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Qinglin Li, 1,* Tianyi Zhang, 2,* Fei Li, 3, 4,* Zhi Mao, 1 Hongjun Kang, 1 Ling Tao, 3,* Feihu Zhou, 1, 3,* Yue Cai 1, 3, 4,* 1Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Institution of Hospital Management, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 3Department of Cardiology, Xijing Hospital, Xi’an 710032, People’s Republic of China; 4Department of Infectious Diseases, Huo Shen Shan Hospital, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feihu Zhou Tel +86 10 6693 8148Email feihuzhou301@126.comYue Cai Tel + 86 159 0238 8078Email caiyueclear1981@163.comObjective: Severe or critical patients with coronavirus disease 2019 (COVID-19) are at increased risk for developing acute kidney injury (AKI). However, the rate of AKI in patients of different severities and independent predictive factors associated with AKI are not well understood.Patients and Methods: We enrolled 107 severely or critically ill elderly patients with COVID-19 who were admitted to the intensive care unit (ICU) in Wuhan, China. AKI was defined according to the 2012 KDIGO criteria. We explored the association between AKI and in-hospital mortality using logistic regression. A predictive nomogram was formulated to predict the AKI development of patients with COVID-19 based on multivariate logistic regression.Results: A total of 107 elderly patients were enrolled during the study period. The mean age was 70 (64– 78) years, and 69 (64.5%) were men. For the 107 patients, the degree of severity of COVID-19 was categorized as 37 patients with the severe type (34.6%) and 70 patients with the critical type (65.4%). Overall, 48 of the 107 patients (44.9%) developed AKI during their hospitalization, while AKI occurred in 7 (18.9%) out of the 37 severe patients and 41 (44.9%) out of the 70 critical patients. Of the AKI patients, 35.4% (17/48) required continuous renal replacement therapy, including 14.3% of AKI patients in severe cases and 39.0% of AKI patients in critical cases. Kaplan–Meier analysis demonstrated that patients with AKI had a significantly higher risk for in-hospital mortality than severely and critically ill patients without AKI. Multivariate logistic regression analysis showed that AKI (OR = 33.74; 95% CI = 3.34– 341.29; P = 0.003), septic shock (OR = 15.58; 95% CI = 2.08– 116.78; P = 0.008), invasive mechanical ventilation (OR = 18.44; 95% CI = 2.35– 144.69; P = 0.006), and oxygenation index (OR = 0.99; 95% CI = 0.98– 1.000; P = 0.014) were independent risk factors for in-hospital mortality. A nomogram was established based on the multivariate analysis results. The C-index for the developed AKI model was 0.935 (95% CI, 0.892– 0.978); when 10-fold cross validation was used to validate the model, the corrected C-index was 0.825.Conclusion: AKI is common among COVID-19 patients admitted to the ICU and is recognized as a marker of disease severity. The proposed nomogram accurately predicted AKI development in ICU patients with COVID-19 based on individual characteristics. Therefore, the strategy for kidney protection against severe or critical pneumonia is appropriate.Keywords: coronavirus disease 2019, acute kidney injury, diagnosis, nomogram, in-hospital mortality

Guojin Xia,1,2 Zhenzhen Hu,3 Fuqing Zhou,1,2 Wenfeng Duan,1,2 Min Wang,1,2 Honghan Gong,1,2 Yulin He,1,2 Yanxing Guan4 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of China; 2Jiangxi Province Medical Imaging Research Institute, Jiangxi, People’s Republic of China; 3Department of Thoracic Oncology, Jiangxi Cancer Hospital, Jiangxi, People’s Republic of China; 4Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, Jiangxi, People’s Republic of ChinaCorrespondence: Yulin He; Yanxing Guan 17 Yongwaizheng Street, Nanchang City, Jiangxi Province, People’s Republic of ChinaTel +86-791-88692585Email 33heyulin@163.com; yanxingguan2000@aliyun.comPurpose: We explored changes in spontaneous brain connectivity in patients with diffuse axonal injury (DAI), assessed via functional connectivity density (FCD) tests using different frequency bands.Patients and Methods: In all, 23 patients with DAI (17 males and 6 females) and 23 healthy controls (HCs; 17 males and 6 females) were included. Functional magnetic resonance imaging scans were performed when the participants were in a resting state and the FCD levels in three frequency bands (slow-4: 0.027– 0.073 Hz, slow-5: 0.01– 0.027 Hz, and typical: 0.01– 0.08 Hz) were measured. In addition, Pearson’s correlation coefficient was used to explore the relationship between clinical indices and brain regions with abnormal FCD values.Results: Compared to HCs, DAI patients had significantly greater FCD values in the right extranuclear/limbic lobe/cingulate gyrus and left limbic lobe/hippocampus/parahippocampal gyrus, and significantly lower FCD values in the left precuneus/posterior cingulate gyrus, in the slow-4 band. In the slow-5 band, the DAI patients had higher FCD values in the left inferior temporal gyrus/superior temporal gyrus, left parahippocampal gyrus/limbic lobe, left extranuclear/cingulate gyrus, and right medial frontal gyrus, and lower values in the right inferior frontal gyrus, right inferior parietal lobule, and left cingulate gyrus/limbic lobe. Moreover, compared to HCs, the values in the typical band were higher in the right extranuclear/limbic lobe/hippocampus/parahippocampal gyrus, but were significantly lower in the right precuneus/posterior cingulate gyrus and right inferior parietal lobule/supramarginal gyrus. The abnormal FCD values of these brain regions were linearly correlated with different clinical scale scores.Conclusion: DAI patients had abnormal FCD values in various brain regions, indicating disruption to the brain functional network. Moreover, the values were frequency dependent. Our results provide new evidence for the pathogenesis of functional impairment and may explain the neuropathological or compensatory mechanism of the disease.Keywords: diffuse axonal injury, functional connectivity density, functional magnetic resonance imaging, frequency bands

Yuhong Jin,1 Haiyan Mao,1 Bingyang Liu,1 Fen Zhou,1 Junjie Yang,1 Lei Xu,1 Jingtao Tong,2 Chen Huang,3 Yi Ding1 1Department of Intensive Care, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of China; 2Department of Radiotherapy, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of China; 3Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of ChinaCorrespondence: Chen HuangDepartment of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo 315000, People’s Republic of ChinaTel +86-574-87018701Fax +86- 574-87392232Email drhchen@163.comYi DingDepartment of Intensive Care, Lihuili Hospital, Ningbo Medical Center, Ningbo 315000, People’s Republic of ChinaTel +86-574-87018661Email dingdingnb@163.comObjective: There is a paucity of published data to evaluate the efficacy and safety of imipenem (IPM) and piperacillin-tazobactam (PT) dosing regimens in the treatment of septic patients acquiring continuous renal replacement therapy (CRRT).Methods and Materials: Critically-ill patients were grouped into short-stay and long-stay intensive care unit (ICU) patients. Pathogens were isolated from bloodstream infections in these patients. Minimum inhibitory concentration (MIC) value was determined by agar dilution method. Population PK models were introduced in this study, and differences in the likelihood of achieving efficacious and toxic exposures of IPM and PT for critically-ill patients were assessed.Results: A total of 86 K. pneumoniae bloodstream infection associated isolates were collected, and the MIC50 and MIC90 for short-stay ICU patients were 0.5/4 mg/L and 32/128 mg/L, respectively. IMP 0.5g q8h reached 90% probability of target attainment (PTA) against isolates with MICs ≤ 2 mg/L and was recommended to empirically treat short-stay ICU patients during CRRT based on the target of 40% ƒT>MIC. However, based on a more aggressive target of 100% ƒT>MIC, all the simulated IMP regimens except for IMP 1g q6h failed to achieve > 80% cumulative fraction of response (CFR) in such patients. Unfortunately, the risk of drug-related toxicity for IMP 1g q6h was relatively high (50– 85%). For PT, even the regimen of 4/0.5g q6h failed to provide sufficient antimicrobial exposure in short-stay ICU patients acquiring CRRT.Conclusion: No dose adjustment was required for the conventional IMP and PT regimens in the critically-ill population acquiring CRRT. Empirical treatment of IMP 0.5g q8h/q6h, not for PT, may provide sufficient antimicrobial exposure for short-stay ICU patients during CRRT. PT should be used in the knowledge of MIC results.Keywords: Klebsiella pneumoniae infection, pharmacokinetic/pharmacodynamic, continuous renal replacement therapy; CRRT, intensive care unit; ICU

Feng Zhou,1,2 Xiaofei Zhang,1 Hao Chen,2 Wenxin Zheng2– 4 1Department of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Harold C Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center, Dallas, TX, USACorrespondence: Feng ZhouDepartments of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaTel +86-571-89991702Email fungchew@zju.edu.cnPurpose: To investigate the relationship between dedifferentiated endometrioid carcinomas with neuroendocrine differentiation and mismatch repair deficiency.Patients and Methods: The clinicopathological records and samples of three patients were retrieved from the Pathology Department of Zhejiang University’s School of Medicine Women’s Hospital.Results: The tumors comprised one dominant poorly differentiated component (60– 90% of the neoplasm volume) and one well-differentiated glandular component. The poorly differentiated component showed solid sheets with organoid growth patterns and insular, trabecular and rosette/pseudorosette patterns. Large polygonal cells, vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm were observed in the poorly differentiated area. All three cases were diffusely positive for p16 and for at least two of three neuroendocrine markers (chromogranin, synaptophysin, neural cell adhesion molecule (CD56)) in > 10% of cancer cells. Loss of MMR protein expression was found in two patients: MLH1 and PSM2 in patient 2 and MSH2 and MSH 6 in patient 3. Abnormal P53 and SMARCB1 (INI1) expression was noted in patient 3. All three patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, and two received postoperative chemotherapy and/or radiation therapy. The patients survived disease-free for 60, 26 and 15 months, respectively.Conclusion: Dedifferentiated endometrioid carcinomas with neuroendocrine differentiation may be associated with mismatch repair deficiency and have an improved prognosis.Keywords: dedifferentiated endometrioid carcinoma, large cell neuroendocrine carcinoma, MMR deficiency

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. The Editor and Publisher of Cancer Management and Research wish to issue an Expression of Concern for the published article. Following publication, concerns were raised were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not respond to our queries or provide the requested files to confirm the authenticity of the data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern.

