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Qingbao Guo,1,2,* Manli Xie,3,* Qian-Nan Wang,4,* Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Min-Jie Wang,1– 3 Jiayu Wang,4 Houdi Zhang,2,3 Fang-Bin Hao,1– 3 Gan Gao,1– 3 Si-Meng Liu,1– 3 Xiao-Peng Wang,1– 3 Jing-Jie Li,1– 3 Zheng-Xing Zou,2,3 Qing-Bao Guo,1– 3 He-Guan Fu,2,3 Yi-Qin Han,2,3 Cong Han,2,3 Lian Duan2,3 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurosurgery, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan; Cong Han, Department of Neurosurgery, Department of Neurosurgery, the Fifth Medical Centre (South Campus), Chinese PLA General Hospital, No. 8 Dong-Da Street, Fengtai District, Beijing, 100071, People’s Republic of China, Tel +86-10-66947389 ; +86-13466346163 ; +86-10-66947388, Fax +86-10-62177976, Email duanlian307@sina.com; hc82225@126.comBackground: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD.Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression.Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables.Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late–Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.Keywords: moyamoya disease, complement, Suzuki stage, nomogram

Sumei Wang, Zhiling Cai, Guopeng Gao, Shuangqin Yan Ma’anshan Maternal and Child Health Center, Ma’anshan, Anhiu Province, 243011, People’s Republic of ChinaCorrespondence: Shuangqin Yan, Ma’anshan Maternal and Child Health Center, No. 446 Jiashan Road, Ma’anshan, Anhiu Province, 243011, People’s Republic of China, Tel/Fax +86 555-2364042, Email ShuangqinYan@163.comPurpose: To explore the correlation between maternal anxiety during mid-pregnancy and infant sleep issues based on the anxiety status of mothers in mid-pregnancy.Patients and Methods: A cohort of 2122 primigravida women from Ma’anshan City, Anhui Province, was followed from pregnancy until 6 months postpartum. The study analyzed the impact of maternal anxiety on infant sleep patterns, including primary caregivers, encompassing insufficient sleep duration, frequent nocturnal awakenings, prolonged nocturnal awakening durations, and elongated sleep latency.Results: A total of 1891 mother-infant pairs were included in this analysis. After adjusting for confounding factors, a positive correlation was found between maternal anxiety during mid-pregnancy and insufficient sleep duration (OR=1.69, 95% CI:1.13– 2.52), and elongated sleep latency (OR=2.26, 95% CI:1.61– 3.18).Conclusion: Maternal anxiety during mid-pregnancy is associated with sleep issues in infants. Addressing maternal mental health during pregnancy may enhance sleep quality for mothers and infants, promoting overall maternal-infant health. Keywords: pregnancy anxiety, pregnancy, infant, sleep

Yin-Gang Wu,1,* Bowen Wang,2,* Hao Cui,3,* Hao Zhu,1 Ge Gao1– 3 1Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Neurosurgery, Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China; 3Department of Neurosurgery, Bengbu Medical College, Bengbu, Anhui, 233030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ge Gao, Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of China, Email gegao1012@163.comObjective: To retrospectively evaluate the efficacy and security of Willis covered stent (WCS) deployment for complex vascular diseases of the internal carotid (ICA) and vertebral (VA) arteries.Methods: Retrospective analysis was performed on complex vascular disease patients (n=36) treated with WCSs at our center between March 2017 and December 2022, with a 3– 36-months follow-up surveillance and digital subtraction angiography (DSA) examination.Results: The WCSs were successfully deployed in all the patients. The 36 included lesions were carotid-cavernous sinus fistulas (CCFs; n=10) (27.8%), complex saccular aneurysms (n=10) (27.8%), traumatic pseudoaneurysms (n=7) (19.4%), blood blister-like aneurysms (BBAs; n=5) (13.9%), and iatrogenic carotid or vertebral artery ruptures (n=4) (11.1%). The WCS was released at the communicating segment (n=2) (5.6%), the ophthalmic segment (n=3) (8.3%), the clinoid and cavernous segment (n=28) (77.8%), the petrous segment (n=2) (5.6%) of ICA and the V3 segment (n=1) (2.8%) of VA. Postoperative DSA showed complete lesion occlusion in 26 patients (72.2%) who were immediately treated with WCSs, and endoleaks occurred in 3 patients (8.3%) (endoleaks resolved postadjustment in 7 patients (19.4%)). In patients (n=3) (8.3%) treated with double stents at the break of the ICA, the endoleak remained in 1 CCF patient (2.8%) during the 3-month follow-up, and the residual shunt disappeared after the second stent system was placed 3 months later. No aneurysm, bleeding or infarct recurrence reported, and only 1 patient (2.8%) had mild asymptomatic in-stent stenosis. Deaths and procedural complications did not occur during follow-up.Conclusion: Treatment with a WCS for intracranial complex vascular diseases resulted in satisfactory clinical outcomes and appeared effective and safe. Controlled, multicenter, large sample sizes and longer follow-up periods studies are necessary.Keywords: Willis covered stents, complex vascular diseases, endovascular treatment

Jichan Shi,1,&ast; Gexin Gao,2,&ast; Jing Pan,3 Lian-Peng Wu,4 Hongye Ning,1 Zhengxin Wu,1 Xinchun Ye,1 Xiangao Jiang1 1Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 2Department of Nursing, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Geriatric Medicine, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 4Department of Laboratory, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangao Jiang, Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, 252 BaiLiDong Road, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13676788085, Email xiangaojiang09@163.comObjective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM).Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations.Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P< 0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P< 0.001, kappa=0.781).Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.Keywords: Nontuberculosis mycobacteria, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, strain identification, resistance

