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In this paper, the use of recycled aggregate concrete (RAC) for the upper slabs in steel-concrete composite beams is proposed. Perfobond rib connector (PBL), a relatively new type of shear connectors, has been widely used to ensure composite action between the steel and concrete elements in composite beams. For the past decades, several studies on assessing the performance of PBLs have been conducted, but very few focused on the PBLs that are embedded in RAC slabs. This paper presents results of an experimental and numerical simulation study that focused on characterizing the behavior of PBL fabricated using RAC. In the experimental program, a total of six standard push-out specimens, divided into three groups, were fabricated and loaded to failure. Test results indicated that the ductility of the PBLs using RAC materials decreased as the perforated steel plate thickness decreased, while the PBL ultimate strength increased by 4.3% and 12.8% for steel plate thicknesses of 10.0 mm and 12.0 mm, respectively, as compared to specimens with 8.0 mm steel plate thickness. Finite element (FE) models for PBLs embedded in RAC were developed, and numerical results were validated by corresponding experimental results. An extensive parametric numerical analysis was conducted to assess the effects of different parameters such as transverse steel rebar diameter and perforated steel plate strength and thickness on the performance of such connectors. Numerical simulation results showed that the PBL ultimate strength obtained based on the perforated plate fracture failure mode increases linearly as the steel rebar diameter increases. Also, numerical results indicated that as steel plate strength and thickness increase, failure mode changes from steel plate fracture to rupture of reinforced concrete dowels. Furthermore, existing published analytical formulas for predicting behavior of PBLs were assessed via a comparison with experimental and numerical results developed in this study. The outcomes of this study contribute in providing fundamental knowledge in a new sustainable application of PBL in steel-concrete composite beams with RAC slabs.

Hai Feng,1,* Yunhui Zhuo,2,* Xuemei Zhang,2 Yuyao Li,1 Yue Li,1 Xiangjuan Duan,2 Jia Shi,1 Chengbin Xu,3 Yueqiu Gao,1,2 Zhuo Yu2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Informatics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yueqiu Gao, Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email gaoyueqiu@shutcm.edu.cn Zhuo Yu, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) remains a serious medical therapeutic challenge as conventional curative avenues such as surgery and chemotherapy only benefit for few patients with limited tumor burden. Immunotherapy achieves clinical progress in the treatment of this prevalent malignant disease by virtue of the development of tumor immunology; however, most patients have experienced minimal or no clinical benefit in terms of overall survival. The complexity and diversity of tumor microenvironment (TME) built by immune and stromal cell subsets has been considered to be responsible for the insufficiency of immunotherapy. The advance of bioanalytical technology boosts the exploration of the composition and differentiation of these infiltrated cells, which reflect the immune state of the TME and impact the efficacy of the antitumor immune response. Targeting these cells to remodel the TME is one of the important immunotherapeutic approaches to improve HCC treatment. In this review, we focused on the role of these non-cancerous cells in the tumor progression, and elaborated their function on cancer immunotherapy when manipulating them as potential targets.Keywords: immune cells, stromal cells, tumor microenvironment, hepatocellular carcinoma, immunotherapy

