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Zhou Zhou,1– 3 Pei-Wen Zhu,3 Wen-Qing Shi,3 You-Lan Min,3 Qi Lin,3 Qian-Min Ge,3 Biao Li,3 Qing Yuan,3 Yi Shao3 1Institute of Pathogenic Biology, Medical College, University of South China, Hengyang 421001, Hunan, People’s Republic of China; 2Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, Hunan, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of ChinaCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Tel/ Fax +86 791-88692520Email freebee99@163.comPurpose: Brain function in patients with acute eye pain (EP) has not been extensively studied. An understanding of the alterations in short-range functional connectivity density (shortFCD) and long-range functional connectivity density (longFCD) in patients with EP remains elusive. The aim of the present study was to compare the functional connectivity density (FCD) between patients with EP and healthy controls (HCs) using resting-state functional connectivity.Methods: A total of 40 patients with EP (26 males and 14 females) and 40 HCs (26 males and 14 females) of similar age underwent functional magnetic resonance (MR) examination at the resting state. The shortFCD and longFCD values were compared using the one-sample t-test. The differences between patients with EP and the HCs were evaluated using receiver operating characteristic (ROC) curves.Results: In the patients with EP, significantly reduced shortFCD values were observed in the left posterior lobe of the cerebellum, right inferior parietal lobule, and left anterior lobe of the cerebellum, and significantly reduced longFCD values were observed in both the left and right posterior lobe of the cerebellum. Significantly increased shortFCD values were also observed in both superior frontal gyri (Brodmann area 6), and increased longFCD values were observed in the left inferior temporal gyrus and left superior frontal gyri (Brodmann area 11). Compared with the HCs, less reduction was noted among the shortFCD values of patients with EP in the right posterior lobe of the cerebellum, right supramarginal gyrus, left middle temporal gyrus, bilateral superior frontal gyri, and bilateral caudate nuclei.Conclusion: EP patients shown variation of binarized shortFCD and long FCD in brain areas including premotor cortex, ventral cortical visual system, newest part of the cerebellum, cerebellum control unconscious proprioception, inhibition of involuntary movement, somatosensory association cortex, nucleus involving reward system and ventral cortical visual system which might provide an explanation of brain functional compensation for chronic eye pain and visual impairment in the EP patients.Keywords: eye pain, magnetic resonance imaging, functional connectivity density

Yebei Qiu,1,2,* Xiaocheng Cao,1,2,* Lihua Liu,3,4 Xiaozheng Cao,3,4 Qing Yuan,5 Xiang Li,5 Yinghong Cui,1,5 Chang Xu,1,2 Chang Zou,4,6 Kaiqun Ren,1,2 Jianguo Cao1,2 1The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of China; 2The Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of China; 3Pharmacy Department, The Second Clinical Medical School of Jinan University, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China; 4Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China; 5Department of Preclinical Medicine, Medical College, Hunan Normal University, Changsha, Hunan 410013, People’s Republic of China; 6Clinical Medical Research Center, The Second Clinical Medical School of Jinan University, Shenzhen People’s Hospital, Shenzhen 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianguo Cao; Kaiqun RenKaiqun Ren the Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of ChinaTel +86-0731-88912434Email caojianguo2005@126.com; kaiqunren@126.comBackground: Manganese superoxide dismutase (MnSOD) induces FoxM1 expression, subsequently contributing to migration in several cancer cells. Isovitexin (ISOV) was recently found to downregulate MnSOD and FoxM1, decreasing stemness in hepatocellular carcinoma (HCC) stem-like cells (HCSLCs). The current study aimed to determine whether inhibition of migration, invasion and EMT in HCSLCs by ISOV results from MnSOD/FoxM1 signaling blockade and subsequent Twist1, Slug, ZEB1 and MMP-2 downregulation.Materials and Methods: We examined the migratory and invasive capabilities and EMT phenotype in HCC cells and their HCSLCs, respectively, by wound-healing assay, transwell invasion assay and Western blot after treatment with non-cytotoxic concentrations of ISOV, and explored the mechanism by which ISOV affects migration, invasion and EMT by MnSOD or FoxM1 knockdown and/or overexpression in HCSLCs or HCC cells.Results: The results showed that ISOV not only downregulated MnSOD and FoxM1 but also suppressed the migratory and invasive capabilities and reversed the EMT phenotype in HCSLCs, which was reflected by elevated E-cadherin protein amounts, and reduced N-cadherin, Twist1, Slug, ZEB1 and MMP-2 protein levels. The suppressive effects of ISOV on the migratory and invasive capabilities and EMT phenotype could be potentiated by MnSOD or FoxM1 knockdown in HCSLCs, and attenuated by MnSOD or FoxM1 overexpression in HCC cells. Importantly, FoxM1 overexpression reversed MnSOD knockdown combined with ISOV suppression on the migratory and invasive capabilities and EMT phenotype in HCSLCs, while having little effects on MnSOD expression.Conclusion: Collectively, the above findings demonstrated that ISOV suppresses migration, invasion and EMT in HCSLCs by blocking MnSOD/FoxM1 signaling subsequently inhibiting the expression of EMT-related transcription factors and MMP-2.Keywords: hepatocellular carcinoma, cancer stem cell, isovitexin, epithelial-mesenchymal transition, MnSOD, FoxM1, Twist1, MMP-2

