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He L, Lei Y, Hou J, Wu J, Lv G. Onco Targets Ther. 2020;13:5901–5911. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jiongliang Wang,1,2,&ast; Zhikai Zheng,1,2,&ast; Tianqing Wu,1,2,&ast; Wenxuan Li,1,2,&ast; Juncheng Wang,1,2 Yangxun Pan,1,2 Wei Peng,1,2 Dandan Hu,1,2 Jiajie Hou,1,2 Li Xu,1,2 Yaojun Zhang,1,2 Minshan Chen,1,2 Rongxin Zhang,2,3 Zhongguo Zhou1,2 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongguo Zhou, Department of Liver Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343117, Email zhouzhg@sysucc.org.cn Rongxin Zhang, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Dongfeng Road East 651, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-411-84672130, Email zhangrx@sysucc.org.cnObjective: To evaluate whether surgery-related complications are increased after hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin plus fluorouracil/leucovorin for conversion compared with primary hepatocellular carcinoma (HCC) resection and the optimal timing of conversion surgery (CS).Background: HAIC has been widely used for advanced HCC, especially initially unresectable HCC, to facilitate conversion to curative-intent resection in approximately 23.8% of cases. However, the optimal timing of surgery to reduce surgical complications must be clarified.Methods: Data from 320 HCC patients, including 107 initially unresectable patients in the HAIC-Surgery group and 213 patients in the Surgery group, were retrospectively collected and analyzed. Survival outcomes and the incidence of surgery-related complications were compared.Results: There was no significant difference in recurrence-free survival (RFS) between the HAIC-Surgery group and the Surgery group (HR: 1.140, 95% CI: 0.8027– 1.618, p=0.444). The HAIC-Surgery group had a higher incidence of surgery-related complications than the Surgery group [biliary leakage (10.3% vs 4.2%, p=0.035), abdominal bleeding (10.3% vs 3.8%, p=0.020), pleural effusion (56.1% vs 23.0%, p< 0.0001) and ascites effusion (17.8% vs 5.2%, p< 0.0001)]. In the HAIC-Surgery group, postoperative liver function decreased and abdominal bleeding increased with more preoperative HAIC cycles (Spearman=0.229, p=0.042, Spearman=0.198, p=0.041, respectively). The pathological complete remission (pCR) rate after 3– 5 HAIC cycles was significantly higher than that after 1– 2 cycles (29.4% vs 13.2%, p=0.043).Conclusion: The prognosis of advanced HCC after conversion surgery is comparable to that after direct surgery. Rather than increasing pCR, more HAIC cycles can exacerbate liver dysfunction and surgery-related complications.Keywords: hepatocellular carcinoma, conversion therapy, hepatic artery chemotherapy infusion

Guiyuan Ma,1 Jianmei Hou,1 Sha Peng,1 Yanhui Liu,1 Zhengkun Shi,1 Yuhua Fan,1 Jinghui Zhang1– 3 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 3Mobile Health-Ministry of Education Laboratory, Changsha, 410008, People’s Republic of ChinaCorrespondence: Jinghui Zhang, Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, People’s Republic of China, 410008, Tel +86 15874032339, Email zhangjh-1206@163.comBackground: With the aging of China’s population, the incidence rate of chronic diseases is rising. At the same time, residents’ health awareness is also increasing. Implementing Internet +home care is an inevitable trend in adapting social development. Currently, Internet +home care is in the pilot stage in China, relevant institutional measures are neither standardized nor perfect, and there is no set of quality supervision indicators (QSIs).Purpose: The construction of Internet +home care QSIs in China will provide a theoretical basis for Internet +home care quality supervision.Materials and Methods: The Service-Quality model was used as the theoretical framework, and a literature review, semi-structured interviews, focus group discussions, and Delphi consultations determined the contents of the QSIs and the weight of each indicator.Results: Internet +home care QSIs were constructed and included 5 first-level indicators, 17 secondary indicators, and 69 tertiary indicators. The effective recovery rates of the two rounds of Delphi expert consultation were 100% and 85%, the expert authority coefficients were 0.810 and 0.833, and the Kendall harmony coefficients were 0.189 and 0.125 (P< 0.01). The final set of Internet +home care QSIs was as follows: tangibility (4 secondary and 16 tertiary indicators), reliability (4 secondary and 19 tertiary indicators), guarantee (5 secondary and 20 tertiary indicators), responsiveness (2 secondary and 8 tertiary indicators), and empathy (2 secondary and 6 tertiary indicators).Conclusion: The construction of Internet +home care QSIs based on the SERVQUAL model is scientifically valid, and the indicators are reliable. They provide guidance and reference values for the continuous improvement and promotion of Internet +home care. This work also provides a theoretical basis for researching and developing an Internet +home care quality supervision platform.Keywords: SERVQUAL model, Internet +home care, delphi survey, quality supervision indicator