Jichan Shi,1,* Gexin Gao,2,* Zhijie Yu,3,* Kaihuai Wu,4 Youquan Huang,5 Lian-Peng Wu,6 Zhengxing Wu,1 Xinchun Ye,1 Chaochao Qiu,1 Xiangao Jiang1 1Department of Infectious Disease, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Nursing School, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Hematology, Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Departments of Infectious Diseases, Taishun People’s Hospital, Wenzhou, 325000, People’s Republic of China; 5Departments of Infectious Diseases, Yongjia People’s Hospital, Wenzhou, 325000, People’s Republic of China; 6Department of Laboratory, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangao Jiang, Department of Infectious Disease of Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, 252 Baili East Road, Lucheng District, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13587691822, Fax +86 577 88070007, Email jiang_xiangao@126.comBackground: Tuberculosis (TB) is still the single pathogen infectious disease with the largest number of deaths worldwide. The relationship that intestinal microbiota disorder and de novo fatty acid synthesis metabolism have with disease progression in multi-drug resistant TB (MDR-TB) has not yet been fully studied.Objective: To investigate the effects of long periods of MDR-TB, pre-extensively drug-resistant TB (pre-XDR-TB), or rifampicin-resistant TB (RR-TB) on gut microbiome dysbiosis and advanced disease.Methods: The sample was chosen between March 2019 and September 2019 in Wenzhou Central Hospital and comprised 11 patients with pre-XDR-TB, 23 patients with RR-TB, and 28 patients with MDR-TB. Healthy individuals were chosen as the control group (CK group). An overnight fast blood sample was drawn via venipuncture into tubes without anticoagulant. For analysis, 300 mg of faeces from patients from the same group was mixed and analysed using DNA extraction, NGS sequencing, and bioinformatics. A QIAamp Fecal DNA Mini Kit was used to isolate the DNA. The extracted DNA was stored at − 20°C.Results: Advanced TB was concurrent with an elevated level of the proportions of acetyl-CoA carboxylase (ACC1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthase (FASN) to GAPDH in de novo fatty acids synthesis, and Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus were increased significantly in RR-TB patients compared to healthy individuals, whereas their abundance in the pre-XDR-TB and MDR-TB groups showed little change in comparison with the control group. Proteobacteria levels were greatly increased in the RR-TB and MDR-TB patient groups but not in the patients with pre-XDR-TB or the healthy subjects. The pre-XDR-TB group exhibited alterations of the intestinal microbiome: coliform flora showed the highest abundance of Verrucomicrobiales, Enterobacteriales, Bifidobacteriales and Lactobacillales. De novo fatty acids synthesis was enhanced in patients and was associated with the gut microbiome dysbiosis induced by the antimicrobials, with Bacteroidetes, Bacteroidales, and Bacteroidaceae displaying the most important correlations on a phylum, order, and family level, respectively.Conclusion: The progression to advanced TB was observed to be a result of the interaction between multiple interrelated pathways, with gut–lung crosstalk potentially playing a role in patients with drug-resistant TB.Keywords: multi-drug resistant TB disease, gut commensal, microbial imbalance, de novo fatty acids synthesis, microbiome biosignature alterations

Hao Cheng,1 Zhen Yu,1 Cheng-lan Yan,1 Hui-dan Yang,1 Chong Gao,2 Hong-yan Wen1 1Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Hong-yan Wen, Email wenhongyan@sxmu.edu.cnBackground: Patients with systemic sclerosis (SSc) have poor prognosis without cure methods. We began, 10 years ago, to relieve active SSc using short-term intravenous high-dose methylprednisolone pulse (MP-Pulse) and then maintain remission using long-term and low-dose oral glucocorticoids (LTLD-GC).Methods: Total 46 of SSc patients with interstitial lung disease (ILD) and induration of skin during January 2006 to December 2019 were analyzed retrospectively, who were followed up for 10 years or more. The patients were treated with MP-Pulse (15 mg/kg/day, 4 days/week, for 2 weeks) with (n=21) or without (n=25) LTLD-GC (prednisone 5– 10 mg/day or methylprednisolone 4– 8 mg/day). The biographic and clinical data, including occurrence of infection or any adverse reactions, were collected at baseline, 6 months, 1 year, and annually through 10 years after treatment.Results: From baseline to 10 years, compared with MP-Pulse alone, MP-Pulse/LTLD-GC significantly reduced skin and lung fibrosis and improved lung function: Rodnan skin score (mRSS: 22.1± 12.4 to 8.16± 2.5, P< 0.001), forced vital capacity (FVC: 71.7% to 89.83%, P< 0.001), forced expiratory volume in the first second (FEV1: 75.7% to 87.88%, P< 0.001), diffusing capacity of the lung for carbon monoxide (DLCO: 63.4% to 87.73%, P< 0.001), and high-resolution chest computerized tomography scan (HRCT score: 3.96± 2.81 to 1.42± 0.83, P< 0.001). None of the 46 patients had femoral head necrosis, compression fracture, death, or life-threatening adverse events.Conclusion: These outcomes indicate that intravenous MP-Pulse combined with oral LTLD-GC could achieve significant remission and better long-term (10 years) efficacy without severe adverse effects in SSc patients with ILD and induration of skin.Keywords: glucocorticoids, low-dose, pulse, systemic sclerosis, safety

