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Lin Qi,1,* Yanglei Li,2,* Chengqi Kong,2,* Siqi Li,2 Qinyue Wang,2 Hanqin Pan,2 Shuyi Zhang,3 Xinkai Qu,2 Ming Li,1 Mingxuan Li,2,4 Kailei Shi2 1Department of Computed Tomography, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiac Care Unit, Tongren Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kailei Shi; Mingxuan Li, Email shikailei@fudan.edu.cn; 19211280015@fudan.edu.cnBackground: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (− 74.84± 6.93 HU vs − 79.04± 8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (− 78.46± 8.56HU vs − 83.13± 8.34 HU) and LCXs (− 73.83± 10.63 HU vs − 81.38± 7.88 HU) of lesion related vessel in stable angina.Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.Keywords: peri-coronary adipose tissue, neutrophil-to-lymphocyte ratio, fat attenuation index, acute myocardial infarction

Guiyun Zhang,1 Yufeng Lu,2 Lin Qi,1 Chunli Yao1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Thoracic Surgery, Sino-Japanese Friendship Hospital of Jilin University, Changchun, 130012, People’s Republic of ChinaCorrespondence: Chunli Yao, Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel +86-431-81136244, Email ycl@jlu.edu.cnIntroduction: Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity.Case Presentation: Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins.Conclusion: We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.Keywords: pilomatricoma, pilomatrixoma, calcifying epithelioma of malherbe, case report

Zixia Wu,1,* Weibo Xia,1,* Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Zhan Shi,1,* Sihui Zhu,2,* Yuncheng Jin,1 Liang Qi,1 Mingzhen Zhou,1 Ziyan Zhou,1 Juan Zhang,1 Baorui Liu,1 Jie Shen1 1Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China; 2The Comprehensive Cancer Centre of Nanjing International Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Shen; Baorui Liu, Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu Province, 210008, People’s Republic of China, Fax +86-025-83106666, Email shenjie2008nju@163.com; baoruiliu@nju.edu.cnBackground: Stereotactic body radiotherapy (SBRT) has emerged as an alternative approach for patients with hepatocellular carcinoma (HCC), and we aim to find potential prognostic biomarkers for HCC patients who received SBRT.Methods: In this study, we retrospectively analyzed HCC patients who underwent SBRT in our institution from January 2018 to December 2022. The inflammatory parameters, along with baseline patients’ characteristics were collected to elucidate the potential relationship with survival benefits and liver toxicities.Results: Overall, 35 patients were enrolled in our study. For the efficacy population (25 patients who underwent SBRT for primary liver lesions), the objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6– 14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2– 22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥ 2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥ 400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%).Conclusion: In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options.Keywords: hepatocellular carcinoma, stereotactic body radiotherapy, lymphocyte-C-reactive protein ratio, survival, liver toxicity

Shang Gao,1 Chenmoji Wang,1 Lijie Qi,2 Songlin Liang,1 Xintian Qu,1 Wei Liu,3,* Nianhu Li4,* 1The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nianhu Li; Wei Liu, Email tigerlee073@126.com; weiliu800109@163.comBackground: The method of action of Bushen Formula (BSHXF) in the treatment of intervertebral disc degeneration (IVDD) was uncovered in this work using in vivo and in vitro tests. To clarify the mechanism of action of BSHXF, we validated the rat intervertebral disc degeneration model and the nucleus pulposus cell degeneration model.Methods: In an in vivo model of IVDD the study explores the impact of BSHXF on mitochondrial function, pro-inflammatory cytokines, pro-apoptotic factors, and matrix metalloproteinases. Additionally, it evaluates the induced degeneration of nucleus pulposus (NP) cells in an in vitro model stimulated by interleukin-1 β (IL-1β). The study measures the effects of BSHXF on both the inflammatory response and mitochondrial function.Results: The MRI results showed that BSHXF reduced intervertebral disc volume reduction and degradation of NP tissue. HE, SO-FG and immunofluorescence further confirmed the protective effect of BSHXF on degenerative intervertebral discs. BSHXF reduced the inflammatory levels of IL-6 IL-1β and TNF-α in degenerative intervertebral disc tissue. Meanwhile, JC-1, mPTP and ROS detection revealed that BSHXF can restore mitochondrial function by regulating the expression of antioxidant proteins, playing a protective role in NP cells. Finally, the WB results showed that BSHXF can alleviate IL-1β mediate the degeneration of NP cells. BSHXF can alleviate NP cell apoptosis by inhibiting the expression of bax, cleaved caspase-3, caspase-3, and cyt-c, and increasing the expression of Bcl-2.Conclusion: This study reveals that BSHXF inhibits the development of inflammatory factors, which may play a significant role in intervertebral disc degeneration. This implies that BSHXF is a suitable herbal medication for future research into inflammatory cytokine treatment.Keywords: intervertebral disc degeneration, nucleus pulposus cell, BSHXF, apoptosis, inflammatory

Na Yan,1 Tong Zhou,1 Mingming Hu,1 Yuxuan Cai,1 Ling Qi,1 Blen Dereje Shiferaw,1 Wei Wang,1– 3 Chunxia Miao4 1School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Research Center for Mental Crisis Prevention and Intervention of College Students in Jiangsu Province, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 3Jiangsu Engineering Research Center of Biological Data Mining and Healthcare Transformation, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4School of Management, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of ChinaCorrespondence: Wei Wang, School of Public Health, Xuzhou Medical University, 209 Tong Shan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email weiwang90@163.com Chunxia Miao, School of management, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email miaochunxia1978@163.comBackground: Previous findings indicate that stress has a profound influence on suicide behavior, but the potential mediating and moderating mechanisms are unknown between uncertainty stress and suicide behavior. The present study, therefore, examined the relationship between uncertainty stress and suicide behavior, the mediating effect of depressive symptoms, and the moderating effect of family relationship in a sample of university students in China.Methods: 1828 university students were assessed anonymously by using the Uncertainty Stress Scale, Center for Epidemiologic Studies Depression Scale, Brief Suicidal Scale, and Family Relationship Scale between May to June in 2021. SPSS 26.0 was used for descriptive statistics and Spearman correlation analysis. PROCESS 3.5 was used to calculate the significance of the mediating and moderating effects of the variables.Results: Moderated mediation model analyses showed that: (a) depressive symptoms partially mediated the link between uncertainty stress and suicide behavior (indirect effect = 0.14, 95%bootstrap CI = 0.10, 0.19). The indirect effect of the depressive symptoms accounted for 67.12% of the total variance in suicide behavior. (b) The indirect association between uncertainty stress and suicide behavior was moderated by family relationship. Specifically, the paths from uncertainty stress to depressive symptoms (interact effect = − 0.06, P< 0.001) and depressive symptoms to suicide behavior (interact effect = − 0.08, P< 0.01) were weakened in the context of higher family relationship.Conclusion: Depressive symptoms play a crucial role in bridging uncertainty stress and suicide behavior, while the family relationship can buffer the mediation impact of depressive symptoms. These findings significantly contribute to the prevention and intervention of suicide in Chinese university students.Keywords: uncertainty stress, depressive symptoms, suicide behavior, family relationship, university students

Shuyun Zhang,1,&ast; Lijuan Wu,1,&ast; Xue Li,1 Li Yang,1 Sujuan Shen,1 Hong Shen,1 Dan Zhao,2 Lin Qi2,3 1Center of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 2Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 3State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Qi, Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China, Tel +86-13962187070, Email drhuan@126.comPurpose: Karyotype analysis of villus chromosomes in spontaneous abortion by high-throughput ligation-dependent probe amplification (HLPA) was performed to explore relationship between spontaneous abortion and chromosomal abnormalities in spontaneous abortion tissues.Patients and Methods: The karyotypes of chromosomes of villus tissues from 516 patients with spontaneous abortion who were admitted to our hospital between 2014 and 2019 were analyzed. The data were grouped by the age (ie, ≤ 29, 30– 35, and ≥ 36 years old) in which embryonic chromosomal abnormality rate, and abnormal distribution of chromosome number in abortion tissue of 294 patients.Results: The examination of 516 samples of spontaneous abortion tissues showed that the chromosomes of 294 samples were abnormal, and the abnormality rate was 60.97%. Among 294 samples with chromosomal abnormalities, 136 (89.47%) samples had numerical chromosomal abnormalities, 15 (9.87%) samples had structural chromosomal abnormalities, and 1 (0.07%) sample had uniparental disomy. A total of 308 couples voluntarily underwent peripheral blood chromosome analysis. The results showed that 56 couples had abnormality in one or both spouses, and rate of embryonic chromosomal abnormality in these 26 cases with chromosomal abnormalities was 100%.Conclusion: Numerical and structural chromosomal abnormalities are among the important causes of embryonic arrest, while the increase in age could also be a high-risk factor for embryonic chromosomal abnormality. Therefore, examination of the karyotypes of embryo chorionic villus may help understand the reasons of embryonic arrest, which could provide important guidance for more genetic counseling for patients with early spontaneous abortion, as well as improving the preconception preparation.Keywords: spontaneous abortion, villus tissue, HLPA test, chromosomal abnormality