Kai Yuan,1,* Jingtian Mei,1,* Dandan Shao,2 Feng Zhou,1 Han Qiao,1 Yakun Liang,3 Kai Li,2 Tingting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s Republic of China; 3Shanghai Institute of Precision Medicine, Shanghai 200125, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting TangShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery,Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Room 701, No. 3 Building, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel/Fax +86 21 6313 7020Email ttt@sjtu.edu.cnKai LiKey Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, People’s Republic of ChinaTel/Fax +86 21-52413903Email likai@mail.sic.ac.cnBackground: Cerium oxide nanoparticles (CeO2NPs) are potent scavengers of cellular reactive oxygen species (ROS). Their antioxidant properties make CeO2NPs promising therapeutic agents for bone diseases and bone tissue engineering. However, the effects of CeO2NPs on intracellular ROS production in osteoclasts (OCs) are still unclear. Numerous studies have reported that intracellular ROS are essential for osteoclastogenesis. The aim of this study was to explore the effects of CeO2NPs on osteoclast differentiation and the potential underlying mechanisms.Methods: The bidirectional modulation of osteoclast differentiation by CeO2NPs was explored by different methods, such as fluorescence microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. The cytotoxic and proapoptotic effects of CeO2NPs were detected by cell counting kit (CCK-8) assay, TdT-mediated dUTP nick-end labeling (TUNEL) assay, and flow cytometry.Results: The results of this study demonstrated that although CeO2NPs were capable of scavenging ROS in acellular environments, they facilitated the production of ROS in the acidic cellular environment during receptor activator of nuclear factor kappa-&Bgr; ligand (RANKL)-dependent osteoclast differentiation of bone marrow-derived macrophages (BMMs). CeO2NPs at lower concentrations (4.0 μg/mL to 8.0 μg/mL) promoted osteoclast formation, as shown by increased expression of Nfatc1 and C-Fos, F-actin ring formation and bone resorption. However, at higher concentrations (greater than 16.0 μg/mL), CeO2NPs inhibited osteoclast differentiation and promoted apoptosis of BMMs by reducing Bcl2 expression and increasing the expression of cleaved caspase-3, which may be due to the overproduction of ROS.Conclusion: This study demonstrates that CeO2NPs facilitate osteoclast formation at lower concentrations while inhibiting osteoclastogenesis in vitro by inducing the apoptosis of BMMs at higher concentrations by modulating cellular ROS levels.Keywords: cerium oxide nanoparticles, osteoclast, osteoclastogenesis, ROS, apoptosis

Jun Gao,1,* Enliang Li,1,* Weiwei Liu,1,* Qingping Yang,2 Chunyan Xie,3 Jiyuan Ai,1 Fan Zhou,1 Wenjun Liao,1 Linquan Wu1 1Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Assisted Reproductive, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linquan Wu; Wenjun LiaoDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 791 86311529Fax +86 791 86262262Email wulqnc@163.com; liaowenjun120@sina.comPurpose: This study aimed to investigate the functions of the circular RNA circMYLK (hsa_circ_0002768) in the development of hepatocellular carcinoma (HCC) and to identify the underlying mechanisms of the circMYLK/miR29a/KMT5C axis.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to explore the expressions of circMYLK, miR-29a and KMT5C in HCC tissues and cells. A potential miRNA (miR-29a) regulated by circMYLK was also explored, and the target relationship between miR-29a and KMT5C was confirmed. FISH, qRT-PCR, Western blotting, and dual-luciferase reporter assays were used to examine the circMYLK/miR29a/KMT5C signaling pathways involved in HCC development. Additionally, HCC cells were implanted into nude mice subcutaneously to test the role of circMYLK in tumor growth.Results: circMYLK was determined to be significantly upregulated in HCC tissues and cells. Suppression of circMYLK repressed HCC cell proliferation, migration, and invasion while increasing apoptosis. In addition, FISH, qRT-PCR, and Western blotting, as well as dual-luciferase reporter assays, revealed that circMYLK could bind to miR-29a. In rescue experiments, miR-29a had the potential to eliminate the inhibitory effect of circMYLK knockdown in HCC. Moreover, miR-29a was found to target the KMT5C gene, which was positively regulated by circMYLK. Finally, a nude mouse tumorigenicity assay showed that injection of circMYLK siRNA into nude mice drastically suppressed xenograft tumor formation in vivo.Conclusion: Our current study demonstrated that circMYLK promotes HCC progression by acting as a competing endogenous RNA of miR-29a, which regulates the downstream oncogene KMT5C.Keywords: hepatocellular carcinoma, circMYLK, miR-29a, KMT5C

Linglong Chen,1 Yaru Zhan,2 Fei He,3 Shouhua Zhang,3 Lin Wu,2,4 Honghan Gong,2,4 Fuqing Zhou,2,4 Xianjun Zeng,2,4 Haibo Xu1 1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of Hematology, Jiangxi Provincial Children’s Hospital, Nanchang, 330000, People’s Republic of China; 4Jiangxi Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Haibo XuDepartment of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaEmail xuhaibo1120@hotmail.comHonghan GongDepartment of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaEmail 2805794252@qq.comObjective: Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients.Methods: Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients.Results: The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A.Conclusion: Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.Keywords: acute lymphoblastic leukemia, resting-state fMRI, functional connectivity density, chemotherapy-related cognitive impairment, executive function

Zhan Zhang,1,* Jin-Peng Jia,2,* Yin-Jiang Zhang,3,* Gang Liu,4,5 Fan Zhou,6 Bi-Cheng Zhang7 1Department of Rehabilitation Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China; 2Department of Orthopaedics, General Hospital of Chinese People’s Liberation Army, Beijing 100853, People’s Republic of China; 3School of Pharmacy, Minzu University of China, Beijing 100081, People’s Republic of China; 4Department of Urology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei, People’s Republic of China; 5Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University, Huangshi 435000, Hubei, People’s Republic of China; 6Department of Urology, Wuhan Fourth Hospital, Pu’ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, Hubei, People’s Republic of China; 7Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bi-Cheng Zhang Email bichengzhang@hotmail.comBackground: Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA ADAMTS9-AS2 have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of ADAMTS9-AS2 in bladder tumor cells were explored in our study.Materials and Methods: Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the ADAMTS9-AS2 and ADAMTS9 expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of ADAMTS9-AS2 on proliferation, migration, and invasion in bladder tumor cells.Results: First, ADAMTS9-AS2 downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that ADAMTS9-AS2 expression was positively related to ADAMTS9, which is in accordance with the results from GEO database. Second, ADAMTS9-AS2 contributed to the inhibition of proliferation, migration, and invasion in bladder tumor cells. Third, ADAMTS9-AS2 was linked with PI3K/AKT/mTOR pathway related-molecules, several key autophagy, and apoptotic proteins.Conclusion: Conjointly, our findings suggested that ADAMTS9-AS2 might function as a tumor suppressor to restrain the proliferation, migration, and invasion in bladder tumor cells. The potential mechanism of ADAMTS9-AS2 related to PI3K/AKT/mTOR signal pathway was further identified. Of note, we found that ADAMTS9-AS2 has a significant effect on several key autophagy and apoptotic proteins. Therefore, these observations will provide supportive evidence to ADAMTS9-AS2 as a potential biomarker in patients with bladder tumor.Keywords: lncRNA ADAMTS9-AS2, proliferation, PI3K/AKT/mTOR, bladder tumor

Fachen Zhou,1,2,* Jin Wang,2,* Xinming Chi,3 Xin Zhou,3 Zhou Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhou WangDepartment of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong Province 250021, People’s Republic of ChinaTel +86 53 168777893Email wangzhoushandong@163.comXin ZhouDepartment of Histology and Embryology, Dalian Medical University, No. 9 West Part of Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 41 186110314Email 18642818055@163.comPurpose: Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells.Materials and Methods: We screened differentially expressed lncRNAs between high- and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting.Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1.Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.Keywords: lung cancer, long non-coding RNA, TM4SF1-AS1, metastasis, PI3K/AKT signaling pathway

Yixiu Pei,1,2 Yong Zhang,3 Yanyan Zhu,1,2 Yanlin Zhao,1,2 Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 791 8869 5132Email fq.chou@yahoo.comObjective: To investigate the functional connectivity (FC) and its variability in the primary somatosensory cortex (S1) of patients with low-back-related leg pain (LBLP) in the context of the persistent stimuli of pain and numbness.Patients and Methods: We performed functional magnetic resonance imaging on LBLP patients (n = 26) and healthy controls (HCs; n = 34) at rest. We quantified and compared static FC (sFC) using a seed-based analysis strategy, with 6 predefined bilateral paired spherical regions of interest (ROIs) in the S1 cortex. Then, we captured the dynamic FC using sliding window correlation of ROIs in both the LBLP patients and HCs. Furthermore, we performed a correlational analysis between altered static and dynamic FC and clinical measures in LBLP patients.Results: Compared with controls, the LBLP patients had 1) significantly increased static FC between the left S1back (the representation of the back in the S1) and right superior and middle frontal gyrus (SFG/MFG), between the left S1chest and right SFG/MFG, between right S1chest and right SFG/MFG, between the left S1face and right MFG, and between the right S1face and right inferior parietal lobule (P < 0.001, Gaussian random field theory correction); 2) increased dynamic FC only between the right S1finger and the left precentral and postcentral gyrus and between the right S1hand and the right precentral and postcentral gyrus (P < 0.01, Gaussian random field theory correction); and 3) a negative correlation between the Barthel index and the increased static FC between the left S1face and right inferior parietal lobule (P = 0.048).Conclusion: The present study demonstrated the hyperconnectivity of the S1 cortex to the default mode and executive control network in a spatial pattern and an increase in the tendency for signal variability in the internal network connections of the S1 cortex in patients with LBLP.Keywords: primary somatosensory cortex, static functional connectivity, dynamic functional connectivity, chronic low-back-related leg pain, chronic pain, resting-state functional MRI