Tongtong Wang,1,&ast; Yingchu Liu,2,&ast; Chunyu Zhu,1,&ast; Siyuan Yang,3 Di Yang,4 Jiang Xiao,4 Guiju Gao4 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of General Practice and Continuing Education, Capital Medical University, Beijing, People’s Republic of China; 3Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiju Gao, Professor of Medicine Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Email guiju.gao@163.comBackground: Rifampicin is a known inducer of the cytochrome P450 (CYP2B6) enzyme, which can lead to a decrease in the concentration of efavirenz. Therefore, we conducted a study to evaluate the effect of daily rifampicin intake on efavirenz 600mg pharmacokinetics and HIV-1 virological suppression.Methods: Patients receiving antiretroviral therapy containing efavirenz (600mg daily), and we collected efavirenz concentration at four visit points: ART day 14 (PK1), ART day 42 (PK2), ART day 140 (PK3), and ART day 336 (PK4), and performed pharmacokinetics analysis.Results: From February 2017 to November 2020, 29 HIV/TB co-infection patients were included. Ninety percent of patients had a concentration of ≥ 1000ng/mL of efavirenz during the study. All patients had efavirenz Cmax ≥ 1000ng/mL, 86% patients showed good virology response.Conclusion: Our study shows that the use of rifampicin in HIV/TB co-infection patients does not affect efavirenz drug concentrations, that virological suppression is good and that no efavirenz dose adjustment is required.Keywords: HIV/TB, rifampicin, efavirenz, pharmacokinetics

Yang Wang, Ge Gao, Xiangpin Wei, Yang Zhang, Jian Yu Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Jian Yu, Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Tel + 86 551 62283413, Fax + 86 551 62283413, Email yujianqi024@163.comPurpose: Patients with glioblastoma (GBM) have poor prognosis and limited therapeutic options, largely because of chemoresistance to temozolomide (TMZ) treatment. Ubiquitin conjugating enzyme E2 T (UBE2T) plays a key role in regulating the malignancy of various tumors, including GBM; however, its role in TMZ resistance of GBM has not been elucidated. The purpose of this study was to clarify the role of UBE2T in mediating TMZ resistance and investigate the specific underlying mechanism.Methods: Western blotting was used to detect the protein levels of UBE2T and Wnt/β-catenin-related factors. CCK-8, flow cytometry, and colony formation assays were used to examine the effect of UBE2T on TMZ resistance. Wnt/β-catenin signaling pathway activation was inhibited using XAV-939, and a xenograft mouse model was generated to clarify the function of TMZ in vivo.Results: UBE2T knockdown sensitized GBM cells to TMZ treatment, whereas UBE2T overexpression promoted TMZ resistance. The specific UBE2T inhibitor, M435-1279, increased the sensitivity of GBM cells to TMZ. Mechanistically, our results demonstrated that UBE2T induces β-catenin nuclear translocation and increases the protein levels of downstream molecules, including survivin and c-Myc. Inhibition of Wnt/β-catenin signaling using XAV-939 blocked TMZ resistance due to UBE2T overexpression in GBM cells. In addition, UBE2T was shown to facilitate TMZ resistance by inducing Wnt/β-catenin signaling pathway activation in a mouse xenograft model. Combined treatment with TMZ and UBE2T inhibitor achieved superior tumor growth suppression relative to TMZ treatment alone.Conclusion: Our data reveal a novel role of UBE2T in mediating TMZ resistance of GBM cells via regulating Wnt/β-catenin signaling. These findings indicate that targeting UBE2T has promising potential to overcome TMZ resistance of GBM.Keywords: glioblastoma, temozolomide, drug resistance, UBE2T, Wnt/β-catenin

Renjie Wu,1– 3,&ast; Luchao Lv,1– 3,&ast; Chengzhen Wang,1– 3 Guolong Gao,1– 3 Kaiyang Yu,1– 3 Zhongpeng Cai,1– 3 Yiyun Liu,1– 3 Jun Yang,1– 3 Jian-Hua Liu1– 4 1Key Laboratory of Zoonosis of Ministry of Agricultural and Rural Affairs, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China; 3National Risk Assessment Laboratory for Antimicrobial Resistance of Microorganisms in Animal, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China; 4Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Hua Liu, College of Veterinary Medicine, South China Agricultural University, Wushan Road 483, Guangzhou, 510642, People’s Republic of China, Email jhliu@scau.edu.cnPurpose: The objective of this study was to elucidate the characteristics and mechanism of formation of the fusion plasmid pHNSHP24 carrying mcr-1.1.Materials and Methods: mcr-1.1-bearing Escherichia coli SHP24 and the corresponding transconjugant were subjected to whole-genome sequencing (WGS) combining the Illumina and MinION platforms to obtain the complete sequences of the fusion plasmid and its original plasmids.Results: Complete sequence analysis and S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) results indicated that E. coli SHP24 carried four plasmids: mcr-1.1-harboring phage-like plasmid pHNSHP24-3, F53:A-:B- plasmid pHNSHP24-4, pHNSHP24-1, and pHNSHP24-2. However, the plasmid pHNSHP24 carrying mcr-1.1 presents in the transconjugant differed from the four plasmids in the donor strain SHP24. Further analysis showed that pHNSHP24 may be the fusion product of pHNSHP24-3 and pHNSHP24-4 and is formed through a replicative transposition mechanism mediated by IS 26 in E. coli SHP24.Conclusion: This study is the first to report the fusion of an mcr-1.1-harboring phage-like pO111 plasmid and an F53:A-:B- plasmid mediated by IS 26. Our findings revealed the role of phage-like and fusion plasmids in the dissemination of mcr-1.1.Keywords: fusion plasmid, mcr-1.1, IS 26, pO111 plasmid

Jichan Shi,1,&ast; Gexin Gao,2,&ast; Zhijie Yu,3,&ast; 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&ast;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

