (54.6% from fat). The blood samples were collected and plasma concentrations of valsartan/amlodipine were measured using high-performance liquid chromatography-mass spectrometry. The non-compartmental module of Phoenix WinNonlin Version 8.2 was used to calculate pharmacokinetic parameters. The BE module of WinNonLin was used to analyze the statistics of the maximum plasma concentration (Cmax), the area under the concentration-time curve from zero to the last quantifiable time point (AUC0-t), and the area under the concentration-time curve from zero to infinity(AUC0–∞) in plasma. 88 healthy subjects were enrolled and divided into in a fasted group and a fed group.Results: The Cmax, AUC0–t, and AUC0–∞ of valsartan in plasma under fed conditions were 51%, 56%, and 57% lower, respectively, than those under fasted conditions, and the 90% confidence interval (90% CI) were outside the 80.00– 125.00% range. All the pharmacokinetic parameters for amlodipine under fed conditions were similar to those observed under fasted conditions, and the 90% CIs were within the 80.00– 125.00% range. The incidence of treatment emergent adverse events (TEAE) was similar between the fasted group and the fed group, while adverse drug reaction (ADR) was more frequent in the fasted group which may be related to the higher blood concentrations of valsartan, but all were mild.Conclusion: The result indicated that the high-fat meal had a significant effect on the pharmacokinetics of valsartan, but no effect on amlodipine. All treatments were safe and well tolerated in healthy subjects under fed and fasted conditions.Keywords: amlodipine, valsartan, high-fat meal, pharmacokinetics

Xuan Yi,1 Xinxing Wan,1 Md Asaduzzaman Khan,2,3 Xiaoying Sun,1 Zhouqi Wang,1 Ke Chen,1 Lin Peng4 1Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Research Division, Nature Study Society of Bangladesh, Dhaka, 1000, Bangladesh; 3Pulmonary Department, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, 02118, USA; 4Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of ChinaCorrespondence: Lin Peng, Department of Nephrology, The First Hospital of Changsha, Changsha, People’s Republic of China, Tel +86-731-8466-7510, Email plin1018@163.com Ke Chen, Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8861-8239, Email chenke520@yeah.netPurpose: Adipogenesis is one of the major pathways for generating obesity or overweight that can cause a range of metabolic disorders. Circular RNAs (circRNAs), a specific type of RNAs, have a significant influence on metabolic disorders. This study aims to find differentially expressed circRNAs (DECs) during human subcutaneous adipose tissue (SATs) adipogenesis.Patients and Methods: The human adipose tissue-derived stromal cells (hADSCs) were isolated from human SATs (n = 3), and then induced into adipocytes. Total RNAs were extracted from hADSCs and adipocytes, and he DECs were detected using circRNA microarray. The GO and KEGG pathways of DECs were analyzed by bioinformatic methods, and partial DECs were further validated by quantitative polymerase chain reaction (qPCR).Results: Our study detected a total of 1987 DECs, among which, 1134 were found upregulated and 853 were downregulated. GO analysis showed that the upregulated DECs have catalytic activity in intracellular organelle and cytoplasms, whereas downregulated DECs are enriched in organelle lumen, and are involved in positive regulation of developmental process. In addition, pathway results demonstrated that upregulated DECs are involved in platinum drug resistance and cellular senescence, and downregulated DECs are enriched in proteoglycans in cancer and focal adhesion pathway. Two circRNAs, namely has_circ_0001600 and has_circ_0001947 were validated to be significantly upregulated in adipocytes compared to hADSCs.Conclusion: Our study explored DECs between hADSCs derived from SATs and adipocytes, and report that two circRNAs named has_circ_0001600 and has_circ_0001947 might be important factors involved in human adipogenesis, however, the molecular mechanism should be further explored.Keywords: circRNA microarray, subcutaneous adipose tissue, human adipose tissue-derived stromal cells, adipogenesis, SAT

Haili Huang,1 Yi Dai,1 Xinghuai Sun,1– 3,&ast; Yuan Fang1,&ast; 1Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, People’s Republic of China; 2State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, People’s Republic of China; 3NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinghuai Sun; Yuan Fang, Email xhsun@shmu.edu.cn; fangyuandoc@163.comPurpose: This study aimed to investigate the outbreak of acute primary angle-closure (APAC) during the COVID-19 Omicron variant pandemic in Shanghai.Methods: This single-center retrospective observational study included all newly diagnosed patients with APAC in Eye, Ear, Nose, and Throat Hospital of Fudan University from December 15, 2022, to January 14, 2023 (pandemic group) during the COVID-19 pandemic of Omicron Variant, and from November 15, 2021, to February 14, 2022 (control group) when the infection rate of COVID-19 is very low in Shanghai. Demographic features, intraocular pressure, axial length, anterior chamber depth, lens thickness and pupil diameter were compared between the two groups.Results: A total of 223 patients (261 eyes) were included in the pandemic group and 75 patients (82 eyes) in the control group. The number of APAC patients and eyes in the pandemic group is 8.92-fold and 9.55-fold of the monthly average number in the control group. The onset dates of acute angle-closure were mainly between December 17 and December 31, 2022. In the pandemic group, 72.65% of patients with APAC had a recent COVID-19 infection. Among the COVID-19-positive patients, 72% suffered APAC attacks within 24h of the occurrence of COVID-19 symptoms and 92% within 3 days. The pandemic group showed a longer time from symptoms to treatment and larger pupil diameter than the control group (7.92 ± 6.14 vs 3.63 ± 2.93 days, p = 0.006; 4.53 ± 1.17 vs 3.78 ± 1.24 mm, p = 0.003, respectively).Conclusion: An outbreak of APAC attack was observed in our eye center during the COVID-19 Omicron variant pandemic in Shanghai. There may be a correlation between the onset of APAC and new COVID-19 Omicron variant infection, but the exact reason needs to be investigated further.Keywords: acute primary angle-closure, COVID-19 pandemic, omicron variant, Shanghai