Zhenli Min,1,2,* Yue Zhu,1,3,* Xing Hong,1 Zhijun Yu,1,2 Min Ye,1,2 Qiong Yuan,1,2 Xiamin Hu4 1Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan 430081, People’s Republic of China; 2New Medicine Innovation and Development Institute, College of Medicine, Wuhan University of Science and Technology, Wuhan 430081, People’s Republic of China; 3Stem Cell Lab, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430081, People’s Republic of China; 4College of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiamin Hu; Qiong Yuan Tel +862165883592; +86 27 68893640Email huxm@sumhs.edu.cn; yuanqiong@wust.edu.cnPurpose: The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities.Methods: Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound 7h exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis.Results: The IC50 value of 7h against SW620 cells was 12 nM, being more potent than curcumin (IC50 = 9.36 μM), adriamysin (IC50 = 3.28 μM) and oxaliplatin (IC50 = 13.33 μM). Further assays showed that 7h inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that 7h decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells.Conclusion: A new MCACs 7h was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that 7h exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that 7h was a promising candidate as an anti-colon cancer drug for future development.Keywords: 1, 5-diheteroarylpenta-1, 4-dien-3-one, colon cancer, cell proliferation, cell apoptosis, ATM gene

Jiduo Liu,* Yingchun Zhou,* Qing Yuan, Mingfeng Xiao Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingfeng Xiao Email beef168@163.comAbstract: Lineage switch is very rare in blastic crisis of chronic myeloid leukemia (CML-BC). Here, we report a case of CML-BC in which the blast lineage switched from myeloid to B-lymphoid. A 35-year-old male was initially admitted to our hospital because of abdominal distention for over a year and dizziness for one week. Prior to presentation at our hospital, he visited a local hospital because of abdominal distention where his white blood cell count and bone marrow (BM) smear indicated CML. Results from peripheral blood (PB) counts, bone marrow analysis, immunophenotyping by flow cytometry, and the detection of the Philadelphia chromosome were consistent with a diagnosis of myeloid blast crisis from CML. The patient received chemotherapy with imatinib for induction, which diminished the number of blasts. However, after three months, the blasts were increased in the PB and BM. The BM study and immunophenotyping by flow cytometry revealed B-lymphoblastic leukemia. In accordance with his first admission, a chromosome study revealed a karyotype of 46, XY, t(9; 22)(q34; q11) in all 20 cells analyzed, and B-lymphoblastic transformation from CML was diagnosed. Despite three months of treatment with DVCP (daunorubicin, vincristine, cyclophosphamide and prednisone) chemotherapy in combination with dasatinib, the patient did not achieve complete remission. The patient decided to stop treatment and was discharged from the hospital for financial reasons. This case implicates the Philadelphia chromosome with p210 BCR-ABL1 fusion proteins as a key molecule in CML-BC. Further research is needed to assess the frequency, treatment, and prognosis of CML-BC patients with lineage switch.Keywords: CML, myeloid blastic crisis, B-lymphoblastic transformation, Philadelphia chromosome, BCR-ABL1 fusion gene

Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of ChinaTel +86 1 861 137 7633Fax +86 1064286498Email dfguorongjuan@163.comPurpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrial

Qian-Min Ge,* Yu-Ting Zou,* Wen-Qing Shi, Yu-Qing Zhang, Biao Li, You-Lan Min, Qing Yuan, Yi Shao Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comObjective: At present, little is known regarding the specific risk factors of ocular metastasis (OM) in elderly patients with lung cancer. This study aimed to find out the risk factors of ocular metastasis.Methods: A total of 1615 elderly patients with lung cancer were recruited into this retrospective study between April 2001 and July 2016. These patients were divided into two groups, namely OM and non-ocular metastasis (NOM). Student’s t-tests, nonparametric rank sum tests, and Chi-square tests were applied to describe whether there were significant differences between the OM group and NOM group. We compared a range of serum biomarkers between the two groups of patients, including alkaline phosphatase, calcium, hemoglobin, alpha-fetoprotein, carcinoembryonic antigen, CA-125, CA-199, CA-153, CA-724, cytokeratin-19 fragment (CYFRA21-1), TPSA and neuron specific enolase (NSE). We used binary logistic regression analysis to determine the risk factors and receiver operating curve (ROC) analyses to assess the diagnostic value for OM in CRC patients.Results: The incidence of OM in elderly patients with lung cancer was 2.0%. Binary logistic regression indicated that CA-125, CA-153, and total prostate specific antigen (TPSA) were identified as independent risk factors of OM in patients with lung cancer (P< 0.001, P< 0.001, and P=0.003, respectively). The sensitivity and specificity of OM diagnosis were as follows: CA-125, 81.25% and 81.57%; CA-153, 68.75% and 83.78%; and TPSA, 81.25% and 90.03%, respectively.Conclusion: The serum concentrations of CA-125, CA-153, and TPSA have predictive value in the diagnosis of OM in elderly patients with lung cancer.Keywords: elderly people, lung cancer, ocular metastases, risk factors

Quan Yuan,1 Honghao Yu,1 Jianhua Chen,1 Xiaoyu Song,2 Li Sun3 1Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Institute of Translational Medicine, China Medical University, Shenyang 110122, People’s Republic of China; 3Department of Nephrology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Quan YuanDepartment of Orthopedic Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110001, People’s Republic of ChinaEmail wateryuan@163.comBackground: MicroRNAs (miRNAs) can act as negative regulators of gene expression, and play a crucial role in cancer progression. The aim of this study was to investigate the role of miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma cells in vitro and in vivo.Methods: The function of miR-1294 and its association with PKM2 in osteosarcoma cells were studied by real-time PCR, CCK-8, Western blot, scratch test, transwell assay, flow cytometry, and dual-luciferase reporter assays. The effect of miR-1294 on tumor growth in vivo was evaluated in a subcutaneous xenograft model of osteosarcoma.Results: miR-1294 was downregulated in osteosarcoma cells. Forced overexpression of miR-1294 inhibited cell proliferation, migration, and invasion, and induced G0/G1 arrest and apoptosis. Consistently, protein expression levels of proliferating cell nuclear antigen, c-Myc, cyclin D1, active matrix metalloproteinase 2, and active matrix metalloproteinase 9 were decreased, and cleaved caspase 3 and cleaved PARP were increased following miR-1294 overexpression. Moreover, we demonstrated that PKM2 was a target of miR-1294 in osteosarcoma cells, and the effects caused by miR-1294 mimic were reversed by the overexpression of PKM2. Furthermore, we found that upregulation of miR-1294 inhibited tumorigenesis of osteosarcoma cells in vivo, which was accompanied by downregulation of PKM2.Conclusion: Our results revealed that miR-1294/PKM2 signaling cascade exerts important roles in the regulation of tumor progression, implying that this pathway may serve as a potential therapeutic target in osteosarcoma.Keywords: pyruvate kinase M2, miR-1294, osteosarcoma, cell proliferation, cell apoptosis, tumorigenesis