Qun Li,1,2,&ast; Meiling Chen,2,3 Hongxin Zhao,1,2 Fengting Yu,2,4 Liting Yan,1,2 Jiang Xiao,1,2 Guiju Gao,1,2 Di Yang,1,2 Fujie Zhang1,2,&ast; 1Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3The Medical Statistic Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fujie ZhangClinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaTel +86 10 84322581Email treatment@chinaaids.cnBackground: Whether intermittent low-level viremia (iLLV/blip) or persistent low-level viremia (pLLV) increases the risk of virologic failure (VF) in HIV-1 patients is controversial. The objective of this study was to investigate the incidence of blip/pLLV and the association between blip/pLLV and VF in a Chinese antiretroviral therapy cohort.Methods: HIV-1 patients who underwent antiretroviral therapy (ART) from 2005 to 2018 and had at least two viral load (VL) measurements after a minimum of 6 months ART treatment were included. VF was defined as one or more VL measurements of ≥ 1000 copies/mL. Blip was described as an isolated VL measurement between 50 and 999 copies/mL, and pLLV was defined as two or more consecutive VL measurements between 50 and 999 copies/mL. Blip and pLLV were categorized separately into three groups: 50– 200, 201– 400 and 401– 999 copies/mL. The Cox proportional hazard model was used to explore the association between blip/pLLV and VF.Results: In total, 8098 participants were enrolled in this long-term cohort study. A 94.3% of the participants were male and among which 77.3% were infected through homosexual transmission. Blip occurred in 4.0% (325/8098) of the patients with an incidence of 0.73 per 100 person-years (/100 PYS) of follow-up (95% CI: 0.71– 0.76), whereas pLLV occurred in 1.3% of the patients (102/8098) with an incidence of 0.23/100 PYS of follow-up (95% CI: 0.21– 0.25). All the three categories of pLLV were associated with VF: pLLV 50– 200 [aHR: 3.82 (1.95– 7.47)], pLLV 201– 400 [aHR: 5.36 (2.35– 12.22)] and pLLV 401– 999 [aHR: 13.51 (8.28– 22.02)]. However, blip is not significantly associated with VF in any category.Conclusion: Our study suggested that patients with pLLV had an increased risk of subsequent VF. Therefore, if pLLV occurs in patients, monitoring and corresponding measurements must be strengthened to avoid the subsequent VF.Keywords: HIV-1, blip, persistent low-level viremia, virologic failure

Guangyu Gao &ast;, Xinya Shi, Jiaofeng Shen &#x002ADepartment of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiaofeng ShenDepartment of Oncology, The Second Affiliated Hospital of Soochow University, 1055, Sanxiang Road, Suzhou, 215004, Jiangsu, People’s Republic of ChinaEmail jfshenzz@163.comBackground: Lymph node metastasis is a major cause of cancer-related death in patients with colorectal cancer (CRC), but current strategies are limited to predicting this clinical behavior. Our study aims to establish a lymph node metastasis prediction model based on miRNA and mRNA to improve the accuracy of prediction.Methods: GSE56350, GSE70574, and GSE95109 were downloaded from the Gene Expression Omnibus (GEO) database and 569 colorectal cancer statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs were calculated by using R software. Besides, gene ontology and enriched pathway analysis of target mRNAs were analyzed by using FunRich. Furthermore, the mRNA–miRNA network was constructed using Cytoscape software. Gene expression level was also detected by performing qRT-PCR (quantitative real-time PCR) in colorectal cancer and lymph node tissues.Results: In total, 5 differentially expressed miRNAs were selected, and 34 mRNAs were identified after filtering. The research of KEGG indicated that mRNAs are enriched in many cancer pathways. Differentially expressed miRNAs were most enriched in the cytoplasm, nucleoside, transcription factor activity, and RNA binding. KEGG pathway analysis of these target genes was mainly enriched in 5 pathways including fatty acid elongation, MAPK signaling pathway, autophagy, signaling pathways regulating pluripotency of stem cells, and Th17 cell differentiation. The results of qRT-PCR indicated that hsa-miR-100 and hsa-miR-99a were differentially expressed in lymph node metastatic colorectal cancer tissues and lymph node non-metastasis tissues which all target HS3ST2. Besides, we also found they have a significant difference in colorectal cancer tissues compared with normal tissues.Conclusion: By using microarray and bioinformatics analyses, differentially expressed miRNAs were identified and a complete gene network was constructed. To our knowledge, HS3ST2 and related molecules including hsa-miR-100 and hsa-miR-99a were firstly identified as potential biomarkers in the development of lymph node metastatic colorectal cancer.Keywords: microRNA, colorectal cancer, lymph node metastasis, prognostic signature

Yin-gang Wu,1,2 Yingjiu Chao,1 Ge Gao,1 Dejun Bao,1 Yongfei Dong,1 Xiangpin Wei,1 Chaoshi Niu1,2 1Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China; 2Brain Function and Brain Disease Anhui Provincial Key Laboratory, Hefei, Anhui, 230001, People’s Republic of ChinaCorrespondence: Chaoshi NiuDepartment of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of ChinaTel +86 18963788788Email niuchaoshi@126.comPurpose: Posttraumatic cerebral infarction (PTCI) is a common and relatively serious complication of traumatic brain injury (TBI) without a clear etiology. Evaluating risk factors in advance is particularly important to predict and avoid the occurrence of PTCI.Patients and Methods: We retrospectively analyzed 297 patients with moderate to severe TBI admitted to the Department of Neurosurgery in our hospital from January 2019 to September 2020 and evaluated the effects of various factors such as age, sex, admission Glasgow Coma Scale (GCS), skull base fracture, subarachnoid hemorrhage (SAH), brain herniation, hypotensive shock, and decompressive craniectomy on the incidence of PTCI. We also performed a multivariate logistics regression analysis on the relevant factors identified and evaluated the diagnostic value of each risk factor in advance by receiver operating characteristic (ROC) analyses.Results: Among the patients, 32 (10.77%) suffered PTCI. The incidence rates of PTCI in those with GCS scores of 3– 8 and 9– 12 were 15.87% (30/189) and 1.85% (2/108), respectively, while the rates were 18.84% (13/69), 15.03% (29/193), 18.57% (13/70), and 20.59% (14/68) in those with skull base fractures, traumatic SAH, brain herniation, and hypotensive shock, respectively, and 14.38% (23/160) in those who underwent decompressive craniectomy. These differences in PTCI incidence were statistically significant. However, the differences in PTCI incidence caused by patient age and sex were not statistically significant.Conclusion: Low GCS score, skull base fractures, traumatic SAH, brain herniation, hypotensive shock, and decompressive craniectomy are risk factors for the occurrence of PTCI, while age and sex are not significantly correlated with the occurrence of PTCI.Keywords: moderate or severe traumatic brain injury, posttraumatic cerebral infarction, risk factor