Surface mechanical strengthening is an effective way to improve the fatigue performance, among which surface rolling has been vastly utilized for its significant enhancement in fatigue strength. However, traditional rolling process is only suitable for components with rotational symmetry, limiting its application. Herein, a newly developed technology named "spinning rolling (SR)" was developed to strengthen the surfaces of platy components. A common Al alloy, 7075, was selected for verifying the effect. It is found that compared with the most popular technology, shot peening (SP), SR can provide deeper and higher residual stress, lower surface roughness, and comparable hardening layer, and consequently, significantly higher fatigue lives. Accordingly, there is a transition in the fatigue crack source from point‐like to line‐like, confirming a strong crack propagation resistance along depth direction. This study indicates the advantages of the SR technology, providing a greater resistance against fatigue damage of platy components. Highlights: We developed a new surface strengthening technology—spinning rolling (SR), which has wider applicability and better fatigue life extension effect.The fatigue lives of 7075 aluminum alloy plates processed by SR are highly improved by even one order of magnitude at the same stress amplitude.There is a transition in the fatigue crack source from point‐like to line‐like, confirming a strong crack propagation resistance along depth direction due to SR. [ABSTRACT FROM AUTHOR]

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value. 2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and β-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while β-catenin protein was highly expressed in the middle stage of embryo development. 3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/β-catenin pathway protein expression. 4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/β-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, β-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of β-catenin and p-ERK were consistent with Western blot results. 5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/β-catenin pathways. [ABSTRACT FROM AUTHOR]

As an important control element in steam heating piping systems, the safety and stability of inverted bucket steam valves determine the reliable operation of the system. Therefore, it is necessary to investigate the acoustic mechanism of inverted bucket steam valves. Aiming at the difficulty of numerical simulation in accurately predicting the aerodynamic noise of inverted bucket steam valves, this paper proposes a new method for simulating the aerodynamic noise of inverted bucket steam valves based on multiband analysis (LES). The flow field of the inverted bucket steam valve is numerically simulated using the LES method to obtain wall pressure pulsation information and fluid velocity pulsation information, which are used as excitation sources for acoustic simulation. The characteristics of dipole and quadrupole sound sources were obtained by applying the FW-H method and experimentally verified. The results show that a new multifrequency band analysis method for inverted bucket steam valves is effective by comparing the numerical simulation results, in which the dipole source dominates in the low-frequency band, in the medium frequency range, the quadrupole source outperforms the dipole source, but in the high frequency range, the quadrupole source is dominant. The experimental results are in good agreement with the simulation results, and the correctness of the numerical simulation is confirmed by the fact that there is less than a 3% difference between the findings of the numerical simulation and the experimental data. [ABSTRACT FROM AUTHOR]