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Yue Wang,1,&ast; Shuang Tan,2,&ast; Evenki Pan,3 Yutong Ma,3 Xue Wu,3 Zhe Yu,1 Kui Jiang1 1Department of Medical Oncology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Gynecology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kui Jiang; Zhe Yu, Department of Medical Oncology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China, Tel +8617709873696 ; +8618641103913, Email jk0411@163.com; deepriveryu@outlook.comAbstract: Hormonal therapy is an important treatment option for estrogen receptor (ER)-positive patients with advanced ovarian cancer. Although ER overexpression has been previously used as an indicator for hormonal therapy, the clinical outcomes of advanced ovarian cancer patients receiving hormonal therapy remain unsatisfactory. Additional biomarkers for screening patients are needed to improve its efficacy. In this study, we reported a metastatic ovarian cancer case with estrogen receptor 1 (ESR1) gene amplification and protein overexpression, which showed sustained partial response to hormonal therapy, including letrozole and tamoxifen, and displayed an overall survival of 47 months. The response to the therapy was evaluated by imageological examinations, cancer antigen-125 (CA-125) tests, and circulating tumor DNA (ctDNA) sequencing using capture-based hybrid next-generation sequencing. Our clinical data suggested that ESR1 amplification might be a potential predictor of response to hormonal therapy in ovarian cancer. The combination of tumor detection techniques including imaging, CA-125 and ctDNA would enable confirmation of tumor response with high confidence.Keywords: ESR1 amplification, ovarian cancer, hormonal therapy, letrozole, tamoxifen, circulating tumor DNA

Jie Li,1,&ast; Siwen Chen,1,&ast; Hui Xue,2,&ast; Haoyi Wang,3,&ast; Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, People’s Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 17774015977, Email bin_ni@163.com Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China, Tel +86 15558078770, Email yuzhaonan870213@163.comIntroduction: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterations, described the distribution of hotspot variants, analyzed the frequency of variant alleles, and notably distinguished actionable, novel variants.Results: The most commonly affected genes were EGFR, TP53, KRAS, CDKN2A, and PIK3CA in both tDNA and cfDNA samples. EGFR and CTNNB1, PIK3CA and PTEN, ERBB2 and SMO were found to have frequent co-occurring alterations in tDNA samples, while EGFR and SMO, KRAS and PDGFRA, PIK3CA and KDR were in cfDNA samples. A large number of primary druggable variants were identified in tDNA samples, while numerous drug-resistance variants, rare actionable variants, and non-EGFR actionable variants were detected in cfDNA samples. Novel variants were enriched in KDR, KIT, TP53, ABL1, FGFR1 in tDNA samples while the majority of novel variants were distributed in PDGFRA, EGFR, KIT, ROS1, BRCA2 in cfDNA samples. Variant allele frequency in tDNA samples was significantly (P < 0.001) higher than that in cfDNA samples.Conclusion: The results revealed considerable differences in the alteration characteristics between the two kinds of specimens. To date, this study represents the largest real-world investigation of its kind, derived from the largest number of patients in East-China. It reinforced and expanded the mechanism of molecular analysis of neoplastic genetic profiles.Keywords: real world study, non-small cell lung cancer patients in East-China, tumor tissue DNA, cell-free circulating tumor DNA, next-generation-sequencing, genetic alteration

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Jing Zhao, Qianqian Kong, Minghuan Wang, Hao Huang, Xirui Zhou, Yinping Guo, Yi Zhang, Lingshan Wu, Zhiyuan Yu, Xiang Luo Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xiang Luo, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 27-83663337, Email flydottjh@163.comPurpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD.Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55– 85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD.Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p < 0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p < 0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p < 0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p < 0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564).Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associated with WMH, lacunes, and CSVD burden. Our findings further suggest patients with CSVD may exhibit abnormal sleep-wake patterns.Keywords: cerebral small vessel disease, daytime sleepiness, sleep disorders, white matter hyperintensities, lacunes