The gas-solid-based synergistic reduction of pellets is an innovative and effective method for iron ore smelting. With the development and utilization of iron resources, ore reserves have been greatly depleted; therefore, as a scarce mineral resource, the comprehensive utilization of limonite has become increasingly important. To study the reduction kinetics of pellets in depth, this study used coke and reducing gases (CO and H2) to study the reduction characteristics and changes occurring in carbon-containing limonite pellets. The results showed that the total weight loss percentage of pellets gradually increased with the temperature. The C/O molar ratio had a greater effect on the total weight loss percentage of pellets in a N2 atmosphere, but it had no significant effect in CO or H2 atmospheres. The maximum reaction rate increased with increasing temperature. The reduction reaction was the most difficult to proceed in the N2 atmosphere, and the reaction was most likely to occur in the CO atmosphere. The analysis of pellets by EPMA and XRD found that the pellets reduced in the N2 atmosphere had the lowest porosity, and the pellets reduced in the H2 atmosphere had the highest porosity, which was more conducive to gas diffusion. Some of the unreduced Si, Al, Mn, Ca, and Fe in the pellets reduced in the N2 atmosphere precipitated in the form of oxides, but when a reducing gas (CO, H2) was introduced, precipitation did not occur.

Dandan Zheng,1,2,* Chengwei Jiang,3,* Ning Yan,2 Yayun Miao,2 Keren Wang,2 Ge Gao,3 Yan Jiao,4 Xiangkai Zhang,2 Miao He,5 Zhaoying Yang2 1Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, People’s Republic of China; 2Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 3Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 5Department of Anesthesia, The Second Hospital of Jilin University, Changchun, Jilin 130022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Miao HeDepartment of Anesthesia, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, Jilin 130022, People’s Republic of ChinaEmail hemiao@jlu.edu.cnZhaoying YangDepartment of Breast Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, People’s Republic of ChinaEmail zyyang@jlu.edu.cnBackground: Wntless (Wls) is an essential protein that is necessary for the secretion of Wnt proteins. While numerous researches have demonstrated that aberrations in Wnt/β-catenin expression lead to tumorigenesis and progression in many cancer types, the effects of Wls in breast cancer (BC) are less studied.Methods: The mRNA and protein expression of Wls in BC cell lines were detected by RT-qPCR and Western blot; the protein expression of patient samples was detected by immunohistochemistry (IHC). The associations between Wls expression and clinicopathological factors as well as survival time, including overall survival (OS) and disease-free survival (DFS) were analyzed. Bioinformatics analysis was used to reveal the correlation between Wls genes and associated genes or pathways.Results: Wls was overexpressed in BC cell lines and tissues. The expression level of Wls was significantly correlated with tumor size, estrogen receptor (ER), progesterone receptor (PR), Ki-67, molecular classification, and follow-up status. Spearman correlation analysis showed that Wls protein expression was negatively correlated with ER and PR, which was confirmed by bioinformatics analysis in mRNA level. However, there were positive relationships with MBNG (modified Black’s nuclear grade), tumor size, Ki-67, molecular classification, follow-up, and vital status. Univariate and multivariate analysis showed that Wls was an independent prognostic factor for OS and DFS in BC patients. Moreover, Wls was a significant prognostic indicator of OS and DFS in a hormone receptor-positive (HR+) subgroup. GSEA showed that estrogen and androgen response, as well as epithelial-mesenchymal transition pathways, were up-regulated in the Wls high-expression group.Conclusion: Overexpression of Wls is a significant marker of worse prognosis in BC and might play a crucial role in the HR+ subgroup.Keywords: wntless, estrogen receptor, progesterone receptor, androgen receptor, breast cancer, prognosis

Chenglong Sun,1,2,* Fei Zhou,3,* Xuefei Li,4 Chao Zhao,4 Wei Li,3 Jiayu Li,3 Anwen Xiong,3 Jia Yu,3 Guanghui Gao,3 Qi Wang,3 Fengying Wu,3 Caicun Zhou3 1Radiotherapy Department, Anhui No. 2 Provincial People’s Hospital, Hefei 230041, Anhui, People’s Republic of China; 2Medical College of Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 4Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengying Wu; Caicun ZhouDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel +086 13167060870; +086 13301825532Email fywu@163.com; caicunzhoudr@126.comIntroduction: Immune checkpoint inhibitor (ICI) monotherapy has limited efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs). With the wide use of ICI-based combinations, the efficacy of different ICI combination strategies in patients with NSCLC and BMs needs to be further elucidated.Methods: We retrospectively reviewed 526 patients with non-small cell lung cancer (NSCLC) treated with ICIs from January 2016 to December 2019 in the Shanghai Pulmonary Hospital. Patients with BMs treated with ICIs were further divided into two groups: those with BM prior to the ICI treatment (pBM group), and those with BM after the treatment (aBM group). We assessed intracranial progression-free survival (IPFS), systemic progression-free survival (SPFS), overall survival (OS), intracranial objective response rate (IORR), and intracranial disease control rate (IDCR).Results: We found 77 patients out of 526 with BMs; 69 presented the BMs prior to the ICI treatments and 8 showed BMs after the ICI treatments. In the pBM group, the median IPFS and SPFS were 7.39 months and 5.39 months, respectively. Combination therapy significantly improved both the IPFS (p=0.007) and the SPFS (p=0.007) when compared with monotherapy. Further analysis demonstrated that ICIs combined with chemotherapy significantly improved both the IPFS (p=0.009) and the SPFS (p=0.006) when compared with monotherapy. While ICIs combined with anti-angiogenic therapy improved the SPFS (p=0.005) but not the IPFS (p=0.139). The median OS was 27.43 months for patients in the pBM group. Further analyses suggested that combination treatment also improved the OS when compared with monotherapy (p=0.003). Subgroup analysis results showed that ICIs combined with chemotherapy led to better OS than ICIs monotherapy (p=0.006). Radiotherapy had no significant impact on survival (IPFS p=0.272, OS p=0.142) in the patients of the pBM group.Conclusion: ICIs combined with chemotherapy demonstrated survival benefits over ICI monotherapy in patients with NSCLCs and BMs.Keywords: NSCLC, immune checkpoint inhibitors, brain metastases, survival, chemotherapy, anti-angiogenesis