Haitao Fan,1 Junhui Hou,2 Siqing Liu,3 Zuomin Xiao,4 Jia Cui5 1Department of Urology, The Second Hospital of Jilin University, Changchun, Jilin 130041, People’s Republic of China; 2Department of Oncology & Radiotherapy, Qingdao Central Medical Group, Qingdao, Shandong 266000, People’s Republic of China; 3Department of Outpatient, Qingdao Special Service Sanatorium of PLA Navy, Qingdao, Shandong 266071, People’s Republic of China; 4Department of Clinical Laboratory, Jinan Jigang Hospital, Jinan, Shandong 250101, People’s Republic of China; 5Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, People’s Republic of ChinaCorrespondence: Jia CuiDepartment of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, People’s Republic of ChinaEmail dalian_cuijia@163.comPurpose: DARS antisense RNA 1 (DARS-AS1) is a long non-coding RNA that has been validated as a critical regulator in several human cancer types. Our study aimed to determine the expression profile of DARS-AS1 in prostate cancer (PCa) tissues and cell lines. Functional experiments were conducted to explore the detailed roles of DARS-AS1 in regulating PCa carcinogenesis. Furthermore, the detailed mechanisms by which DARS-AS1 regulates the oncogenicity of PCa cells were uncovered.Methods: Reverse transcription quantitative polymerase chain reaction was performed to analyze DARS-AS1 expression in PCa tissues and cell lines. Cell Counting Kit-8 assays, flow cytometry analyses, Transwell assays, and tumor xenograft experiments were conducted to determine the regulatory effects of DARS-AS1 knockdown on the malignant phenotype of PCa cells. Bioinformatics analysis was performed to identify putative microRNAs (miRNAs) targeting DARS-AS1, and the direct interaction between DARS-AS1 and miR-628-5p was verified using RNA immunoprecipitation and luciferase reporter assays.Results: DARS-AS1 was highly expressed in PCa tissues and cell lines. In vitro functional experiments demonstrated that DARS-AS1 depletion suppressed PCa cell proliferation, promoted cell apoptosis, and restricted cell migration and invasion. In vivo studies revealed that the downregulation of DARS-AS1 inhibited PCa tumor growth in nude mice. Mechanistic investigation verified that DARS-AS1 functioned as an endogenous miR-628-5p sponge in PCa cells and consequently promoted the expression of metadherin (MTDH). Furthermore, the involvement of miR-628-5p/MTDH axis in DARS-AS1-mediated regulatory actions in PCa cells was verified using rescue experiments.Conclusion: DARS-AS1 functioned as a competing endogenous RNA in PCa by adsorbing miR-628-5p and thereby increasing the expression of MTDH, resulting in enhanced PCa progression. The identification of a novel DARS-AS1/miR-628-5p/MTDH regulatory network in PCa cells may offer a new theoretical basis for the development of promising therapeutic targets.Keywords: DARS antisense RNA 1, non-coding RNA, ceRNA theory, target therapy

Guohong Huang,* Yimei Yang,* Mengxin Lv, Tian Huang, Xiaoyan Zhan, Wei Kang, Jianghou Hou Clinical Research Center of Kunming Maternal and Child Health Hospital, Kunming 650031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianghou HouClinical Research Center of Kunming Maternal and Child Health Hospital, Kunming 650031, People’s Republic of ChinaEmail houjiangh@126.comBackground: Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a high mortality rate. lncRNA SFTA1P is highly expressed in HCC. We aimed to study the role of SFTA1P in HCC and its relationship with miR-4766-5p.Materials and Methods: The levels of SFTA1P in HCC tissues and cell lines were determined. Relationship between SFTA1P and clinical features and prognosis was studied. The influence of SFTA1P on HCC cell viability, migration, invasion and apoptosis was studied in vitro. Rescue experiments were conducted after the binding site between SFTA1P and miR-4766-5p confirmed by dual-luciferase assay. The protein expression of AKT, p-AKT, mTOR and p-mTOR in HCC cells with knockdown of SFTA1P was determined by Western blotting. A tumor study in nude mice was conducted in order to assess the effects of SFTA1P on tumor growth characteristics.Results: SFTA1P was up-regulated in HCC tissues and cell lines. SFTA1P expression was closely related to tumor size, vascular invasion and TNM stage. Knockdown of SFTA1P inhibited HCC cell viability, migration and invasion and promoted cell apoptosis. MiR-4766-5p was a target of SFTA1P and knockdown of SFTA1P could decrease the protein expression of p-AKT and p-mTOR. Rescue experiments showed that miR-4766-5p mimics could attenuate the promoting role of SFTA1P on HCC cell viability, invasion and migration, and inhibiting role on cell apoptosis. Moreover, we used nude mice models and also found that the knockdown of SFTA1P reduced tumor volume and weight.Conclusion: lncRNA SFTA1P could promote tumor development in HCC by down-regulating miR-4766-5p expression via PI3K/AKT/mTOR signaling pathway. It may be a potential therapeutic target for HCC.Keywords: hepatocellular carcinoma, SFTA1P, miR-4766-5p, PI3K/AKT/mTOR signaling pathway, tumor growth