Xian Sun,1 Xi Zhou,1 Weiming He,2 Wei Sun,2 Zheng Xu1 1School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Zheng Xu, School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Tel +86-15951978958, Email xuzheng@njucm.edu.cn Wei Sun, Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel +86-13505199810, Email yfy0074@njucm.edu.cnAbstract: Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.Keywords: gut microbial ecosystem, TCM herb, extra-intestinal disease, co-housing, fecal microbiota transplantation

Ni Meng, Xiaolong Cheng, Mengyao Sun, Yushan Zhang, Xueke Sun, Xifu Liu, Jing Chen Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Anti-Tumor Molecular Target Technology Innovation Center; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Science, Hebei Normal University, Shijiazhuang, 050024, People’s Republic of ChinaCorrespondence: Jing Chen; Xifu Liu, Email jingchen@hebtu.edu.cn; xfliu@hebtu.edu.cnIntroduction: The monkeypox (Mpox) virus epidemic presents a significant risk to global public health security. A35R, a crucial constituent of EEV, plays a pivotal role in virus transmission, serves as a vital target for vaccine development, and has potential for serological detection. Currently, there is a dearth of research on nanobodies targeting A35R. The purpose of this study is to identify specific nanobodies target A35R, so as to provide new antibody candidates for Mpox vaccine development and diagnostic kit development.Methods: Three nanobodies specific to the monkeypox virus protein A35R were screened from a naïve phage display library. After four rounds of panning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA). Further, the nanobody fusion protein was constructed in pNFCG1-IgG1-Fc vector and expressed in HEK293F cells and purified by affinity chromatography. The specificity and affinity of the nanobodies were identified by ELISA. The binding kinetics of the VHH antibody to A35R were assessed via employment of a bio-layer interferometry (BLI) apparatus, thereby determining the nanobodies affinity.Results: The three purified nanobodies showed specific high-affinity binding MPXV A35R, of them, VHH-1 had the best antigen binding affinity (EC50 = 0.010 ug/mL). In addition, VHH-1 on Protein A biosensor can bind Mpox virus A35R, with an affinity constant of 54 nM as determined in BLI assay.Conclusion: In sum, we has obtained three nanobody strains against Mpox virus A35R with significant affinity and specificity, therefore laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of Mpox virus.Keywords: monkeypox virus, A35R, nanobody, phage display library

Xiaofeng Sun,1 Junhong Cai,1 Hongkui Yu,1 Ting Zhang,1 Lanlang Zhang2 1Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518102, People’s Republic of China; 2Department of Hemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of ChinaCorrespondence: Lanlang Zhang, Department of Hemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China, Tel +86-13603098960, Email 710394655@qq.comBackground: Transvaginal four-dimensional hysterosalpingo-contrast sonography (TVS 4D-HyCoSy) is a pivotal diagnostic tool in the assessment and management of infertility. Conventionally, a 20mL syringe is employed for contrast agent injection, either at a constant or pulsatile pressure. However, in cases of bilateral fallopian tube obstruction, continued injection can lead to discomfort and excessive pressure within the uterine cavity, necessitating discontinuation of the examination.Case Presentation: In this illuminating case study, a patient underwent TVS 4D-HyCoSy due to infertility concerns. Initial contrast agent injection failed to visualize both fallopian tubes, accompanied by acute pain. Bilateral tubal obstruction was diagnosed, prompting an innovative approach. A 2.5mL syringe was chosen for pulsed injection, leading to successful visualization of patency in one fallopian tube. Remarkably, the patient achieved natural pregnancy within three months of the examination.Conclusion: Pulsed injection using a small-volume syringe emerges as a promising technique in cases of fallopian tube obstruction during TVS 4D-HyCoSy. This method not only enhances patient comfort but also improves the likelihood of visualizing fallopian tube patency, contributing to accurate infertility assessments. As a supplementary technique, it addresses limitations associated with constant pressure injection and offers a novel approach to enhance diagnostic success.Keywords: hysterosalpingography, tubal obstruction, contrast agent, pulsed injection, small-volume syringe

