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Dan Luo,1– 3,* Yonghui Hou,1– 3,* Jiheng Zhan,1,2,* Yu Hou,1– 3 Zenglu Wang,4 Xing Li,1,2 Lili Sui,5 Shudong Chen,1,2 Dingkun Lin1,2 1Research Laboratory of Spine Degenerative Disease, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Spinal Minimally Invasive Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3Laboratory of Osteology and Traumatology of Traditional Chinese Medicine, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4ICU Critical Care Medicine Department, Guangdong Second Provincial Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China; 5The First College of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dingkun Lin; Shudong Chen, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, People’s Republic of China, Tel +86-020-81887233, Email lindingkuntcm@126.com; chenshudong_med@163.comPurpose: Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF’s therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets.Methods: The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence.Results: The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway.Conclusion: BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.Keywords: Bu Shen Huo Xue formula, BSHXF, spinal cord injury, SCI, oxidative stress, neuroprotection, Nrf2 signaling pathway

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

Jun Zhan,1,2 Dingding Wang,1,2 Chuanxiang Luo,3 Haiyan Bi4 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Medical College, Qingdao University, Qingdao, People’s Republic of China; 4Office for Medical and Health Service, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Haiyan Bi, Office for Medical and Health Service, West China Second University Hospital, Sichuan University, Email 649927649@qq.comAbstract: Umbilical vascular thromboembolism is a rare condition that can lead to serious consequences such as fetal hypoxia, fetal growth restriction, and even stillbirth. However, there is currently a lack of research on the pathology, pathogenesis, clinical management, and prognosis of this condition. Therefore, the purpose of this article is to analyze this condition’s high-risk factors, clinical characteristics, pregnancy management, and discuss its corresponding pregnancy outcomes. Databases such as PubMed are searched using the relevant keywords of umbilical vascular thromboembolism in worldwide. And related information is analyzed such as maternal risk factors, fetal risk factors, umbilical cord and placental risk factors, and pregnancy outcomes. The literature search yields 113 articles, 64 of which meet the inclusion criteria for umbilical vascular thromboembolism. There are 4 retrospective cohort studies and 8 case series, the rest are all case reports. A total of 262 cases of umbilical vascular thromboembolism are found. The most common maternal complications and fetal related risk factors are diabetes (25 cases, 9.5%) and stillbirths (106 cases, 40.5%), respectively. Among these 262 cases, 98 (37.4%) cases are found by prenatal ultrasound to have umbilical vascular thromboembolism and the fetus is in a viable state with complete clinical information. In addition, considering the effectiveness and safety of low molecular weight heparin in thromboembolic conditions, twenty-four patients of umbilical artery thromboembolism attempted to use low molecular weight heparin during observation. Maternal diabetes was the highest risk factor for this condition. When umbilical artery thromboembolism occurs, the incidence of stillbirth increases. Premature patients with this condition can continue their pregnancy under close external monitoring. However, due to the small sample size, further research is needed.Keywords: umbilical vascular thromboembolism, umbilical vein thromboembolism, umbilical artery thromboembolism, fetal growth restriction, umbilical vein varix, low molecular weight heparin

Junwei Zhan,1 Chengfei Peng,2 Yuxin Liu,1 Zhanhua Bi,1 Guoxiu Lu,1 Shanhu Hao,1 Yanan Tong,1 Guoxu Zhang1 1Department of Nuclear Medicine, General Hospital of Northern Theater Command, Shenyang, 110016, People’s Republic of China; 2Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Guoxu Zhang; Yanan Tong, Department of Nuclear Medicine, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenyang, 110016, People’s Republic of China, Email zhangguoxu_502@163.com; tongyn1119@foxmail.comObjective: Atrial fibrillation (AF) is a common arrhythmia. This study explored serum miR-29b-3p expression in AF patients and its value in predicting AF recurrence after radiofrequency catheter ablation (RFCA).Methods: Totally 100 AF patients who underwent RFCA were enrolled, with 100 individuals without AF as controls. Serum miR-29b-3p expression in participants was determined using RT-qPCR. The correlation between miR-29b-3p and atrial fibrosis markers (FGF-21/FGF-23) was assessed by Pearson analysis. The diagnostic efficacy of serum miR-29b-3p and FGF-21/FGF-23 in predicting AF recurrence after RFCA was analyzed by the receiver operating characteristic (ROC) curves. The Kaplan-Meier method was adopted to evaluate the effect of miR-29b-3p expression on the incidence of AF recurrence after RFCA. The independent risk factors for AF recurrence after RFCA were analyzed by logistic regression analysis.Results: Serum miR-29b-3p was poorly expressed in AF patients. After RFCA, AF patients showed elevated serum miR-29b-3p expression. Serum miR-29b-3p expression in AF patients negatively correlated with serum FGF-21 and FGF-23 concentrations. The cut-off values of serum miR-29b-3p, FGF-21, and FGF-23 in identifying AF recurrence were 0.860 (sensitivity: 100.00%, specificity: 39.71%), 222.2 pg/mL (sensitivity: 96.88%, specificity: 32.35%) and 216.3 ng/mL (sensitivity: 53.13%, specificity: 70.59%), respectively. Patients with low miR-29b-3p expression had a significantly higher incidence of AF recurrence than patients with high miR-29b-3p expression. Serum miR-29b-3p expression was one of the independent risk factors for AF recurrence after RFCA.Conclusion: Low miR-29b-3p expression in AF patients has certain predictive values and is one of the independent risk factors for AF recurrence after RFCA.Keywords: miR-29b-3p, atrial fibrillation, radiofrequency catheter ablation, recurrence, fibrosis marker, logistic regression analysis