Yijin Chen,1,2,&ast; Hongtao Liu,2,3,&ast; Zhikang Yu,2,4 Yang Yang,1,2 Qingyan Huang,2,4 Changqing Deng,1,2 Hui Rao,2,4 Heming Wu2,4 1Department of Gastroenterology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gastrointestinal Surgery, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heming Wu, Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +86 753-2131-591, Email wuheming1986@126.comBackground: Alcoholics are prone to alcoholic cirrhosis (ALC). Aldehyde dehydrogenase 2 (ALDH2) is involved in alcohol metabolism. Herein, the relationship between ALDH2 genotypes and ALC was analyzed among Hakka alcoholics in southern China.Methods: A total of 213 alcoholics and 214 non-alcoholics were included in the study. The ALDH2 gene rs671 polymorphism was analyzed, life history, disease history, and auxiliary examination results of these participants were collected.Results: The alcoholics had higher level of total serum protein, and serum globulin, lower level of serum albumin, serum albumin/globulin ratio, serum prealbumin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) than non-alcoholics. In the 213 alcoholics, 180 developed ALC. There were 206 non-ALC persons in the 214 non-alcoholics. The proportion of the ALDH2 rs671 G/G homozygous (&ast;1/&ast;1) was significantly lower in ALC patients (83.3%) than that of other groups (100.0% in non-ALC in alcoholics, 95.6% in non-ALC in non-alcoholics), while the proportion of the G/A heterozygous (&ast;1/&ast;2) was significantly higher in ALC patients (16.7%) than that of other groups (0% in non-ALC in alcoholics, 4.4% in non-ALC in non-alcoholics). Logistic regression analysis indicated that participants with low level of NLR (adjusted OR 5.543, 95% CI 2.964– 10.368, P< 0.001), LMR (adjusted OR 9.256, 95% CI 4.740– 18.076, P< 0.001), and PLR (adjusted OR 6.047, 95% CI 3.372– 10.845, P< 0.001), and ALDH2 G/A genotype (adjusted OR 6.323, 95% CI 2.477– 16.140, P< 0.001) had a significantly higher risk of ALC.Conclusion: ALDH2 polymorphism rs671 &ast;1/&ast;2 genotype is a potential risk factor for the development of ALC among Hakka alcoholics.Keywords: ALDH2, alcoholics, alcoholic liver cirrhosis, gene polymorphism, Hakka

Shirui Li,1 Zhihui Gao,1 Meihan Zhong,1 Zhujun Yu,1 Jianan Li,2 Haoran Bi1,3,4 1Department of Biostatistics, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Environment and Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Haoran Bi, Department of Biostatistics, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262660, Email bihaoran1989@sina.com Jianan Li, Key Laboratory of Environment and Health, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262659, Email lijianan512133@163.comPurpose: The emergence of the mutant virus has exacerbated the COVID-19 epidemic, and vaccines remain an effective and viable means of resistance. As a socially influential young group, university students’ awareness and acceptance of the COVID-19 vaccine are crucial to achieving herd immunity. This study aimed to assess the awareness and acceptance of the COVID-19 vaccine among Chinese university students and identify possible factors associated with their awareness level and vaccine hesitancy.Patients and Methods: An anonymous cross-sectional survey was conducted among Chinese university students between 10 and 28 June 2021. We collected information on the demographic characteristics, awareness and acceptance of the COVID-19 vaccine, and influencing factors. Sleep disturbances and anxiety disorders were also evaluated. Multinomial logistic regression analyses were performed.Results: Among the 721 participants (aged 18 to 23 years) with a female predominance (68.9%), 40.4% of cases exhibited moderate awareness the COVID-19 vaccine, and 87.4% of cases expressed high acceptance of the vaccine. Participants’ awareness of the COVID-19 vaccine was associated with gender, ethnicity, region of residence, grade level, satisfaction with current state of pandemic control, the perceived likelihood of a COVID-19 pandemic rebound, the source number of COVID-19 information, concerns about differences in vaccine manufacturers, acceptance of current state-approved vaccines and insomnia level. Furthermore, age, preferred channels for vaccination and the acceptance of current state-approved vaccines were significantly associated with their acceptance of the vaccine.Conclusion: This study reflected Chinese university students’ high acceptance, but insufficient awareness of the COVID-19 vaccine, some students have insomnia and anxiety problems. These require the government to take measures such as individualized publicity and education, adding professional psychological counseling courses to improve the university students’ awareness of vaccines and public health events, and comprehensively promote vaccination to cope with the ever-changing situation of the COVID-19 epidemic.Keywords: university students, COVID-19 vaccine, mental health, vaccine hesitancy

RF fingerprinting is an emerging technology for identifying hardware-specific features of wireless transmitters and may find important applications in wireless security. In this study, the authors present a new RF fingerprinting scheme using deep neural networks. In particular, a long short-term memory based recurrent neural network is proposed and used for automatically identifying hardware-specific features and classifying transmitters. Experimental studies using identical RF transmitters showed very high detection accuracy in the presence of strong noise (signal-to-noise ratio as low as −12 dB) and demonstrated the effectiveness of the proposed scheme.