Wei Li, Jun Zhao, Ruiping Hao, Shujuan Wang, Ming Chen, Huijun Liu, Le Qi, Zaijun Hao Department of Anaesthesiology, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region, People’s Republic of ChinaCorrespondence: Zaijun Hao, Department of Anesthesiology, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region, 017000, People’s Republic of China, Tel/Fax +8615204778880, Email dengdairy@126.comPurpose: Evaluate the efficacy and safety of remimazolam besylate combined with esketamine for outpatient colonoscopy.Patients and methods: A total of 150 outpatients undergoing colonoscopy were randomized into two groups. A MOAA/S score ≤ 3 was maintained. The primary outcome was the rate of successful colonoscopy completion. Time indicators, hemodynamic parameters, the consumption of lidocaine, esketamine, propofol and remimazolam besylate, MOAA/S scores and bispectral index (BIS) values, the lowest SpO2, body movement, the use of rescue medication, endoscopist and patient satisfaction, recall of the procedure, mini-mental state examination (MMSE), fatigue level and adverse events were recorded.Results: Procedure completion was equivalent between groups (P > 0.05). Both induction and awakening times were significantly shorter in the P group (P < 0.05). There were no significant differences in colonoscopy time and discharge time (P > 0.05). The lowest SpO2 was significantly lower in the P group, while the level of fatigue was higher (P < 0.05). Patient satisfaction was significantly higher in the R group (P < 0.05). Endoscopist satisfaction was significantly higher in the P group (P < 0.05). There were no significant differences in both systolic and diastolic blood pressure between groups except at T5 and T6 (P > 0.05). Both HR and RR were significantly lower in the P group from T3 to T5 (P < 0.05). BIS values were significantly lower in the P group from T3 to T5, while MOAA/S was significantly lower in the P group at T3 and T4 (P < 0.05). Pain on injection was significantly higher in the P group (P < 0.05).Conclusion: Remimazolam besylate has a similar efficacy to propofol when combined with subanesthetic doses of esketamine during outpatient colonoscopy. Remimazolam besylate combined with esketamine resulted in less injection pain and more stable hemodynamics, although it prolonged induction and awakening time.Keywords: remimazolam besylate, propofol, esketamine, colonoscopy

Zhao C, Li Y, Hu X, et al. Onco Targets Ther. 2020;13:11827–11838. At the author’s request, we, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, the authors raised concerns regarding the duplication of images from Figures 2 and 4 with images from other unrelated articles. Specifically, Images for Figure 2C have been duplicated with images for Figure 2D from Fu Y, Cai L, Lei X, et al. RETRACTED ARTICLE: Circular RNA ABCB10 promotes hepatocellular carcinoma progression by increasing HMG20A expression by sponging miR-670-3p. Cancer Cell Int. 2019;19:338. https://doi.org/10.1186/s12935-019-1055-z; Figure 3B from Xing Z, Zhang Z, Gao Y, et al. The lncRNA LINC01194/miR-486-5p Axis Facilitates Malignancy in Non-Small Cell Lung Cancer via Regulating CDK4. Onco Targets Ther. 2020;13:3151-3163. https://doi.org/10.2147/OTT.S235037 and Figure 3H from Peng Y, Li X, Liu H, et al. RETRACTED ARTICLE: microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway. Nanoscale Res Lett. 2020;15:196. https://doi.org/10.1186/s11671-020-03416-8. Images for Figure 4B have been duplicated with images for Figure 5C from Zhang D, Ma Y, Ma Z, et al. Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis. Acta Biochimica et Biophysica Sinica. 2020;52:1071-1080. https://doi.org/10.1093/abbs/gmaa099. The authors were cooperative and explained that after becoming aware of the concerns, they evaluated the study and were unable to verify the validity of the reported findings or explain how the images came to be duplicated. As verifying the validity of published work is core to the integrity of the scholarly record, the authors found it necessary to retract the article and we, the Editors and Publisher, agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Fukutin-related protein (FKRP, MIM ID 606596) variants cause a range of muscular dystrophies associated with hypo-glycosylation of the matrix receptor, α-dystroglycan. These disorders are almost exclusively caused by homozygous or compound heterozygous missense variants in the FKRP gene that encodes a ribitol phosphotransferase. To understand how seemingly diverse FKRP missense mutations may contribute to disease, we examined the synthesis, intracellular dynamics, and structural consequences of a panel of missense mutations that encompass the disease spectrum. Under non-reducing electrophoresis conditions, wild type FKRP appears to be monomeric whereas disease-causing FKRP mutants migrate as high molecular weight, disulfide-bonded aggregates. These results were recapitulated using cysteine-scanning mutagenesis suggesting that abnormal disulfide bonding may perturb FKRP folding. Using fluorescence recovery after photobleaching, we found that the intracellular mobility of most FKRP mutants in ATP-depleted cells is dramatically reduced but can, in most cases, be rescued with reducing agents. Mass spectrometry showed that wild type and mutant FKRP differentially associate with several endoplasmic reticulum (ER)-resident chaperones. Finally, structural modelling revealed that disease-associated FKRP missense variants affected the local environment of the protein in small but significant ways. These data demonstrate that protein misfolding contributes to the molecular pathophysiology of FKRP-deficient muscular dystrophies and suggest that molecules that rescue this folding defect could be used to treat these disorders.

Sheng Ye,1 Huichun Xiao,1 Jian Chen,1 Di Zhang,1 Li Qi,1 Ting Peng,2 Yanyang Gao,2 Qianbing Zhang,3 Jinqing Qu,2 Lei Wang,4 Ruiyuan Liu1 1Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, People’s Republic of ChinaCorrespondence: Jinqing Qu; Ruiyuan Liu, Email cejqqu@scut.edu.cn; ruiyliu@smu.edu.cnIntroduction: The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy.Methods: The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy.Results: CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo.Conclusion: This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.Keywords: copperphosphotungstate, NIR-II absorption nanorods, NIR-II photothermal therapy, GSH depletion, chemodynamic therapy, synergistic therapy

Zhan Lu,1,2,&ast; Yiyue Huang,1,2,&ast; Juntao Huang,1,2,&ast; Hang-Hang Ni,1,2 Tai Luo,1 Xingyu Wei,1 Xue Bai,1 Lunnan Qi,1– 3 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Lunnan Qi, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-7715301253 ; +86-135-1788-6990, Email xiangbangde@gxmu.edu.cn; qilunan_gxmu@163.com; wangzhennuo@aliyun.comPurpose: Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs.Patients and Methods: 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves.Results: A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥ 225× 109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs > 5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥ 225× 109/L and CTCs > 5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan–Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS).Conclusion: The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.Keywords: hepatocellular carcinoma, liver resection, early recurrence, platelet count, circulating tumor cells

Shengjie Yang,1,&ast; Weijuan Tan,1,&ast; Xiao Ma,2 Lu Qi,1 Xinghe Wang1 1Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Surgery Medicine, Zhangqiu People’s Hospital, Jinan, 250200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinghe Wang, Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road Yangfangdian, Haidian District, Beijing, People’s Republic of China, Tel +86-15301378575, Email wangxh@bjsjth.cnAbstract: Cancer-related neuropathic pain is a common adverse effect in the process of cancer development and treatment and has gradually attracted the attention of researchers. The purpose of this article is to systematically review the articles on cancer-related neuropathic pain published between 2012 and 2021 and visualize the data through CiteSpace and R software. The results show that in the past 10 years, a total of 5715 articles have been published, involving 118 categories, of which the most is Clinical Neurology, followed by Neurosciences, Pharmacology Pharmacy. The country with the most published articles is the United States, followed by China and Italy. A total of 22,228 authors were involved in the study of cancer-related neuropathic pain. These historical opinions about cancer-related neuropathic pain could be an important practical basis for further research into potential development trends.Keywords: cancer, neuropathic pain, bibliometric, author, country, institution

Licui Qi,1 Ning Kang,2 Xiaoyi Chen,3 Zelin Li,2 Chenqian Deng,3 Shuchun Chen1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 2Graduate School, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 3Graduate School, Hebei North University, Zhangjiakou, 075000, People’s Republic of ChinaCorrespondence: Shuchun Chen, Endocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email chenshuc2014@163.comPurpose: This study aims to explore the predictive value of plasma atherogenic index of plasma (AIP) for microalbuminuria (MAU) in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods: This study was a retrospective study, which included 335 newly diagnosed T2DM patients. They were divided into microalbuminuria group (group A, n = 105 cases) and no microalbuminuria group (group B, n = 230 cases) according to whether microalbuminuria occurred. General information and laboratory examination indexes of patients were collected, and AIP was calculated. Multivariate logistic regression analysis was used to analyze the independent risk factors of microalbuminuria in T2DM patients, and receiver operating characteristic curve (ROC) was established to evaluate the predictive value of AIP on MAU of newly diagnosed T2DM patients.Results: According to general data analysis, AIP level in group A was significantly higher than that in group B (P < 0.05). Multivariate logistic regression analysis showed that AIP was an independent risk factor for microalbuminuria (P < 0.05). The receiver operating characteristic curve showed that the area under the curve (AUC) of AIP was 0.772 (P < 0.05), which had a good predictive value for the occurrence of MAU in newly diagnosed T2DM patients. The waist-hip ratio, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin and AIP were used to make a joint model, and the AUC was 0.841 (P < 0.05), which had a better predictive value for the occurrence of MAU.Conclusions: AIP is an independent risk factor and could predict the occurrence of MAU in newly diagnosed T2DM patients. AIP provides clinicians a reliable basis to quickly identify high-risk patients and formulate appropriate treatment strategies.Keywords: plasma arteriosclerosis index, microalbuminuria, type 2 diabetes, dyslipidemia, diabetic nephropathy