Chunmei Jin,1 Rong Shi,1 Xue Jiang,1 Fuxian Zhou,1 Jixiang Qiang,1 Changshan An2 1Department of Clinical Laboratory, Yanbian University Hospital, Yanji, People’s Republic of China; 2Department of Respiratory Medicine, Yanbian University Hospital, Yanji, People’s Republic of ChinaCorrespondence: Changshan An Tel +86-433-2660064Email cs_an2003@aliyun.comIntroduction: Carbapenem-resistant Enterobacteriaceae (CRE) pose a serious threat to clinical patient management and public health, as they are generally resistant to most antibiotics and cause infections with high mortality rates. Klebsiella pneumoniae ranks second among Enterobacteriaceae species that cause nosocomial infections. In this study, we investigated the epidemic characteristics of carbapenem-resistant K. pneumoniae (CRKP) in the pediatric intensive care unit (PICU) of Yanbian University Hospital.Materials and Methods: A total of 14 non-duplicate CRKP strains, collected from March 2015 to November 2019, were subjected to automated microbial identification and antimicrobial susceptibility tests using the Phoenix-100 ID/AST system. The strains were also subjected to genotypic resistance testing, polymerase chain reaction assays to detect genes encoding carbapenemases and other β-lactamases, multi-locus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE)-based homology analysis.Results: Two carbapenemase genes, KPC-2 and NDM-1 (in eight and six strains, respectively), were detected. MLST enabled the division of the strains into two sequence types, ST11 and ST1224 (containing eight and six strains, respectively). PFGE results classified the 14 strains into clonotypes A–D, of which clonotypes A and B belonged to ST11, while clonotypes C and D belonged to ST1224.Conclusion: Our study reveals that epidemics of the KPC-2-ST11 and NDM-1-ST1224 strains occurred in the PICU of Yanbian University Hospital. Surveillance and strict implementation of prevention and control measures are crucial to prevent the occurrence and rapid spread of nosocomial infections.Keywords: Klebsiella pneumoniae, carbapenemase, sequence type 1224, pediatric intensive care unit

Chunmei Jin,1 Fuxian Zhou,1 Qingsong Cui,2 Jixiang Qiang,1 Changshan An3 1Department of Clinical Laboratory, Yanbian University Hospital, Yanji, People’s Republic of China; 2Department of Intensive Care Unit, Yanbian University Hospital, Yanji, People’s Republic of China; 3Department of Respiratory Medicine, Yanbian University Hospital, Yanji, People’s Republic of ChinaCorrespondence: Changshan An Tel +86-0433-2660064Email cs_an2003@aliyun.comBackground: Infections caused by the carbapenem-resistant Enterobacter cloacae (CREC) bring great challenges to the clinical treatment and pose a serious threat to public health. In this study, we investigated the molecular characteristics of CREC in a tertiary hospital.Materials and Methods: A total of 12 non-duplicate CREC strains isolated during the period of November 2016 to July 2019 were subjected to automated microbial identification and antimicrobial susceptibility testing (AST) using the BD Phoenix-100 identification and antimicrobial susceptibility testing (ID/AST) system. The strains were also subjected to phenotypic screening for the detection of antibiotic resistance genes such as the carbapenemase and other β-lactamase genes, with the use of the polymerase chain reaction assay (PCR). Finally, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE)-based homology analysis were applied.Results: Four types of carbapenemases namely IMP-26, NDM-5, NDM-1, and KPC-2 were identified in 12 CREC strains. IMP-26 was the most prevalent type (6/12 strains, 50 %), followed by NDM-5 (3/12 strains, 25 %). The results of MLST revealed that these 12 strains could be divided into five sequence types (STs) among which ST544 was the dominant type (6/12 strains, 50 %). The PFGE results divided the 12 strains into four clusters.Conclusion: Our study indicated that the epidemics of the IMP-26-producing E. cloacae ST544 strain did occur in the intensive care unit (ICU) of a tertiary hospital. Therefore, early surveillance and strict implementation of control measures are crucial for the prevention of nosocomial infections and transmissions in hospitals.Keywords: Enterobacter cloacae, carbapenemase, IMP-26, ST544

Shang-zhou Chen,* Yang Zhang,* Shu-ying Lei, Fa-qiong Zhou Department of Dermatovenereology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fa-qiong ZhouDepartment of Dermatovenereology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Road, Enshi 445000, People’s Republic of ChinaTel +86 18672068166Email 1039643683@qq.comObjective: The SAM- and SH3-domain containing 1 gene (SASH1) has been considered as a tumor suppressor in some cancers. Nevertheless, the effect of SASH1 on the proliferation and invasion of human skin squamous cell carcinoma (cSCC) remains poorly understood. Therefore, the purpose of the present study was to observe the potential role of SASH1 in cSCC and investigate its underlying mechanisms.Methods: The overexpression of SASH1 was constructed by transfecting the pcDNA3.1/SASH1 vector into SCL-1 and A431 cells, and SASH1 knockdown was generated by transfecting the SASH1 siRNA into cSCC cells. Then, cell proliferation, invasion, apoptosis, and Akt pathway were observed.Results: The expression levels of SASH1 mRNA and protein were greatly reduced in cSCC cells. The overexpression of SASH1 inhibited the viability and invasion of cSCC cells, while its knockdown induced the viability and invasion of cSCC cells. The overexpression of SASH1 also suppressed the expression levels of p-Akt and its target genes, including cyclin D1, Bcl-2, and metal matrix proteinase 2(MMP-2). By contrast, SASH1 knockdown exerted the opposite role. Furthermore, inhibition of Akt obviously decreased the inducible effect of cSCC knockdown on the proliferation and invasion of cSCC cells.Conclusion: Overall, these results found that SASH1 inhibits the proliferation and invasion of cSCC cells via suppressing Akt cascade, indicating a tumor inhibitory effect of SASH1 in cSCC cells.Keywords: human skin squamous cell carcinoma, SASH1, Akt

Ya Sun,1,2,* Shuo Yang,3,* Erpeng Qi,1 Fangyi Liu,1 Fubo Zhou,1 Yuhan Lu,1 Ping Liang,1 Huiyi Ye,4 Xiaoling Yu1 1Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Department of Ultrasound, Aerospace Central Hospital, Beijing 100049, People’s Republic of China; 3Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 4Radiology Department, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoling YuDepartment of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaEmail dyuxl301@aliyun.comPurpose: The purpose of our study was to evaluate the role of contrast-enhanced ultrasound (CEUS) with magnetic resonance imaging (MRI) and computed tomography (CT) in the pathological diagnosis of pancreatic cystic neoplasms (PCNs).Methods: A total of 90 patients (66 women, 24 men) aged 18– 71 years were studied prospectively. CEUS was performed in all patients, whereas MRI was performed in 85 patients and CT in 69 patients. We analyzed the sensitivity and accuracy of these three imaging modalities to diagnose the PCNs. Neoplasm size, location, shape, intralesional mural nodules, septa and duct dilatation were also assessed by different radiologists.Results: There were no significant differences in sensitivity for discriminating PCNs from pancreatic cystic lesions between CEUS and MRI (p=0.614) or between CEUS and CT (p=0.479). The diagnostic accuracy of CEUS for classifying PCNs was 64.4% (58/90), which was higher than that of CT (53.6%, 37/69, P=0.017), and lower than that of MRI (70.6%, 60/85, p=0.791). Regarding tumor size for lesions larger than 3 cm, CEUS was superior to CT in differentiating the specific type of PCN (p=0.041), and CEUS had the same value as MRI (p=0.774). Furthermore, CEUS is valuable for precisely characterizing internal structures, for instance, septa (p=0.003, compared with CT; p=0.443, compared with MRI) and nodules (p= 0.018, compared with CT; p=0.033, compared with MRI). The number of septa (p=0.033) and cyst morphology (p=0.016) were meaningful indicators in differentiating serous and mucinous adenoma. There was no significant difference in evaluating size and detecting duct dilatation among the three imaging methods.Conclusion: CEUS compares favorably with MRI in displaying the inner structure of PCNs and offers advantages over CT. CEUS can contribute in an important way to the diagnosis of pancreatic cystic neoplasms.Keywords: contrast-enhanced ultrasound, computed tomography, magnetic resonance imaging, pancreatic cystic neoplasms, diagnostic evaluation

Qianqian Shi, Faying Zhou, Jing Mei, Haimei Yang, Huiyun Li Department of Neurology, Daping Hospital, Army Medical University, Chongqing 400042, People’s Republic of ChinaCorrespondence: Huiyun LiDepartment of Neurology, Daping Hospital, Army Medical University, Chongqing 400042, People’s Republic of ChinaTel +86 23 68757851Fax +86 23 68711956Email lihuiyun1359@163.comObjective: To explore the effect of Type 2 diabetes mellitus (T2DM) on the development of neuropsychiatric symptoms (NPS) in early Alzheimer’s disease (AD).Methods: From September 2017 to March 2019, a cross-sectional study was conducted on the clinical data of 158 early AD patients over 65 years old in the Department of Neurology of Daping Hospital. All early stage of AD patients were divided into early stage of AD with NPS group and early stage of AD without NPS group according to the presence or absence of NPS. Clinical data of age, sex, body mass index (BMI), smoking and alcohol consumption, history of hypertension, hyperlipidemia, white matter leisure (WML) and T2DM, MMSE, CDR and NPI-Q scores were collected. Multivariate logistic regression analyses were performed to examine the relationship between T2DM and NPS in early AD.Results: Compared with the early stage of AD group without NPS, the early stage of AD group with NPS was older, the proportion of women was higher, the proportion of T2DM, hypertension, hyperlipidemia and WML was higher, and the MMSE score was lower (P< 0.05). T2DM was an independent risk factor for NPS in early stage of AD patients (OR 3.48, 95% CI 2.91– 3.84). The incidence of T2DM in AD patients with depression, anxiety, nighttime behavioral disturbances, and appetite disturbances was significantly higher than in AD patients without these symptoms. T2DM was an independent risk factor of depression (OR 2.04, 95% CI 1.71– 2.38), anxiety (OR 1.69, 95% CI 1.38– 1.97), nighttime behavioral disturbances (OR 1.95, 95% CI 1.75– 2.13) and appetite disturbances (OR 1.62, 95% CI 1.33– 1.94) in early AD patients.Conclusion: T2DM was an important independent risk factor for NPS in early AD, which promotes the occurrence of depression, anxiety, nighttime behavioral disturbances and appetite disturbances in early AD.Keywords: Alzheimer’s disease, type 2 diabetes, neuropsychiatric symptoms