Qi Yuan, 1–3 Wei Wang, 1–3 Qian Zhang, 1–3 Yuchao Wang, 1–3 Chuanzhen Chi, 1–3 Chunhua Xu 1–3 1Endoscopic Center of the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China; 2Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing, Jiangsu 210029, People’s Republic of China; 3Department of Respiratory Medicine, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of ChinaCorrespondence: Chunhua XuDepartment of Respiratory Medicine, The Affiliated Brain Hospital of Nanjing Medical University, 215 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaEmail xuchunhua_doctor@163.comObjective: The study aimed to clarify clinical features and prognostic factors of thoracic oligo-postoperative recurrences that underwent local therapy of non-small-cell lung cancer (NSCLC).Methods: From 2332 patients of resected pathological stage I–IIIA NSCLC between 2008 and 2015, a total of 542 patients in follow developed recurrence. Thoracic oligo-recurrence was defined as 1– 3 loco-regional confined to lung lobe, hilar/mediastinal lymph nodes, bronchial stump, or chest wall. This study included 56 thoracic oligo-recurrences. Local therapy included secondary surgery, stereotactic radiotherapy, radiotherapy with a 45 Gy or higher dose, and proton radiation therapy, performed with radical intent. We retrospectively reviewed the postoperative data and performed the univariate and multivariate analysis by Kaplan-Meier methods and Cox regression models, respectively.Results: Thoracic Oligo-recurrence was identified in 56(542,10.3%) patients, mainly in lung lobe(n=22,39%) and regional lymph nodes(n=19,34%). Compared with distant oligo-recurrences, more of the thoracic oligo-recurrences were II–III in pathological stage at initial surgery(p=0.002) and less were adenocarcinoma(p=0.005). The 5-year postoperative survival rate and postoperative progression-free survival rate of thoracic oligo-recurrence were 10.8% and 6.7%, respectively. Median post-recurrence survival (PRS) was 31 months, and the median postoperative progression-free survival (PR-PFS) was 17 months. Multivariate analyses revealed that time to recurrence ≥ 12 months was associated with improved PRS [odds ratio (OR) 0.74, confidence interval (CI) 0.65– 0.85], and regional lymph node oligo-recurrence was associated with poor PRS [OR 1.48, CI 1.38– 1.60]. All the five long-term (≥ 5-year) progression-free survivors were with a solitary pulmonary recurrence.Conclusion: Thoracic postoperative oligo-recurrence of non-small-cell lung cancer is a limited but highly heterogeneous population, with different prognosis at different recurrence sites. Local therapy for thoracic oligo-recurrence of NSCLC achieved favourable PRS in a selected population. Pulmonary solitary oligo-recurrence may achieve a long survival time.Keywords: oligo-recurrence, NSCLC, postoperative recurrence, local therapy

Yuan-Yuan Wu,* Shui-Feng Wang,* Pei-Wen Zhu, Qing Yuan, Wen-Qing Shi, Qi Lin, Biao Li, You-Lan Min, Qiong Zhou, Yi Shao Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Zhou; Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail 1357483244@qq.com; freebee99@163.comPurpose: The purpose was to investigate the differences in spontaneous functional connectivity (FC) of the primary visual cortex (V1) between patients with neovascular glaucoma (NVG) and healthy controls (HCs) using resting-state functional magnetic resonance imaging data.Methods: A total of 18 patients with NVG (nine males and nine females) and 18 HCs with similar age and sex background were enrolled in the study and inspected using resting-state functional magnetic resonance imaging. The differences in FC of the V1 between the two groups were compared using the independent samples t-test. We used the receiver operating characteristic (ROC) curve to compare the average FC values of NVG subjects with those of HCs.Results: FC in the left V1 and right fusiform gyrus, bilateral cuneus, and left precuneus was significantly decreased in the NVG group compared with that reported in the HC group. Meanwhile, patients with NVG presented increased FC between the right V1 and bilateral middle frontal gyrus. However, they also exhibited declining FC between the right V1 and left precuneus, and bilateral cuneus. The ROC curve analysis of each brain region indicated that the accuracy of the area under the ROC curves regarding NVG was excellent.Conclusion: NVG involves aberrant FC in the V1 in different brain areas, including the visual-related and cognitive-related regions. These findings may assist in unveiling the underlying neural mechanisms of impaired visual function in NVG.Keywords: neovascular glaucoma, functional connectivity, spontaneous brain activity, primary visual cortex

Qiu Y, Cao X, Liu L, et al. Cancer Manag Res. 2020;12:5759‒5771. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged duplication of cell migration and invasion images throughout the article. Specifically, Figure 1B, panel 0h HCSLC, appears to have been duplicated with the image from Figure 2C, panel 0h 0.0 µM ISOV. Figure 3B, panel 24h Ad-shMnSOD, appears to have been duplicated with the image from Figure 5G, panel 24h Mock. Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)-, appears to have been duplicated with the image from Figure 4G, panel 24h Ad-GFP+/Ad-MnSOD-/ISOV (10µM)+. Figure 1B, panel 24h HCSLC, appears to have been duplicated with an image from Figure 5c, panel 24h Isovitexin (0µg/mL) Ad-GFP from Liu et al, 2021 (https://doi.org/10.1155/2021/9972057). The authors responded to our initial queries but were unable to provide a satisfactory explanation for the alleged image duplication, nor were they able to provide adequate original data for their study. The decision was made to retract the article and the authors agreed with this decision. 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