Liang Wang,&ast; Chao Li,&ast; Lianlei Wang, Lei Qi, Xinyu Liu Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Qi; Xinyu Liu Tel +86-531-82165995Fax +86-531-82165993Email qilei_spine@hotmail.com; newyuliu@163.comBackground: Sciatica-related spinal imbalance could be observed in lumbar disc herniation (LDH) patients. However, their characteristics and recovery process remained unclear. The purpose was to analyze the radiological characteristics of spinal imbalance related to sciatica and recovery following endoscopic discectomy.Methods: The records of LDH patients with sciatica and spinal imbalance receiving endoscopic discectomy were retrospectively reviewed. The patients were divided to Group A (sagittal imbalance), Group B (coronal imbalance) and Group C (sagittal and coronal imbalance). The whole-spine x-ray was performed at pre-operation, immediately post-operation, 3-month and 6-month follow-up and related radiological parameters were measured.Results: A total of 110 LDH patients (18.3%) presented with spinal imbalance were included and there were 31 patients in Group A, 38 patients in Group B and 41 patients in Group C. In this study, 77.2% of the coronal imbalance patients present with trunk shifted to contralateral side of disc herniation and 65.3% of the sagittal imbalance patients present with forward trunk. Most patients present mild and moderate sagittal and coronal imbalance. The magnitude of sagittal and coronal imbalance in Group C was significantly more severe than that of Group A and Group B. Most patients (≥ 75%) acquired spinal balance immediately after surgery. The sagittal imbalance improved better than coronal imbalance and single plane imbalance improved better than biplane imbalance. At the postoperative 6-month follow-up, all patients recovered to normal sagittal and coronal balance.Conclusion: Sciatica-related spinal imbalance occurs in 18.3% of the LDH patients receiving endoscopic discectomy. Different subgroups of spinal imbalance present different characteristics. Spontaneous correction of the spinal imbalance could be achieved when sciatica was relieved immediately after surgery and well maintained during follow-up.Keywords: sciatica, lumbar disc herniation, spinal imbalance, radiological characteristics, recovery, endoscopic discectomy

Honglei Hu,1,2,&ast; Shuting Zheng,1,2,&ast; Meirong Hou,1,2 Kai Zhu,1,2 Chuyao Chen,1 Zede Wu,1,2 Li Qi,3 Yunyan Ren,1 Bin Wu,4 Yikai Xu,1 Chenggong Yan,1,5 Bingxia Zhao2,6 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Medical Image Processing, Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 4Institute of Respiratory Diseases, Respiratory Department, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 6Experimental Education/Administration Center, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bingxia Zhao; Yikai Xu, Tel +86 20 61647272; +86 20 62787333, Email bingxiaz@gmail.com; yikaixu917@gmail.comBackground: Radiotherapy (RT) is clinically well-established cancer treatment. However, radioresistance remains a significant issue associated with failure of RT. Phototherapy-induced radiosensitization has recently attracted attention in translational cancer research.Methods: Cu-Sb-S nanoparticles (NPs) coated with ultra-small Au nanocrystals (Au@Cu-Sb-S) were synthesized and characterized. The biosafety profiles, absorption of near-infrared (NIR) laser and radiation-enhancing effect of the NPs were evaluated. In vitro and in vivo spectral computed tomography (CT) imaging and photoacoustic (PA) imaging were performed in 4T1 breast cancer-bearing mice. The synergetic radio-phototherapy was assessed by in vivo tumor inhibition studies.Results: Au@Cu-Sb-S NPs were prepared by in situ growth of Au NCs on the surface of Cu-Sb-S NPs. The cell viability experiments showed that the combination of Au@Cu-Sb-S+NIR+RT was significantly more cytotoxic to tumor cells than the other treatments at concentrations above 25 ppm Sb. In vitro and in vivo spectral CT imaging demonstrated that the X-ray attenuation ability of Au@Cu-Sb-S NPs was superior to that of the clinically used Iodine, particularly at lower KeV levels. Au@Cu-Sb-S NPs showed a concentration-dependent and remarkable PA signal brightening effect. In vivo tumor inhibition studies showed that the prepared Au@Cu-Sb-S NPs significantly suppressed tumor growth in 4T1 breast cancer-bearing mice treated with NIR laser irradiation and an intermediate X-ray dose (4 Gy).Conclusion: These results indicate that Au@Cu-Sb-S integrated with spectral CT, PA imaging, and phototherapy-enhanced radiosensitization is a promising multifunctional theranostic nanoplatform for clinical applications.Keywords: Au@Cu-Sb-S nanoparticle, phototherapy, radiotherapy, spectral CT, photoacoustic imaging

Many cancer patients still lack effective treatments, and pre-existing or acquired resistance limits the clinical benefit of even the most advanced medicines. Recently, much attention has been given to the role of metabolism in cancer, expanding from the Warburg effect to highlight unique patterns that, in turn, may improve diagnostic and therapeutic approaches. Our recent metabolomics study revealed that ribitol can alter glycolysis in breast cancer cells. In the current study, we investigate the combinatorial effects of ribitol with several other anticancer drugs (chrysin, lonidamine, GSK2837808A, CB-839, JQ1, and shikonin) in various breast cancer cells (MDA-MB-231, MCF-7, and T-47D). The combination of ribitol with JQ1 synergistically inhibited the proliferation and migration of breast cancer cells cell-type dependently, only observed in the triple-negative MDA-MB-231 breast cancer cells. This synergy is associated with the differential effects of the 2 compounds on expression of the genes involved in cell survival and death, specifically downregulation in c-Myc and other anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1), but upregulation in p53 and cytochrome C levels. Glycolysis is differentially altered, with significant downregulation of glucose-6-phosphate and lactate by ribitol and JQ1, respectively. The overall effect of the combined treatment on metabolism and apoptosis-related genes results in significant synergy in the inhibition of cell growth and induction of apoptosis. Given the fact that ribitol is a metabolite with limited side effects, a combined therapy is highly desirable with relative ease to apply in the clinic for treating an appropriate cancer population. Our results also emphasize that, similar to traditional drug development, the therapeutic potential of targeting metabolism for cancer treatment may only be achieved in combination with other drugs and requires the identification of a specific cancer population. The desire to apply metabolomic intervention to a large scope of cancer types may be one of the reasons identification of this class of drugs in a clinical trial setting has been delayed.

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study

Litong Qi,1 Qiuling Zhang,2 Zeqi Zheng,3 Zhaohui Pei,4 Hong Mao,5 Tingbo Jiang,6 Dmitri Kazei,7 Elke Kahler,8 Yong Huo1 1Peking University First Hospital, Beijing, 100034, People’s Republic of China; 2The Affiliated Hospital of Hangzhou Normal University, Hangzhou City, Zhejiang, 310015, People’s Republic of China; 3The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi, 330000, People’s Republic of China; 4The Third Hospital of Nanchang, Nanchang City, Jiangxi, 330000, People’s Republic of China; 5The Central Hospital of Wuhan, Wuhan City, Hubei, 430014, People’s Republic of China; 6The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu, 215006, People’s Republic of China; 7Abbott Healthcare Products BV, Weesp, 1381 CT, The Netherlands; 8Abbott Laboratories GmbH, Hannover, 30173, GermanyCorrespondence: Yong HuoDepartment of Cardiology, Peking University First Hospital, No. 8 Xishiku St. Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86 139 01333060Email huoyong@263.net.cnIntroduction: The lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥ 18 years) who had elevated baseline fasting serum triglycerides (TG).Methods: Patients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥ 500 and < 1000 mg/dL or moderate HTG, with baseline TG > 200 and < 500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019).Results: The mean TG end-of-treatment effect of OM3EE was – 29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were – 12.12% and – 23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience.Discussion: These data indicate that OMACOR therapy at a dose of 2– 4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated.Keywords: omega-3 PUFAs, hypertriglyceridemia, triglycerides, clinical trial, China, statin

Donghui Hou,1 Weihua Li,2 Sicong Wang,3 Yao Huang,1 Jianwei Wang,1 Wei Tang,1 Lina Zhou,1 Linlin Qi,1 Ning Wu,1,4,&ast; Shijun Zhao1,&ast; 1Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3GE Healthcare, Life Sciences, Beijing, People’s Republic of China; 4PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijun Zhao; Ning WuDepartment of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing, 10021, People’s Republic of ChinaTel +86-10-8778-8550; Tel/Fax +86-10-8778-7523Email zsj.2001@163.com; cjr.wuning@vip.163.comPurpose: Although patients with primary and acquired epidermal growth factor receptor (EGFR) T790M positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired EGFR T790M mutations in patients with NSCLC before treatment.Patients and Methods: We enrolled two groups of patients with primary or acquired EGFR T790M mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on 21L858R and 19del to exclude the effect of coexistent mutations.Results: Primary, compared to acquired, T790M mutation tends to coexist with 21L858R (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The T790M mutation contributed to these differences independently of coexistent mutations.Conclusion: We identified clinicopathologic and CT imaging differences between primary and acquired T790M mutations. These findings provide insights into developing future personalized T790M mutation status-based theranostic strategies.Keywords: non-small-cell lung cancer, T790M mutation, osimertinib, clinicopathologic characteristic, computed tomography

Hengshuo Zhang, Lu Chen, Ziyu Wang, Fuan Wang, Yu Shan, Linzeng Qi, Yunzhen Chen Department of Spine Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Yunzhen Chen Email qilucyz@yeah.netObjective: To examine the association between single nucleotide polymorphisms (SNPs) rs2228570, rs731236, rs7975232, and rs1544410 and lumbar disc degeneration (LDD) predisposition.Methods: A search strategy was carried out, and the data were extracted after being chosen by the inclusion and exclusion criteria. Pooled odds ratios and 95% confidence intervals were calculated to assess the association between the aforementioned SNPs and LDD under allelic, dominant, recessive, heterozygous, and homozygous genetic models. In addition, a case–control study involving 46 LDD cases and 45 controls was also performed in the analysis to verify the result.Results: A total of 17 studies were included in this meta-analysis. The pooled results did not show any association between vitamin D receptor (VDR) gene polymorphisms and LDD. But, interestingly, in subgroup analysis, the rs2228570 polymorphism was associated with LDD under the allelic (OR = 0.70, 95% CI = 0.56– 0.87, p = 0.002), recessive (OR = 0.60, 95% CI = 0.43– 0.84, p = 0.003), and homozygous (OR = 0.47, 95% CI= 0.28– 0.79, p = 0.004) genetic models in the Asian population. SNPs rs731236 and rs7975232 still did not show any obvious association. We obtained a similar result from the case–control study: rs2228570 had an obvious relationship with LDD under allelic and homozygous genetic models. At the same time, we found that rs2228570 was also associated with the degree of low back pain (visual analogue scale, VAS score) in LDD population.Conclusion: SNP rs2228570 was significantly associated with LDD predisposition and the degree of low back pain in the Asian population.Keywords: vitamin D receptor, single nucleotide polymorphism, lumbar disc degeneration, visual analogue scale, meta-analysis, case-control study