Yu Luo, Feng Liu, Chunhui Yan, Wei Qu, Liang Zhu, Zheng Guo, Fan Zhou, Wei Zhang Department of Urology, The 161st Hospital of the People’s Liberation Army, Wuhan, Hubei 430010, People’s Republic of ChinaCorrespondence: Feng LiuDepartment of Urology, The 161st Hospital of the People’s Liberation Army, No. 68, Huangpu Road, Wuhan, Hubei 430010, People’s Republic of ChinaEmail liufwh@163.comPurpose: The long non-coding RNA cancer susceptibility 19 (CASC19) is recognized as an important regulator in gastric cancer, colorectal cancer, and non-small cell lung cancer. Nevertheless, to the best of our knowledge, the expression status and detailed roles of CASC19 in clear cell renal cell carcinoma (ccRCC) have not been elucidated. Hence, we aimed to determine CASC19 expression in ccRCC and investigate its roles in ccRCC oncogenicity. The molecular mechanisms underlying CASC19 functions in ccRCC were also determined.Methods: CASC19 expression was measured by using reverse transcription-quantitative polymerase chain reaction. The effects of CASC19 on ccRCC cell proliferation, colony formation, migration, and invasiveness in vitro, as well as on tumor growth in vivo, were examined by the MTT assay, colony formation assay, cell migration and invasiveness assays, and tumor xenograft in nude nice, respectively.Results: CASC19 was overexpressed in ccRCC tissues and cell lines. High expression of CASC19 was closely associated with unfavorable clinicopathological parameters and predicted negative clinical outcomes in patients with ccRCC. Knockdown of CASC19 decreased ccRCC cell proliferation, colony formation, migration, and invasiveness, as well as attenuated tumor growth in vivo. Mechanistically, CASC19 functioned as a competing endogenous RNA and upregulated the expression of ETS proto-oncogene 1 (ETS1) through sponging microRNA-532 (miR-532). Furthermore, rescue assays revealed that inhibiting miR-532 or restoring ETS1 expression partially abolished the impacts of CASC19 knockdown on ccRCC cells.Conclusion: The CASC19/miR-532/ETS1 regulatory pathway is crucial for the malignant manifestations of ccRCC, which makes it an attractive target for potential treatments of ccRCC.Keywords: cancer, MTT assay, cell migration, invasiveness, xenograft, knockdown

Jinrong Qiu, 1,* Fuping Zhou, 1,* Xinchun Li, 2,* Sufang Zhang, 2 Zhuo Chen, 2 Zenghui Xu, 2 Gaoxiong Lu, 2 Zhi Zhu, 3 Na Ding, 2 Jinxing Lou, 4 Zhenlong Ye, 2 Qijun Qian 1, 2, 4 1Department of Biotherapy, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 2Shanghai Baize Medical Laboratory, Shanghai, People’s Republic of China; 3Department of Pathology, Changhai Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 4Shanghai Mengchao Cancer Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qijun Qian; Zhenlong YeShanghai Baize Medical Laboratory, Yuanguo Road, Shanghai 201805, People’s Republic of ChinaEmail qian@shcell.org; yezl@shcell.orgObjective: The evaluation of lymphocyte subsets is widely regarded as an important factor for monitoring tumor progression and response to therapy. This study was designed to establish a comprehensive and detailed assessment of peripheral lymphocyte subsets with a multi-parametric flow cytometry assay for response prediction and prognosis evaluation of cancer patients.Methods: Peripheral blood samples collected from 40 cancer patients and 23 age- and sex-matched healthy volunteers were tested for 29 lymphocyte subsets by flow cytometry. The univariate analysis was applied to establish the reference interval of healthy samples, and the ratio and proportion of 29 lymphocyte subsets between patient samples and healthy controls were compared to evaluate their clinical significance by Mann–Whitney U-test model.Results: The reference ranges of 29 lymphocyte subsets were established with a normal distribution and no significant differences were observed between genders. Compared with healthy control group, lower proportion and ratio of specific parameters, such as Naïve Th cells (p< 0.01), Naïve Tc cells (p< 0.01), CM (central memory) Tc cells (p< 0.01), Naïve T cells/Memory T cells (p< 0.001), Naïve T cells/EM (effector memory) T cells (p< 0.001) and Naive Th cells/Memory Th cells (p< 0.001), and higher proportion and ratio of EM Th cells (p< 0.001), EM Tc cells (p< 0.01), effector Tc cells (p< 0.05), EM Th cells/CM Th cells (p< 0.01) and EM Tc cells/CM Tc cells (p< 0.01), as well as Breg (p< 0.001), B cells (p< 0.05) and CD16-NK cells (p< 0.001) were found in cancer cohorts.Conclusion: This study suggests that the changes in certain lymphocyte subsets might be helpful to evaluate the immunity of cancer patients, and holds great potential for clinical application.Keywords: solid tumor, lymphocyte subsets, clinic significance, reference intervals, flow cytometry

Yu Qian,1,2,* Yuan Wu,3,* Zilong Yuan,4 Xiaohui Niu,5 Yaoyao He,4 Jun Peng,6 Fuxiang Zhou,1 Shaozhong Wei,7 Desheng Hu,3 Yunfeng Zhou1 1Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 4Department of Radiology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 5College of Informatics, Huazhong Agricultural University, Wuhan, Hubei, People’s Republic of China; 6Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 7Department of Surgery, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunfeng ZhouDepartment of Radiation and Medical Oncology, Zhongnan Hospital, 169 Donghu Road, Wuhan, Hubei, People’s Republic of ChinaTel +86 139 0715 4247Fax +86 27 6781 2892Email yfzhouwhu@163.comDesheng HuDepartment of Radiation Oncology, Hubei Cancer Hospital, 16 Zhuodaoquan S Road, Wuhan, Hubei, People’s Republic of ChinaTel +86 27 8767 0318Fax +86 27 8767 0151Email hds13907174495@163.comPurpose: Circulating tumour cells (CTCs) have been found to correlate with treatment response and prognosis in some cancers; however, such correlations have not been reported in nasopharyngeal carcinoma (NPC). We aimed to determine the relationship between CTCs and the treatment response in NPC.Patients and methods: In this prospective study, we ascertained the karyotype of CTCs and identified a possible correlation between karyotype and treatment response in locally advanced NPC (LANPC). We prospectively collected peripheral blood from LANPC patients. CTCs were measured by negative enrichment with immunofluorescence in situ hybridization (imFISH) and a centromere of chromosome 8 (CEP8) probe. Chromosome 8 was karyotyped in CTCs, which were identified as triploid, tetraploid or multiploid. Patients were then treated with platinum-based induction chemotherapy followed by concurrent chemoradiotherapy. CTCs were measured before and after treatment.Results: We detected CTCs in 27 of 50 (54%) patients, which served as a baseline value. The results were independent of age, smoking history and NPC clinical stage. All of the 27 evaluable enrolled patients with detectable CTCs showed decreases in both total CTCs and CTCs of different ploidies after treatment (P

Yanxia Jin,1,2 Yufeng Shang,1 Hailing Liu,3 Lu Ding,1 Xiqin Tong,1 Honglei Tu,1 Guolin Yuan,4 Fuling Zhou1,5 1Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, People’s Republic of China; 2Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, Hubei Normal University, Huangshi, Hubei 435002, People’s Republic of China; 3Department of Clinical Hematology, Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, People’s Republic of China; 4Department of Hematology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441021, People’s Republic of China; 5Key Laboratory of Tumor Biological Behavior of Hubei Province, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, People’s Republic of ChinaCorrespondence: Fuling ZhouDepartment of Hematology, Zhongnan Hospital, Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan 430071, People’s Republic of ChinaTel +8618986265580Email zhoufuling@whu.edu.cnObjective: Multiple myeloma (MM) patients with bone destruction are difficult to restore, so it is of great clinical significance to further explore the factors affecting MM bone destruction.Methods and results: This study retrospectively analyzed 419 cases with MM. Multiple linear regression analysis showed that those MM patients with a higher concentration of Ca2+ in serum, higher positive rate of CD138 immuno-phenotype and advanced in stage with 13q34 deletion in cytogenetics would be more prone to bone destruction, while total bile acid (TBA) and kappa chain isotope negatively correlated with bone destruction in MM patients. The Kaplan–Meier analysis indicated that Ca2+, serum β2-microglobulin (β2-MG), hemoglobin (HGB), creatinine (CREA), uric acid (UA) and age correlated with the survival of bone destruction in MM patients. Cox regression analysis further showed that the independent prognostic factors of β2-MG and CREA had a higher risk for early mortality in bone destruction patients. Moreover, an index was calculated based on β2-MG and globulin (GLB) to white blood cell (WBC) ratio to predict the poor survival of bone destruction patients.Conclusion: We provide a novel marker to predict the prognosis of myeloma patients using routine examination method instead of bone marrow aspiration, and provide a reference for clinical evaluation.Keywords: multiple myeloma, bone destruction, prediction index, prognosis