Huabo Jiang1 ,* Li Li2 ,* Jingjing Zhang,3 Zhong Wan,4 Yuanyuan Wang,5 Jingjing Hou,6 Yongsheng Yu1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Assisted Reproduction Technology Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Plastic Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Health Medicine, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 6Department of Gastrointestinal Surgery, Institute of Gastrointestinal Oncology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingjing Hou; Yongsheng Yu Email jjhou@xmu.edu.cn; yongshengyu@tongji.edu.cnObjective: EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and has been documented as an oncogene in breast cancer. The microRNA (miR)-101-3p can suppress breast cancer progression by targeting with EZH2. Syn-cal14.1a, a synthetic peptide derived from Californiconus californicus (Cal14.1a), can decrease the cell viability and activate the cell apoptosis in cancer. In this study, we explored whether the synergy of miR-101-3p mimic and syn-cal14.1a could inhibit the expression of EZH2. We also investigated this binding treatment’s effects on the suppression of breast cancer cells.Methods: MiR-101-3p mimic was transfected and syn-cal14.1a was added in SK-BR-3 and MCF-7 breast cancer cells. The expression of EZH2 protein level was determined. Then, cell proliferation, migration, invasion, and apoptosis were observed.Results: MiR-101-3p and syn-cal14.1a, when applied together, exerted a synergistic anti-EZH2 expression in breast cancer cells. The combination of miR-101-3p and syn-cal14.1a synergistically suppressed the EZH2-induced breast cancer cell migration, invasion, and proliferation. In parallel, this synergy treatment was able to promote the apoptosis of breast cancer cells. To our knowledge, this is the first report describing inhibition of EZH2 in human breast cancer cell lines by syn-cal14.1a.Conclusion: The anti-EZH2 roles of miR-101-3p and/or syn-cal14.1a could provide an effective therapeutic strategy in breast cancer. These data provide significant insights into molecular mechanisms of breast cancer and may have benefits in clinical therapeutics for breast cancer.Keywords: breast cancer, miR-101-3p, conotoxins, synthetic peptide, EZH2, synergism

Congda Zhang, Qingyue Li, Fangqi Li, Yuanhao Zhang, Yiyong Tang, Jingyi Hou, Rui Yang Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Rui Yang; Jingyi Hou Tel +86 13694200667; +86 18102769380Fax +86 81332199Email yangr@mail.sysu.edu.cn; houjy7@mail.sysu.edu.cnBackground: Lack of physical therapists has led to increment of self-managed rehabilitations in post-arthroscopic rotator cuff repair (ARCR) in the forms of booklets or leaflets.Purpose: The aim of study is to investigate 1) the acceptance of post-ARCR patients towards an education booklet, and 2) whether it could be a timesaving and laborsaving tool to physical therapists.Methods: An education booklet was established through a systematic review. Patients who underwent ARCR in our hospital were included and randomly assigned to the intervention or control group (27 women, 21 men, mean age= 57.06 years old). Patients in the intervention group received educational booklets, and an evaluation was also obtained after they finished reading. Patients’ understanding of the booklet was determined by asking patients to re-enact training presented in the booklet. Then, a therapist blinded to allocations would personally demonstrate training to patients until patients fully understood the protocol. For the control group, the same therapist coached patients until the whole protocol was clearly understood. The coaching time for patients in both groups was recorded.Results: Out of 48 patients, 24 (50%) were randomly assigned to the intervention group, and 21 (87.50%) completed their questionnaire. Out of these 21 patients, 20 (95.24%) rated the booklet as “excellent and easy to read”, and 17 (80.95%) felt that the booklet was helpful. The re-enaction accuracy was for strengthening training and specific training (71.43% and 61.90%, respectively). As compared to the control group, the time of coaching for the patients to fully master the protocol in the intervention group was significantly less (P< 0.01).Conclusion: Patients highly applauded this booklet, and they cherished the information and support it contained. Nevertheless, the re-enaction accuracy was not high, suggesting that the high level of acceptance does not guarantee full understanding of information sent to patients.Keywords: rotator cuff injuries, arthroscopy, rehabilitation, pamphlets, evaluation studies