Gao G, Shi X, Shen J. Onco Targets Ther. 2021;14:3881—3894. At the authors request, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. The first author (Gao G) has informed the journal that they the published the same article (https://doi.org/10.1186/s12935-021-02058-9) with the journal, Cancer Cell International, without notifying either journal of the dual submission. The author (Gao G) has acknowledged that he used the same or highly similar data from the original manuscript that was used for the article published in Cancer Cell International without the consent of his co-authors. The submission was then made to OncoTargets and Therapy after altering the author list without the knowledge of his co-authors. The Editor has agreed to the authors request to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Ruiqi Wu,* Guanying Gao,* Yan Xu Department of Sports Medicine, Peking University Third Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Xu Tel +86 13701130401Email yanxu@139.comPurpose: Developmental dysplasia of the hip (DDH) can increase the pressure between the joints, which causes secondary hip osteoarthritis. The aim of the present study was to fabricate poly(D, L-lactic acid)-poly(ethylene glycol)-poly(D, L-lactic acid) (PELA) electrospun fibrous scaffolds, immobilized with bone morphogenetic protein-2 (BMP-2), to repair the acetabulum defects.Methods: The characteristics of PELA electrospun were analyzed using scanning electron microscopy, the release kinetics of BMP-2 in vitro were analyzed using enzyme-linked immunosorbent assays. Human mesenchymal stem cells (hMSCs) were used for in vitro experiments, the biocompatibility of the electrospinning materials was investigated using a cell counting kit-8 (CCK-8) kit, and osteogenic differentiation was tested via alkaline phosphatase (ALP) activity and relative gene expression. Eighteen miniature pig animal models were used in the in vivo experiment. The pigs were sacrificed at 24 weeks after surgery, and the reconstructed acetabulum was evaluated using histological sections.Results: Structural analysis revealed that the diameter of the PELA electrospun fiber was 0.8195 ± 0.16 μm. The PELA electrospun fiber materials showed good hydrophilicity and biocompatibility and could continuously release BMP-2 within 27 days: 16.07 ± 0.11 ng of BMP-2 was released from the scaffold. A total of sixteen implants fully filled the defects, and hematoxylin and eosin staining and Goldner’s trichrome staining showed that the simple tendon group (T group) was mostly fibrous tissues, lots of fibroblasts and small amounts of chondrocytes were observed in the polydopamine-coated electrospun fiber group (DP group). The DP plus BMP-2 (DPB) group showed a large number of chondrocytes and partial new bone tissues.Conclusion: PELA electrospun fibrous scaffolds are good sustained-release carriers, which can not only induce implant differentiation into cartilage and bone but also are completely degraded without toxicity. Therefore, the material can be used for bone and cartilage regeneration.Keywords: electrospun fibers, acetabulum reconstruction, bone marrow stem cells, osteogenic growth factor

Peng Xue,1 Ziyu Wu,2 Kunpen Wang,1 Guojun Gao,3 Min Zhuang,4 Miao Yan4 1Department of Urology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China; 2Department of Urology, NO 2 Hospital of Huaian, Huaian, Jiangsu Province, People’s Republic of China; 3Department of Urology, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong Province, People’s Republic of China; 4Department of Oncology, First People Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of ChinaCorrespondence: Miao YanDepartment of Oncology, First People Hospital of Lianyungang, Zhenghua Road 6, Lianyungang, Jiangsu Province 222002, People’s Republic of ChinaTel +86051885605016Email yanmiao_ym@126.comBackground: The current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa).Methods: We reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan–Meier method.Results: The median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥ 20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥ 0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1– 4 (HR=0.228; 95% CI= 0.056– 0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade > 2 adverse events were observed.Conclusion: This multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.Keywords: oligometastases, prostate cancer, stereotactic body radiotherapy, androgen deprivation therapy, radical prostatectomy, metastasis-directed therapy

Yong Yang, Ge Gao, Jun Shi, Jiangnan Zhang Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of ChinaCorrespondence: Ge Gao; Jiangnan ZhangDepartment of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang City, Jiangxi Province, People’s Republic of ChinaTel +86 15279133591; +86 13607042729Email gaoge6116@126.com; zjnss@sina.comBackground: Hyperlipidaemia is related to the development of many cancers. The aim of this study was to explore whether blood lipid levels were associated with increased rates of cancer-specific mortality and all-cause mortality in patients with colorectal cancer (CRC).Methods: Data on 8504 participants from The Irish Longitudinal Study on Ageing (TILDA) were analysed. A total of 304 participants with CRC who had experienced curative surgery were included. Logistic regression analysis was performed to analyse the relationship between blood lipid levels and CRC severity. Cox regression analysis was performed to assess the association between blood lipid levels and cancer-specific mortality and all-cause mortality in patients with CRC.Results: In 304 patients with CRC, the average age was 67.8± 5.4 years. The logistic regression analysis indicated that elevated levels of total cholesterol (2.104 [1.358– 3.650]; P-trend< 0.001), triglycerides (1.665 [1.337– 2.076]; P-trend=0.005) and LDL (2.127 [1.446– 4.099]; P-trend< 0.001) but not HDL (0.688 [0.409– 1.252]; P-trend=0.124) were associated with an increased risk of higher CRC stage after adjustments were made for age, sex, marital status, BMI, drinking status, smoking status, education, physical activity, antilipidaemic medications and self-reported CVDs (≥ 2). Cox proportional hazard analysis showed that higher blood lipid levels of total cholesterol, triglycerides and LDL were independently associated with higher rates of cancer-specific mortality and all-cause mortality. Similar results persisted in the sensitivity analysis using antilipidaemic medications as an additional covariate and the stratification analysis using antilipidaemic medications as a stratified variable.Conclusion: Increased blood lipid levels were associated with an increased risk of cancer-specific mortality and all-cause mortality in patients with CRC after adjusting for potential confounding factors. Clinicians should pay more attention to the prognostic value of increased blood lipids in patients with CRC for the risk of death.Keywords: blood lipids, colorectal cancer, cancer-specific mortality, all-cause mortality, prognostic value