Hu Zhao,1,* Jun Zhan,1,* Qiong Wang,2 Shuqi Yang,1 Xue Xiao1 1Department of Gynecology and Obstetrics, Sichuan University West China Second University Hospital, Chengdu, Sichuan, People’s Republic of China; 2Department of Gynecology and Obstetrics, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue Xiao, Department of Gynecology and Obstetrics, Sichuan University West China Second University Hospital, No. 20, Section 3, Renmin Road South, Chengdu, Sichuan, 610041, People’s Republic of China, Email xue_xiao_west@163.comPurpose: LncRNA HCP5 has been reported to participate in high glucose-induced pathological processes, whereas its role in gestational diabetes mellitus (GDM) is unclear. This study aimed to explore the role of HCP5 in GDM.Methods: This study enrolled a total of 220 pregnant women (gestational age = 1 month). A follow-up study was performed until delivery. The occurrence of GDM was checked every month during follow-up. Plasma samples were collected from all participants and expression of HCP5 was determined with RT-qPCR. The 220 patients were divided into high and low GDM groups, and GDM-free curves were plotted for both groups and compared. The ROC curve was plotted to explore the predictive value of plasma HCP5 on the day of admission for GDM. INS-1 cells were transfected with HCP5 expression vector or siRNA, and cell viability under high glucose was determined by the MTT assay. An ELISA was applied to determine insulin levels in the cell culture medium.Results: During follow-up, the level of HCP5 was increased during pregnancy and the high HCP5 level group showed a significantly higher incidence of GDM. Plasma levels of HCP5 on the day of admission effectively separated GDM patients from healthy controls. HCP5 negatively regulated cell viability and insulin secretion under high glucose treatment.Conclusion: HCP5 may act as a predictor for GDM, and it negatively regulated INS-1 cell viability and insulin secretion under high glucose conditions.Keywords: HCP5, gestational diabetes mellitus, INS-1 cells, insulin

Shuang Li, Niman Li, Linsen Li, Junkun Zhan Department of Geriatrics, The Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Junkun Zhan, Department of Geriatrics, The Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email zhanjunkun@csu.edu.cnIntroduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes. DKD is associated with oxidative stress and inflammation. Versican (VCAN), a chondroitin sulphate proteoglycan, has been proven to participate in oxidative stress and inflammation. This study aimed to explore the overall and sex-based relationship between serum VCAN levels and albuminuria in patients with type 2 diabetes mellitus (T2DM).Methods: 428 patients with T2DM and 84 healthy individuals were enrolled. Patients with diabetes were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups, according to their urinary albumin/creatinine ratio (UACR). Serum VCAN levels were tested using an enzyme-linked immunosorbent assay.Results: Compared with males, female patients were older, and had higher total cholesterol and high-density lipoprotein cholesterol, but lower body mass index, diastolic blood pressure, glycated hemoglobin A1, alanine aminotransferase, urinary albumin (UA), and serum creatinine (SCr) (P < 0.05). The VCAN levels in male patients with T2DM were significantly higher than those in the healthy individuals. Male patients with T2DM with albuminuria (micro and macro) had higher levels of VCAN than in patients with normal albuminuria; the highest level was seen in patients with macroalbuminuria (P < 0.05). In male patients with T2DM, serum VCAN correlated positively with systolic blood pressure, blood urea nitrogen, UA, SCr, and UACR, but correlated negatively with the estimated glomerular filtration rate. The area under the receiver operating characteristic curve of serum VCAN to diagnose albuminuria was 0.702, with a corresponding cut-off value of 0.399 ng/mL (P < 0.001). However, the association between serum VCAN and UACR was not observed in female patients with T2DM.Conclusion: Serum VCAN levels correlated positively with the severity of albuminuria in male patients with T2DM.Keywords: diabetic kidney disease, type 2 diabetes mellitus, versican, biomarker

Suling Jiang,1,&ast; Jian Wang,2,3,&ast; Zhiyi Zhang,4,&ast; Jie Zhan,1 Ruifei Xue,1 Yuanwang Qiu,5 Li Zhu,6 Shaoqiu Zhang,2 Yifan Pan,1 Xiaomin Yan,2 Yuxin Chen,3,7 Jie Li,1– 4 Xingxiang Liu,8 Chuanwu Zhu,6 Rui Huang,1– 4 Chao Wu1– 4 1Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 7Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email doctor_hr@126.comBackground: Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients.Methods: CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA).Results: A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727– 0.803) and 0.766 (95% CI: 0.711– 0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA.Conclusion: A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.Keywords: chronic hepatitis B, liver inflammation, prediction, nomogram, alanine aminotransferase