Binbin Xu,1,2 Jinghui Zhang,1,3 Jianmei Hou,2 Mengdan Ma,2 Zhihong Gong,2 Siyuan Tang2 1Teaching and Research Office of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinghui ZhangTeaching and Research Office of Clinical Nursing, Xiangya Hospital of Central South University, Changsha 410008, People’s Republic of ChinaTel +86 15874032339Email zhangjh-1206@163.comBackground and Aim: The promotion of peripherally inserted central catheter (PICC) maintenance in primary hospitals can benefit discharged patients with PICCs living in remote areas a lot. Yet, no primary hospitals had introduced PICC maintenance technology in Hunan province, China. The present study aimed to evaluate nurses’ attitudes and knowledge of PICC maintenance in primary hospitals in Hunan province, China.Materials and Methods: From November 2018 to January 2019, a total of 560 nurses from 28 community hospitals and 28 township hospitals in 14 cities across Hunan were recruited in the present study. All nurses were registered nurses engaged in clinical work related to intravenous infusion, and their attitudes and knowledge of PICC maintenance were measured by a self-designed questionnaire that was based on literature review and expert consultation.Results: The response rate was 93.6% (560 of 598). Almost all participants could realize the importance and necessity of PICC maintenance. More than 90% of the participants expressed interest in PICC maintenance and showed strong demands for relevant training. However, the nurses’ correct response rate of most knowledge items was at a low level (7.14– 57.68%), with only three items exhibiting the correct response rate of 90% or higher. The factors influencing the nurses’ PICC maintenance knowledge included their nursing experience, professional title, work setting, and department.Conclusion: Although nurses in primary hospitals had a positive attitude toward PICC maintenance, their knowledge level was unsatisfactory, which might be a barrier to the promotion of PICC maintenance technology in primary hospitals in Hunan province, China. Multiple parties should get involved and take measures to improve the nurses’ PICC maintenance knowledge, including the government, nursing associations, large-scale hospitals, and primary hospitals themselves. Besides, new training models and dynamic assessment methods should be explored to improve training effectiveness in the future.Keywords: attitudes, catheter maintenance, knowledge, nurses, peripherally inserted central catheter, PICC, primary hospitals