Intraspecific male-male aggression, which is important for sexual selection, is regulated by environment, experience and internal states through largely undefined molecular and cellular mechanisms. To understand the basic neural pathway underlying the modu

Antibodies are widely used as microbiological reagents, but antibodies that recognize ‘Ca. Liberibacter asiaticus’ are generally lacking.  We have developed and applied immunization and affinity screening methods to create a primary library of recombinant single chain variable fragment (scFv) antibodies in an M13 vector, pKM19.  The antibody population is enriched for antibodies that bind antigens of ‘Ca. Liberibacter asiaticus’ and Diaphorina citri.  The primary library has more than 107 unique antibodies and the genes that encode them.  We have screened this library of antibodies for antibodies that bind to specifically chosen proteins that are present on the surface of ‘Ca. Liberibacter asiaticus’.  These proteins were used as ‘bait’ for affinity-based selection of scFvs that bind to the major outer membrane protein, OmpA; the polysaccharide capsule expressing protein KpsF; a protein component of the type IV pilus (CapF); and two flagellar proteins FlhA and FlgI.  These scFvs have been used in ELISA and dot blot assays against purified protein antigens and ‘Ca. Liberibacter asiaticus’ infected plant extracts.  We also have isolated scFv that bind to surface exposed portions of the TolC proteins and of a protein called InvA.  These proteins may have critical roles in pathogenicity.  Thus far, screening of these scFvs is more efficient when using phage bound, rather than soluble scFvs.  We have demonstrated a technology to produce antibodies and select at will and against any protein target encoded by ‘Ca. Liberibacter asiaticus’.  Future applications will include advanced diagnostic methods for huanglongbing and the development of immune labeling reagents for in planta applications.

Feiyin Zhu,1,2,* Liying Tang,3,4,5,6,* Peiwen Zhu,1 Qi Lin,1 Qing Yuan,1 Wenqing Shi,1 Biao Li,1 Lei Ye,1 Youlan Min,1 Ting Su,3–6 Yi Shao11Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Clinical Medicine, Queen Mary College of Nanchang University, Nanchang, Jiangxi 330031, People’s Republic of China; 3Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen, Fujian 361102, People’s Republic of China; 4Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian 361102, People’s Republic of China; 5Eye Institute of Xiamen University, Xiamen, Fujian 361102, People’s Republic of China; 6School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of China*These authors have contributed equally to this workPurpose: To investigate alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with corneal ulcer (CU) using resting-state functional connectivity (rsFC).Methods: We recruited 24 patients with CU (12 males, 12 females), and 24 healthy controls (HCs; 12 males, 12 females) matched for age, gender and education status. Functional magnetic resonance imaging examinations were performed on all subjects in a resting state and the following parameters determined: rsFC, long-range FCD (longFCD) and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were then used to differentiate patients with CU from HCs.Results: Compared with HCs, CU patients showed significantly reduced rsFC values in the right cerebellum posterior lobe gyrus, right middle frontal gyrus/inferior frontal gyrus/superior frontal gyrus and left inferior parietal lobule/precuneus. Significantly reduced longFCD values were found in the right hippocampus/inferior temporal gyrus and the left inferior temporal gyrus. Moreover, compared with HCs, IFCD values were significantly reduced in the left inferior temporal gyrus/middle temporal gyrus, left limbic lobe/medial frontal gyrus, and left precuneus/limbic lobe, but were significantly increased in the right insula/superior temporal gyrus, left superior temporal gyrus/inferior frontal gyrus/insula, right superior temporal gyrus/postcentral gyrus, and left precentral gyrus.Conclusions: Patients with CU exhibited alterations in spontaneous brain activities in several brain areas. These novel findings may help to reveal the neuropathological mechanisms underlying CU.This study provides a direction for further exploration of underlying neural mechanisms of CU and facilitate the clinical diagnosis and treatment of CU.Keywords: functional connectivity density, corneal ulcer, spontaneous brain activities