The optical constants of single-crystal AlxGa1−xP and AlxGa1−xAs have been widely studied at various Al compositions but have not yet been thoroughly investigated as polycrystalline materials. Using variable-angle spectroscopic ellipsometry, we estimate and analyze the optical constants of polycrystalline Al0.25Ga0.75P and Al0.9Ga0.1As that were non-epitaxially deposited at deposition temperatures of either 250 or 420 °C, and with various dopant species, dopant concentrations, and V/III flux ratios. For wavelengths of 350–400 nm, decreasing the V/III ratio increases the refractive index of Be-doped polycrystalline Al0.25Ga0.75P. For wavelengths >500 nm, as the targeted Be dopant concentration increases for polycrystalline Al0.25Ga0.75P, the amount the extinction coefficient increases and the indirect bandgap decreases depends on the V/III ratio. Furthermore, Si-doped polycrystalline Al0.25Ga0.75P has significantly smaller extinction coefficient values than when it is Be-doped, for the same V/III ratio and targeted doping concentration, at wavelengths >500 nm. Based on our findings, we hypothesize that the dopant species, dopant concentration, and the V/III ratio dictate various types of defect concentrations, which then affect the optical constants and indirect bandgap of polycrystalline Al0.25Ga0.75P. Additionally, for wavelengths >500 nm, we find that polycrystalline Al0.25Ga0.75P and Al0.9Ga0.1As have the lowest extinction coefficient values when deposited at 420 °C, as opposed to 250 °C. Thus, we hypothesize that the deposition temperature is the most significant factor in dictating the optical constants of these polycrystalline III-Vs. Ultimately, this work demonstrates alternative methods to tune the optical constants of polycrystalline Al0.25Ga0.75P and Al0.9Ga0.1As, as opposed to tuning the Al composition. [ABSTRACT FROM AUTHOR]

Yu Luo,1,2,&ast; Heming Wu,2,3,&ast; Qingyan Huang,2,3 Hui Rao,2,3 Zhikang Yu,2,3 Zhixiong Zhong2,3 1Department of Gynaecology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhikang Yu; Zhixiong Zhong, Center for Precision Medicine, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +753-2131-591, Email yuzhikang01@126.com; zhongzhixiong01@126.comObjective: To investigate the frequencies of BRCA1 and BRCA2 mutations in Chinese Hakka patients with ovarian cancer.Methods: The protein coding regions and exon intron boundary regions of the BRCA gene were sequenced using genomic DNA isolated from the lymphocytes of patients with next-generation sequencing. The patients’ family history and clinical records were collected.Results: A total of 195 patients with ovarian cancer were included in the study, and 52 distinct variants of the BRCA gene were identified. It was found that 64 patients (64/195, 32.8%) had BRCA gene mutations, including 32 patients (50.0%) with BRCA1 mutation, 27 patients (42.2%) with BRCA2 mutation, and 5 patients (7.8%) with both mutations. Furthermore, 22 pathogenic mutations were detected in 26 patients, 2 likely pathogenic variants in 2 patients, 12 variants of uncertain significance in 20 patients, and 16 likely benign variants in 24 patients. The mutations were mainly found to occur in exons 8, 14, and 17 of BRCA1 and exons 10, 11, 14, and 15 of BRCA2. The results showed that the BRCA genes possess different mutation hotspots in different ethnic groups. In addition, recurrent mutations were noted in many patients. BRCA1 c.536 A>T, considered a founder mutation, was identified in 10 patients (15.63%, 10/64), followed by BRCA1 c.2635 G>T (6.25%, 4/64) and BRCA2 c.2566 T>C (6.25%, 4/64).Conclusion: The BRCA1 c.536 A>T could be considered to be a founder mutation in this ovarian cancer population. This recurrent BRCA1 mutation has rarely been observed in other ethnic groups. Our findings are expected to provide valuable data for clinical consultation and for designing individualized treatment for ovarian cancer.Keywords: BRCA gene, ovarian cancer, variants, Hakka population