Liqiang Qi,1 Bo Sun,2 Beibei Yang,2 Su Lu2 1Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Liqiang QiDepartment of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of ChinaTel +86-10-67781331Email qiliqiang_qqil@163.comPurpose: circHIPK3 has carcinogenic or anti-tumor effects on different cancers. However, there is no relevant research showing whether circHIPK3 was involved in breast cancer (BCa). In this research, the aim was to analyze the function and possible molecular mechanism of circHIPK3 in BCa.Methods: The expression of circHIPK3 in human BCa tissues and cells was detected by real-time quantitative PCR (RT-qPCR). CircInteractome and dual-luciferase assays were performed to detect circRNA–miRNA targeting relationship. Ribonuclease R treatment, RT-qPCR, Western blot and immunohistochemistry were performed to determine the stability, expressions, abundance of target genes. Loss-of-function or gain-of-function experiments were used to analyze the effects of circHIPK3 and miR-326 on BCa in vivo and in vitro. In vitro, MCF7 and BT20 cells were transfected with circHIPK3 or sicircHIPK3 or miR-326 mimic; in vivo, female BALB/c mice were subcutaneously injected with MCF7 cells (transfected with CirchipK3 or miR-326 mimic) to establish xenograft models.Results: The circular structure of circHIPK3 was abundantly expressed in the cytoplasm and was up-regulated in BCa. Silenced circHIPK3 suppressed malignant phenotype of BCa cells. MiR-326 interacted with circHIPK3 and the two were negatively correlated. Overexpressed circHIPK3 promoted cell viability, proliferation, migration and invasion, but inhibited apoptosis. Moreover, overexpressed circHIPK3 promoted the expressions of EMT-related genes and antiapoptotic genes, but inhibited proapoptotic gene expressions. Overexpressed circHIPK3 promoted tumor growth and Ki-67 levels, inhibited apoptosis in vivo. The above mentioned effects of circHIPK3 were reversed by miR-326 in vitro or in vivo.Conclusion: circHIPK3 promoted proliferation, migration and invasion of BCa cells through regulating miR-326.Keywords: breast cancer, circRNA, circHIPK3, miR-326, malignant progress

Qian Zhang,1,2,* Wanting Xing,1,2,* Jie Zhang,1,2 Junwen Hu,1,2 Lunan Qi,1– 3 Bangde Xiang1– 3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bangde Xiang; Lunan QiDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71# Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86-7715301253; +86-13517886990Email xiangbangde@gxmu.edu.cn; wangzhennuo@aliyun.comPurpose: The purpose of this study was to elucidate the relationship between cytokeratin 19 (CK19) expression and levels of circulating tumor cells (CTCs) in preoperative peripheral blood of patients with hepatocellular carcinoma (HCC), and the potential influence of that relationship on prognosis.Patients and Methods: CanPatrol™ CTC-enrichment technique and in situ hybridization (ISH) were used to enrich and classify CTCs undergoing the epithelial–mesenchymal transition (EMT) from blood samples of 105 HCC patients. CK19 immunohistochemistry staining was performed on HCC tissues and compared with demographic and clinical data.Results: In total, 27 of 105 (25.7%) HCC patients were CK19-positive. CK19-positive patients had significantly lower median tumor-free survival (TFS) than CK19-negative patients (5 vs 10 months, P = 0.047). In total, 98 (93.3%) patients showed pre-surgery peripheral blood CTCs (range: 0– 76, median: 6), and 57 of 105 (54.3%) patients displayed CTC counts ≥ 6. Furthermore, CK19-positive patients with CTC count ≥ 6 showed significantly higher percentage than CK19-negative ones (77.8% vs 46.2%, P = 0.004). CK19-positive patients showed a significantly higher proportion of mesenchymal CTCs among CTCs undergoing EMT than CK19-negative patients (mean rank: 62.28 vs 49.79, P = 0.046). We also found that CK19-positive patients with high CTC count showed significantly shorter median tumor-free survival than CK19-negative patients with low CTC count (5 vs 16 months, P = 0.039).Conclusion: High CTC count and high percentage of mesenchymal CTCs are closely related to the expression of CK19, which is associated with poor prognosis in HCC patients.Keywords: hepatocellular carcinoma, cytokeratin 19, circulating tumor cells, prognosis, tumor-free survival

Licui Qi,1,2 Ning Kang,3 Yong Li,2 Hang Zhao,2 Shuchun Chen2 1Graduate School of Hebei North University, Zhangjiakou, 075000, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Shuchun ChenEndocrinology Department, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaEmail guang6701@sina.comPurpose: This study aims to investigate the predictive value of visceral adiposity index (VAI) and lipid accumulation index (LAP) for microalbuminuria (MAU) in patients with newly diagnosed Type 2 diabetes (T2DM).Patients and Methods: This study included 335 patients with newly diagnosed T2DM patients from Hebei General Hospital. All the patients aged from 18 to 65 years old include 226 males and 109 females. Patients information and blood indicators were Collected and calculated the LAP and VAI scores. All the patients were divided into males (group A) and females (group B), and these groups were then further subdivided into A1 group which arises microalbuminuria, and A2 group which does not. With the same method, women were divided into B1 group and B2 group.Results: Baseline data analysis showed that LAP and VAI levels in A1 and B1 groups were significantly higher than those in A2 and B2 groups (P< 0.05). Logistic regression analysis showed that fasting blood glucose, waist circumference, LAP, and VAI were independent risk factors for the occurrence of microalbuminuria in both males and females. ROC showed that the area under curve (AUC) of waist circumference, fasting blood glucose, LAP and VAI in male patients were 0.626, 0.676, 0.760 and 0.742, respectively, and in female patients were 0.703, 0.685, 0.787 and 0.764, respectively. In addition, the area under the curve of both LAP and VAI was higher in females than in males.Conclusion: This study confirmed that both LAP and VAI had predictive values for the occurrence of urinary microalbumin in newly diagnosed T2DM patients. The predictive value was higher in the female group and the suggestion was more applicable to female patients.Keywords: visceral adiposity index, lipid accumulation index, type 2 diabetes, microalbuminuria

Yajun Yang,1,* Guisen Zhang,2,* Song Zhang,3,* Xiaoyan Bian,1 Lao Qi,2 Shixuan Guo,2 Bozhou Zhang,1 Lei Liu4 1Cataract Department, Baotou Chaoju Eye Hospital, Baotou, 014060, People’s Republic of China; 2Retina Department, Hohhot Chaoju Eye Hospital, Hohhot, 010050, People’s Republic of China; 3Cataract Department, China Medical University, Shenyang, 110122, People’s Republic of China; 4Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bozhou ZhangBaotou Chaoju Eye Hospital, Baotou, Inner Mongolia Autonomous Region, 014060, People’s Republic of ChinaEmail zhangbozhou@chaojueye.cnLei LiuThe First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of ChinaEmail liuleijiao@163.comAim: To use OCTA to collect normative data describing the vascular perfusion of the macula and optic disc in adolescents.Methods: This cross-sectional, school-based study was conducted from Oct 15, 2019, to Nov 30, 2019, in Tuyou County, Baotou, China. All eligible participants underwent a comprehensive questionnaire and ocular examination. The vascular perfusion of the macula and optic disc was determined using a spectral-domain OCTA device.Results: A total of 570 anatomically normal eyes without a history of pathologic disease from 570 adolescents (mean ± SD age, 15.1 ± 1.9 years; 298 girls [52.3%]) were enrolled. In the macula, the mean ± SD perifoveal perfusion density (PD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was 44.2% ± 4.37% and 50.74% ± 3.98%, respectively. The mean ± SD foveal avascular zone (FAZ) was 0.32 mm2 ± 0.11 mm2. The mean ± SD peripapillary vessel density (PVD) was 54.98% ± 3.53%. The inferior hemiretinal SCP-PD, DCP-PD, FAZ, and PVD was larger in girls than boys (P = 0.006, P = 0.001, P < 0.001, and P = 0.006, respectively) Multiple regression analysis confirmed that sex independently affected the DCP-PD, FAZ, and PVD (P < 0.001, P < 0.001, and P = 0.029, respectively) and that axial length (AL) independently affected the FAZ area and PVD (P = 0.004 and P < 0.001, respectively).Conclusion: Quantitative studies of the perifoveal vasculature in adolescents should consider the patient’s sex and AL. Our findings may provide useful information for the understanding and the management of retinal perfusion in Chinese adolescents.Keywords: macula, optic disc, optical coherence tomography angiography, retinal perfusion