Linghong Guo,1 Fuqing Zhou,1 Ning Zhang,1 Hongmei Kuang,1 Zhen Feng2 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of ChinaCorrespondence: Zhen FengDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Number 17, Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, People’s Republic of ChinaTel/Fax +86-791-88698601Email fengzhenly@sina.comPurpose: Alcohol dependence (AD) is a relapsing mental disorder, typically occurring with concurrent tobacco misuse. Studies have reported disruption of the structural connectivity between hemispheres in the brain of individuals with AD. However, alterations in interhemispheric interactions and the specificity of frequency bands in individuals with AD remain unknown. Voxel-mirrored homotopic connectivity (VMHC) allows examination of functional interactions between mirrored interhemispheric voxels. Here, we use VMHC to investigate homotopic connectivity in AD and alcohol and nicotine co-dependence (AND) subjects.Patients and methods: VMHC and seed-based functional connectivity (FC) in 24 AD, 30 AND, and 35 sex-, age-, and education-matched healthy control (HC) subjects were calculated for different frequency bands (slow-5, slow-4, and typical bands).Results: Individuals with AD demonstrated significantly reduced VMHC in bilateral cerebellum posterior lobe (CPL) and increased VMHC in bilateral middle frontal gyrus (MFG) compared to that in HCs in the typical and slow-4 bands; higher VMHC in the MFG was positively correlated with the dependence-severity score. In all bands of the VMHC analysis, no significant differences were found between the AND and other groups. Subsequent seed-based FC analysis demonstrated all regions with abnormal VMHC exhibited altered FC with its counterpart in the contralateral hemisphere in the typical and slow-4 frequency bands. The FC value between bilateral CPL within AD subjects negatively correlated with alcohol intake.Conclusion: Our findings provide further evidence of the role of disruptions within the brain circuitry supporting cognitive control in the development of AD. Alterations in neural activities in the CPL and MFG might be a biomarker of dependence severity in AD patients as assessed using clinical questionnaire and features. Because of the frequency specificity in VMHC, we must consider frequency effects in future AD functional magnetic resonance imaging studies.Keywords: alcohol, dependence, homotopic connectivity, frequency band, resting-state fMRI

Pei Lu, Minyi Xu, Zhongbo Xiong, Fangfang Zhou, Lei Wang Department of Clinical Laboratory, Shanghai No. 8 People’s Hospital, Shanghai, China Correspondence: Pei Lu; Lei WangDepartment of Clinical Laboratory, Shanghai No. 8 People’s Hospital, No. 8, Caobao Road, Xuhui District, Shanghai 200235, ChinaTel +86 21 3428 4588; +86 21 3428 4588Email lu_pei@sohu.com;wolei6610@126.com Objective: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients.Methods: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry.Results: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway.Conclusions: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes. Keywords: colorectal cancer, F. nucleatum, chemoresistance, 5-fluorouracil, oxaliplatin, ANO1

Yong Zhang,1 Yanyan Zhu,2,3 Yixiu Pei,2,3 Yanlin Zhao,2,3 Fuqing Zhou,2,3 Muhua Huang,2,3 Lin Wu,2,3 Daying Zhang,1 Honghan Gong2,31Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Neuroradiology Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 5132Email fq.chou@yahoo.comDaying ZhangDepartment of Pain Clinic, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 3825Email dyzsino@ncu.edu.cnObjective: Chronic low back pain has been observed to decrease movement coordination. However, it is unclear whether the existing alteration of inter-hemispheric synchrony of intrinsic activity in patients with chronic low back-related leg pain (cLBLP). The present study aims to investigate the alteration of homotopic connectivity and its clinical association with the cLBLP patients.Participants and methods: A cohort of cLBLP patients (n=25) and well-matched healthy controls (HCs) (n=27) were recruited and underwent MRI scanning and a battery of clinical tests. The voxel-mirrored homotopic connectivity (VMHC) was used to analyze the interhemispheric coordination in the typical (0.01–0.1 Hz) as well as five specific (slow-6 to slow-2) frequency bands and associated with clinical index in cLBLP patients.Results: We observed that cLBLP patients with lower homotopic connectivity than HCs in the inferior temporal gyrus, the superior temporal gyrus, the basal ganglia, the middle frontal gyrus, and the medial prefrontal cortex in the typical and five specific frequency bands, respectively. In the typical and five specific frequency bands, significant positive correlations were observed between the VMHC values of medial prefrontal cortex and the visual analogue scale scores, while the VMHC values of basal ganglia negative correlated with the values of two-point tactile discrimination (2PD) test for the right hand in cLBLP patients, etc. Further receiver operating characteristic curve analysis revealed that VMHC in the above regions with decreased could be used to differentiate the cerebral functional plasticity of cLBLP from healthy individuals with high sensitivity and specificity.Conclusion: Our results imply that multiscale frequency-related interhemispheric disconnectivity may underlie the central pathogenesis of functional coordination in patients with cLBLP.Keywords: interhemispheric integration, voxel-mirrored homotopic connectivity, chronic low back-related leg pain, chronic pain, resting-state fMRI

Fengru Zhou,1 Feng Shen,1 Zhuojun Zheng,2 Jincheng Ruan11Department of Anus and Intestine Surgery, The Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, People’s Republic of ChinaBackground: Colorectal cancer is a heterogeneous disease with complex genetic and epigenetic changes. LncRNA has recently been regarded as the biomarker in cancers. Novel biomarkers in colon cancer need to be identified.Purpose: The objective of this study was to identify the differentially expressed lncRNAs between colon cancer tissue and adjacent tissue, as well as to explore its biological functions.Patients and methods: There were 130 colon cancer patients included in this study. Of them, 6 colon cancer samples and 3 normal samples were selected for microarray profiling. Another 121 colon cancer samples with complete clinical information were used for immunohistochemical assay and survival analysis. Microarray analysis was performed to determine the differentially expressed lncRNAs between colon cancer tissue and adjacent tissue. Gain-of-function experiments was conducted in vitro and in vivo. In situ hybridization and survival analysis were applied to determine the prognostic impact on survival.Results: LncRNA XIRP2-AS1 was significantly less expressed in colon cancer tissue. XIRP2-AS1 was remarkably downregulated in colon cancer tissues and cell lines. Functionally, XIRP2-AS1 could inhibit the proliferation and invasion ability of colon cancer cells in vitro and in vivo. Clinical sample analysis showed that XIRP2-AS1 had a favorable impact on the overall survival and progression free survival of patients with colon cancer. miR-182 was validated as the target of XIRP2-AS1 according to luciferase reporter assays, RNA immunoprecipitation and RNA pull down.Conclusions: Our results suggested that XIRP2-AS1 may act as a favorable biomarker for patients with colon cancer.Keywords: colon cancer, XIRP2-AS1, proliferation, invasion, survival

Pingping Zhang,1,2,* Junwei Sun,2,* Jindan Kai,2 Yi Peng,2 Xiyou Liu,2 Fuxiang Zhou,1 Jianping Wu21Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430079, People’s Republic of China; 2Department of Oncology, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, Wuhan 430079, People’s Republic of China*These authors contributed equally to this workBackground: ASAP3 was first identified as a protein that promotes cell proliferation in hepatocellular carcinoma and later reported to be an Arf6-specific Arf GTPase-activating protein that regulates cell migration associated with cancer cell invasion.Materials and methods: Patients and tissue samples were from Hubei Cancer Hospital, human lung adenocarcinoma cell lines were obtained from the cell bank of the Chinese Academy of Science, nude mice (BALB/c nu/nu) were obtained from Shanghai SLAC Laboratory Animal Co. Ltd. Our methods contained immunohistochemistry, Western blotting, reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, stable transfection of lung adenocarcinoma cells, chromatin immunoprecipitation (CHIP) and luciferase assay, wound healing and cell migration assay.Results: In this study, we show that ASAP3 overexpression promotes migration and invasiveness in human lung adenocarcinoma cells and accelerates tumor progression in a xenograft mouse model. In patient tumor samples, ASAP3 overexpression was significantly associated with lymph node metastasis and reduced overall survival. We also show that ASAP3 expression is induced under hypoxic conditions through hypoxia-inducible factor 1α (HIF-1α), which binds directly to HER1 or/and HER2 (hypoxia response element) in the ASAP3 promoter. ASAP3 overexpression counteracts the inhibition of lung adenocarcinoma progression caused by HIF-1α knockdown both in vitro and in vivo.Conclusion: Our results identify ASAP3 as a downstream target of HIF-1α that is critical for metastatic progression in lung adenocarcinoma.Keywords: lung adenocarcinoma, ASAP-3, hypoxia-inducible factor-1α, metastasis

Fang Zhou, Zheng Ge, Baoan ChenDepartment of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaAbstract: Quizartinib is an effective therapy for patients with FLT3-ITD acute myeloid leukemia (AML) by continuing to inhibit the activity of FLT3 gene, leading to apoptosis of tumor cells. Multiple clinical trials have proved that it is effective in relapsed or refractory AML with an FLT3-ITD mutation. In this review, we focus on the characteristics of FLT3/ITD mutations, the mechanism and pharmacokinetics of quizartinib, and the mechanisms of resistance to quizartinib. We also summarize clinical experiences and adverse effects with quizartinib and recommend crucial approaches of quizartinib in the therapy of patients with newly diagnosed AML and patients with relapsed/refractory AML, particularly those with FLT3-ITD mutation. Quizartinib presents its advantages as a very promising agent in the treatment of AML, especially in patients with FLT3-ITD mutations. FLT3/ITD mutation can lead to constitutive autophosphorylation of FLT3 and activation of its downstream effectors including RAS/RAF/MEK, MAPK/ERK, PI3K/AKT/mTOR and JAK/STAT5 signal pathways, while Quizartinib can inhibit these downstream pathways through specific FLT3 inhibition. Quizartinib has received US Food and Drug Administration breakthrough therapy designation in patients with relapsed/refractory FLT3-ITD AML based on clinical trials. A larger sample of clinical trials are needed to verify its safety and efficacy, and the efficacy of quizartinib combined with chemotherapy or allogeneic hematopoietic cell transplantation should also be estimated in clinical trials. Meanwhile, for the side effects of quizartinib, further studies are needed to find a way to reduce its toxicity.Keywords: quizartinib, FLT3 inhibitor, FLT3-ITD mutation, AML, clinical trials, targeted therapy