Lu Zhang,1 Zitong Yu,2 Qingxi Qu,1 Xiao Li,1 Xue Lu,1 Hui Zhang1 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Obstetrics, Shouguang People’s Hospital, Shouguang, 262700, People’s Republic of ChinaCorrespondence: Hui Zhang, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan, 250012, People’s Republic of China, Email williamzh@126.comBackground: Long non-coding RNA (lncRNA) and exosomes are implicated in endometriosis development. We measured the expression of an exosomal lncRNA, homeobox transcript antisense RNA (HOTAIR), and explored its molecular mechanism in endometriosis progression.Methods: Expression of HOTAIR and microRNA (miR)-761 in different endometrial tissues was measured. Exosomes were isolated from a culture medium of endometrial stromal cells (ESCs). RT-qPCR was used to measure HOTAIR expression in different exosome types. CCK-8, Edu, wound healing, transwell assays, flow cytometry and tube formation were used to detect the role of exosomal HOTAIR on ESCs and human umbilical vein endothelial cells (HUVECs). The relationship among miR-761, HOTAIR, and histone deacetylase 1 (HDAC1) was verified by dual-luciferase reporter assay. ESCs were transfected with miR-761 mimics or HDAC1 small interfering RNA (si-RNA) to ascertain if alterations in expression of miR-761 or HDAC1 could reverse the effect of exosomal HOTAIR. Then, we detected the effect of the HOTAIR/miR-761/HDAC1 axis on signal transducer and activator of transcription 3 (STAT3)-mediated inflammation. In vivo experiments were conducted to verify in vitro results.Results: HOTAIR expression was upregulated and miR-761 expression was downregulated in ectopic endometrium tissues. HOTAIR was packaged into exosomes and transported from ESCs to surrounding cells. Exosomal HOTAIR promoted the proliferation, migration, and invasion, and inhibited the apoptosis of ESCs. Angiogenesis of HUVECs was enhanced after cultured with exosomal HOTAIR. HOTAIR acted as a competing endogenous RNA to downregulate miR-761 and increase HDAC1 expression. miR-761 overexpression or HDAC1 knockdown reversed the role of exosomal HOTAIR on ESCs and HUVECs. The HOTAIR/miR-761/HDAC1 axis could activate STAT3-related proinflammatory cytokines and stattic (inhibitor of phosphorylated-STAT3) could reverse the effect of HOTAIR on ESCs and HUVECs. In vivo experiments suggested that exosomal HOTAIR promoted the growth of endometrial lesions in vivo.Conclusion: Exosomal HOTAIR promoted the progression and angiogenesis of endometriosis by regulating the miR-761/HDAC1 axis and activating STAT3-mediated inflammation in vitro and in vivo, which may provide promising treatment for endometriosis.Keywords: endometriosis, HOTAIR, exosomes, miR-761, HDAC1, STAT3, inflammation

Yuyao Li,1,&ast; Yue Li,1,&ast; Jinghao Zhang,2 Longshan Ji,3 Man Li,3 Xuehua Sun,2 Hai Feng,1 Zhuo Yu,2 Yueqiu Gao1,2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Yu; Yueqiu Gao, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86 21 2025 6507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cn; gaoyueqiu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) is one of the leading lethal tumors worldwide, and the treatment remains a great medical challenge. Surgery and chemotherapy are current standard curative methods for patients with HCC, but the prognosis is still dismal. Based on unique medical theories and rich practical experience, traditional Chinese medicine (TCM) has been broadly employed to effectively treat HCC for a long history. Recently, systematic clinical trials have been well designed to study the efficacy of TCMs in the treatment of HCC, and the underlying antitumor mechanisms were also deeply explored. Here, we reviewed the published clinical evaluation of some commonly used TCMs in the treatment of HCC, and the related anti-HCC mechanisms through in vitro and in vivo study, promoting the modernization of TCM study in oncology for achieving a substantial reduction of HCC burden in the future.Keywords: traditional Chinese medicine, hepatocellular carcinoma, antitumor mechanism, tumor therapy, active ingredient