Liqiang Qi,1 Bo Sun,2 Beibei Yang,2 Su Lu2 1Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Liqiang QiDepartment of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of ChinaTel +86 10-87787130Email qiliqiang_bj@tom.comIntroduction: Long intergenic non-protein coding RNA 665 (LINC00665) has been revealed to contribute cancer progression in many cancer types including liver and gastric cancer. However, the roles of LINC00665 in breast cancer (BC) remain to be explored.Methods: We explored LINC00665 expression in BC tissues and normal tissues at GEPIA. Then, its expression in BC cells (HCC-1937, MDA-MB-231, and MCF-7) and normal cells (MCF10A) was analyzed with qRT-PCR. In addition, the mechanisms of LINC00665 in BC were explored using bioinformatic analyses, luciferase activity reporter assay, RNA pull-down assay, and rescue experiments.Results: We showed LINC00665 expression was significantly increased in both BC tissues and cells. The knockdown of LINC00625 significantly inhibits BC cell growth and promotes cell apoptosis in vitro, while the overexpression of LINC00625 has the opposite effects on BC progression. LINC00665 could affect BC progression via regulating miR-551b-5p.Discussion: Taken together, our study showed that the LINC00665/miR-551b-5p axis was involved in the progression of BC.Keywords: LINC00665, miR-551b-5p, breast cancer, progression

Yan Yao,1 Tingting Zhang,2 Lingyu Qi,2 Ruijuan Liu,3 Gongxi Liu,3 Jie Li,2 Changgang Sun3,4 1Clinical Medical Colleges, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 2College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 3Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Changgang SunInnovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaTel +86 13583690699Email zhongliuyike@163.comBackground: Tumor microenvironment (TME) cells constitute a vital element of tumor tissues. Increasing evidence has shown that immune response in the microenvironment plays an active role in tumor invasion, metastasis, and recurrence, and is an important factor affecting tumor prognosis. Our study aimed to identify the gene signatures in lung adenocarcinoma (LUAD) microenvironment for prognosis and immunotherapy.Methods: In this study, we evaluated, for the first time, the stromal and immune scores of 594 patients from The Cancer Genome Atlas (TCGA) database with LUAD using the ESTIMATE algorithm. Three hundred and sixty-seven dysregulated immune-related genes were identified. Then, we performed functional enrichment analysis of these genes, and found the best gene model and construct the signature through univariate, Lasso and multivariate COX regression analysis. To assess the independently prognostic ability of the signature, the Kaplan–Meier survival analysis and Cox’s proportional hazards model were performed.Results: Functional enrichment analysis and protein–protein interaction networks showed that the immune-related genes mainly played a role in immune response, activation/proliferation of immune-related cells, and chemokine activity. A prognostic model involving 6 genes was constructed and the signature was identified as an independent prognostic factor and significantly associated with the overall survival (OS) of LUAD. The area under curve (AUC) of the receiver operating characteristic curve (ROC curve) for the 6 genes signature in predicting the 3-year survival rate was 0.708. Finally, four genes (FOXN4, KLHL4, FAM83F and CCR2) can be used as candidate prognostic biomarkers for LUAD.Conclusion: Our findings will help evaluate the prognosis of LUAD and provide new ideas for exploring the potential relationship between TME and LUAD treatment and prognosis.Keywords: lung adenocarcinoma, tumor microenvironment, ESTIMATE algorithm, immune-related gene, prognosis signatures

Meng-ke Fan,1,2 Li-li Qi,3 Qi Zhang,2 Ling Wang1,2 1Department of Orthopedic Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Orthopedic Research Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Ling WangDepartment of Orthopedic Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaEmail wangling2016uw@126.comQi ZhangOrthopedic Research Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaTel +86 031 188602590Email zq_19865@163. comAbstract: Although the mortality rate of osteosarcoma (OS) patients has improved, there are still many unsolved problems concerning how to reduce recurrence and metastasis. In the tumor microenvironment, immune escape plays a more important role in tumor progression and development. Many costimulatory molecules of the B7 family have been reported to be involved in regulating immunological interactions between OS cells and immune cells. Among these molecules, B7-H1 and its receptor, programmed death-1 (PD-1), have been the focus of the fields of tumor immunology and have been recently applied in clinical trials of therapies for several solid tumors. These therapies, referred to as B7-H1/PD-1 checkpoint blockade therapies, are designed to block the interaction between the two molecules. Although the mechanism has been reported in some malignancies, the specific impact of B7-H1/PD-1 expression on OS has not been well defined. Here, we review the expression, function, and regulatory mechanism of the B7-H1/PD-1 axis in OS and introduce and compare the advantages and disadvantages of B7-H1/PD-1 immunotherapies in OS.Keywords: osteosarcoma, immunotherapy, B7-H1, PD-1

Hang Zhao,1 Yunfeng Zhen,1 Zijing Wang,1 Licui Qi,2 Yong Li,3 Luping Ren,1,* Shuchun Chen1,* 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 2Graduate School of Hebei North University, Zhangjiakou, Hebei 07500, People’s Republic of China; 3Graduate School of North China University of Science and Technology, Caofeidian New Town, Tangshan, Hebei 063210, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuchun ChenEndocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaEmail guang6701@sina.comLuping RenEndocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaEmail renluping1122@163.comPurpose: The aims of this study were to determine the relationship between 25-hydroxyvitamin D [25(OH) D] and glycated hemoglobin (HbA1c) levels in male and female patients with type 2 diabetes mellitus (T2DM).Patients and Methods: The participants were adults diagnosed with T2DM recruited from Hebei General Hospital. Patient information and information regarding blood indicators were collected. The subjects were divided into no vitamin D deficiency group [25(OH) D > 20 ng/mL] and vitamin D deficiency group [25(OH) D < 20 ng/mL], and these groups were then further subdivided into male-only or female-only subgroups. And then, the subjects were divided into male group and female group in different 25(OH) D levels.Results: HbA1c levels in the vitamin D deficiency group were significantly higher than those in the no vitamin D deficiency group for all subjects. The same was true for female patients but not for male patients. There was no difference in HbA1c levels between male and female patients with T2DM, regardless of 25(OH) D deficiency. A negative correlation existed between 25(OH) D and HbA1c in all subjects, as well as in the male-only and female-only subgroups. Vitamin D deficiency was associated with high HbA1c levels before and after adjusting for confounding factors in all participants and in the female-only subgroup, but not in the male-only subgroup.Conclusion: This study confirmed that vitamin D deficiency was related with high HbA1c levels in patients with T2DM, and this relationship differs between female and male patients.Keywords: diabetes mellitus, type 2, 25-hydroxyvitamin D, glycated hemoglobin

Ning Yang,1 Feng Qiu,2 Feng Zhu,3 Lei Qi4 1Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, People’s Republic of China; 2Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; 3Department of Thoracic Surgery, Shandong Provincial Chest Hospital, Jinan, Shandong 250013, People’s Republic of China; 4Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, People’s Republic of ChinaCorrespondence: Lei QiDepartment of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong Province 250012, People’s Republic of ChinaEmail walker789sdu@sina.comIntroduction: Lung cancer is one of the most aggressive forms of cancer that leads to a high mortality rate amongst several cancer types and it is a widely recurrent cancer globally. The use of zinc oxide nanoparticles (ZnONPs) in the formulation of sun cream, food flavors, and colorings due to its varied biological properties. The extensive significance of nanoparticles encourages their production but the approaches are a common challenge in concluding the direct beneficial effect for the disease treatment. Hence, in the present study, zinc oxide-loaded syringic acid (ZnO-SYR) phytochemical was used to elucidate the therapeutic effect against lung cancer.Methods: The ZnO-SYR nanoparticles were synthesized and characterized by UV-visible spectroscopy, X-ray diffraction, dynamic light scattering, and FT-IR analysis. The characterized ZnO-SYR was tested on in vivo mouse model of lung cancer (benzo(a)pyrene (BAP)) and in vitro A549 cells.Results: The results demonstrated the significant restoration of body weight with attenuated serum marker enzymes compared to BAP-treated animals. In addition, cytokine estimation revealed ameliorated levels of TNF-α, interleukins, IL-6, IL-1β with evidenced histological observations in ZnO-SYR-treated mice compared to BAP-induced lung cancer mice.Discussion: Furthermore, cytotoxicity analysis demonstrated the altered mitochondrial membrane potential (MMP), with a profound increase in reactive oxygen species (ROS) levels, and apoptosis mechanism by ZnO-SYR compared to control cells. The conclusions of the present study put forward an evident confirmation of the protective and beneficial effects of zincoxide-loaded syringic acid against the BAP-induced lung cancer model.Keywords: zinc oxide nanoparticles, syringic acid, lung cancer, apoptosis, A549

Zhong Lu,1,2 Li Qi,2 Ya-ru Lin,2 Lei Sun,2 Lin Zhang,2 Gui-chun Wang,2 Jia-qiu Li,2 Jin-ming Yu2 1Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, People’s Republic of China; 2Department of Oncology, Clinical College of Weifang Medical University, Weifang 261031, People’s Republic of ChinaCorrespondence: Li QiDepartment of Oncology, Clinical College of Weifang Medical University, Weifang 261031, People’s Republic of ChinaTel +86 0536-3081263Email qili1104doc@126.comIntroduction: Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy. We aim to develop a delivery system with higher efficiency than free drug.Methods: Metformin-bovine serum albumin (met-BSA) nanoparticles (NPs) were prepared using the anti-solvent precipitation method with a stabilizer of BSA for particle growth. The therapeutic effect of the drug was tested by the insulin-resistant HepG2 cells and C57BL/6J mice at a glucose starvation condition. The interaction mechanism of the drug and the protein during the formation of the NPs was tested using a series of spectroscopy.Results: Metformin and BSA formed nonporous and spherical particles of about 200 nm with proper lognormal distribution and thermostability. The cellular uptake, as well as the anti-liver cancer activities of met-BSA, was enhanced dramatically compared with the free drug. The thermodynamic studies suggested that the weak binding of metformin to BSA was governed by hydrogen bonds and van der Waals forces. Moreover, the results of synchronous, circular dichroism (CD) and three-dimensional fluorescence demonstrated that the BSA skeleton and chromophore microenvironments were changed in the presence of metformin.Conclusion: Therefore, met-BSA has been proved as a simple yet effective therapeutic agent for cancer with insulin resistance, promising for future clinic translations in cancer treatment.Keywords: liver cancer, metformin, bovine serum albumin, nanoparticle, spectroscopy