Lan Yu,1 Hui Li,2 Zhiying Li,1 Jianchao Jia,1 Zhouying Wu,1 Min Wang,1 Feng Li,1 Zongqi Feng,1 Huilin Xia,3 Guanxin Gao3 1Clinical Medical Research Center, Inner Mongolia People’s Hospital, Hohhot 010017, People’s Republic of China; 2Department of Oncology, Inner Mongolia People’s Hospital, Hohhot 010017, People’s Republic of China; 3Medical Engineering Department, Inner Mongolia People’s Hospital, Hohhot 010017, People’s Republic of ChinaCorrespondence: Huilin Xia; Guanxin GaoMedical Engineering Department, Inner Mongolia People’s Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, People’s Republic of ChinaEmail nmyyxhl@163.com; 840868023@qq.comIntroduction: Long non-coding RNAs (lncRNAs) are regarded as crucial regulators for cancer initiation and progression. Heart and Neural Crest Derivatives Expressed 2 antisense RNA 1 (HAND2-AS1) was recently proposed to function as tumor suppressor in several human cancers. However, its role in gastric cancer (GC) remains unclear.Methods: HAND2-AS1 expression in GC tissues and normal tissues was analyzed at GEPIA (a web server for gene expression profiling analysis). Moreover, RT-qPCR method was utilized to explore HAND2-AS1 expression in GC cells and normal cell. In vitro experiments were carried out using cell counting kit-8 assay, colony formation assay, and flow cytometry assay, respectively. Bioinformatic analysis and luciferase activity reporter assay were performed to identify the downstream targets of HAND2-AS1.Results: We found HAND2-AS1 has decreased expression in both GC tissues and cells. Overexpression of HAND2-AS1 was able to inhibit GC cell proliferation, colony formation, but promote apoptosis. On the contrary, knockdown of HAND2-AS1 could cause the opposite effects on GC cells. Furthermore, HAND2-AS1 was shown to function as a competitive RNA that binds with microRNA-590-3p (miR-590-3p) to affect the expression of potassium sodium-activated channel subfamily T member 2 (KCNT2).Discussion: Our results indicated the tumor suppressive role of HAND2-AS1 in GC. Also, the newly identified HAND2-AS1/miR-590-3p/KCNT2 axis will help us to understand the role of HAND2-AS1 in cancer.Keywords: HAND2-AS1, miR-590-3p, KCNT2, gastric cancer

Ge Gao,1,* Dianhui Xiu,2,* Bin Yang,3 Daju Sun,1 Xin Wei,4 Youpeng Ding,4 Yanan Ma,4 Zhixin Wang4 1Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 2Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 3Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China; 4Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China *These authors contributed equally to this work Background: Prostate cancer is one of the most commonly diagnosed diseases in males. Methods: RT-qPCR was used to detect miR-129-5p expression in tumor tissues and adjacent normal tissues from patients with prostate cancer. The cell proliferation assay and colony forming assay were used to study the role of miR-129-5p in mediating prostate cancer cell growth. Bioinformatic analysis and dual luciferase assay were performed to predict and confirm ETV1 as a target gene of miR-129-5p. Results: We found that miR-129-5p levels were decreased significantly in human prostate cancer tissues compared with matched normal tissues from patients with prostate cancer. Overexpression of miR-129-5p suppressed prostate cancer cell growth while antagonist of miR-129-5p promoted cell proliferation in immortal prostate cell line RWPE-1. In addition, elevation of miR-129-5p decreased ETV1 expression in prostate cancer cells while downregulation of miR-129-5p increased ETV1 expression in RWPE-1. Mechanistically, ETV1 is confirmed a direct target of miR-129-5p in prostate cancer cells. Through repression of ETV1 expression, miR-129-5p could inactivate YAP signaling in prostate cancer cells. In addition, overexpression of ETV1 attenuated miR-129-5p induced cell proliferation in prostate cancer cells. Correlation analysis further revealed that there was a negative correlation between miR-129-5p levels and ETV1 mRNA levels in tumor tissues from patients with prostate cancer. Conclusion: Our results identified miR-129-5p as a tumor suppressor in prostate cancer via repression of ETV1. Keywords: microRNA, prostate cancer, ETV1, proliferation

Yang Yang,1,* Shengru Liang,2,* Yuqian Li,1,* Fei Gao,1 Yuan Cao,3 Xiaoyu Zhao,4 Guodong Gao,1 Lihong Li1 1Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710038, China; 2Department of Endocrinology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 3Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province 710032, China; 4Department of Neurosurgery, The 986th Hospital of Chinese People’s Libertation Army, Xi’an, Shaanxi Province 710054, China *These authors contributed equally to this work Background: Both protective and therapeutic functions of insulin-like growth factor-1 (IGF-1) in brain injury have been reported, but its effects on cognitive sequelae after septic encephalopathy (SE) remain unclear.Materials and methods: This study was divided into three parts, and a septic model was built by cecal ligation and puncture (CLP). First, survival analysis was performed, and IGF-1’s effects on long-term cognition and depressive emotion were assessed. Second, the characteristics of IGF-1 function in cognition were evaluated. Finally, cytochrome C, caspase-9, tumor necrosis factor receptor (TNFR), and caspase-8 levels as well as cell apoptosis in the hippocampus were evaluated.Results: IGF-1 did not reduce mortality or alleviate depressive symptoms in septic rats, but improved the memory of noxious stimulation and spatial learning and memory. These effects were observed only when IGF-1 was administered within 0–6 hours after CLP. Moreover, cytochrome C and caspase-9 expression levels were increased at 6 hours after CLP in the hippocampus, while TNFR and caspase-8 amounts were not increased until 12 hours after CLP. Cell apoptosis increased at 12 hours after CLP, but was inhibited by IGF-1.Conclusion: Cognitive impairment in rats recovering from SE is associated with cell apoptosis in the hippocampus. Supplementation of IGF-1 reduces cell apoptosis by preventing the over-expression of cytochrome C and TNFR, and results in improved cognitive function. However, improvement only occurs when IGF-1 is administered at the early stage (within 6 hours) of sepsis. As cytochrome C activation occurs earlier than that of TNFR in this study, cytochrome C may be the main factor inducing apoptosis in early SE. Keywords: septic encephalopy, memory, learning, IGF-1, cytochrome C, TNFR, apoptosis