Xiao Ran,1 Dao Wen Wang,2 Zhen Yu,1 Rongxue Wu,3 Qin Zhang4 1Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 2The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 3Department of Biological Sciences Division/ Cardiology, University of Chicago, Chicago, IL, 60637, USA; 4Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Qin Zhang Email qzhang8@tjh.tjmu.cnAim: Tissue kallikrein (TK) exerts protective effects on cardiac cerebrovascular diseases (CCVDs). Changes in TK level in plasma are associated with ischemic stroke and coronary artery disease (CAD); however, a causal correlation could not be established. Therefore, we investigated the association between TK levels and CCVDs in a community-based cross-sectional study in China.Methods: A total of 6043 subjects (4242 men and 1801 women) were enrolled in this community-based cross-sectional study. Then, TK levels were measured using an enzyme-linked immunosorbent assay kit. Multivariate linear regression model and logistic regression were used to assess the correlations between TK levels and CCVDs. Subsequently, the receiver operating characteristic (ROC) curve was drawn to assess the value of TK level in evaluating the risk of ischemic stroke. Finally, the influence of various medications was evaluated on TK levels.Results: The TK level was significantly lower in subjects with ischemic stroke (P < 0.001) and hypertension (P < 0.001) and negatively associated with ischemic stroke (P < 0.001) but not associated with hypertension, coronary heart disease, and diabetes compared to the traditional risk factors. The diagnostic accuracy for ischemic stroke, as quantified by the area under the curve, was 0.892 (95% CI, 0.884– 0.900) for TK level, deeming it as a promising assessment tool. Moreover, no appreciable influence of various drugs therapy was found in TK levels (P = 0.222) except for those taking antilipemic agents.Conclusion: TK is a strong and independent endogenous protective factor against ischemic stroke in the Chinese population and could be a promising biomarker for the risk of ischemic stroke.Keywords: tissue kallikrein, ischemic stroke, cardiac cerebral vascular disease, risk factor

Zaoqin Yu,1,&ast; Wei Li,1,&ast; Xiaofang Shangguan,2 Yuanxuan Cai,2 Qianyan Gao,1 Ximin Wang,1 Yuan Chen,3 Dong Liu,1 Chengliang Zhang1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Liu; Chengliang ZhangDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86-27-83663643; +86-27-83663519Email ld2069@outlook.com; clzhang@tjh.tjmu.edu.cnBackground: Despite the great signs of progress in cancer pain management in China, the associated pain remains under-treated. Poor knowledge among the medical staff is an important factor contributing to the under-treatment of cancer pain. This study aimed to evaluate the knowledge, practices, and perceived barriers in cancer pain management among the medical staff at oncology units in China.Patients and Methods: A cross-sectional survey was conducted with the medical staff (including physicians, nurses, and pharmacists) at oncology units in tertiary hospitals of China between December 2020 and January 2021. The questionnaire assessed the knowledge, practices, and perceived barriers in cancer pain management.Results: A total of 1262 medical staff responded to the questionnaire; the response rate was 94.2%. Most participants had good knowledge of the three-step analgesic ladder of the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) guidelines for Adult Cancer Pain. Knowledge deficit was prominent in questions on opioid dose titration and rotation and adverse effects of opioids; the correct response rate was less than 40%. Training, work experience in oncology, and education level were significantly related to knowledge of cancer pain management (all P < 0.001). In clinical practice for cancer pain management, approximately 57.2% of medical staff were unfamiliar with opioid dose titration and rotation; only 14.4% treated cancer pain through multidisciplinary collaboration. Poor medication compliance, difficult individualized analgesia protocols, and insufficient multidisciplinary participation were the most frequently perceived barriers by the medical staff for pain management.Conclusion: These findings suggested a further need for integrating recent guidelines to strengthen continued training (especially among juniors and those with low education levels) and patient education to improve the knowledge and clinical practices of cancer pain management among the medical staff in China. Multi-disciplinary management is required for the effective treatment of cancer pain.Keywords: cancer pain, medical staff, knowledge, practices, barriers, multi-disciplinary management