Changjiang Yu,1,&ast; Wei Guo,1,2,&ast; Zhulai Zhang,1,&ast; Yuting Ma,3,&ast; Xiaobei Cao,1 Na Sun,1 Yingyao Cui,1 Yunshen Wang,1 Wenyu Cui,1 Yongsheng Xu,1 Jianghua Zhan2,4 1Department of Pediatric Respiratory Medicine, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China; 2Graduate School of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Infection, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China; 4Department of Pediatric Surgery, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongsheng Xu, Department of Pediatric Respiratory Medicine, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, 300134, People’s Republic of China, Email xxyyss@126.com Jianghua Zhan, Graduate School of Tianjin Medical University, Department of Pediatric Surgery, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, 300134, People’s Republic of China, Email zhanjianghuatj@163.comPurpose: Metagenomic next-generation sequencing (mNGS) is an emerging technique for pathogen detection. However, most literature on the clinical application of pediatrics generally comprises case reports or small-scale cohort studies.Patients and Methods: A total of 101 children with community-acquired severe pneumonia admitted to Tianjin Children’s Hospital from November 2021 to February 2022 were included. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS. The performances of mNGS and conventional tests on pulmonary infection diagnosis and pathogen identification were compared.Results: According to our data, mNGS had a broader spectrum for pathogen detection. The mNGS results of BALF showed that the number of children with severe pneumonia hospitalized for mycoplasma pneumoniae infection was more than that for other bacterial infections during the COVID-19 epidemic. In addition, 43 cases (42.6%) had been identified with mixed infection, including 36 cases (35.6%) of Mycoplasma pneumoniae mixed with other pathogenic bacteria. Analytically, the mNGS exhibited significantly enhanced detection in the BALF as compared with the conventional laboratory pathogenic detection approaches (P < 0.05). The Pearson correlation analysis revealed positive correlation between the time of fever during hospitalization and the number of mycoplasma sequences (P < 0.05).Conclusion: Compared with traditional methods, mNGS has a higher etiological detection rate and can comprehensively detect various pathogens of severe pneumonia. Therefore, mNGS of bronchoalveolar lavage fluid should be performed in children with severe pneumonia, which is of great significance for guiding treatment.Keywords: mNGS, severe pneumonia, pathogen, BALF, children

Shuang Li, Niman Li, Linsen Li, Yi Wang, Youshuo Liu, Yanjiao Wang, Junkun Zhan Department of Geriatrics, the Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yanjiao Wang; Junkun Zhan, Department of Geriatrics, the Second Xiangya Hospital, Institute of Aging and Age-Related Disease Research, Central South University, Changsha, Hunan, People’s Republic of China, Email ls330013@163.com; zhanjunkun@csu.edu.cnBackground: Previous studies suggested protective effects of bilirubin against cardiovascular disease, with a possible gender difference. However, the relationship between serum total bilirubin (TBIL) with diabetic macro- and microvascular complications remains unknown. We aimed to examine the association of macro- and microvascular complications with serum TBIL levels.Methods: Serum TBIL was measured in 648 patients with T2DM. Demographic and clinical data were obtained from the inpatient medical record system. Serum TBIL was measured with an automatic biochemistry analyzer according to routine protocols. Parameters of vascular complications, including ankle-brachial index, carotid intima-media thickness, estimated glomerular filtration rate and the urinary albumin to creatinine ratio, were measured and calculated. The association between TBIL and diabetic macro- and microvascular complications was analyzed.Results: In multivariable logistic regression, after adjustment for age, sex, body mass index and diabetic duration, higher serum TBIL levels were significantly associated with decreased odds of microalbuminuria (OR = 0.31, [95% CI] 0.16– 0.61, P = 0.003) and chronic kidney disease (OR = 0.19, [95% CI] 0.09– 0.41, P < 0.001). These associations were only found in male but not in female patients. However, no significant relationship was found between TBIL and peripheral arterial disease or carotid hypertrophy.Conclusion: Our findings suggest that physiological higher TBIL level might be a protective factor for diabetic microvascular complications.Keywords: total bilirubin, diabetic macrovascular complications, diabetic microvascular complications, gender difference

Fangqing Wang,1,&ast; Nianlu Li,2,&ast; Wenbo Wang,1 Long Ma,3 Yaru Sun,4 Hong Wang,1 Jinhua Zhan,5 Dexin Yu1 1Department of Radiology, Qilu Hospital, Shandong University, Affiliated Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Physical and Chemical Laboratory, Shandong Academy of Occupational Health and Occupational Medicine, Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250002, People’s Republic of China; 3The Testing Center of Shandong Bureau of China Metallurgical Geology Bureau, Shandong Normal University, Jinan, 250014, People’s Republic of China; 4Department of Nuclear Medicine, The Second Hospital of Shandong University, Affiliated Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 5School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinhua Zhan, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, People’s Republic of China, Email jhzhan@sdu.edu.cn Dexin Yu, Department of Radiology, Qilu Hospital, Shandong University, Affiliated Hospital of Shandong University, Jinan, 250012, People’s Republic of China, Tel +86-18560081629, Fax +86-531-86927544, Email yudexin0330@sina.comPurpose: Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC.Methods: CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo.Results: Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2β, and AUC0–t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment.Conclusion: Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.Keywords: caramelized nanotheranostic system, combining chemo-photothermal therapy, magnetic resonance imaging monitoring, double-triggering, triple negative breast cancer

Peiming Zhang,1 Jie Zhan,2 Shuting Wang,1 Yuyuan Tang,1 Huishan Chen,1 Yiqiao Wang,1 Xiaojing Wei,1 Hao Wen,3 Ting Pan,4 Ze Chen,1 Chunzhi Tang,1 Nenggui Xu,1 Liming Lu1 1Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou City, Guangdong Province, People’s Republic of China; 2Postdoctoral Research Station, Department of Rehabilitation, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou City, Guangdong Province, People’s Republic of China; 3Department of Neurology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou City, Guangdong Province, People’s Republic of China; 4TCM Department, Foshan Fosun Chancheng Hospital, Foshan City, Guangdong Province, People’s Republic of ChinaCorrespondence: Liming Lu, Clinical Research and Data Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, No. 232, Waihuan East Road, University Town, Xiaoguwei Street, Panyu District, Guangzhou City, Guangdong Province, People’s Republic of China, Tel +8613751779800, Fax +862039358716, Email lulimingleon@126.com Chunzhi Tang, Email jordan664@163.comPurpose: Accumulating research suggests that psychotherapy helps improve abstinence but the difference in the efficacy of multiple psychotherapies in alcohol use disorder (AUD) remains to be explored.Patients and Methods: A systematic search of databases (Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and EBSCO) for studies (published from inception to April 10th.) of adults diagnosed with AUD accepting psychotherapies was conducted. Studies covering 9 countries and regions. The qualitative analysis pooled 2646 individuals from 34 randomized controlled trials (RCTs) and the networks included 1928 participants (23 RCTs). The outcomes included percentage of days abstinent (PDA), change in drinks per drinking day (change in DDD), and change in craving compared among individuals accepting various psychotherapies. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and was registered on the International Prospective Register of Systematic Reviews (PROSPERO).Results: For the network of PDA, motivational enhancement treatment (MET) (35.44, 11.78 to 59.09, high-certainty) and couple therapy (CT) (28.89, 13.42 to 44.36, moderate-certainty) were significantly different from treatment as usual (TAU) with the surface under the cumulative ranking curve (SUCRA) mean rank 1.9 and 1.9 respectively. TAU+supportive psychotherapy (SP) was better than TAU for the change in DDD in the high-quality direct comparison.Conclusion: The motivational enhancement and the couple therapy show potential amelioration for alcohol abstinence. Additionally, the preferred interventions are different for improving PDA and change in DDD. The evidence network remains to be strengthened.Keywords: alcohol use disorder, psychotherapy, randomized controlled trial, systematic review, network meta-analysis