Yongkang Liu,1 Cuiping Yuan,1 Xiao Chen,1 Xiaokun Fang,1 Jingru Hao,1 Maodong Zhou,1 Xin Sun,1 Minghua Wu,2 Zhongqiu Wang1 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Zhongqiu Wang, Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email zhqwang2012@126.com Minghua Wu, Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email yfy0069@njucm.edu.cnPurpose: White matter hyperintensities (WMH) are the common marker of cerebral small vessel disease (CSVD). Dyslipidemia plays a notable role in the pathogenesis of CSVD. However, the relationship between dyslipidemia and WMH is poorly elucidated. This study aims to investigate the association between serum lipid fractions and WMH in patients with acute ischemic stroke (AIS).Patients and Methods: A total of 901 patients with AIS were included in this study. The burden of WMH, including deep white matter hyperintensities (DWMH), periventricular white matter hyperintensities (PVWMH), and total WMH load, were evaluated on magnetic resonance imaging (MRI) by the Fazekas scale. All the WMH burden were set as dichotomous variables. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. The association of serum lipid fractions with WMH burden was analyzed using univariate and multivariate logistic regression models.Results: The average age of the participants was 67.6± 11.6 years, and 584 cases (64.8%) were male. About 33.5% (n = 302) patients were smoker, and 23.5% (n = 212) patients had a history of alcohol consumption. The proportion of previous diabetes, ischemic cardiomyopathy and hypertension was 39.0% (n = 351), 21.2% (n = 191) and 75.9% (n = 684), respectively. The average of serum HDL-c, TC, TG, LDL-c levels for all participants were 1.26 ± 0.28 mmol/l, 4.54 ± 1.06 mmol/l, 1.67 ± 1.09 mmol/l, 3.08 ± 0.94 mmol/l. There were no statistical associations between HDL-c, TG, TC, LDL-c and each type of WMH burden (P > 0.05) in multivariate logistic regression analysis. Similar findings were found in subgroup analysis based on gender classification.Conclusion: Serum lipid levels were not associated with the presence of any type of WMH in patients with AIS.Keywords: white matter hyperintensities, HDL-c, triglyceride, total cholesterol, LDL-c, acute ischemic stroke

Xu Wang, Zhanli Jia, Jinze Li, Huichai Yang, Xuemei Sun, Yueping Liu Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of ChinaCorrespondence: Xu Wang; Yueping Liu, Department of Pathology, the Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, Hebei, 050011, People’s Republic of China, Email xv1904@163.com; annama@163.comBackground: Primary breast lymphoma (PBL) is a very rare form of non-Hodgkin’s lymphoma (NHL). A primary T-cell lymphoma in the breast with no previously identified lymphomatous lesions is an even rarer form of this malignancy.Case Presentation: A biopsy of a breast mass in a 60-year-old Caucasian man showed a morphologic-immunophenotypic profile with features characteristic of an ALK-positive (AKT+), anaplastic large cell lymphoma. Fluorescence in situ hybridization (FISH) analysis of fixed, paraffin-embedded tissue of this lesion was performed at our institution for IRF4/DUSP22 gene rearrangement. No rearrangement was detected. The patient presented with mutations in the following genes; BCOR_p.Q600X, DNMT3A_p.F609fs, NOTCH1_p.P2320fs, and IDH2_p.R140Q. However, the patient’s consultation was complicated by the fact that he had been diagnosed with breast cancer at a local hospital and had come to our institution for further consultation. The histology findings were confirmed by immunohistochemistry and FISH. Computed tomography and positron emission tomography did not reveal nodules elsewhere in the body, which allowed the staging of the patient to be completed. However, although the patient had previously received the chemotherapy CCOP regimen (ie, cyclophosphamide, vincristine, prednisolone acetate) he did not go into remission in a timely manner and relapsed after six months, followed by a drastic deterioration in his condition after four months, resulting in his death in less than one month.Conclusion: This report of a male patient describes a case of a rare T-cell lymphoma of the breast that occurs considerably more frequently in female patients. The differential diagnosis of the histology of this tumor showed mutations that occur more often in lymphoblastic lymphoma or leukemia. This rare malignancy and associated mutations led to the death of this patient during treatment.Keywords: tumors, lymphopoietic system, male breast, diagnostic histopathology, misdiagnosis

Guan H, Mei Y, Mi Y, et al. Onco Targets Ther. 2018;11:4893-4899. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figure 4 with images from an unrelated article. Specifically, The images for Figure 4B, NC and si-ANRIL, have been duplicated with images for Figure 2C, NC and miR-183, 48h, respectively from Sun X, Xu Y, Zhang S, et al. (2018). MicroRNA‑183 suppresses the vitality, invasion and migration of human osteosarcoma cells by targeting metastasis‑associated protein 110.3892/etm.2021.10947. Experimental and Therapeutic Medicine. 2018;15:5058-5064. https://doi.org/10.3892/etm.2018.6068. In addition, the images for Figure 4A, NC and si-ANRIL, 0h and 4A, Blank and NC, 12h, have been duplicated. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

This article is devoted to the characteristics of Russian and Chinese national personalities (RNP, СNP) based on the material of phraseological units, proverbs, and sayings with the concept of "family." Russian and Chinese national personalities are considered for the first time in the article, which has yet to previously be described in a comparative aspect. The family's traditional spiritual and cultural values of Russian and Chinese cultures are analyzed for the first time. Their ideas and attitudes toward marriage, love, women, men, wives, husbands, parents, children, and relations to relatives indicate common or different cultural attitudes among representatives of both linguistic cultures. This is the scientific novelty of this study. This study shows that phraseological units, proverbs, and sayings with the concept of family recorded in Russian and Chinese lexicographic sources differ in quantitative and substantive terms. Russian and Chinese personalities view traditional family values such as marriage, love, women, men, wives, husbands, parents, children, relatives, etc. differently. For the Chinese, family and kinship relations are of great importance, and the preservation of these relations is carried out with the help of cultural values such as marital harmony, procreation, filial piety, fraternal friendship, and peaceful family relations.