Zhi Wang,1,2 Laura E Pascal,2 Uma R Chandran,3 Srilakshmi Chaparala,3 Shidong Lv,2,4 Hui Ding,2 Lin Qi,1 Zhou Wang2,5– 7 1Department of Urology, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 3Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA; 4Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 6Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 7Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USACorrespondence: Zhou Wang Email wangz2@upmc.eduBackground: Elongation factor for RNA polymerase II 2 (ELL2) was reported as a putative tumor suppressor in the prostate. ELL2 is frequently down-regulated in prostatic adenocarcinoma specimens, and loss of ELL2 induced murine prostatic intraepithelial neoplasia and enhanced AR-positive prostate cancer cell proliferation. However, the ELL2 gene appears to be amplified in AR-negative neuroendocrine prostate tumors, suggesting a potential oncogenic role for ELL2 in AR-negative prostate cancer cells. In this study, we explored the potential function of ELL2 in PC-3 and DU145, two AR-negative prostate cancer cell lines.Materials and Methods: The role of ELL2 in PC-3 and DU145 cells was studied using siRNA-mediated ELL2 knockdown. Genes regulated by ELL2 knockdown in PC-3 cells were identified and analyzed using RNA-Seq and bioinformatics. The expression of representative genes was confirmed by Western blot and/or quantitative PCR. Cell growth was determined by BrdU, MTT and colony formation assays. Cell death was analyzed by 7-AAD/Annexin V staining and trypan blue exclusion staining. Cell cycle was determined by PI staining and flow cytometry.Results: ELL2 knockdown inhibited the proliferation of PC-3 and DU145 cells. RNA-Seq analysis showed an enrichment in genes associated with cell death and survival following ELL2 knockdown. The interferon-γ pathway was identified as the top canonical pathway comprising of 55.6% of the genes regulated by ELL2. ELL2 knockdown induced an increase in STAT1 and IRF1 mRNA and an induction of total STAT1 and phosphorylated STAT1 protein. Inhibition of cell proliferation by ELL2 knockdown was partly abrogated by STAT1 knockdown. ELL2 knockdown inhibited colony formation and induced apoptosis in both PC-3 and DU145 cells. Furthermore, knockdown of ELL2 caused S-phase cell cycle arrest, inhibition of CDK2 phosphorylation and cyclin D1 expression, and increased expression of cyclin E.Conclusion: ELL2 knockdown in PC-3 and DU145 cells induced S-phase cell cycle arrest and profound apoptosis, which was accompanied by the induction of genes associated with cell death and survival pathways. These observations suggest that ELL2 is a potential oncogenic protein required for survival and proliferation in AR-negative prostate cancer cells.Keywords: DU145, PC-3, STAT1, IRF, CDK2

Zhen Zhu,1,* Lanlan Ling,2,* Lezhong Qi,1 Yue Chong,3 Li Xue4 1Department of Urology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Health Management Center, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Urology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Urology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li XueDepartment of Urology, Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwulu Road, Xi’an, Shaanxi 710004, People’s Republic of ChinaTel/Fax +86-29-87679533Email xueli1979@xjtu.edu.cnIntroduction: Bruton’s tyrosine kinase (BTK) inhibitors have long been known in the treatment of B-cell malignancies. Recently, BTK inhibitors have also become promising novel treatment reagents for prostate cancer. The current study was designed to investigate expression of BTK in prostate cancer tissues in comparison with benign hyperplasia and effect of BTK inhibitor on prostate cancer cell proliferation, migration and invasion.Methods: BTK expression was assessed by immunohistochemistry; migration and invasion prostate cancer cell lines (DU145 and PC3) were assessed by Transwell migration and wound-healing assay; cancer cell proliferation was assessed using MTT assay kit; expression of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) was assessed by immunoblotting.Results: Strong expression of BTK was detected in the prostate cancer tissues, especially in the tumors from prostate cancer patients with bone metastasis. BTK inhibitor (Ibrutinib) significantly inhibited cell proliferation, migration and invasion of prostate cancer cells as well as protein synthesis of MMP-2 and MMP-9 by the tumor cells. Overexpressing BTK could partially but significantly block the inhibitory effect of Ibrutinib on cell proliferation, migration and invasion, and protein synthesis of MMP-2 and MMP-9 of the cancer cells.Conclusion: These findings suggested that BTK could serve as not only a biomarker but also a therapeutic target for the prostate cancer and that Ibrutinib may be applied as a therapeutic drug for the prostate cancer.Keywords: Bruton’s tyrosine kinase, BTK, prostate cancer, matrix metalloproteinase, MMP

Yi-Ming Xu,1 Teng Zhang,1 Hai Xu,1 Liang Qi,1 Wei Zhang,1 Yu-Dong Zhang,1 Da-Shan Gao,2 Mei Yuan,1 Tong-Fu Yu1 1Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2 12sigma Technologies, San Diego, California, USACorrespondence: Mei Yuan; Tong-Fu YuDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, 210009 Tel +86-13405835354; +86-13813810516Fax +86-02568136861Email yuanmeijiangsu@163.com; njmu_ytf@163.comPurpose: The purpose of this study is to compare the detection performance of the 3-dimensional convolutional neural network (3D CNN)-based computer-aided detection (CAD) models with radiologists of different levels of experience in detecting pulmonary nodules on thin-section computed tomography (CT).Patients and Methods: We retrospectively reviewed 1109 consecutive patients who underwent follow-up thin-section CT at our institution. The 3D CNN model for nodule detection was re-trained and complemented by expert augmentation. The annotations of a consensus panel consisting of two expert radiologists determined the ground truth. The detection performance of the re-trained CAD model and three other radiologists at different levels of experience were tested using a free-response receiver operating characteristic (FROC) analysis in the test group.Results: The detection performance of the re-trained CAD model was significantly better than that of the pre-trained network (sensitivity: 93.09% vs 38.44%). The re-trained CAD model had a significantly better detection performance than radiologists (average sensitivity: 93.09% vs 50.22%), without significantly increasing the number of false positives per scan (1.64 vs 0.68). In the training set, 922 nodules less than 3 mm in size in 211 patients at high risk were recommended for follow-up CT according to the Fleischner Society Guidelines. Fifteen of 101 solid nodules were confirmed to be lung cancer.Conclusion: The re-trained 3D CNN-based CAD model, complemented by expert augmentation, was an accurate and efficient tool in identifying incidental pulmonary nodules for subsequent management.Keywords: computer-aided detection, computed tomography, pulmonary nodules, convolutional neural network

When a child shows signs of potential motor developmental disorders, early diagnosis of central nervous system (CNS) impairment is beneficial. Known as the first CNS-controlled mobility for most of infants, mobility during crawling usually has been used in clinical assessments to identify motor development disorders. The current clinical scales of motor development during crawling stage are relatively subjective. Objective and quantitative measures of infant crawling afford the possibilities to identify those infants who might benefit from early intervention, as well as the evaluation of intervention progress. Thus, increasing researchers have explored objective measurements of infant crawling in typical and atypical developing infants. However, there is a lack of comprehensive review on infant-crawling measurement and analysis toward bridging the gap between research crawling analysis and potential clinical applications. In this narrative review, we provide a practical overview of the most relevant measurements in human infant crawling, including acquisition techniques, data processing methods, features extraction, and the potential value in objective assessment of motor function in infancy; meanwhile, the possibilities to develop crawling training as early intervention to promote the locomotor function for infants with locomotor delays are also discussed.

Qian Song,1 Honggang Pang,2 Lei Qi,1 Chen Liang,1 Tuo Wang,1 Wei Wang,1 Ruichun Li1 1Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China; 2Department of Peripheral Vascular Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of ChinaCorrespondence: Ruichun LiDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaEmail fourcycle@126.comBackground: MicroRNAs have been recently reported to play an important role in tumorigenesis and progression in several forms of tumors. Previous studies have shown that microRNA-622 (miR-622) was associated with glioma proliferation and invasion. However, the clinical significance of miR-622 in glioma has not been elucidated. The aim of our study was to investigate the clinical values of miR-622, as well as investigate the potential molecular mechanisms in glioma.Materials and methods: qRT-PCR and Western blot analysis were used to analyze the expression of miR-622 and ZEB2, respectively. Kaplan–Meier analysis and Cox’s proportional hazards model were used in survival analysis. MTT assay, wound healing assay, transwell assay and flow cytometry analysis were carried out to detect the impact of miR-622 on glioma cell proliferation, migration, invasion and apoptosis.Results: Our result indicated that miR-622 expression was greatly decreased in glioma tissues and cell lines and the downregulation of miR-622 was significantly associated with the advanced pathological grade and low Karnofsky performance score of glioma. In addition, Kaplan–Meier curves with log-rank analysis revealed a close correlation between downregulation of miR-622 expression and low overall survival rate in glioma patients. Furthermore, Cox regression analysis demonstrated that downregulated miR-622 could be considered as an independent poor prognostic indicator in glioma patients. Finally, our findings demonstrated that miR-622 overexpression remarkably suppressed glioma cell proliferation, migration and invasion, while facilitated apoptosis by suppressing ZEB2 in vitro.Conclusion: Our study suggested that miR-622 may be identified as a valuable prognostic biomarker and a promising therapeutic target for glioma patients.Keywords: glioma, microRNA-622, prognosis, overall survival, ZEB2