Dian Zhang,1,2,&ast; Minshan Feng,1,&ast; Wei Liu,3,&ast; Jie Yu,1 Xu Wei,1 Kexin Yang,1 Jiawen Zhan,1 Wei Peng,1,2 Mingyi Luo,1,2 Tao Han,1 Zhefeng Jin,1 He Yin,1 Kai Sun,1 Xunlu Yin,1 Liguo Zhu1 1Department of Spinal Surgery, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Nursing, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xunlu Yin; Liguo Zhu, Department of Spine, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China, Email yin_xun_lu@163.com; zhlg95@aliyun.comAbstract: Neck pain and low back pain are major challenges in public health, and intervertebral disc (IVD) biomechanics is an important multidisciplinary field. To date, no bibliometric literature review of the relevant literature has been performed, so we explored the emerging trends, landmark studies, and major contributors to IVD biomechanics research. We searched the Web of Science core collection (1900– 2022) using keywords mainly composed of “biomechanics” and “intervertebral disc” to conduct a bibliometric analysis of original papers and their references, focusing on citations, authors, journals, and countries/regions. A co-citation analysis and clustering of the references were also completed. A total of 3189 records met the inclusion criteria. In the co-citation network, cluster #0, labeled as “annulus fibrosus tissue engineering”, and cluster #1, labeled as “micromechanical environment”, were the biggest clusters. References by MacLean et al and Holzapfel et al were positioned exactly between them and had high betweenness centrality. There existed a research topic evolution between mechanobiology and mechanical repair strategies of IVDs, and the latter had been identified as an emerging trend in IVD biomechanics. Numerous landmark studies had contributed to several fields, including mechanical testing of normal and pathological IVDs, mechanical evaluation of new repair strategies and development of finite element model. Adams MA was the author most cited by IVD biomechanics papers. Spine, the European Spine Journal, and the Journal of Biomechanics were the three journals where the most original articles and their references have been published. The United States has contributed most to the literature (n = 1277 papers); however, the research output of China is increasing. In conclusion, the present study suggests that IVD repair is an emerging trend in IVD biomechanics.Keywords: emerging trend, co-citation, CiteSpace, annulus fibrosus

JuanMei Zhan, Fenfang Yang, Cenhong Ge, Xiaojia Yu Department of Medical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, People’s Republic of ChinaCorrespondence: Fenfang Yang, Department of Medical Examination Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310006, People’s Republic of China, Email Fenfy1987@163.comBackground: Cervical cancer is the fourth most frequent malignancy among women globally, with approximately 604,000 new cases and 341,000 deaths per year. Necroptosis is a newly discovered mechanism of cell death involved in biological behaviors of cancer.Methods: LASSO Cox regression analysis was conducted to construct a prognostic necroptosis-related signature. lncRNA–miRNA–mRNA regulatory axis was constructed with a ceRNA network. qRT-PCR was performed to verify our result.Results: A total of 54 necroptosis-related genes were differentially expressed in cervical cancer (all p < 0.05). We also summarized genetic mutation landscape of necroptosis-related genes in cervical cancer. We then developed a necroptosis-related prognostic signature including 13 necroptosis-related genes (ATRX, AXL, DDX58, IDH1, ITPK1, MAP3K7, SLC39A7, TARDBP, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TRIM11) for cervical cancer. Cervical cancer patients with high riskscore had a poor overall survival (HR = 2.128, p = 0.00194) with an AUC of 0.725, 0.763 and 0.637 in 3-year, 5-year, and 10-year ROC curve. Consensus clustering analysis revealed that all cervical cancer cohort could be divided into three subtypes, which was correlated with different prognosis and immune infiltration (p < 0.05). A PPI network revealed TNF as the hub gene and TNF expression was correlated with immune infiltration (all p < 0.05), microsatellite instability (p < 0.012) and drug sensitivity (p < 0.05). The ceRNA network was performed and identified a lncRNA NUTM2B-AS1/miR-361-5p/TNF regulatory axis for cervical cancer. qRT-PCR result also suggested that TNF was upregulated in cervical cancer (p < 0.001) and associated with a poor overall survival (p = 0.007). Univariate and multivariate analysis demonstrated TNF expression, lymph node metastasis and clinical stage were prognosis factors of cervical cancer patients (p < 0.05).Conclusion: We developed a necroptosis-related prognostic signature including 13 necroptosis-related genes for cervical cancer. Moreover, we also identified a lncRNA NUTM2B-AS1/miR-361-5p/TNF regulatory axis, which may play a vital role in the progression of cervical cancer. Further studies should be conducted to verify these results.Keywords: cervical cancer, necroptosis, prognostic signature, NUTM2B-AS1, miR-361-5p