Lirui He, Yunpeng Lei, Jianing Hou, Jianlong Wu, Guoqing Lv Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518000, People’s Republic of ChinaCorrespondence: Guoqing LvPeking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong 518000, People’s Republic of ChinaEmail GuoqingLv123@126.comBackground: Gastric cancer (GC) is an aggressive malignancy with high lethality. Systematic chemotherapy is the main therapeutic strategy for advanced GC patients. The overexpression of Axl is associated with poor prognosis and regulates tumor growth and metastasis in many types of cancer. However, the role of Axl in GC progression remains elusive.Materials and Methods: Western blot and quantitative real-time PCR assay (RT-PCR) assays were used to detect the expression of Gas6, Axl, ZEB1 and epithelial-mesenchymal transition (EMT)-related markers in GC cells. Cell proliferation was determined by EdU cell proliferation assay and CCK-8 assay. Transwell invasion assay was performed to explore the effect of Axl and ZEB1 on cell invasion. Tumor xenografts and lung metastasis models were conducted to examine the effect of Axl on the growth and lung metastasis of GC cells.Results: In our study, we found that high levels of Gas6 and Axl expression were associated with reduced overall survival (OS) in GC patients and the expression of Gas6 and Axl was upregulated in GC cell lines. Ectopic expression of Axl induced EMT and promoted GC cell invasion and proliferation. The knockdown of Axl inhibited EMT and suppressed the proliferation and invasion of GC cell. In vivo study showed that inhibition of Axl impaired tumor growth and lung metastasis of GC cells. Mechanistic investigations revealed that Axl promoted EMT, invasion, and proliferation via upregulating ZEB1 expression in GC cells.Conclusion: Our results demonstrated that the Gas6/Axl/ZEB1 signaling pathway regulated EMT, invasion, and proliferation in GC cells and might represent a potential therapeutic target for GC treatment.Keywords: gastric cancer, Gas6/Axl signaling pathway, ZEB1, EMT, invasion, proliferation

Tiejun Ren, Chang Liu, Jianfeng Hou, Fengxiao Shan Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, People’s Republic of ChinaCorrespondence: Tiejun RenDepartment of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, No. 288, Zhongzhou Road, Luoyang, Henan 471000, People’s Republic of ChinaTel +86-379-638922158Email sumujd@163.comPurpose: Non-small cell lung cancer (NSCLC) is the largest type of lung cancer (LC) with a higher mortality rate. Circular RNAs (circRNAs) have been shown to play an important role in cancer progression. Therefore, this study was to explore the function of hsa_circ_0043265 in NSCLC.Methods: The expression levels of hsa_circ_0043265, microRNA-25-3p (miR-25-3p) and forkhead box P2 (FOXP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Ribonuclease R (RNase R) and Actinomycin D (ActD) were used to verify the authenticity and stability of hsa_circ_0043265. Cell counting kit-8 (CCK-8), flow cytometry and transwell assays were used to evaluate the abilities of proliferation, apoptosis, migration and invasion of NSCLC cells. Also, Western blot (WB) analysis was performed to assess the levels of apoptosis, epithelial–mesenchymal transition (EMT) and proliferation-related proteins and FOXP2 protein. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to verify the interaction between miR-25-3p and hsa_circ_0043265 or FOXP2. Besides, mice xenograft models were constructed to confirm the effect of hsa_circ_0043265 on NSCLC tumor growth in vivo.Results: Hsa_circ_0043265 was lowly expressed in NSCLC tissues and cells, and its overexpression inhibited the proliferation, migration, invasion and EMT process, while improved the apoptosis of NSCLC cells. MiR-25-3p could be sponged by hsa_circ_0043265, and its overexpression could invert the suppression effect of overexpressed-hsa_circ_0043265 on NSCLC progression. Moreover, FOXP2 was a target of miR-25-3p, and its silencing also could reverse the inhibition effect of overexpressed-hsa_circ_0043265 on NSCLC progression. In addition, hsa_circ_0043265 overexpression reduced the tumor growth of NSCLC in vivo.Conclusion: Hsa_circ_0043265 could sponge miR-25-3p to improve FOXP2 expression, thereby inhibiting NSCLC progression. This study showed that hsa_circ_0043265 could be a potential biomarker for early diagnosis of NSCLC.Keywords: NSCLC, hsa_ciingrc_0043265, miR-25-3p, FOXP2, progression