Xin Wang,1 Jun-Fei Luo,2 Lin Qi,3,4 Qing Long,1 Jia Guo,1 Hong-Hong Wang11Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2The College of Literature and Journalism, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Hunan Key Laboratory of Tumor Models and Individualized Medicine, the Second Xiangya Hospital, Changsha, Hunan, People’s Republic of ChinaBackground and purpose: Self-monitoring of blood glucose (SMBG) is important to the management of diabetes mellitus, yet most patients with type 2 diabetes mellitus (T2DM) do not perform SMBG as recommended. The current status and influential factors of SMBG in China have not been well investigated. This study aimed to describe the present status of SMBG adherence in China and investigate the influential factors based on electronic questionnaires.Patients and methods: A cross-sectional study was conducted from June to July of 2017 at hospitals in Changsha, China. Seven hundred and twenty-one patients with T2DM completed the information‑motivation‑behavioral (IMB) skills questionnaire and other electronic questionnaires composed of demographic and clinical characteristics as well as diabetes-related and psychological scales. Univariate comparisons and multivariate logistic regression were used to explore the relationships among SMBG adherence and related factors.Results: Seven hundred and twenty-one patients with valid questionnaires were included. Only 27.5% (198/721) of the patients with T2DM were SMBG adherent based on the guideline of the Chinese Diabetes Society (CDS) in 2017. Among all groups of treatment regimens, the rate of SMBG adherence was highest at 36.6% (82/224) in patients on oral hypoglycaemic drugs (OHAs). In multivariable analysis, the treatment of OHAs (OR =3.731, CI 2.162–6.437) and diet/exercise (OR =3.534, CI 1.841–6.783), the patient having their own blood glucose meter (OR =6.916, CI 4.054–11.800) and a higher education level (OR =3.780, CI 1.688–8.466) were significantly associated with SMBG adherence.Conclusion: Most Chinese patients with T2DM did not perform SMBG as recommended. The treatment of OHAs and diet/exercise, the patient having their own blood glucose meter, a higher education level and other factors were correlates of SMBG adherence. There is clearly a need for prospective, multicenter, large-scale studies to explore the reasons for patients’ failure to practice SMBG adherence.Keywords: type 2 diabetes mellitus, self-monitoring of blood glucose, adherence, glycemic control, China

Fubin Feng,1 Tingting Zhang,2 Fang Yin,3 Cun Liu,2 Jing Zhuang,1 Lingyu Qi,2 Xue Wang,4 Jia Li,5 Lu Wang,1 Jinhui Tian,6 Changgang Sun1,7 1Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, China; 2College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China; 3Department of Pediatrics, Weifang People’s Hospital, Weifang, Shandong Province, China; 4Department of Medicine, Qingdao University, Qingdao, Shandong Province, China; 5Department of Oncology, Weifang Medical University, Weifang, Shandong Province, China; 6Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, China; 7Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, China Purpose: Numerous HER2-targeted therapy clinical trials have demonstrated efficacy and safety in the first-line treatment of metastatic breast cancer (MBC). However, the direct or indirect comparison of these drugs is unclear. This network meta-analysis can solve this issue to some extent. Materials and methods: PubMed, Embase, and the Cochrane Library were searched for Phase II/III randomized controlled trials (RCTs) on metastatic HER2-positive breast cancer for first-line treatment up to December 16, 2017. Paired meta-analyses were performed to compare the regimens directly with the TP (trastuzumab plus taxane) regimen. Bayesian network meta-analysis was used to synthesize available evidence of direct or indirect comparison. Results: The database search identified 1,935 articles, among which 13 articles (10 RCTs) were eligible for the analysis involving 5,177 patients treated with 11 different regimens. The progression-free survival (PFS) in the Bayesian network meta-analysis suggested that the PTP (pertuzumab and trastuzumab plus taxane) regimen had the highest probability to be the preferred treatment (surface under the cumulative ranking [SUCRA]: 0.967) followed by the TPC (carboplatin and trastuzumab plus taxane) regimen (SUCRA: 0.923). The PTP regimen (SUCRA: 0.926) was similarly preferred for overall survival (OS). For objective response rate (ORR), the PTC regimen might be the optimal treatment (SUCRA: 0.935), followed by the PTP regimen. Conclusion: Overall, PTP might be the optimal first-line treatment for HER-2-positive MBC to improve the PFS and OS. Meanwhile, TPC might be most effective treatment in terms of the ORR. Regarding safety, the two regimens showed acceptable grade 3 or greater hematologic toxicity and heart failure. Keywords: breast cancer, metastasis, HER2-positive, HER2-targeted agents, network meta-analysis, randomized controlled trial

Tingting Zhang,1 Yan Yao,2 Fubin Feng,3 Wenge Zhao,2 Jinhui Tian,4 Chao Zhou,3 Xue Wang,5 Shengjie Dong,6 Jia Li,2 Lingyu Qi,7 Changgang Sun3,8 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Clinical Medical College, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, People’s Republic of China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 5Clinical Medical Colleges, Qingdao University, Shinan District, Qingdao, Shandong Province, People’s Republic of China; 6Department of the Joint and Bone Surgery, Yantaishan Hospital, Yantai, Shandong Province, People’s Republic of China; 7College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, People’s Republic of China; 8Department of Oncology, Affiliated Hospital of Weifang Medical University, Kuiwen District, Weifang, Shandong Province, People’s Republic of China Background: Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of the efficacy of different chemotherapy regimens in adults with advanced-stage HL.Materials and methods: We searched for relevant randomized controlled trials (RCTs) in titles/abstracts in PubMed, Embase, and the Cochrane Library. The search was last updated on April 3, 2018. RCTs that assessed the effectiveness of one of the following treatments were included: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); four cycles of increased dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) followed by two or four cycles of standard dose of BEACOPP (4× BEACOPPescalated + 2 or 4× BEACOPPbaseline); brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD); doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (Stanford V); mechlorethamine (cyclophosphamide), vincristine, procarbazine, and prednisone (M[C]OPP); sequential or alternating chemotherapy regimens with ABVD as the footstone (eg, COPP/ABVD or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/ABVD); eight cycles of BEACOPPescalated; hybrid MOPP/ABV; and M[C]EC (M[C]OPP with epidoxorubicin, bleomycin, vinblastine [EBV], and lomustine, doxorubicin, and vindesine [CAD]).Results: Overall, we screened 3,564 citations and deemed 18 reports of 16 trials eligible and included them in our network meta-analysis. A total of 11,928 participants were randomly assigned to one of the 12 combinations of chemotherapy regimens, of which 11,476 participants were analyzed. For the overall survival (OS), no differences were observed within any interventions when the ABVD regimen was used as the reference treatment. Similarly, relative to A+AVD, 8× BEACOPPescalated and 6× BEACOPPescalated also showed no differences (HR =1.07, 95% credible interval (CrI): 0.58–1.95; HR =0.62, 95% CrI: 0.16–1.83; and HR =0.71, 95% CrI: 0.30–1.72, respectively). In terms of complete remission (CR), enough evidence exists to support a maximum clinical treatment effect for 6× BEACOPPescalated (OR =1.88, 95% CrI: 1.20–2.96; and OR =3.43, 95% CrI: 1.87–6.24).Conclusion: When compared across the 12 combined chemotherapy regimens, six cycles of BEACOPPescalated may be the optimal treatment for patients with advanced-stage HL. Keywords: advanced-stage Hodgkin lymphoma, combined chemotherapy, overall survival, network meta-analysis, randomized controlled trial

Autosomal recessive homozygous or compound heterozygous mutations in FKRP result in forms of muscular dystrophy-dystroglycanopathy varying in age of onset, clinical presentation, and disease progression, ranging from the severe Walker-Warburg, type A,5 (MDDGA5), muscle-eye-brain (MDDGB5) with or without cognitive deficit, to limb-girdle type 2I (MDDGC5). Phenotypic variation indicates degrees of functionality of individual FKRP mutation, which has been supported by the presence of residual expression of functionally glycosylated α-dystroglycan (DG) in muscles of both animal models and patients. However, direct evidence showing enhancement in glycosylation of α-DG by mutant FKRP is lacking. Using AAV9-mediated overexpression of mutant human FKRP bearing the P448L mutation (mhFKRP-P448L) associated with severe congenital muscular dystrophy (CMD), we demonstrate the restoration of functional glycosylation of α-DG and reduction in markers of disease progression. Expression of mhFKRP-P448L also corrects dystrophic phenotypes in the models of L276I mutation with mild disease phenotype and causes no obvious histological or biomarker alteration in C57BL/6 normal mice. Our results confirm the existing function of mutant FKRP. The results also suggest that mutant FKRP could be an alternative approach for potential gene therapy should normal FKRP gene products be immunogenic.