Loy Eid,&ast; Xiyuan Mao,&ast; Binfan Zhao, Jiayi Mao, Shutong Qian, Yuyu Zhang, Ying Zhang, Lu Zhang, Liying Cheng, Yuguang Zhang, Xiaoming Sun Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuguang Zhang; Xiaoming Sun, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China, Email zhangyg18@126.com; drsunxm@126.comBackground: Facial fat compartments and their role in facial aging have gained increased recognition and are playing a significant role in facial rejuvenation. The superficial fat compartments glide inferiorly during the aging process, leading to the flattening and elongation of the face and the appearance of facial bulges, folds, and grooves.Patients and Methods: Ultrasound imaging of the facial soft tissues was performed on nine female volunteers to demonstrate the change in superficial facial fat compartments from an upright to supine position. The net suture jowl and medial cheek fat compartment repositioning technique was operated on 165 Asian patients between September 2020 and July 2021. Volume and projection change of malar and jowl regions, as well as change in elevation of malar protrusion were measured 1, 3, and 6 months postoperatively using a three-dimensional imaging system.Results: Ultrasound measurements confirmed the medial and middle cheek, nasolabial, and jowl fat compartments changed in thickness during positional changes with age-related differences. Postoperative three-dimensional imaging showed volume and projection increase in the malar region (2.23mL and 1.11mm) and decrease in the jowl region (− 0.18mL and − 0.52mm) by the 6-month follow-up date, and malar projection saw a superior displacement of 3.08mm.Conclusion: The superficial fat glide inferiorly within their compartments under the force of gravity and naturally reposition themselves when the effect of gravity is reversed. The net suture technique offers a minimally invasive method for lifting the jowl fat, volumizing the mid-cheek and achieving facial rejuvenation by repositioning the superficial fat compartments.Keywords: fat compartments, facial rejuvenation, face lift, facial aging

Yun-E Xu,1,&ast; Di-Shu Ao,1,&ast; Xin Sun,1 Wei Chen,2 Xue Luo,1 Can Zhao,1 Sheng-Yu Wang,1 Hong Song1 1Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Department of Hepatobiliary Surgery, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Song, Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Tel +86-18985259977 ; +86-0851-28643582, Email hongsong@zmu.edu.cnPurpose: Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The results support in vitro adenovirus studies, including isolation and culture, pathogenesis research, and antiviral drug screening.Methods: HSAEC1-KT, HuLEC-5a and HELF cells were cocultured in RADA16-I hydrogel scaffolds to construct an airway organoid model. Adenovirus was used to infect this model for adenovirus-related studies. The morphological characteristics and the proliferation and activity of airway organoids before and after adenovirus infection were evaluated. The expression of the airway organoid marker proteins CC10, KRT8, AQP5, SPC, VIM and CD31 was detected. TEM and qPCR were used to detect adenovirus proliferation in airway organoids.Results: HSAEC1-KT, HuLEC-5a and HELF cells cocultured at 10:7:2 self-assembled into airway organoids and maintained long-term proliferation in a RADA16-I hydrogel 3D culture system. The organoids stably expressed the lumen-forming protein KRT8 and the terminal airway markers AQP5 and SPC. Adenoviruses maintained long-term proliferation in this model.Conclusion: An airway-organoid model of adenovirus infection was constructed in vitro from three human lung-derived cell lines on RADA16-I hydrogels. The model has potential as a novel research tool for adenovirus isolation and culture, pathogenesis research, and antiviral drug screening.Keywords: nano-self-assembling peptide, RADA16-I hydrogels, airway organoids, adenovirus

Zhenyu Chen,1,2,&ast; Zhongbing Liu,1,&ast; Shuzao Wang,1,&ast; Cai Cheng,1,&ast; Xiaoduan Sun,1 Zerong Liu,3 Jun Wei,1 Jun Jiang,4,5 Huaqi Lan,1 Meiling Zhou,6 Pei Jing,6 Yan Lin,1 Xiangyu Zhou,7 Zhirong Zhong1,3,8 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2The Second People’s Hospital of China Three Gorges University, Yichang, 443000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of General Surgery (Thyroid Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 5Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Thyroid and Vascular Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Key Laboratory of Luzhou City for Aging Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyu Zhou; Zhirong Zhong, Email xiangyuzhou971@vip.126.com; zhongzhirong@126.comBackground: Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug with good analgesic and anti-inflammatory effects. However, it suffers from poor solubility, short circulation time, and off-target binding profile, which significantly limit its clinical application. Here, we loaded FA into stealth lipid microspheres modified with the arginine-glycine-aspartic acid (RGD) peptide (cRGD-FA-SLM), and examined the therapeutic potential of the resulting platform for the treatment of rheumatoid arthritis (RA).Methods: cRGD-FA-SLM was prepared by high pressure homogenization, and its toxicity and uptake by macrophages were examined using cultures of RAW264.7 cells. Hemolysis and hepatotoxicity tests were performed to assess the safety of the developed platform, while its pharmacokinetics, biodistribution, and therapeutic efficacy were investigated in a collagen-induced arthritis rat model.Results: cRGD-FA-SLM showed homogeneous spherical morphology and efficient encapsulation of FA. The developed platform was non-toxic to normal macrophages and was selectively internalized by lipopolysaccharide-activated macrophages in vitro, while it distributed mainly to arthritic joints and significantly prolonged FA in circulation in vivo. cRGD-FA-SLM also significantly reduced the expression of prostaglandin E2 and alleviated joint edema and bone erosion, showing prolonged analgesic effects in arthritic rats.Conclusion: cRGD-FA-SLM shows good inflammation-targeting ability and prolongs drug circulation in vivo, suggesting promise as an anti-inflammatory and analgesic agent for targeted RA treatment.Graphical Abstract: Keywords: flurbiprofen axetil, lipid nanospheres, cRGD, long circulation, rheumatoid arthritis