Yaoguang Zhou,1,2,&ast; Jing Wang,3,&ast; Na Zhou,1,&ast; Jingye Zhan,1,2,&ast; Luna Sun,1,2 Chenqi Xing,1,2 Nianqi Liu,1,2 Xing Wang,4 Weizhi Liu1,2 1The Emotion & Cognition Lab, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, People’s Republic of China; 2Lab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Sports and Health, Shanghai Lixin University of Accounting and Finance, Shanghai, 201620, People’s Republic of China; 4Shanghai University of Sport, Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhi LiuThe Emotion & Cognition Lab and Lab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel/Fax +86-21-81871671Email 13024141970@163.comXing WangShanghai University of Sport, Shanghai, 200438, People’s Republic of ChinaEmail 18930132117@163.comBackground and Purpose: The role of posttraumatic stress disorder (PTSD) in the path from traumatic exposure (TE) to academic performance (AP) is still not explicitly illustrated. The current study aimed to examine the moderator role of PTSD on the relationship between TE and AP, and then to investigate whether this moderator role is influenced by gender.Participants and Methods: A sample of Chinese students (n=235) who had experienced the major earthquake of Wenchuan was chosen. PTSD and TE were measured by the Impact of Event Scale – Revised (IES-R) and an earthquake-related experience questionnaire, respectively. AP was collected from their up-to-date general examination. Data for 221 participants (53.4% female; mean age=14.03 years, SD=0.824) were finally included in the analysis. Parsimonious latent-variable interaction analysis and hierarchical regression analysis were adopted to examine the moderator role of PTSD.Results: The average IES-R score was 27.57 (SD=13.265, range 0– 67). The average score for earthquake exposure was 5.86 (SD=2.069, range 1– 12). The results showed that both TE and the interaction term of PTSD&ast;TE had significant negative correlations with AP, while PTSD was not associated with AP. Subsequent hierarchical regression analysis found that the relationship of the interaction term and AP was only significant in female students, and a simple slope plot showed a distinct pattern of the moderating effect of PTSD in both genders.Conclusion: This study supported that PTSD moderated the connection between TE and AP in middle school students who had undergone a major earthquake trauma, which was influenced by gender. Students who experienced major trauma with drastic exposure history and manifested PTSD symptoms need specified intervention to avoid further deterioration in performance in school.Keywords: trauma, posttraumatic stress disorder, academic performance, moderator, gender difference

Yunxiu Luo,1,&ast; Xiaopeng Huang,2,&ast; Jiabin Zhan,3 Shuai Zhang2 1Department of Radiation Oncology, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, People’s Republic of China; 3Department of Otolaryngology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin ZhanDepartment of Otolaryngology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, People’s Republic of ChinaTel +86-18907669339Email jiabin2021hainan@163.comShuai Zhang Tel +86-1387642896Email 46370976@qq.comPurpose: Due to the limitations of currently available biomarkers, new biomarkers are needed to accurately predict the prognosis of patients with hepatocellular carcinoma (HCC) patients.Methods: In this study, we screened for differentially expressed genes (DEGs) in the tumor and the adjacent tissues using the four gene expression array (GSE14520, GSE45267, GSE121248, GSE62232) of the Gene Express Omnibus (GEO) database.Results: Subsequently, 47 overlapping DEGs were identified in four GEO datasets, which were mostly located on chromosomes 5q and 6q, distributed in the liver and CD105-positive endothelial cells, and closely related to HCC. Function enrichment revealed 47 DEGs were related to HCC, and involved in steroid /lipid /retinol metabolism, bile secretion and p53 signalling pathway. The Kaplan–Meier plotter analysis (http://www.kmplot.com/) identified 26 and 40 genes associated with the 5-year overall survival (OS) and relapse-free survival (RFS). We found that CD5L and SRD5A2 were independent prognostic factors for 5-year OS (P=0.036) and RFS (P=0.044) in HCC patients from GSE14520, respectively. Clinicopathological features including BCLC stage, cirrhosis, and risk signature for predicted metastasis were used to construct and validate a nomogram for 5-year OS with C-index of 0.732 and 0.717 in the training and validation cohort, respectively. SRD5A2, BCLC stage and gender was independent prognostic factors for RFS which were used to build a nomogram with the C-index of 0.666 and 0.682 in the training and validation cohort, respectively.Conclusion: CD5L can facilitate individualized, targeted therapy for HCC patients.Keywords: hepatocellular carcinoma, CD5L, prognostic, nomogram, SRD5A2