Ting-Juan Zhang,1–3,* Xiang-Mei Wen,2–4,* Jing-Dong Zhou,1–3,* Yu Gu,1–3 Zi-Jun Xu,2–4 Hong Guo,2–4 Ji-Chun Ma,2–4 Qian Yuan,1–3 Qin Chen,2–4 Jiang Lin,2–4 Jun Qian1–31Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Zhenjiang Clinical Research Center of Hematology, Zhenjiang, Jiangsu, People’s Republic of China; 3The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People’s Republic of China; 4Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China*These authors contributed equally to this work Background: Our previous study has reported that aberrant SOX30 methylation was associated with poor prognosis in AML, and it correlated with disease progression in MDS. Herein, we further determined SOX30 methylation and its clinical significance in the other myeloid malignance – chronic myeloid leukemia (CML). Methods: SOX30 methylation was examined by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR, whereas SOX30 expression was detected by real-time quantitative PCR. Results: SOX30 methylation was identified in 11% (10/95) CML patients. SOX30 methylation was associated with lower hemoglobin and platelets (P=0.006 and 0.032, respectively). Importantly, significant differences were observed in the distributions of clinical stages and cytogenetics (P=0.006 and 0.002, respectively). The frequency of SOX30 methylation in chronic phase (CP) stage occurred with lowest frequency (4/74, 5%), higher in accelerated phase (AP) stage (1/7, 14%), and the highest in blast crisis (BC) stage (12/31, 39%). In addition, SOX30 methylated patients tended to have a higher level of BCR-ABL transcript than SOX30 non-methylated patients (P=0.063). In two paired CML patients, SOX30 methylation showed lower density in CP stage (19% and 17%, respectively), and was significantly increased in BC stage (89% and 69%, respectively) during disease progression. Additionally, SOX30 methylated CML patients presented a lower SOX30 transcript level than SOX30 non-methylated CML patients (P=0.046). Conclusion: Our study revealed that SOX30 methylation correlated with disease progression in chronic myeloid leukemia.Keywords: SOX30, methylation, chronic myeloid leukemia, progression

Pei-Wen Zhu,* Ying-Xin Gong,* You-Lan Min, Qi Lin, Biao Li, Wen-Qing Shi, Qing Yuan, Lei Ye, Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang 330006, Jiangxi, People’s Republic of China*These authors have contributed equally to this workPurpose: Colorectal cancer (CRC) is a common tumor of the digestive tract that tends to metastasize and leads to high mortality. Ocular metastases (OM) from colorectal cancer are being increasingly diagnosed, and they can lead to a poor prognosis. Serum lipids are a known risk factor for cardiovascular disease, and are also relevant to the occurrence of CRC. In this study, we examined the levels of serum lipids and tried to determine whether there were correlations with the occurrence of OM in patients with colorectal cancer, in order to determine whether serum lipid levels may be a risk factor for OM in this patient population.Patients and methods: Records from a total of 703 patients treated for colorectal cancer from August 2005 to August 2017 were involved in this study. Student’s t-tests, nonparametric rank sum tests, and Chi-square tests were applied to describe whether there were significant differences between the OM group and non-ocular metastases (NOM) group. We used binary logistic regression analysis to determine the risk factors and receiver operating curve (ROC) analyses to assess the diagnostic value for OM in CRC patients.Results: There were no significant differences in gender, age, histopathology type, or tumor classifications between the OM and NOM groups. The levels of serum TC, HDL, and LDL were significantly different between patients with and without lymph node metastases as well as male and female patients. The OM group had higher serum HDL levels compared to the NOM group. Binary logistic regression indicated that HDL was a risk factor for OM in colorectal cancer patients. The ROC curves showed that the AUC of HDL was 0.660. The cutoff value of HDL was 1.27 mmol/L, with a sensitivity of 0.619 and a specificity of 0.650. Conclusion: HDL levels are correlated with ocular metastases in colorectal cancer patients. Keywords: high-density lipoprotein, ocular metastases, colorectal cancer, independent risk factor

Yanqin Zhang,1,2 Feng Chen,1 Xinghua Xiao,1 Weinan Pan,2 Qing Yuan,3 Jianguo Cao31Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 2Department of Pharmacy, Hunan Food and Drug Vocational College, Changsha, 410208, People’s Republic of China; 3Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of ChinaBackground: Chrysin is a natural flavonoid which has been identified as a candidate anti-cancer agent due to its inhibitory effect on a variety of cancer cells, including targeted inhibition of sphere formation in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which chrysin modulates HCC spheres remains unclear.Materials and methods: In this study, we investigate the effect of chrysin on the regulation of SHP-1 and its downstream signal molecule STAT3 to explain the mechanism by which chrysin inhibits sphere formation of HCC cell lines.Results: Here, we found that SHP-1 protein expression was markedly down-regulated in the spheres from both SMMC-7721 and MHCC97H cells. Chrysin significantly inhibited sphere formation and upregulated the expression of SHP-1 protein in both SMMC-7721 and MHCC97H cells, as well as reduced p-STAT3 and Twist1 expressions in SMMC-7721 cells. Furthermore, knockdown of SHP-1 in SMMC-7721 cells resulted in the induction of p-STAT3 and Twist1 protein expression and antagonizing the inhibitory effect of chrysin on sphere formation in SMMC-7721 cells.Conclusion: Overall, the study findings demonstrated that chrysin acts as a candidate for the treatment of HCC through modulating SHP-1/STAT3 signaling pathway.Keywords: chrysin, hepatocellular carcinoma, SHP-1, STAT3, sphere formation