Xinlin Li,1,2,&ast; Baojuan Yang,3,4,&ast; Mengfei Xu,1,2 Fangyi Li,3,4 Zhaoli Geng,1,2 Weiqiang Cui,3,4 Xingfu Sun,3,4 Yanle Li,3,4 Yi Liu1,2 1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of High Efficiency and Clean Mechanical Manufacture, Ministry of Education, School of Mechanical Engineering, Shandong University, Jinan, 250061, People’s Republic of China; 4National Demonstration Center for Experimental Mechanical Engineering Education, Shandong University, Jinan, 250061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liu, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-88381630, Email yiliu@sdu.edu.cn Yanle Li, Key Laboratory of High Efficiency and Clean Mechanical Manufacture, Ministry of Education, Shandong University School of Mechanical Engineering, No. 17923, Jingshi Road, Jinan, 250061, People’s Republic of China, Tel +86-531-88392208, Email yanle.li@sdu.edu.cnIntroduction: The lack of osteoinductive, angiogenic and antimicrobial properties of hydroxyapatite coatings (HA) on titanium surfaces severely limits their use in orthopedic and dental implants. Therefore, we doped SiO2, Gd2O3 and CeO2 nanoparticles into HA to fabricate a HASiGdCe coating with a combination of decent antibacterial, angiogenic and osteogenic properties by the plasma spraying technique.Methods: The HASiGdCe coating was analyzed by SEM (EDS), surface roughness tests, contact angle tests, XRD, FTIR spectroscopy, tensile tests and electrochemical dynamic polarization tests. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1) were used as representative bacteria to verify the antibacterial properties of the HASiGdCe coating. We evaluated the cytocompatibility and in vitro osteoinductivity of the HASiGdCe coating by investigating its effect on the cell viability and osteogenic differentiation of MC3T3-E1 cells. We assessed the in vitro angiogenic activity of the HASiGdCe coating by migration assay, tube formation assay, and RT‒PCR analysis of angiogenic genes in HUVECs. Finally, we used infected animal femur models to investigate the biosafety, antimicrobial and osteointegration properties of the HASiGdCe coating in vivo.Results: Through various characterization experiments, we demonstrated that the HASiGdCe coating has suitable microscopic morphology, physical phase characteristics, bonding strength and bioactivity to meet the coating criteria for orthopedic implants. The HASiGdCe coating can release Gd3+ and Ce4+, showing strong antibacterial properties against MRSA and PAO-1. The HASiGdCe coating has been shown to have superior osteogenic and angiogenic properties compared to the HA coating in in vitro cellular experiments. Animal implantation experiments have shown that the HASiGdCe coating also has excellent biosafety, antimicrobial and osteogenic properties in vivo.Conclusion: The HASiGdCe coating confers excellent antibacterial, angiogenic and osteogenic properties on titanium implants, which can effectively enhance implant osseointegration and prevent bacterial infections, and it accordingly has promising applications in the treatment of bone defects related to orthopedic and dental sciences.Graphical Abstract: Keywords: hydroxyapatite coatings, SiO2, Gd2O3, CeO2, osseointegration, antibacterial

Zhaopeng Li,1,&ast; Deyong Bu,1,&ast; Xiaobin Wang,1 Lin Zhu,2 Daoyan Lei,3 Fengling Tang,1 Xianghua Sun,1 Cheng Chen,4 Xiang Ji,5 Song Bai1 1Department of Geriatric General Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, People’s Republic of China; 2Department of Ultrasound, the Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 3Department of Ultrasound, Jiangchuan District People’s Hospital, Yuxi, Yunnan, 652600, People’s Republic of China; 4Department of Breast Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, People’s Republic of China; 5Department of Day Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyong Bu; Song Bai, Department of Geriatric General Surgery, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, People’s Republic of China, Tel/Fax +86-0871-5324-888, Email pdyka@163.com; baisong523@163.comPurpose: The present study explored the anti-tumor effects of chidamide plus oxaliplatin on colorectal cancer (CRC) and examined its underlying mechanism.Material and Methods: First, the Combination Index (CI) of chidamide and oxaliplatin was evaluated via CCK-8 assay. Second, the effects of chidamide and oxaliplatin monotherapy and the combined treatment on cell proliferation, invasion, migration, and apoptosis were detected. Third, whole-transcriptome RNA sequencing (RNA-seq) was performed to seek the potential targeted gene by which chidamide plus oxaliplatin exerted anti-tumor effects. Fourth, the validation of the targeted gene and the signal pathway it regulated were performed. Finally, the anti-tumor effect of chidamide plus oxaliplatin on mice xenograft was examined.Results: Chidamide and oxaliplatin acted synergistically to inhibit CRC growth in vitro and in vivo (CI< 1). Besides, compared with oxaliplatin monotherapy, chidamide could significantly enhance oxaliplatin-induced inhibition in cell proliferation, invasion, and migration, and promotion in HCT-116 and RKO cell apoptosis (P< 0.05). The RNA-seq displayed that, compared to oxaliplatin monotherapy, RPS27A mRNA was evidently decreased in HCT-116 cells treated with chidamide plus oxaliplatin (P< 0.001). Then, we found RPS27A was highly expressed in CRC tissues and CRC cell lines (P< 0.001). Silence of RPS27A attenuated proliferation and induced apoptosis in HCT-116 and RKO cells via downregulation of MDM2 expression and upregulation of P53. Next, RPS27A overexpression could partially reverse chidamide plus oxaliplatin induced growth inhibition and apoptosis in HCT-116 and RKO cells (P< 0.01). RPS27A overexpression could promote the upregulation of MDM2 and downregulation of P53 after the combined treatment of chidamide with oxaliplatin.Conclusion: Chidamide and oxaliplatin acted synergistically to suppress CRC growth by the inhibition of the RPS27A-MDM2-p53 axis.Keywords: chidamide, oxaliplatin, colorectal cancer, synergism