Yu L, Li H, Li Z, et al. Onco Targets Ther. 2020;13:3187–3196. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2D and 3D with similar images from an unrelated article, specifically: Figure 2D, panels pcDNA3.1 and pHAND2-AS1 appear to have been duplicated with similar images in Figure 5C from Kang et al, 2019 (https://doi.org/10.2147/OTT.S204004). Figure 3D, panels si-NC and si-HAND2-AS1 appear to have been duplicated with similar images in Figure 5C from Kang et al, 2019 (https://doi.org/10.2147/OTT.S204004). The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Guozhen Gao,1,* Wenjun Li,2,* Sha Liu,1,* Dongmei Han,1 Xingwei Yao,1 Juanjuan Jin,1 Dezhi Han,1 Weijing Sun,1 Xiangjun Chen1 1Department of Burn and Plastic Surgery, The 253rd Hospital of PLA, Hohhot, Inner Mongolia 010051, China; 2Department of Cardio and Nephrology, The 253rd Hospital of PLA, Hohhot, Inner Mongolia 010051, China *These authors contributed equally to this work Purpose: In our previous study, we identified that lncRNA ILF3 antisense RNA 1 (ILF3-AS1) is increased and has oncogenic roles in melanoma. However, the cause of the upregulation of ILF3-AS1 and the modulation between ILF3-AS1 and ILF3 in melanoma are still unknown. This study aimed to investigate the significances of the interaction between ILF3-AS1 and ILF3 in melanoma.Materials and methods: The expression of ILF3 in melanoma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR). The interactions between ILF3-AS1 and ILF3 were explored by the RNA immunoprecipitation assay, the transcription inhibition assay, qRT-PCR, the chromatin immunoprecipitation assay, and Western blot. Gain-of-function and loss-of-function assays were performed to investigate the effects of ILF3 and ILF3-AS1 on melanoma proliferation, migration, and invasion.Results: ILF3 is also increased in melanoma tissues and cell lines. Increased expression of ILF3 predicts poor survival of melanoma patients. Mechanistic investigation revealed that ILF3 directly binds ILF3-AS1, increases ILF3-AS1 transcript stability, and upregulates ILF3-AS1 transcript levels. ILF3-AS1 represses the binding of EZH2 to the promoter of ILF3, induces euchromatin formation at ILF3 promoter, and activates ILF3 transcription. Thus, ILF3 and ILF3-AS1 form positive feedback loop, which induces the upregulation of ILF3 and ILF3-AS1 in melanoma. The expression of ILF3-AS1 is positively correlated with ILF3 in melanoma tissues. Functional assays revealed that overexpression of ILF3 promotes melanoma proliferation, migration, and invasion. Depletion of ILF3 inhibits melanoma proliferation, migration, and invasion. Moreover, concurrent depletion of ILF3 and ILF3-AS1 significantly suppresses melanoma proliferation, migration, and invasion.Conclusion: Both ILF3-AS1 and ILF3 are increased in melanoma. ILF3-AS1 and ILF3 positively regulate each other. Concurrent targeting ILF3-AS1 and ILF3 has significant tumor-suppressive roles in melanoma. Our data suggested that targeting the positive feedback loop between ILF3 and ILF3-AS1 may be promising therapeutic strategies for melanoma. Keywords: lncRNA, ILF3-AS1, feedback loop, ILF3, melanoma, progression

Yang Y, Gao G, Shi J, Zhang J. Risk Manag Healthc Policy. 2020;13:855–863. The Editor-in-chief and Publisher of Risk Management and Healthcare Policy wish to retract the published article. Following a review of the article by The Irish Longitudinal Study on Ageing (TILDA) investigation team, it was found the numbers reported in the study with colorectal cancer to be inaccurate, with a sample far higher than that reported with colorectal cancer in the TILDA public archive. Thus, the observations and findings reported in the study were not supported by the TILDA dataset. Despite several attempts, the authors could not be contacted for an explanation and the decision was made to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Guangwei Gao,* Ying Yao,* Kun Li, Dhahiri Saidi Mashausi, Dongsheng Li, Hema Negi, Suchitra Kamle, Hao Chen, Zhenghua Wu, Huchen Zhou, Dawei Li School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Several aminoacyl-tRNA synthetases have been reported to be overexpressed for charging essential aminoacyl-tRNAs in many cancer types. In this study, we aimed to explore the potential role of leucyl-tRNA synthetase (LARS) as an anticancer target. MTT assay was performed to screen inhibitors to human LARS (hsLARS) from compounds AN2690 and its derivatives, compounds 1–6, in U2OS and SKOV3 cells. The compound with the strongest inhibitory ability was further investigated for its inhibitory effect in cancer cell lines and in an animal tumor model. Additionally, a LARS-rescue experiment was performed to explore the potential target in U2OS using Western blot and flow cytometry. Luciferase reporter assay was designed to analyze the effect of of hsLARS inhibitor on p21 activation. We identified an hsLARS inhibitor (compound 2) that suppressed the proliferation of U2OS and SKOV3 cells in vitro. A LARS-rescue experiment demonstrated that the proliferation inhibition was induced by targeting intracellular LARS. In addition, the hsLARS inhibition was shown to activate the p21 early transcription and promote cell apoptosis, as well as reduce implanted EMT6 tumor progression in mice. Our results suggest that LARS might serve as a potential anticancer target through the p21 signaling pathway and that the nutritional signaling pathway may provide a valuable anticancer strategy for further investigation. Keywords: leucyl-tRNA synthetase, apoptosis, mouse model, anticancer target

Lingling Shan,1 Ming Liu,2 Chao Wu,1 Liang Zhao,1 Siwen Li,3 Lisheng Xu,1 Wengen Cao,1 Guizhen Gao,1 Yueqing Gu3 1Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, People’s Republic of China; 2Department of Biology, University of South Dakota, Vermillion, SD, USA; 3Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX) as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6)-isothiocyanate-arginine-paclitaxel (FA-FITC-Arg-PTX) and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu-PTX), composed of folic acid (FA, target), amino acids (Arg or Glu, linker), and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo) in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. Keywords: multi-small molecules, paclitaxel, prodrugs, targeting, tumor therapy