Jiaqi Liu,1,* Lili Gu,2,* Qing Huang,1 Shunda Hong,1 Xianjun Zeng,1 Daying Zhang,2 Fuqing Zhou,1 Jian Jiang1 1Department of Radiology, 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to measure brain alterations in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN) and compare their differences using a voxel-based morphometry (VBM) technique. Materials and methods: Thirty-three patients with HZ, 22 patients with PHN, and 28 well-matched healthy controls (HCs) were recruited. Magnetic resonance imaging data were acquired for all subjects and analyzed using the VBM method. The changes in gray matter volume (GMV) in HZ and PHN groups were compared with those in HC group, and the GMV differences were also compared between the PHN and HZ groups. Further correlation analysis and receiver operating characteristic curves were used to confirm the significance of GMV changes in various brain regions. Results: Compared with HCs, decreased GMV was found in the bilateral insular lobes and increased GMV was found in the bilateral thalamus in the HZ group. In the PHN group, GMV decreased in the bilateral insula lobes, right middle frontal gyrus, bilateral precentral gyrus, and left postcentral gyrus and increased in the left cerebellar posterior lobe, right parahippocampal gyrus, and right lentiform nucleus. In addition, the PHN group exhibited increased GMV in the left cerebellar tonsil, culmen, and left lentiform nucleus and decreased GMV in the right precentral gyrus compared with the HZ group. Further correlation analysis and receiver operating characteristic curves revalidate the significance of most of these abnormal brain regions. Conclusion: The VBM method revealed widespread GMV abnormalities in HZ and PHN patients. The brains of PHN patients have broader abnormalities in nonpain-related regions, suggesting the complexity of a central mechanism. When PHN patients were compared with HZ patients, the left cerebellar tonsil, culmen, and left lentiform nucleus corresponded to greater area under the curve, suggesting that abnormalities in these regions are risk factors for HZ patients’ transformation to PHN. Keywords: chronic pain, neuroimaging, ROC, fMRI, VBM

Lili Gu,1,* Shunda Hong,2,* Jian Jiang,2 Jiaqi Liu,2 Xintian Cao,1 Qing Huang,2 Xianjun Zeng,2 Fuqing Zhou,2 Daying Zhang1 1Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: Postherpetic neuralgia (PHN) detrimentally affects brain function. Recent studies have suggested that frequency-dependent changes in electroencephalography in chronic pain patients and blood oxygenation level dependent (BOLD) fluctuations can reflect neuronal activity in different frequencies. The current study aimed to investigate PHN-related brain oscillatory activity in a specific frequency band by using the amplitude of low-frequency fluctuation (ALFF) method.Materials and methods: ALFF changes were analyzed across different frequencies (slow-4 band: 0.027–0.073 Hz; slow-5 band: 0.01–0.027 Hz; and typical band: 0.01–0.08 Hz) in the brains of PHN patients and compared with those in the brains of healthy controls (HCs) during resting-state fMRI. Eighteen HCs and PHN patients underwent fMRI scanning.Results: In the typical band, compared with HCs, PHN patients showed prominently decreased ALFF in the right prefrontal cortex (Brodmann area 10/46) and increased ALFF in the bilateral brain stem/cerebellum anterior lobe (BS/CAL). In the slow-4 band, PHN patients exhibited significantly decreased ALFF in the bilateral cuneus/lingual gyrus and the right prefrontal cortex. In the slow-5 band, PHN patients presented significantly increased ALFF in the bilateral BS/CAL and left parieto-occipital cortex. Moreover, the increased ALFF in the left parieto-occipital cortex in the slow-5 band was positively correlated with VAS scores (P=0.022), and the increased ALFF in the bilateral BS/CAL in the slow-5 band was positively correlated with disease duration (P=0.020).Conclusion: Our results suggested that the intrinsic brain activity of PHN patients was abnormal and frequency dependent, especially the bidirectional alteration in ALFF across the slow-4 and slow-5 frequencies in the brains of PHN patients. Keywords: amplitude of low-frequency fluctuation, postherpetic neuralgia, functional magnetic resonance imaging, resting state, pain

Lei Wang, Minyi Xu, Pei Lu, Fangfang Zhou Department of Clinical Laboratory, Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai 200235, People’s Republic of China Background: In recent years, microRNAs (miRNAs) have been reported to be aberrantly expressed in colorectal cancer (CRC). The deregulation of miRNAs is implicated in the formation and progression of CRC, and participates in the regulation of a wide range of biological behaviors. Considering the crucial role of miRNAs in CRC, miRNAs are thought to have significant promise in the diagnosis and therapy of patients with this malignancy. Material and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-769 expression in CRC tissues and cell lines. MTT assay and flow cytometry analysis were used to determine the effects of miR-769 upregulation in CRC cell proliferation and apoptosis, respectively. The influence of miR-769 overexpression in CRC cell migration and invasion was evaluated through migration and invasion assays. Notably, the possible mechanisms underlying the action of miR-769 in CRC cells were explored. Results: In the present study, miR-769 was frequently found to be poorly expressed in CRC tissues and cell lines. Functional assays showed that recovery of miR-769 expression suppressed CRC cell proliferation, migration, and invasion, increased cell apoptosis in vitro, and inhibited tumor growth in vivo. Cyclin-dependent kinase 1 (CDK1) was the direct target of miR-769 in CRC cells. CDK1 was overexpressed in CRC tissue samples and negatively correlated with miR-769 expression. In addition, CDK1 inhibition imitated the tumor suppressor activity of miR-769 in CRC cells, and restoration of CDK1 expression partially abolished the tumor-suppressing roles of miR-769 in malignant CRC cells. Conclusion: The results of this study demonstrated that miR-769 was downregulated in CRC and directly targeted CDK1 to be implicated in the regulation of CRC cell proliferation, apoptosis, migration and invasion. Thus, the miR-769/CDK1 axis might be an effective thera­peutic target for treating patients with CRC. Keywords: colorectal cancer, microRNA-769, proliferation, apoptosis, metastasis, cyclin-dependent kinase 1

Jun Zhang,1,* Feng Zhou,2,* Xiaoxiang Ge,3 Xu Ran,4 Yeping Li,4 Si Chen,5 Xiaotong Dai,5 Dafang Chen,5 Baoguo Jiang6 1Department of Neurology, Peking University People’s Hospital, Beijing, China; 2Department of Data Science, Tsinghua University, Beijing, China; 3Office of Academic Affairs, Army Military Medical University, Chongqing, China; 4Department of Research and Development, Chongqing Hospital Management Limited Company (Doctor-Patient Experience Research Base, National Health and Family Planning Commission of the People’s Republic of China), Chongqing, China; 5Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; 6Department of Orthopedics, Peking University People’s Hospital, Beijing, China *These authors contributed equally to this work Background and aims: Patient satisfaction is one of the important ways to measure the results of treatment and the quality of medical services. The purpose of the present study was to verify the reliability and validity of the indicator system for evaluating satisfaction of outpatients and inpatients in Chinese hospitals.Methods: The study was based on the satisfaction questionnaire program of the national doctor–patient experience research center with data from 99,802 outpatients and 229,215 inpatients, collected in China between 2016 and 2017. We adopted exploratory factor analysis for validity analysis and the method of split-half reliability and Cronbach’s α coefficient for reliability analysis.Results: In the validity analysis of the indicator system for outpatients, the factor loading was between 0.438 and 0.919, and the reliability was excellent. In the validity analysis of the indicator system for nonsurgical inpatients, the factor loading of the secondary indicators was between 0.417 and 0.75, and the reliability was excellent. In the validity analysis of the indicator system for surgical inpatients satisfaction, the factor loading of the secondary indicators range was 0.391–0.751, and the reliability was excellent.Conclusion: The indicator systems for evaluating satisfaction of outpatients, surgical inpatients and nonsurgical inpatients all have excellent reliability and good validity. They can be widely used for an outpatient and inpatient satisfaction questionnaire in Chinese hospitals. Keywords: patient satisfaction questionnaire, reliability, validity, evaluation

Wenyong Tan,1,2 Ming Yang,3 Hongli Yang,2 Fangbin Zhou,2 Weixi Shen1 1Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, People’s Republic of China; 2Clinical Medical Research Center, The Second Clinical Medical College (Shenzhen People Hospital), Jinan University, Shenzhen, People’s Republic of China; 3Shenzhen Jingmai Medical Scientific and Technique Company, Shenzhen, People’s Republic of China Abstract: Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted. Keywords: breast cancer, drug therapy, biomarker, predictive factor

Guozeng Xu,1,2,* Yuehan Zhou,3,* Fuxiang Zhou1,2 1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, China; 3Department of Pharmacology, Guilin Medical University, Guilin 541004, Guangxi, China *These authors contributed equally to this work Introduction: Chemokines are closely related with tumor immunity, progression, and metastasis. We aimed to construct a multi-RNA classifier of chemokine family genes for predicting tumor recurrence in stage I–III patients with colorectal cancer (CRC) after operation. Patients and methods: By analyzing microarray data, the Cox regression analysis was conducted to determine survival-related chemokine family genes and develop a multi-RNA classifier in the training set. The prognostic value of this multi-RNA classifier was further validated in the internal validation and external independent sets. Receiver operating characteristic curves were used to compare the prediction ability of the combined model of this multi-RNA classifier and stage, and this multi-RNA classifier and stage alone. Results: Nine survival-related chemokines were identified in the training set. We identified a nine-chemokine classifier and classified the patients as high-risk or low-risk. Compared with CRC patients with high-risk scores, CRC patients with low-risk scores had longer disease-free survival in the training (HR=2.353, 95% CI=1.480–3.742, P0.05) sets. This nine-chemokine classifier may only be applied in Marisa’s C2, C5, and C6 subtypes patients. Conclusion: Our nine-chemokine classifier is a reliable prognostic tool for some specific biological subtypes of CRC patients. It might contribute to guide the personalized treatment for high-risk patients. Keywords: classifier, colorectal cancer, chemokine, survival analysis, risk classification, microarray

A rock physics based seismic interpretation workflow has been developed to extract volumetric rock properties from seismically derived P- and S-wave impedances, Ip and Is. This workflow was first tested on a classic rock physics velocity-porosity model. Next, it was applied to two case studies: a carbonate and a clastic oil field. In each case study, we established rock physics models that accurately relate elastic properties to the rock’s volumetric properties, mainly the total porosity, clay content, and pore fluid. To resolve all three volumetric properties from only two inputs, Ip and Is, a site-specific geology driven relation between the pore fluid and porosity was derived as a hydrocarbon identifier. In order to apply this method at the seismic spatial scale, we created a coarse-scale elastic and volumetric variables by using mathematical upscaling at the wells. By using Ip and Is thus upscaled, we arrived at the accurate interpretation of the upscaled porosity, mineralogy, and water saturation both at the wells and in a simulated vertical impedance section generated by interpolation between the wells.