Jie Tong,1,&ast; Tingting Zhang,1,&ast; Qiang Wang,1 Xudong Zhao,2 Xirong Sun,1 Manji Hu1 1Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manji Hu; Xirong Sun, Email hmj2008tj@qq.com; xirongsun@163.comBackground: To promote the balanced development with the population, China has phased out a one-child policy in 2016, and a two-child policy was launched, which has led to dramatic changes in family structure. The transition could be a huge challenge for adolescents who are in a period of psychological vulnerability.Purpose: This study explored the differences and predictors of family dynamics and functioning between two-child and one-child families in the context of China’s two-child policy.Methods: We used the Self-rating scale of Systemic Family Dynamics (SSFD) and Family Assessment Device-General Functioning (FAD-GF) to investigate the family dynamics, family functioning, and family structure and status of 3289 adolescents under the background of China’s two-child policy.Results: Results revealed that the mean scores for family atmosphere, personalization, disease concept, overall family dynamics, and family functioning health rate of the one-child families were higher than those of the two-child families. Parental marital status, mother’s education, annual household income, and family economic satisfaction in two-child and one-child families was positively correlated with family dynamics and functioning, but not significantly associated with living style, parental age and employment. Family financial satisfaction, parental marital status, and distress in the family were predictors of family dynamics and functioning, and parental preference was also an important factor in two-child families.Conclusion: The findings suggest family atmosphere, personality, disease concept, family dynamics, and family functioning of the one-child families were better than those of the two-child families. Unlike one-child families, parental preference is an important predictor of family dynamics and functioning in two child families. This study increases our understanding of adolescents psychological problems during family structure transitions under the background of fertility policy, providing psychologists with more evidence-based evidence and intervention directions.Keywords: family structure, family dynamics, family functioning, adolescents, two-child families

Xiaonan Sun,1 Zhichao Yuan,1 Lu Zhang,1 Min Ren,2 Jing Yang,2 Yidan Xu,1 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, People’s Republic of China, Email haojiqing@ahmu.edu.cnPurpose: Elucidation of the oncogenic role of SLC35A2 in human tumors and the potential function and clinical significance in breast cancer.Methods: Pan-cancer analysis was performed via various bioinformatics tools to explain the pathogenic role of SLC35A2. A prognostic nomogram was also developed based on the SLC35A2 expression and clinicopathological characteristics in breast cancer patients. In addition, the role of SLC35A2 was validated in breast cancer by in vivo and in vitro experiments.Results: SLC35A2 expression is increased in 27 tumor types, and its high expression is substantially correlated with poor prognosis in patients with a variety of cancers. Receiver operating characteristic (ROC) curves showed that SLC35A2 expression levels could accurately distinguish most tumor tissues from normal tissues. High SLC35A2 expression was linked to increased immune infiltration in myeloid-derived suppressor cells (MDSC), as well as immune checkpoints, ferroptosis-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI). SLC35A2 may be involved in tumorigenesis by regulating the glycosylation process. Furthermore, multivariate Cox analysis showed that SLC35A2 was an independent prognostic factor for breast cancer. And the nomogram model had good predictive accuracy for the prognosis of breast cancer patients. Meanwhile, cellular experiments demonstrated that knockdown of SLC35A2 could significantly inhibit the proliferation, migration and invasion of breast cancer cells, while increasing the protein level of E-cadherin and decreasing N-cadherin. A nude mouse xenograft model showed that inhibition of SLA35A2 expression could significantly inhibit tumor growth.Conclusion: SLC35A2 has good diagnostic and prognostic values in multiple cancers and is closely related to tumor immune infiltration. In addition, SLA35A2 as an oncogene in breast cancer may be involved in the progression of epithelial mesenchymal transition (EMT).Keywords: SLC35A2, pan-cancer, breast cancer, prognostic, tumor microenvironment, EMT