Jia-Xiang Liu, Qing Yuan, You-Lan Min, Ying He, Qian-Hui Xu, Biao Li, Wen-Qing Shi, Qi Lin, Qing-Hai Li, Pei-Wen Zhu, Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, People’s Republic of ChinaObjective: Breast cancer is the most common primary lesion resulting in intraocular metastasis (IOM). In this study, we investigated the differences between breast cancer patients with and without IOM, and clarified the risk factors for IOM in patients with breast cancer.Methods: A total of 2,381 patients with breast cancer were included in this study from January 2005 to December 2017. The chi-square test and Student’s t-test were applied to evaluate differences between the IOM and non-IOM (NIOM) groups. Risk factors were calculated using binary logistic regression analysis. Receiver operating curve (ROC) analysis was used to assess the diagnostic value of IOM in patients with breast cancer.Results: The IOM incidence in patients with breast cancer was 1.35%. No significant differences were detected in age, gender, menopausal status, or histopathology between the IOM and NIOM groups. The IOM group had more axillary lymph node metastases, lower ApoA1 and higher ApoB, compared with the NIOM group. Binary logistic regression indicated that ApoA1 and ApoB were risk factors for IOM in breast cancer patients (P-values and P-values=0.005, respectively). ROC curve analysis revealed area under the curve values for ApoA1 and ApoB of 0.871 and 0.633, using cutoff values of 1.165 and 0.835 g/L, respectively. The sensitivity and specificity values for ApoA1 were 0.813 and 0.849, respectively, while those for ApoB were 0.813 and 0.481.Conclusion: Our data indicate that ApoA1 and ApoB are risk factors for IOM in patients with breast cancer and that ApoA1 is more reliable than ApoB at distinguishing IOM from NIOM in patients with breast cancer.Keywords: breast cancer, intraocular metastases, apolipoprotein A1, apolipoprotein B

Jian-Hua Chen,1 Quan Yuan,1 Ya-Nan Ma,2 Shi-Han Zhen,2 De-Liang Wen2 1Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Health Policy and Management, School of Public Health, China Medical University, Shenyang, China Purpose: The evidence from recent epidemiological studies investigating the relationship between bone mineral density (BMD) and the risk of breast cancer (BC) remains inconsistent. Materials and methods: The PubMed, EMBASE, and Web of Science databases were comprehensively searched by two independent authors to identify related cohort studies from the inception of the databases through January 31, 2018. Similarly, two researchers separately extracted the data from the selected studies, and any differences were resolved by discussion. Summarized relative risks (RRs) and 95% CIs were summarized via inverse variance weighted random-effects meta-analysis. Heterogeneity among studies was assessed with the I² statistic. Results: Ten studies with 1,522 BC patients among 81,902 participants were included in this meta-analysis. Compared to the participants with the lowest BMD at the lumbar spine, those with the highest BMD had a significantly lower RR for BC (RR =0.75; 95% CI =0.60–0.93; I2=23.0%). In the subgroup analyses, although the directions of the results were consistent with those of the main findings, not all showed statistical significance. We failed to detect an association between BMD at the femoral neck or total hip and the risk of BC (RR =0.94; 95% CI =0.66–1.33; I2=72.5%). Furthermore, the results of the dose–response analysis did not show a significant association between BMD at the lumbar spine, femoral neck, or total hip and the risk of BC. Funnel plot and statistical analyses showed no evidence of publication bias. Conclusion: There is no relationship between BMD and the risk of BC. More prospective cohort studies are warranted to further investigate this issue. Keywords: bone mineral density, breast cancer, cohort studies, meta-analysis, risk