Wang L, Xu M, Lu P, Zhou F. OncoTargets and Therapy. 2018;11:9013–9025 The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2E and 7A with similar images from unrelated articles, specifically: Figure 2E, panel HCT116 mir-769 mimics appears to have been duplicated with a similar image in Figure 3A from Liao et al, 2018 (https://doi.org/10.3892/or.2018.6624). Figure 7A, panel miR-NC, appears to have been duplicated with a similar image in Figure 7A from Yao et al, 2018 (https://doi.org/10.2147/OTT.S190303). The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Chao Liu,1,* Zhi Mao,1,* Pan Hu,1,* Xin Hu,1 Hongjun Kang,1 Jie Hu,1 Zhifang Yang,2 Penglin Ma,3 Feihu Zhou1,4 1Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China; 3Department of Critical Care Medicine, the 309th Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4National Clinical Research Center for Kidney Diseases, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to compare the effectiveness of different fluids on critically ill patients who need fluid resuscitation through a systematic review and network meta-analysis (NMA). Data sources: Electronic databases were searched up to March 2018 for randomized controlled trials comparing the effectiveness of different fluids in critically ill patients. The primary outcome was mortality, and the secondary outcomes were the incident of acute kidney injury (AKI) and risk of receiving renal replacement therapy (RRT). A Bayesian NMA was conducted, and the quality of evidence contributing to each network estimate was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria. Results: We deemed 49 trials eligible, including 40,910 participants. The quality of evidence was rated as moderate in most comparisons. There was no significant difference among resuscitation fluids in mortality. NMA at the 9-node level showed the most effective fluid was balanced crystalloid (BC) (80.79%, the ranking of resuscitation fluid based on cumulative probability plots and surface under the cumulative ranking curves [SUCRAs]). NMA at the 10-node level showed that the most effective fluid was Plasma-Lyte (77.52%). Results of sensitivity analyses in mortality did not reveal any significant changes in the findings for primary outcomes. High-molecular-weight hetastarch (H-HES) was associated with an increased incidence of AKI when compared with gelatin (odds ratio [OR], 0.43; 95% credibility interval [CrI], 0.19–0.94), low-molecular-weight hetastarch (L-HES; OR, 0.50; 95% CrI, 0.30–0.87), BC (OR, 0.55; 95% CrI, 0.34–0.88), and normal saline (OR, 0.56; 95% CrI, 0.34–0.93). Meanwhile, H-HES was also associated with an increased risk of receiving RRT when compared with BC (OR, 0.51; 95% CrI, 0.27–0.93) and normal saline (OR, 0.52; 95% CrI, 0.24–0.96). Conclusion: BCs, especially the Plasma-Lyte, are presumably the best choice for most critically ill patients who need fluid resuscitation. Meanwhile, the use of H-HES was associated with an increased incidence of AKI and risk of receiving RRT. Registration: PROSPERO (CRD42017072728). Keywords: fluid resuscitation, critically ill, crystalloids, colloids, systematic review, network meta-analysis

Peifen Zheng, Weifeng Wang, Muxi Ji, Qin Zhu, Yuliang Feng, Feng Zhou, Qiaona He Department of Gastroenterology, Zhejiang Hospital, Hangzhou, People’s Republic of China Objective: TMEM119 is a member of transmembrane proteins family, which is abnormally expressed in human cancers and associated with tumorigenesis. In this study, we focused on the expression of TMEM119 and its role in cell invasion and migration in gastric cancer. Methods: Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed to examine the expression of TMEM119 in gastric cancer tissues and cell lines. After transfection with TMEM119 siRNA or recombined TMEM119-expressing vector, the invasion and migration ability of MKN45 and SGC-7901 cells was measured by transwell assay. The expression of TMEM119, p-STAT3, STAT3, VEGF, MMP2, and MMP9 proteins in SGC-7901 and MKN45 cells treated with TMEM119 siRNA, TMEM119-expressing vector, or AG490 was measured by Western blotting. Results: We found that higher TMEM119 expression was found in gastric cancer tissues and cell lines and was associated with lower survival rate. TMEM119 knockdown inhibited SGC-7901 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. TMEM119 overexpression promoted MKN45 cell invasion and migration, along with the expression of p-STAT3, VEGF, MMP2, and MMP9. Additionally, AG490 treatment significantly corrected TMEM119-induced MKN45 cell migration and invasion and expression of p-STAT3, VEGF, MMP9, and MMP2 proteins. Conclusion: The results indicated that TMEM119 promotes gastric cancer cell migration and invasion through activation of STAT3 signaling pathway, and TMEM119 may therefore act as a novel therapeutic target for gastric cancer. Keywords: gastric cancer, TMEM119, migration, invasion, STAT3, VEGF, MMP2, MMP9

Qiang-Hua Zhou,1,2,* Chuang-Zhong Deng,1,* Jie-Ping Chen,1 Kang-Bo Huang,1,2 Ting-Yu Liu,1,2 Kai Yao,1,2 Zhuo-Wei Liu,1,2 Zi-Ke Qin,1,2 Yong-Hong Li,1,2 Sheng-Jie Guo,1,2 Yun-Lin Ye,1,2 Fang-Jian Zhou,1,2 Wenlin Huang,1,3 Ran-Yi Liu,1 Hui Han1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; 2Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; 3Guangdong Provincial Key Laboratory of Tumor Targeted Drugs, Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Co. Ltd., Guangzhou, China *These authors contributed equally to this work Purpose: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methods: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.Results: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.Conclusion: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients. Keywords: penile neoplasms, serum markers, laminin, gamma 2, neoplasm metastasis

Muhua Huang,1,2 Fuqing Zhou,1,2 Lin Wu,1,2 Bo Wang,1,2 Hui Wan,3 Fangjun Li,3 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China Background and purpose: The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients.Patients and methods: Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers.Results: Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score (ρ = 0.379, p = 0.036).Conclusion: Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients. Keywords: default mode network, dorsal attention network, multiple sclerosis, resting-state functional MRI, Granger causality test, anticorrelation

Fuqing Zhou,1,2 Yanlin Zhao,1,2 Muhua Huang,1,2 Xianjun Zeng,1,2 Bo Wang,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, China; 2Neuroradiology Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, China Background: Abnormalities in both cerebral structure and intrinsic activity have been increasingly reported in patients with chronic insomnia disorder (CID). However, the interhemispheric integration function in CID is still not well understood. Functional homotopy reflects an essential aspect of the intrinsic functional architecture involved in interhemispheric coordination. Methods: In this study, voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with CID (n=29). Results: Reduced homotopic connectivity was observed in the middle occipital/posterior middle temporal gyrus in CID patients relative to control subjects. Further analyses demonstrated different insomnia-related heterotopic connectivity patterns in the right and left middle occipital/posterior middle temporal gyrus. Furthermore, within the CID group, the connectivity coefficient within the connectivity network of the middle occipital/posterior middle temporal gyrus was associated with anxiety measures. Conclusion: Negative significant findings of group differences were found in terms of both the local gray matter density and fractional anisotropy of the white matter skeletal measures in this study; this structural finding, together with the results of VMHC, suggested that disruptions in the intrinsic functional architecture of interhemispheric communication associated with CID can be observed in the absence of detectable microstructural or local morphometric changes in white and gray matter. Keywords: homotopic connectivity, interhemispheric integration, voxel-mirrored homotopic connectivity, chronic primary insomnia, sleep disorders, resting-state fMRI

Shunda Hong,1,* Lili Gu,2,* Fuqing Zhou,1 Jiaqi Liu,1 Muhua Huang,1 Jian Jiang,1 Laichang He,1 Honghan Gong,1 Xianjun Zeng1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to explore intrinsic functional connectivity patterns in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Patients and methods: Thirty-three right-handed HZ patients (13 males; mean age 57.15±9.30 years), 22 right-handed PHN patients (9 males; mean age 66.13±6.77 years), and 28 well-matched healthy controls (HC) (9 males; mean age 54.21±7.72 years) underwent resting-state functional magnetic resonance imaging for intrinsic functional connectivity analyses. Functional connectivity density (FCD) was calculated and compared among the PHN, HZ, and HC groups. In addition, the Pearson correlation coefficient was calculated to compare various clinical indices in the regions with abnormal FCD values. Results: Compared with the HC, both HZ and PHN patients showed significantly decreased FCD in the precuneus, and patients with HZ displayed significantly increased FCD in the brainstem/limbic lobe/parahippocampalgyrus, whereas patients with PHN displayed significantly increased FCD in the hippocampus (correlation thresholds r=0.25, voxel level of P

Fangbin Zhou,1,2 Yaying Zhou,3 Ming Yang,1 Jinli Wen,3 Jun Dong,4 Wenyong Tan1 1Department of Oncology, The Second Clinical Medical College, Shenzhen People’s Hospital, Jinan University, Shenzhen, People’s Republic of China; 2Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, People’s Republic of China; 3Clinical Medical Research Center, The Second Clinical Medical College, Shenzhen People’s Hospital, Jinan University, Shenzhen, People’s Republic of China; 4Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, People’s Republic of China Background: Circulating endothelial cells (CECs) and their subpopulations could be potential novel biomarkers for various malignancies. However, reliable enumerable methods are warranted to further improve their clinical utility. This study aimed to optimize a flow cytometric method (FCM) assay for CECs and subpopulations in peripheral blood for patients with solid cancers.Patients and methods: An FCM assay was used to detect and identify CECs. A panel of 60 blood samples, including 44 metastatic cancer patients and 16 healthy controls, were used in this study. Some key issues of CEC enumeration, including sample material and anticoagulant selection, optimal titration of antibodies, lysis/wash procedures of blood sample preparation, conditions of sample storage, sufficient cell events to enhance the signal, fluorescence-minus-one controls instead of isotype controls to reduce background noise, optimal selection of cell surface markers, and evaluating the reproducibility of our method, were integrated and investigated. Wilcoxon and Mann–Whitney U tests were used to determine statistically significant differences.Results: In this validation study, we refined a five-color FCM method to detect CECs and their subpopulations in peripheral blood of patients with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects (P