Qinghua Wang,1–3,* Shujun Jiang,1,2,* Anying Song,1,2 Siyuan Hou,1,2 Qinfeng Wu,4 Longju Qi,5 Xiang Gao1,21State Key Laboratory of Pharmaceutical Biotechnology, 2MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, 3Laboratory Animal Center, Nantong University, 4Department of Rehabilitation, Affiliated Hospital of Nantong University, Nantong University, 5Interventional Therapy Department of the Third People’s Hospital of Nantong City, Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this workAbstract: Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and it occurs at a higher frequency in males. HOXD-AS1, an important cancer-associated long noncoding RNA (lncRNA), contributes to the development and progression of several cancers. However, the exact roles of HOXD-AS1 in NSCLC progression are still unknown. Here, we investigated the underlying mechanisms of HOXD-AS1 in human NSCLC tissues. We found that lncRNA HOXD-AS1 was specifically upregulated (P

Hands-and-knees-crawling is an important motor developmental milestone and a unique window into the development of central nervous system (CNS). Mobility during crawling is regularly used in clinical assessments to identify delays in motor development. However, possible contribution from CNS impairments to motor development delay is still unknown. The aim of this study was to quantify and compare inter-limb muscle synergy and kinematics during crawling among infants at a similar developmental age, however, clinically determined to be typically developing (TD, N = 20) infants, infants at risk of developmental delay (ARDD, N = 33), or infants with confirmed developmental delay (CDD, N = 13). We hypothesized that even though all of the groups are at a similar developmental age, there would be differences in kinematic measures during crawling, and such differences would be associated with CNS impairment as measured by electromyography (EMG) features. Surface EMG of eight arm and leg muscles and the corresponding joint kinematic data were collected while participants crawled on hands and knees at their self-selected velocity. Temporal-spatial parameters and normalized Jerk-Cost (JC) function (i.e., smoothness of movement) were computed from the measured kinematics. The inter-limb muscle synergy and the number of co-activating muscles per synergy were measured using EMGs. We found that the infants with CDD demonstrated higher normalized JC values (less movement smoothness), fewer muscle synergies, and more co-activating muscles per synergy, compared to infants with TD (p < 0.05) and ARDD (p < 0.05). Furthermore, the normalized JC values were correlated (p < 0.05) with the number of co-activation muscles per synergy. Our results suggest a constrained neuromuscular control strategy due to neurological injury in infants with CDD, and such constrain may contribute to the reduced movement smoothness in infant crawling.

Hui Fu,1,2,* Lisha Qi,2,3,* Lu Chen,1,2 Yuchao He,1,2 Ning Zhang,1,2 Hua Guo1,2 1Department of Tumor Cell Biology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, 2The Key Laboratory of Tianjin Cancer Prevention and Treatment, National Clinical Research Center for Cancer, 3Department of Pathology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Metastasis involves epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition. Ovol2 belongs to the Ovo-like family (Ovol) of evolutionarily conserved zinc-finger transcription factors that regulate gene expression in various differentiation processes. Recent studies have demonstrated that Ovols affect mesenchymal–epithelial transition by inducing the expression of miR-200 in a range of human cancers. Downregulated Ovol2 expression is involved in the invasion and metastasis of breast and prostate cancers, but little is known about its expression and prognostic value in other cancers, including hepatocellular carcinoma (HCC). This study was designed to explore the clinical and prognostic significance of Ovol2 in patients with HCC. The expression of Ovol2 in tumor samples from patients with HCC and HCC cell lines was examined using Western blotting, real-time polymerase chain reaction, and immunohistochemistry. The expression levels of EMT-related markers, including E-cadherin, N-cadherin, and vimentin, were detected in relation to Ovol2 expression. The prognostic significance of Ovol2 in patients with HCC was statistically analyzed by Kaplan–Meier and Cox regression analyses. Ovol2 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues. Low expression of Ovol2 was detected in HCC tissues with poor histological differentiation, microvascular invasion, and cirrhosis. A significant relationship was observed between Ovol2 and EMT marker expression levels. Kaplan–Meier analysis showed that overall survival was significantly worse in patients with HCC with low Ovol2 expression, indicating that Ovol2 deletion was an independent predictor of unfavorable prognosis in patients with HCC. Elevated Ovol2 expression may suppress HCC cell invasion and metastasis via restricting EMT. Keywords: Ovol2, hepatocellular carcinoma, prognosis, epithelial–mesenchymal transition, mesenchymal–epithelial transition

Although the role of roots has been highlighted in carbon and nutrient cycles in forest ecosystems, root production, turnover and total belowground carbon allocation (TBCA) under different management regimes in Moso bamboo forests have not been determined to date. In this study, sequential soil cores were collected at two soil depths (0-20 cm and 20-40 cm) to assess the effects of understory removal on root production, turnover, and TBCA in Moso bamboo forests in subtropical China. A total of 1080 sequential soil cores were collected from April 2011 to March 2012. Understory removal significantly reduced fine root biomass and production for both soil layers (p < 0.05). Total fine root biomass was 781.9, 419.2, and 638.7 g m-2 for an unmanaged stand (stand I), pesticide-treated stand (stand II), and hand-weeded stand (stand III), and fine root production was 467.5, 235.1, and 321.6 g m-2 a-1, respectively. Understory removal did not significantly affect fine root turnover (0.5-0.6 a-1). Fine root turnover showed a strong relationship with fine root production, but not with fine root biomass, indicating that fine root production was the main driver of fine root turnover. TBCA calculated from the component cumulative approach was in order of stand I (481.9 g C m-2 a-1) > stand II (457.7 g C m-2 a-1) > stand III (404.9 g C m-2 a-1), though the differences were not statistically significant (p > 0.05). However, TBCA calculated from the mass balance approach showed a reverse trend compared to the component cumulative approach. The TBCA of stand III was significantly higher than that of stand I and stand II (p < 0.05), demonstrating that the belowground process is complex and standardizing the method of estimation of TBCA is extremely important in global carbon cycle modeling.

Understanding spatial and temporal variation in soil respiration (RS) in different forest ecosystems is crucial to estimate the global carbon balance. Bamboo forest is a special forest type in southern China covering an area of 5.38 million ha, 70% of which are Moso bamboo (Phyllostachys heterocycla (Carr.) Mitford cv. Pubescens) forests. Bamboo forests contribute more than 10% to the whole carbon stock of forest ecosystems in China, and therefore play a critical role in the regional and national carbon balance. However, little information on the seasonal dynamic of RS and the carbon balance of Moso bamboo forests is available. In this study, litter removal and trenching methods were applied to partition RS into root respiration (RR), litter respiration (RL) and soil organic matter derived respiration (RM), and to study their seasonal dynamics and carbon balance in a pure Moso bamboo forest. Monthly RS, its source components and combined monthly environmental factors were measured. RS and its source components showed a significant seasonal variability with higher values from June to August and lower values from December to February driven by soil temperature and moisture (P < 0.001). Annual average RS, RR, RL and RM were 2.37, 0.69, 0.58 and 1.10 μmol m-2 s-1 with Q10 values of 1.25, 1.15, 1.19 and 1.26, respectively. Annual RS was 8.97 t C ha-1, and RR, RL and RM contributed 29%, 22% and 49%, respectively. Annual NEP was 4.72 t C ha-1 y-1, indicating that the Moso bamboo forest studied is a significant carbon sink.

Limb-girdle muscular dystrophy type 2i (LGMD2i) affects thousands of lives with shortened life expectancy mainly due to cardiac and respiratory problems and difficulty with ambulation significantly compromising quality of life. Limited studies have noted impaired gait in patients and animal models of different muscular dystrophies, but not in animal models of LGMD2i. Our goal, therefore, was to quantify gait metrics in the fukutin-related protein P448L mutant (P448L) mouse, a recently developed model for LGMD2i. The Noldus CatWalk XT motion capture system was used to identify multiple gait impairments. An average galloping body speed of 35 cm/s for both P448L and C57BL/6 wild-type mice was maintained to ensure differences in gait were due only to strain physiology. Compared to wild-type mice, P448L mice reach maximum contact 10% faster and have 40% more paw surface area during stance. Additionally, force intensity at the time of maximum paw contact is roughly 2-fold higher in P448L mice. Paw swing time is reduced in P448L mice without changes in stride length as a faster swing speed compensates. Gait instability in P448L mice is indicated by 50% higher instances of 3 and 4 paw stance support and conversely, 2-fold fewer instances of single paw stance support and no instance of zero paw support. This leads to lower variation of normal step patterns used and a higher use of uncommon step patterns. Similar anomalies have also been noted in muscular dystrophy patients due to weakness in the hip abductor muscles, producing a Trendelenburg gait characterized by "waddling" and more pronounced shifts to the stance leg. Thus, gait of P448L mice replicates anomalies commonly seen in LGMD2i patients, which is not only potentially valuable for assessing drug efficacy in restoring movement biomechanics, but also for better understanding them.

Precise spectroscopic information on the fast neutron induced fission of the 238U(n,f) reaction was recently gained using a new technique which involved coupling of the Miniball high resolution y-ray spectrometer and the LICORNE directional neutron source. The experiment allowed measurement of the isotopic fission yields for around 40 even-even nuclei at an incident neutron energy of around 2 MeV where yield data are very sparse. In addition spectroscopic information on very neutron-rich fission products was obtained. Results were compared to models, both the JEFF-3.1.1 data base and the GEF code, and large discrepancies for the S1 fission mode in the Sn/Mo isotope pair were discovered. This suggests that current models are overestimating the role played by spherical shell effects in fast neutron induced fission. In late 2017 and 2018 the nu-ball hybrid spectrometer will be constructed at the IPN Orsay to perform further experimental investigations with directional neutrons coupled to a powerful hybrid Ge/LaBr3 detector array. This will open up new possibilities for measurements of fission yields for fast-neutron-induced fission using the spectroscopic technique and will be complimentary to other methods being developed.

Prompt fission gamma-ray spectra (PFGS) have been measured for the 239Pu(n,f) reaction using fast neutrons at Ēn=1.81 MeV produced by the LICORNE directional neutron source. The setup makes use of LaBr3 scintillation detectors and PARIS phoswich detectors to measure the emitted prompt fission gamma rays (PFG). The mean multiplicity, average total energy release per fission and average energy of photons are extracted from the unfolded PFGS. These new measurements provide complementary information to other recent work on thermal neutron induced fission of 239Pu and spontaneous fission of 252Cf.