Jun Yang,1 Bin Li,2 Qiu-Yue Yu,2 Lei Ye,3 Pei-Wen Zhu,3 Wen-Qing Shi,3 Qing Yuan,3 You-Lan Min,3 Yu-Lin He,2 Yi Shao3 1Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang, China; 2Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, China Background: The results of previous studies have indicated that pain-associated diseases can result in marked functional and anatomical alterations in the brain. However, differences in spontaneous brain activity occurring in toothache (TA) patients remain unclear.Objective: This study investigated intrinsic brain activity changes in TA subjects using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: A total of 18 patients with TA (eight males, and 10 females) and 18 healthy controls (HCs) who were matched for gender, age, and educational status were enrolled. Resting-state functional MRI was used to examine the participants. Spontaneous cerebral activity variations were investigated using the ALFF technique. The mean ALFF values of the TA patients and the HCs were classified using receiver operating characteristic (ROC) curves. The correlations between ALFF signals of distinct regions of the cerebrum and the clinical manifestations of the TA patients were evaluated using Pearson’s correlation analysis.Results: Compared with HCs, TA patients showed notably higher ALFF in the left postcentral gyrus, right paracentral lobule, right lingual gyrus, right inferior occipital gyrus, left fusiform gyrus, and right superior occipital gyrus. ROC curve analysis of each brain region showed that the accuracy area under the curve was excellent. In the TA group, the visual analog scale of the left side was positively correlated with the ALFF signal values of the right paracentral lobule (r=0.639, P=0.025).Conclusion: Multiple brain regions, including pain- and vision-related areas, exhibited aberrant intrinsic brain activity patterns, which may help to explain the underlying neural mechanisms in TA. Keywords: toothache, functional MRI, ALFF, intrinsic brain activity, pain, resting-state

Mitochondrial DNA (mtDNA) mutations have long been proposed to play important roles in the pathogenesis of diabetes mellitus (DM). A large proportion of these mutations are localized at the mt-tRNA genes. Owing to its high mutation rate, a growing number of mt-tRNA mutations have been reported; however some of them are neutral genetic polymorphisms and will not result in the alteration of the mitochondrial function responsible for DM. In this study, we reassessed a recent reported “pathogenic” mutation, tRNAGly T10003C, in a clinical manifestation of DM. We first performed the conservation assessment of this mutation between different species. Moreover, the bioinformatics analysis was used to predict the secondary structure of mt-tRNAGly in wild type version and the mutant carrying the T10003C mutation. We also screened the presence of the T10003C mutation in 500 unrelated DM patients and 300 healthy controls. We noticed that the T10003C mutation was not very conserved and did not cause the secondary structure change of mt-tRNAGly. Moreover, this mutation was absent in the 500 unrelated DM patients and controls, suggesting that this mutation may be a rare event in the human population. In conclusion, the current study showed no association between the T10003C mutation and DM in humans.

You-Lan Min,1,* Ting Su,2,* Yong-Qiang Shu,3 Wen-Feng Liu,1 Ling-Long Chen,3 Wen-Qing Shi,1 Nan Jiang,2 Pei-Wen Zhu,1 Qing Yuan,1 Xiao-Wei Xu,1 Lei Ye,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006 Jiangxi, China; 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, Fujian, China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006 Jiangxi, China *These authors contributed equally to this work Objective: Previous studies have demonstrated that strabismus or amblyopia can result in markedly brain function and anatomical alterations. However, the differences in spontaneous brain activities of strabismus with amblyopia (SA) patients still remain unclear. This current study intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in SA subjects. Patients and methods: A total of 16 patients with SA (6 males and 10 females) and 16 healthy controls (HCs; 6 males and 10 females) similarly matched in age, gender, and education status were recruited and examined with the resting-state functional MRI. The spontaneous brain activity changes were investigated using the ALFF technique. The receiver operating characteristic curve was performed to classify the mean ALFF signal values of the SA patients from HCs. The correlations between the ALFF values of distinct brain regions and the clinical manifestations in SA patients were evaluated in terms of the Pearson’s correlation analysis. Results: Compared with HCs, SA patients had significantly decreased ALFF in the left cerebellum posterior lobe, left middle frontal gyrus, and bilateral thalamus. In contrast, SA patients showed increased ALFF values in the right superior frontal gyrus, right precuneus, left cuneus, and bilateral precentral gyrus. Nonetheless, there was no linear correlation between the mean ALFF values in brain regions and clinical features. Conclusion: Diverse brain regions including vision-related and motion-related areas exhibited aberrant intrinsic brain activity patterns, which imply the neuropathologic mechanisms of oculomotor disorder and vision deficit in the SA patients. Keywords: strabismus, amblyopia, functional MRI, ALFF, spontaneous brain activity