Chao Liu,* Zhi Mao,* Hongjun Kang, Xin Hu, Shengmao Jiang, Pan Hu, Jie Hu, Feihu Zhou Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Background: A long-axis in-plane (LA-IP) approach and a short-axis out-of-plane (SA-OOP) approach are the two main approaches used in ultrasound (US)-guided vascular catheterization. However, the efficacy and safety of these approaches remain controversial. Therefore, we performed this meta-analysis to compare the two techniques in vascular catheterization. Materials and methods: Relevant studies were searched in PubMed, Embase, and the Cochrane Library databases from database inception until August 2017. Randomized controlled trials comparing a long-axis approach with a short-axis approach for US-guided vascular cannulation were selected. The RevMan software was used to analyze the results, and trial sequential analysis (TSA) was further applied to determine whether the currently available evidence was sufficient and conclusive. Results: Eleven studies met the inclusion criteria. Overall, 1,210 patients were included. The total success rate was similar between the SA-OOP and LA-IP approaches for US-guided vascular catheterization (risk ratio [RR], 1.01; 95% CI, 0.99–1.04; P=0.35; I2=48%). In the radial artery (RA; RR, 1.00; 95% CI, 0.96–1.05; P=0.88; I2=49%) and internal jugular vein (IJV; RR, 1.00; 95% CI, 0.98–1.02; P=0.99; I2=0%) subgroups, the total success rate was also similar and was confirmed by the TSA. For populations with subclavian vein (SCV) and axillary vein catheterization, the SA-OOP approach showed a benefit for first-attempt success rate. No significant differences in first-attempt success rate, cannulation times, or complications were found between the two approaches. Conclusion: Despite a similar total success rate between the SA-OOP approach and the LA-IP approach when used for RA and IJV catheterization (as confirmed by TSA), further robust well-designed trials are warranted to evaluate other outcomes. There is insufficient evidence to definitively state that the SA-OOP approach was superior to the LA-IP approach when used for SCV and axillary vein catheterization. High-quality trials are needed to confirm or refute this finding. Keywords: ultrasound guidance, long-axis in-plane, short-axis out-of-plane, vascular catheterization, radial artery, internal jugular vein

Fuqing Zhou,1,2 Lili Gu,3 Shunda Hong,1,2 Jiaqi Liu,1,2 Jian Jiang,1,2 Muhua Huang,1,2 Yong Zhang,3 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China Objective: The aim of this study was to explore the amplitude of intrinsic low-frequency oscillations (LFOs) in patients with discogenic low-back and leg pain (LBLP).Participants and methods: We obtained and compared the LFO amplitude from 25 right-handed discogenic LBLP patients (13 males; mean age 55.16±1.83 years) and 27 well-matched healthy controls (15 males; mean age 52.96±1.63 years). The LFO amplitude was examined using the voxel-wise amplitude of low-frequency fluctuations (ALFFs), and partial correlation analysis was performed to determine the relationship between the regions with altered ALFF values and clinical parameters in discogenic LBLP patients.Results: Compared with healthy controls, the patients with discogenic LBLP showed a significant increase in ALFF in the affective system of the pain matrix (left anterior cingulate cortex, right anterior insula/frontal operculum, and bilateral orbitofrontal cortex) and information-processing regions (middle occipital/temporal gyrus). In addition, a significant decrease in ALFF was observed in the default mode network (DMN; inferior parietal lobule (IPL) and medial prefrontal cortex [mPFC]) and the processing system of the pain matrix (basal ganglia/thalamus/midbrain, postcentral gyrus [PoCG], and fusiform gyrus). Several regions with altered ALFF were associated with disease duration, visual analog scale scores, Barthel index, and fine sensory modality measurements (two-point tactile discrimination of the left and/or right leg). Further operating characteristic curves analysis suggested that the mean ALFF values in the right IPL, left IPL/PoCG, left anterior cingulate cortex, and left mPFC could serve as markers to separate individuals with discogenic LBLP from healthy subjects.Conclusion: Our results revealed widespread abnormalities in ALFF in the pain matrix and information-processing regions as well as a decrease in ALFF in the DMN. These results open up an important new avenue to better understand the nature of the link between intrinsic activity and peripheral pain and sensory impairment in discogenic LBLP patients. Keywords: amplitude of low-frequency fluctuations, resting state functional magnetic resonance imaging, discogenic low-back and leg pain, amplitude of low-frequency fluctuations

Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Yongming Tan,1,2 Jianqiang Guo,1,2 Yong Zhang,3 Laichang He,1,2 Honghan Gong1,2 1Department of Radiology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Pain Clinic, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China Objective: Advanced magnetic resonance imaging studies have shown functional plasticity or reorganization and metabolite alterations of N-acetyl aspartate in the sensorimotor cortex (SMC), a hallmark region and key brain network, in patients with cervical spondylotic myelopathy (CSM). However, the nature of perfusion in the SMC and the relationship between regional cerebral blood flow (CBF), motor function scores, and structural damage of the cervical cord in patients with CSM are not fully understood.Materials and methods: All right-handed participants underwent pseudo-continuous arterial spin labeling pulse sequence scanning, and CBF was then calculated and compared between CSM and healthy groups. Clinical and structural associations were assessed in the SMC. Receiver operating characteristic (ROC) and leave-one-out cross-validation analyses were used to estimate the sensitivity and specificity of the significantly altered CBF in the SMC to distinguish myelopathy-related impairment.Results: A total of 18 pairs of CSM patients and well-matched healthy subjects were included in the analyses. Compared with healthy subjects, CSM patients exhibited significantly decreased CBF in the left premotor ventral/precentral operculum (PMv/PrCO) and the bilateral dorsal anterior cingulate cortex (dACC); and increased CBF in the left paracentral lobule (PCL), the right PCL/supplementary motor area (PCL/SMA), and the right postcentral gyrus (PoCG; Gaussian random field correction at P

Guoying Deng,1,* Feng Zhou,1,* Zizheng Wu,2–4 Fei Zhang,1 Kerun Niu,2,3 Yingjie Kang,5 Xijian Liu,6 Qiugen Wang,1 Yin Wang,7 Qian Wang1 1Trauma Center, 2Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 3Department of Orthopaedics, Shanghai General Hospital of Nanjing Medical University, 4Department of Orthopaedics, Baoshan Branch of Shanghai General Hospital of Shanghai Jiaotong University, 5Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 6College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 7Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a trans­well migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic. Keywords: metastasis inhibition, photothermal nanoparticles, SRC/FAK signaling pathway, survival curves, MMPs

Chunling Du,* Jinchang Lu,* Lei Zhou, Bo Wu, Feng Zhou, Liang Gu, Donghui Xu, Yingxin Sun Department of Respiratory Medicine, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Objective: To explore the effect of cigarette smoke (CS) on the development of squamous metaplasia in human airway epithelial cells and the role of MAPK- and FoxA2-signaling pathways in the process.Materials and methods: In an in vitro study, we treated the bronchial epithelial cell line BEAS2B with CS extract, followed by treatment with the ERK inhibitor U0126, the JNK inhibitor SP600125, or the p38 inhibitor SB203580. In vivo, we used a CS-induced rat model. After treatment with CS with or without MAPK inhibitors for 90 days, lung tissues were harvested. p-ERK, p-p38 and p-JNK protein levels in cells and lung tissue were measured using enzyme-linked immunosorbent assays, mRNA- and protein-expression profiles of FoxA2, E-cadherin, CD44, and ZO1 were measured using quantitative real-time polymerase chain reaction and Western blotting, respectively, and morphological changes in bronchial epithelial cells were observed using lung-tissue staining.Results: In both the in vitro and in vivo studies, phosphorylation of the ERK1/2, JNK, and p38 proteins was significantly increased (P

Suhua Huang,1 Fuqing Zhou,2,3 Jian Jiang,2,3 Muhua Huang,2,3 Xianjun Zeng,2,3 Shan Ding,1 Honghan Gong2,3 1Department of Radiology, Jiangxi Province Children’s Hospital, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China Abstract: Several neuroimaging studies have suggested that brain impairment and plasticity occur in patients with chronic primary insomnia (CPI); however, the effects of insomnia on the intrinsic organization of the brain remain largely unknown. In this study, a voxel-based functional connectivity strength (FCS) assessment, a data-driven method based on a theoretical approach, was applied to investigate the effects of insomnia on the intrinsic organization of the whole brain in 27 treatment-naïve CPI patients and 26 well-matched healthy controls (HCs). Compared with HCs, CPI patients exhibited decreased FCS primarily in the right dorsolateral prefrontal cortex, the right medial prefrontal cortex (MPFC), the left basal ganglia/insula, and the right cerebellum anterior lobe (CAL) due to decreased functional connectivity patterns. These results suggest that poor sleep quality could impair FCS within the brain, including the MPFC and the CAL, which are important for cognitive control and modulating motor and limbic functions. Additionally, a receiver operator characteristic analysis revealed that altered FCS has moderate sensitivity (76.9%–88.5%) and specificity (59.3%–70.4%) as a reference indicator to discriminate CPI patients from HCs. Taken together, these findings provide evidence for abnormal intrinsic brain activity in CPI patients and might improve our understanding of the pathophysiological processes that occur in insomnia patients. Keywords: functional connectivity strength, disconnection, chronic primary insomnia, sleep disorders, resting-state fMRI

Mengye Zhu,1,* Fuqing Zhou,2,* Lingchao Li,1 Qin Yin,3 Mizhen Qiu,1 Yong Zhang1 1Department of Pain Clinic, 2Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 3Department of Pain Clinic, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Spinal cord injury (SCI) complicated by epidural anesthesia, though rare, can result in neuropathic pain. However, the treatment for this kind of life-altering injury remains a challenge. A 7-year-old girl was referred with dyskinesia and severe pain in her right lower extremity due to an accidental SCI following lumbar puncture. After treatment with analgesics such as gabapentin, mecobalamin, and dexamethasone/methylprednisolone for 1 week, the myodynamia had improved, but progressive pain persisted. After treatment with neurotropin, a gradual decrease in visual analog scale score from 7 to 0 was observed. We herein first describe that neurotropin produced sustained relief of pain induced by SCI. This case suggests that neurotropin might be a promising drug in treating pediatric neuropathic pain caused by SCI. Keywords: spinal cord injury, pain, neurotropin, children