Junxia Zhang,1,* Qiang Zhou,2,* Ge Gao,3,* Yanfen Wang,1 Zhihui Fang,1 Guanlin Li,4 Mengfei Yu,5 Lingfei Kong,6 Ying Xing,3 Xiaoqun Gao11Department of Anatomy, Basic Medical College, Zhengzhou University, Henan, People’s Republic of China; 2Department of Pathology, Children’s Hospital of Zhengzhou City, Henan, People’s Republic of China; 3Department of Physiology, Basic Medical College, Zhengzhou University, Henan, People’s Republic of China; 4Department of Laboratory, The First Affiliated Hospital of Zhengzhou University, Henan, People’s Republic of China; 5Department of Pharmacy, Zhengzhou Central Hospital, Zhengzhou University, Henan, People’s Republic of China; 6Department of Pathology, Henan Provincial People’s Hospital, Henan, People’s Republic of China *These authors contributed equally to this workAbstract: Glioblastoma is one of the most common malignant tumors in the nervous system in both adult and pediatric patients. Studies suggest that abnormal activation of receptor tyrosine kinases contributes to pathological development of glioblastoma. However, current therapies targeting tyrosine kinase receptors have poor therapeutic outcomes. Here, we examined anticancer effects of ponatinib, a multi-targeted tyrosine kinase inhibitor, on glioblastoma cells both in the U87MG cell line and in the mouse xenograft model. We showed that ponatinib treatment reduced cell viability and induced cell apoptosis in a dose-dependent manner in U87MG cells. In addition, ponatinib suppressed migration and invasion of U87MG cells effectively. Furthermore, ponatinib-treated tumors showed an obvious reduction of tumor volume and an increase of apoptosis as compared with vehicle-treated tumors in the mouse xenograft model. These findings support a potential application of ponatinib as a chemotherapeutic option against glioblastoma cells.Keywords: cancer therapy, glioma, glioblastoma multiforme

Yi Xia Zhang1, Jun Zheng2, Guo Gao1, Yi Fei Kong1, Xiao Zhi1, Kan Wang1, Xue Qing Zhang1, Da Xiang Cui11Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 2Wheat Research Institute, Academy of Agricultural Sciences, Linfen, Shan Xi, People's Republic of ChinaAbstract: In this paper, a new method of one-pot biosynthesizing of gold nanoparticles (GNPs), using chloroplasts as reductants and stabilizers is reported. The as-prepared GNPs were characterized by ultraviolet visible spectroscopy, transmission electron microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy (FTIR). The cytotoxicity of the GNPs was evaluated using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against gastric mucous cell line GES-1 and gastric cancer cell line MGC-803. Rhodamine 6G as a Raman probe was used for investigating surface-enhanced Raman spectroscopy (SERS) enhancement of GNPs. The transmission electron microscopy results indicated that the GNPs were spherical in structure and almost 20 nm in diameter. Ultraviolet visible spectroscopy exhibited an absorption peak at 545 nm. The GNPs exhibited high crystallinity, with the (111) plane as the predominant orientation, clarified by X-ray powder diffraction. In addition, a potential mechanism was proposed to interpret the formation process of GNPs, mainly based on the analysis of FTIR results. The FTIR spectrum confirmed that the GNPs were carried with N–H groups. Toxicological assays of as-prepared GNPs revealed that the green GNPs were nontoxic. SERS analysis revealed that the GNPs without any treatment could substantially enhance the Raman signals of rhodamine 6G. The Raman enhancement factor was calculated to be nearly 1010 orders of magnitude. In conclusion, the GNPs with good biocompatibility and excellent SERS effect were successfully synthesized using chloroplasts. These biogenetic GNPs have great potential for ultrasensitive detection of biomarkers in vitro and in vivo based on SERS.Keywords: green synthesis, room temperature, gold nanospheres, MTT, SERS

We selected the submerged macrophyte Vallisneria natans (Lour.) Hara for investigating the effects of nutrient loadings (nitrogen (N)-phosphorus (P) in mg·L-1: (1) 0.5, 0.05; (2) 1.0, 0.1; (3) 5.0, 0.5; (4) 10.0, 1.0) on root physiological characteristics using sand culture during the growth season (June to October). Results showed that the best root growth was in macrophytes exposed to moderate nutrient conditions (N-P 2, in 1.0 and 0.10 mg· L-1), and high nutrient loadings induced declines in root growth. Analysis of root antioxidant enzyme (superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT)) activities, protein content and cell ultrastructure revealed that the root of V. natans was subject to the stress of senescence during the end of the growth season. Moreover, high nutrient loadings increased oxidative stress in aging roots of V. natans, and made the cell ultrastructure of roots vulnerable to damage during senescence. The results for the changes in CAT activity suggest that CAT can serve as an important component of antioxidant defense mechanism in aging roots of V. natans to protect against nutrient loading induced oxidative injury in the early period.

The lithium-sulfur (Li-S) battery is one of the most promising substitutes for current energy storage systems because of its low cost, high theoretical capacity, and high energy density. However, the high solubility of intermediate products (i.e., lithium polysulfides) and the resultant shuttle effect lead to rapidly fading capacity and a low coulombic efficiency, which hinder the practical application of Li-S batteries. In this study, block copolymers are constructed with both an ethylene oxide unit and a styrene unit and then used as binders for Li-S batteries. Electrochemical performance improvements are attributed to the synergistic effects contributed by the different units of the block copolymer. The ethylene oxide unit traps polysulfide, which bonds strongly with the intermediate lithium polysulfide, and enhances the transport of lithium ions to reach high capacity. Meanwhile, the styrene unit maintains cathode integrity by improving the mechanical properties and elasticity of the constructed block copolymer to accommodate the large volume changes. By enabling multiple functions via different units in the polymer chain, high sulfur utilization is achieved, polysulfide diffusion is confined, and the shuttle effect is suppressed during the cycle life of Li-S batteries, as revealed by operando ultraviolet–visible spectroscopy and S K-edge X-ray absorption spectroscopy.