Jiaoyang Zhan,1 Shuang Wu,2 Xu Zhao,3 Jingjing Jing4– 6 1Department of Anorectal Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2College of Computer Science and Technology, Changchun Normal University, Changchun, Jilin, People’s Republic of China; 3Mathematical Computer Teaching and Research Office, Liaoning Vocational College of Medicine, Shenyang, Liaoning, People’s Republic of China; 4Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 5Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Jingjing Jing; Xu Zhao Email hellojjjing@163.com; jjjing@cmu.edu.cn; master1080@163.comBackground: Glioma is one of the most prevalent tumors in the central nervous system of adults and shows a poor prognosis. This study aimed to develop a DNA damage repair (DDR)-related gene signature to evaluate the prognosis of glioma patients.Methods: Differentially expressed genes (DEGs) were extracted based on 276 DDR genes. Then, a gene signature was developed for the survival prediction in glioma patients by means of univariate, multivariate Cox, and least absolute shrinkage and selector operation (Lasso) analyses. After analyzing the clinical parameters, a nomogram was constructed and assessed. A total of 693 gliomas from the Chinese Glioma Genome Atlas (CGGA) were used for external validation. In addition, we used glioma tumor tissues for qPCR experiment to verify.Results: A 12-DDR-related gene signature was identified from the 75 DEGs to stratify the survival risk of glioma patients. The overall survival of high-risk group was significantly shorter than that of low-risk group (P < 0.001). Besides, according to the risk score assessment, patients in high- or low-risk group also had significant correlations with clinicopathological parameters, including age (P < 0.01), grade (P < 0.001), IDH status (P < 0.001) and 1p19q codeletion status (P < 0.001). The nomogram provided favorable C-index and calibration plots. The C-index of training set and verification set was 0.761 and 0.746, respectively, and the calibration curve also showed that both training set and verification set were close to the standard curve. The qPCR results showed that there were significant differences in the expression of some typical DDR-related genes in tumor tissues and paracancer tissues (P(WEE1)=0.0002, P(RECQL)=0.0117, P(RPA1)=0.021, P(RRM1)=0.0035, P(PARP4)=0.0006, P(ELOA)=0.0023).Conclusion: Our study developed a novel 12 DDR-related gene signature as a practical prognostic predictor for glioma patients. A nomogram combining the signature and clinical parameters was established as an individual clinical prediction tool.Keywords: DNA damage repair-related gene signature, glioma, prognosis, nomogram, qPCR

Keying Liang, Shengsheng Mei, Xiangzheng Gao, Shanshan Peng, Jinbiao Zhan Department of Biochemistry, Cancer Institute of the Second Affiliated Hospital (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), School of Medicine, Zhejiang University, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Jinbiao ZhanDepartment of Biochemistry, Cancer Institute of the Second Affiliated Hospital (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of ChinaTel/Fax +86 571-88208273Email jzhan2k@zju.edu.cnPurpose: T-DM1 is an antibody–drug conjugate (ADC) consisting of trastuzumab and DM1 linked together. T-DM1 binds to human epidermal growth factor receptor-2 (HER2) in tumors and then triggers the endocytosis of T-DM1 and release of payload. Therefore, endocytosis efficacy is considered as a critical step for the initiation of T-DM1 therapy; however, the endocytosis mechanism of T-DM1 remains poorly understood. Meanwhile, HER2 is regarded as an internalization-resistant receptor, which hinders the endocytosis and effectiveness of T-DM1. The present study is to explore the T-DM1 endocytosis pathway, which may provide insights into the internalization mechanism of ADCs and help to improve efficacy.Methods: Confocal microscopy and flow cytometry were used to analyse T-DM1 intracellular trafficking and endocytosis efficiency, while Western blot assay was performed to detect T-DM1 degradation.Results: We found that intracellular T-DM1 was increased to 50% within 12 h. T-DM1 was colocalized with cholera toxin B (CTxB), a lipid raft marker, within 2 h and then degraded in lysosome. Upon overexpression of caveolin-1 (CAV-1) and utilization of caveolae/lipid-raft disruptors, we found that temporal CAV-1 upregulation significantly facilitated T-DM1 endocytosis and degradation, whereas nystatin and lovastatin disrupted caveolae/lipid-raft structure and inhibited T-DM1 degradation. We demonstrate that T-DM1 internalizes through the lipid raft-mediated endocytosis in a CAV-1 dependent manner, rather than through the clathrin-mediated endocytosis in HER2-positive cancer cells.Conclusion: Our findings suggest that modulation of the caveolae/lipid-raft mediated endocytosis may be a possible option for improving the clinical therapeutic effect of T-DM1 because it plays a key role in regulating T-DM1 internalization.Keywords: antibody–drug conjugate, T-DM1, endocytosis, lipid rafts, caveolae, caveolin-1

Jipang Zhan, Xuhua Tang, Fang Wang, Jiande Han Department of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of ChinaCorrespondence: Jiande HanDepartment of Dermatology, the First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, Guangzhou, Guangdong, 510080, People’s Republic of ChinaTel +86-138-0274-3924Fax +86-020-8293-8840Email hanjd@mail.sysu.edu.cnPurpose: Unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the relationship between eicosatetraenoic acid (ETA) and psoriasis remains unclear. Therefore, We performed a cross-sectional study in the general American population to investigate the association between daily dietary ETA, EPA, and DHA intake and the risk of psoriasis.Participants and Methods: This study applied data from the National Health and Nutrition Examination Survey (NHANES) 2003– 2006 and 2009– 2014. Dietary n3 polyunsaturated fatty acids (PUFA) were calculated based on two 24-hour dietary recall interviews. We defined psoriasis by responding to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?”. Multivariable logistic regression analysis, trend tests, subgroup analysis, and interaction tests were used to evaluate the associations of ETA, EPA, and DHA intake with the risk of psoriasis, respectively.Results: A total of 15,733 participants were included in this study. In our optimal multivariate-adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of psoriasis were 0.30 (0.12, 0.88), 1.92 (0.78, 4.74), 1.28 (0.72, 2.27) for daily dietary ETA, EPA, and DHA intake, respectively. Trend tests showed a dose–effect relationship between daily dietary ETA intake and the lower risk of psoriasis. Subgroup analysis and tests for interaction showed that the association was stable in different subgroups.Conclusion: Our study revealed that there might be a dose–effect association of daily dietary ETA intake with the lower risk of psoriasis in American adults.Keywords: psoriasis, diet, eicosatetraenoic acid, long-chain n3 polyunsaturated fatty acid, NHANES