Jianli Ge,1,&ast; Shasha Geng,1,&ast; Yang Gao,2 Guangwei Ren,3 Xiaoming Sun,1,4 Hua Jiang1 1Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 2Department of General Practice, Huamu Community Health Service Center, Shanghai, 201204, People’s Republic of China; 3Science and Education Department, Sanlin Community Health Service Center, Shanghai, 200124, People’s Republic of China; 4Department of General Practice, Zhongshan Hospital, Fudan University Medical School, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoming Sun, Fudan University Medical School, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Email xm_sun2003@aliyun.com Hua Jiang, Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China, Email Huajiang2013@tongji.edu.cnBackground: There is a high incidence rate of age-related hearing loss. Severe hearing loss may increase the prevalence of mental illness, cognitive impairment, and even the risk of all-cause death.Purpose: Construction of the three-level and two-stage screening mode for age-related hearing loss of the community and to evaluate its effectiveness.Materials and Methods: A total of 401 participants (aged 60 years or older) from five typical communities were enrolled in the study. The risk factors assessment of age-related hearing loss was completed by using a cross-sectional survey and receiver operating characteristic (ROC) curve. Multiple screening method was adopted and verified by serial and parallel tests, respectively. Based on research data, incorporate risk factors assessment, the Hearing Handicap Inventory for the Elderly Screening Version (HHIE-s) and pure tone audiometry (PTA) were used to construct the screening mode.Results: Multiple screening series testing and multiple screening parallel testing, including risk factors assessment, HHIE-s, and PTA, were used for verification: the sensitivity, specificity, and Kappa index were 70.5% and 9.2%, 95.0% and 71.6%, 0.26 and 0.63, respectively. Finally, the three-level and two-stage screening mode for age-related hearing loss was established. “Three-level” was defined as the risk factors assessment/HHIE-s (high-risk population), PTA (suspect population), and comprehensive hearing loss assessment (confirmed population). “Two-stage” was defined as the population screening by general practitioner in the community and target screening by otolaryngologist of the tertiary hospitals.Conclusion: The three-level and two-stage screening mode for age-related hearing loss consists of the following framework: from population screening to target screening, from suspicious diagnosis to accurate diagnosis, from primary health care to tertiary hospitals. The study objective is to structure a new secondary prevention and treatment mode for age-related hearing loss with primary health care as the core, so as to help the front-end management of healthy aging.Keywords: age-related hearing loss, three-level and two-stage mode, screening, general practitioners, self-management

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Xuqi Sun,1,&ast; Yangyang Wang,2,3,&ast; Hongbin Ge,2,3 Cao Chen,2,3 Xu Han,2,3 Ke Sun,4 Meng Wang,4 Xiaobao Wei,2,3 Mao Ye,2,3 Qi Zhang,2,3,5,6 Tingbo Liang2,3,5,6 1Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Zhejiang University Cancer Center, Hangzhou, People’s Republic of China; 6Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingbo Liang; Qi Zhang, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel/Fax +86-0571-87236601, Email liangtingbo@zju.edu.cn; qi.zhang@zju.edu.cnBackground: The heterogeneity of hepatocellular carcinoma (HCC) leads to the unsatisfying predictive performance of current staging systems. HCC patients with pathological tumor micronecrosis have an immunosuppressive microenvironment. We aimed to develop novel prognostic models by integrating micronecrosis to predict the survival of HCC patients after hepatectomy more precisely.Methods: We enrolled 765 HCC patients receiving curative hepatic resection. They were randomly divided into a training cohort (n= 536) and a validation cohort (n = 229). We developed two prognostic models for postoperative recurrence-free survival (RFS) and overall survival (OS) based on independent factors identified through multivariate Cox regression analyses. The predictive performance was assessed using the Harrell concordance index (C-index) and the time-dependent area under the receiver operating characteristic curve, compared with six conventional staging systems.Results: The RFS and OS nomograms were developed based on tumor micronecrosis, tumor size, albumin-bilirubin grade, tumor number and prothrombin time. The C-indexes for the RFS nomogram and OS nomogram were respectively 0.66 (95% CI, 0.62– 0.69) and 0.74 (95% CI, 0.69– 0.79) in the training cohort, which was significantly better than those of the six common staging systems (0.52– 0.61 for RFS and 0.53– 0.63 for OS). The results were further confirmed in the validation group, with the C-indexes being 0.66 and 0.77 for the RFS and OS nomograms, respectively.Conclusion: The two nomograms could more accurately predict RFS and OS in HCC patients receiving curative hepatic resection, thereby aiding in formulating personalized postoperative follow-up plans.Keywords: hepatocellular carcinoma, micronecrosis, postoperative survival