Xing Lin,1 Jian Zhan,2 Jin Jiang,3 Yikun Ren3 1Department of Biological Immunotherapy, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Shapingba District, Chongqing, 400030, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou Province, 563000, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jin Jiang; Yikun RenThe First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 177 4992 3714; +86 151 9609 7005Email m17749923714@163.com; renyikunde@163.comBackground: Activated microglia are polarized into the M1 or M2 phenotype. We previously reported that electroacupuncture (EA) effectively prevented nuclear factor-κB (NF-κB) nuclear translocation and improved neuronal C-X-C motif 3 chemokine ligand 1 (CX3CL1) expression, repressing microglial activation by upregulating neuronal cylindromatosis (CYLD) expression in the periischemic cortex. However, the potential mechanisms are unclear. Therefore, we explored whether EA improved CYLD protein expression to regulate microglial polarization-mediated neuroinflammation and the potential mechanisms in an ischemic stroke model.Methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in male Sprague-Dawley (SD) rats. The rats were treated with EA at the Baihui, Hegu and Taichong acupoints once daily beginning 2 h after focal cerebral ischemia. CYLD gene interference was used to investigate the role of CYLD in microglial polarization. We used neurobehavioral evaluations and TTC staining to examine the neuroprotective effect of EA via CYLD upregulation. Immunofluorescence and RT-qPCR were used to measure NLRP3 activation, M1/M2 microglial activation, pro-/anti-inflammatory gene mRNA expression and crosstalk (CX3CL1/CX3CR1 axis) between neurons and microglia. Western blotting was used to assess the underlying molecular mechanism.Results: CYLD inhibited M1 microglial activation and improved M2 microglial activation after 72 h of reperfusion. CYLD overexpression decreased the NLRP3 mRNA level. CYLD suppressed microglial overactivation by inhibiting NLRP3 activation. CYLD gene silencing partially weakened EA improvement of neurological function deficits and reduction of infarct volumes after 72 h reperfusion. In addition, EA inhibited M1-like phenotypic microglial activation and promoted M2-like phenotypic microglia through upregulating CYLD expression. Finally, EA-mediated modulation of the CX3CL1/CX3CR1 axis and NLRP3 inflammasome was reversed by CYLD gene silencing in the periischemic cortex.Conclusion: EA-induced upregulation of neuronal CYLD expression plays anti-inflammatory and neuroprotective roles and regulates the interaction between neurons and microglia, thereby suppressing M1 and improving M2 microglial activation in the periischemic cortex.Keywords: microglial polarization, cerebral ischemia, neuroinflammation, CYLD, electroacupuncture, NLRP3 inflammasome, CX3CL1/CX3CR1 axis

Jiabin Zhan,1,* Shuai Zhang,2,* Xin Wei,1 Yihui Fu,3 Jing Zheng1 1Department of Otolaryngology, Hainan General Hospital, Haikou 570311, Hainan, China; 2Department of Radiation Oncology, Hainan General Hospital, Haikou 570311, Hainan Province, China; 3Department of Respiratory Medicine, Hainan General Hospital, Haikou 570311, Hainan Province, China *These authors contributed equally to this work Objective: To analyze the etiology of nasopharyngeal hemorrhage after radiotherapy for nasopharyngeal carcinoma (NPC) and evaluate the relevant management and rescue approaches. Methods: Seventeen cases of nasopharyngeal hemorrhage caused by radiotherapy of NPC, treated between January 2015 and March 2018, were retrospectively analyzed to study the etiology of nasopharyngeal hemorrhage. The management and rescue strategies, including anterior and posterior nostril packing, endoscopic nasopharynx electrocoagulation, and digital subtraction angiography embolization, were assessed for their effectiveness. Results: Nasopharynx hemorrhage after radiotherapy of NPC was mainly associated with erosion of the internal carotid artery or maxillary artery by the tumor. Among the 17 cases, 11 patients were treated by digital subtraction arterial angiography embolization, and 3 were treated by endoscopic nasopharynx electrocoagulation. Overall, 13 patients survived, while 4 died. Conclusion: Anterior and posterior nostril packing, endoscopic nasopharynx electrocoagulation, and digital subtraction angiography embolization are suitable for treating nasopharyngeal hemorrhage. However, effective hemostasis depends on early identification of the bleeding vessels. Keywords: nasopharyngeal carcinoma (NPC), nasopharyngeal hemorrhage, radiotherapy, prognosis

Lingfu Zhang,1 Lianyuan Tao,1 Limei Guo,2 Jun Zhan,3 Chunhui Yuan,1 Zhaolai Ma,1 Bin Jiang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, People’s Republic of China Background: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC.Materials and methods: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P

The effect of coal ratio on the high-lead slag reduction was reported in this article. First, the phase diagrams of the PbOFeO- SiO2-2%CaO-10%ZnO slag system at various temperatures and coal ratios were thermodynamically constructed. Next, the density, the melting temperature, the viscosity, the chemical composition and the phase transformation of the reduced slag were investigated. The thermodynamic results indicated that the variation of coal ratio could affect the chemical composition of the reduced slag, which led the physical properties of the reduced slag to change further. The experimental results illustrated that the content of lead and copper in the reduced slag decreased, while the contents of iron, silicon, calcium and zinc in the reduced slag increased as the coal ratio increased, which led the density and viscosity of the reduced slag to decrease further. The melting temperature of the reduced slag increased sharply when the coal ratio varied in the range of 1.5% to 3%. The mineralogy of the reduced slag indicated that lead mainly existed in the reduced slag in the form of metallic lead, while the iron and zinc were mainly enriched in the reduced slag in the form of a silicate phase. The industrial verification test results demonstrated that the average recovery rate of the lead exceeded 96.0%, the average lead content in the reduced slag was below 2.0% and the average fume rate was approximately 12.0%.

Jieqiong Zhan,1,2,* Zhiqiang Ma,2,* Dan Wang,3 Xinfang Li,2 Xiangui Li,2 Lijing Le,2 Anfeng Kang,2 Pengwei Hu,1 Lan She,2 Feng Yang1,2 1Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei, 2Department of Inorganic Chemistry, School of Pharmacy, 3Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nonspecific targeting, large doses and phototoxicity severely hamper the clinical effect of photodynamic therapy (PDT). In this work, superparamagnetic Fe3O4 mesoporous silica nanoparticles grafted by pH-responsive block polymer polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) were fabricated to load the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency of PDT. Compared to free RB, the nanocomposites (polyethylene glycol-b-polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB–MMSNs]) could greatly enhance the cellular uptake due to their effective endocytosis by mouse melanoma B16 cell and exhibited higher induced apoptosis although with little dark toxicity. RB–MMSNs had little dark toxicity and even much could be facilitated by magnetic field in vitro. RB–MMSNs demonstrated 10 times induced apoptosis efficiency than that of free RB at the same RB concentration, both by cell counting kit-8 (CCK-8) result and apoptosis detection. Furthermore, RB–MMSNs-mediated PDT in vivo on tumor-bearing mice showed steady physical targeting of RB–MMSNs to the tumor site; tumor volumes were significantly reduced in the magnetic field with green light irradiation. More importantly, the survival time of tumor-bearing mice treated with RB–MMSNs was much prolonged. Henceforth, polyethylene glycol-b-polyaspartate-modified magnetic mesoporous silica (MMSNs) probably have great potential in clinical cancer photodynamic treatment because of their effective and low-toxic performance as photosensitizers’ vesicles. Keywords: magnetic mesoporous silica, rose bengal, polymer polyethylene glycol-b-poly(aspartic acid), magnetic targeting, pH responsive, photodynamic therapy

The diffusion technology has been developed for the formation of binary clusters involving elements of group III and V in silicon. It is shown that by controlling the concentration of elements of group III and V atoms, multilayer silicon-based heterojuns can be formed in the surface region of silicon with enriched AIIIBV nanocrystals, followed by enriched with various combinations of Si2AIIIBV unit cells (1 – 5 m thick). This creates a practical new material based on silicon - a continuous graded-gap structure, i.e. heterojunsby a smooth transition from the band gap of III – V semiconductor compounds to the band gap of silicon. [ABSTRACT FROM AUTHOR]

Huan Wang,1,2,* Xiangui Li,1,* Zhiqiang Ma,1 Dan Wang,3 Linzhao Wang,1,2 Jieqiong Zhan,1,4 Lan She,1 Feng Yang1 1Department of Inorganic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 2Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 3Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 4Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China *These authors contributed equally to this article Abstract: In this study, a highly effective transmembrane delivery vehicle based on PEGylated oxidized mesoporous carbon nanosphere (oMCN@PEG) was successfully fabricated in a facile strategy. oMCN@PEG exhibited a narrow size distribution of 90 nm, excellent hydrophilicity, good biocompatibility, and a very high loading efficiency for doxorubicin (DOX). The drug system (oMCN@DOX@PEG) exhibited excellent stability under neutral pH conditions, but with dramatic releases of DOX at reduced pH conditions. Pharmacokinetics study revealed that oMCN@DOX@PEG could prolong the circulation of DOX in the blood stream. The endocytosis, cytotoxicity, and anticancer effect in vitro and in vivo of the drug-loaded nanoparticles were also evaluated. Our results showed that the nanoparticles efficiently penetrated the membrane of tumor cells, subsequently released drugs, and efficiently inhibited the growth of cancer cells both in vitro and in vivo. Especially, oMCN@DOX@PEG also exhibited significant antimetastasis effect in advanced stage of malignant cancer, improving the survival time of tumor-bearing mice. The results suggested that oMCN@PEG might be a promising anticancer drug delivery vehicle for cancer therapy. Keywords: drug delivery, hydrophilic, mesoporous carbon nanoparticles, tumor metastasis

Cong Xue,1 Ying Tian,2 Jing Zhang,3 Yuanyuan Zhao,1 Jianhua Zhan,2 Wenfeng Fang,1 Li Zhang1 1Department of Medical Oncology, 2Department of Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 3Department of Medical Oncology, The First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, Guangzhou, People’s Republic of China Purpose: BIBF 1120 is a potent triple angiokinase inhibitor now being evaluated in many types of tumors. We examine the antitumor effects of BIBF 1120 on nasopharyngeal carcinoma (NPC) in vitro and in vivo. Materials and methods: The effect of BIBF 1120 on NPC cell proliferation was evaluated using the Cell Counting Kit 8 assay. The activities of BIBF 1120 as a single agent and in combination with cisplatin (DDP) in NPC tumor xenografts were evaluated by measuring microvessel density and expression of vascular endothelial growth factor signaling. Results: BIBF 1120 exhibited limited inhibition of the growth of three NPC cell lines. Concurrent administration of BIBF 1120 and DDP provided greater antitumor effects compared to that observed with the use of either inhibitor as a single agent in the NPC xenograft model. Microvessel density and expression of vascular endothelial growth factor signaling were significantly reduced. Conclusion: BIBF 1120, either as a single agent or in combination with DDP, demonstrates significant antitumor and antiangiogenic effects in the NPC xenograft model. Our results indicate that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. Keywords: BIBF 1120, nasopharyngeal carcinoma, antiangiogenesis, microvessel density