Haoyuan Xu,&ast; Wanpeng Li,&ast; Huankang Zhang, Huan Wang, Li Hu, Xicai Sun, Dehui Wang Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xicai Sun; Dehui Wang, Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye, Ear, Nose, and Throat Hospital, Fudan University, 83 Fen Yang Road, Shanghai, People’s Republic of China, Email laryngeal@163.com; wangdehuient@sina.comObjective: To investigate the effects of endoscopic endonasal surgery (EES) on longitudinal quality of life (QoL) in patients with malignant tumors of the anterior skull base.Methods: Eligible patients prospectively completed the Anterior Skull Base Surgery Questionnaire (ASBQ) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires in referring to 3 different periods throughout their treatment and recovery.Results: Forty patients were included. The median volume coronal maximum length of the tumor was 3.6 cm (95% CI 2.7– 4.1cm). Overall QoL significantly worsened at 1 month postoperatively but returned to baseline after 1 year. Unrelieved symptoms in specific domains prompted further evaluation of individual items. Transient worsening of taste (p=0.011) and olfaction (p=0.004) lasted for 1 month but gradually relieved within the first postoperative year, but vision consistently worsened over the course of the treatment (p=0.126). Age> 50 years (p< 0.001), comorbidities (p< 0.001), tumor necrosis (p< 0.001) and recurrence (p=0.001) were associated with worse preoperative QoL. Poor long-term QoL was noted in those undergoing adjuvant therapy (p=0.032). Overall ASBQ scores (p=0.024), subdomain scores in specific symptoms (p=0.016), and vision scores (p=0.009) were worse only in patients with the greater coronal maximum diameter at 1-month postoperatively. Greater coronal maximum diameter was related to worse preoperative subdomain scores regarding specific symptoms (p=0.030) and decreased postoperative long-term decreased vision scores (p=0.014).Conclusion: Long-term site-specific and sinonasal QoL eventually stabilized after EES. Greater coronal maximum diameter was significantly associated with worsened vision function. Temporarily worse olfactory, vision, and taste function may be tied to decreased short-term QoL.Keywords: quality of life, endoscopic endonasal surgery, anterior skull base, malignant tumors, prospective study

Lu Li,1,&ast; Rong Ai,1,&ast; Xiwei Yuan,1 Shiming Dong,1 Dandan Zhao,1 Xiaoye Sun,2 Tongguo Miao,1 Weiwei Guan,1 Peilin Guo,1 Songhao Yu,1 Yuemin Nan1 1Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Organ Transplant Center, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86 311-66781227, Fax +86 311-87023626, Email nanyuemin@163.comPurpose: As the major subtype of liver cancer, hepatocellular carcinoma (HCC) suffers from high mortality and is prone to recurrence. Long non-coding RNAs (lncRNAs) are well characterized to be pivotal players contributing to HCC pathogenesis and progression. Therefore, this study intended to probe the biological functions of LINC00886 in hepatocarcinogenesis.Patients and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analysis of LINC00886, microRNA-409-3p (miR-409-3p), microRNA-214-5p (miR-214-5p), RAB10 and E2F2 expression. Subcellular localization of LINC00886 was identified through a fluorescent in situ hybridization (FISH) kit and a subcellular assay. Additionally, proliferated cells were determined with EdU as well as cell counting kit-8 (CCK-8) assays. Scratch and Transwell assays were applied to detect migratory and invasive cells. Apoptotic cells were measured via TUNEL staining assay. Furthermore, targeted binding between LINC00886 and miR-409-3p or miR-214-5p was validated utilizing dual-luciferase reporter assays. RAB10, E2F2 and NF-κB signaling-associated protein levels were evaluated utilizing Western blot.Results: LINC00886, RAB10 and E2F2 levels were aberrantly increased, with the abnormal expressed decline of miR-409-3p and miR-214-5p, in HCC tissues, cells and peripheral blood mononuclear cells (PBMCs). Silencing LINC00886 attenuated the proliferative, migratory, invasive, and anti-apoptotic potential of HCC cells, while LINC00886 overexpression proceeded in the contrary direction. Mechanistically, miR-409-3p and miR-214-5p were validated as binding targets for LINC00886 and inverted the biological functions of LINC00886 during HCC progression. Furthermore, the LINC00886-miR-409-3p/miR-214-5p axis could regulate RAB10 and E2F2 expression via mediating NF-κB pathway activation in hepatocarcinogenesis.Conclusion: Our findings indicated that LINC00886 facilitated HCC progression via absorbing miR-409-3p or miR-214-5p to upregulate RAB10 and E2F2 through activation of NF-κB pathway, offering a promising novel target for HCC therapy.Graphical Abstract: Keywords: LINC00886, miR-409-3p, miR-214-5p, hepatocellular carcinoma, NF-κB signaling

Yiming Zhang,1,2,&ast; Yiming Dou,1,2,&ast; Yang Liu,1,2 Mingyuan Di,1,2 Hanming Bian,1,2 Xun Sun,1,2 Qiang Yang1,2 1Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 2Clinical School of Orthopedics, Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xun Sun; Qiang Yang, Department of Spine Surgery, Tianjin Hospital, 406 Jiefang SouthRoad, Hexi District, Tianjin, 300211, People’s Republic of China, Email sunxun_tju@yeah.net; yangqiang1980@126.comAbstract: Extracellular vesicles (EVs) are nanoscale bilayer phospholipid membrane vesicles released by cells. Contained large molecules such as nucleic acid, protein, and lipid, EVs are an integral part of cell communication. The contents of EVs vary based on the cell source and play an important role in both pathological and physiological conditions. EVs can be used as drugs or targets in disease treatment, and changes in the contents of EVs can indicate the progression of diseases. In recent years, with the continuous exploration of the structure, characteristics, and functions of EVs, the potential of engineered EVs for drug delivery and therapy being constantly explored. This review provides a brief overview of the structure, characteristics and functions of EVs, summarizes the advanced application of EVs and outlook on the prospect of it. It is our hope that this review will increase understanding of the current development of medical applications of EVs and help us overcome future challenges.Keywords: extracellular vesicle, nanotherapeutic, disease diagnosis, engineered exosome, advances applications