Jianlin Hou,1,* Maoyi Xu,2,* Weimin Wang,3 Joseph C Kolars,4 Yang Ke5 1Institute of Medical Education & National Center for Health Professions Education Development, Peking University, Beijing, People’s Republic of China; 2China Medical Tribune, Beijing, People’s Republic of China; 3Health Science Center, Peking University, Beijing, People’s Republic of China; 4University of Michigan Medical School, Ann Arbor, MI, USA; 5School of Oncology, Peking University, Beijing, People’s Republic of China*These authors contributed equally to this work.Correspondence: Yang Ke Email keyang@bjmu.edu.cnObjective: Mergers of health science faculties in China have resulted in two different admission pathways for medical students. A uniform-code model prioritizes admission to a specific institution with secondary assignment to major. A separate-code model prioritizes admission directly to a school within an institution. This study investigates the impact of these two admission pathways on medical student selection and on the satisfaction of students with their major.Methods: Medical students at 16 medical schools across China completed a questionnaire survey. Descriptive calculation, chi-square tests, and probit models were used for analysing the data.Results: A total of 3132 completed surveys were included in the analysis. Compared with the students admitted under the uniform-code pathway, a significantly larger proportion of the students admitted under the separate-code pathway had medicine as the first preferred major (89.6% vs 79.6%, p=0.000); compared with those students enrolled into medicine not as their first preferred major, a significantly larger proportion of students enrolled into medicine as their first preferred major were willing to study medicine if choosing again (80.1% vs 62.4%, p=0.000) or to recommend the major to other students (73.3% vs 65.2%, p=0.000). Probit models showed that medical students admitted under the separate-code admission pathway were more likely to choose medicine as their first preferred major at application (β=0.96, p=0.000); medical students admitted into medical school as their first preferred major were more likely to be willing to study medicine if choosing again (β=0.53, p=0.000) or to recommend the medical major to other students (β=0.18, p=0.010).Conclusion: Separate-code admission is more likely to result in matriculants who choose medicine as their first preferred major and are more likely to be intrinsically interested in medicine than those applicants assigned to medicine from the uniform admission process.Keywords: university merger, admission, selection, medical students, China

Jianhao Hou, 1, 2,* Jinjun Qian, 2,* Zhenlin Li, 3, 4,* Aixiu Gong, 5 Sixia Zhong, 2 Li Qiao, 2 Shihui Qian, 3, 4 Yanxin Zhang, 2 Renjie Dou, 2 Rui Li, 2 Ye Yang, 2 Chunyan Gu 1, 2 1The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, People’s Republic of China; 2School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of China; 3Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, People’s Republic of China; 4Jiangsu Provincial Platform for Conservation and Utilization of Agricultural Germplasm, Nanjing 210028, People’s Republic of China; 5Department of Stomatology, Children’s Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ye YangSchool of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of ChinaTel +86 25 8581 1597Email yangye876@sina.comShihui QianJiangsu Province Academy of Traditional Chinese Medicine, Shizi Street Hongshan Road, Nanjing 210028, People’s Republic of ChinaEmail njqsh2005@126.comPurpose: Abelmoschus manihot (L.) Medik. (Malvaceae) derived Huangkui capsules (HKC) represent a traditional Chinese medicine that has been widely applied to the clinical therapy of kidney and inflammatory diseases. The present study aimed to determine the potential therapeutic effects and underlying mechanisms of the ingredients on Multiple Myeloma (MM), an incurable disease that exhibits malignant plasma cell clonal expansion in the bone marrow.Methods: A 5TMM3VT syngeneic MM-prone model was established and treated with HKC. Murine pre-osteoblast MC3T3-E1 and pre-osteoclast Raw264.7 cells were treated with nine flavonoid compounds extracted from the flowers of Abelmoschus manihot. MC3T3-E1 and Raw264.7 cells were then examined by alizarin red staining and tartrate-resistant acid phosphatase activity staining, respectively. The proliferation of two human MM cells (ARP1, H929) was examined by performing an MTT assay following treatment with flavonoid compounds. Additionally, the cell cycle was analyzed via staining and flow cytometry. The differential expressions of certain proteins were detected via Western blotting, transcriptomic RNA-sequencing as well as RT-qPCR.Results: The results revealed that MM-prone animals appeared to be protected following HKC treatment, as evidenced by a prolonged survival rate. Furthermore, four of the nine flavonoid compounds [Hyperin/Hyperoside, HK-2; Cannabiscitrin, HK-3; 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-β-D-glucopyranoside, HK-11; 8-(2’’-pyrrolidione-5’’-yl)-quercetin, HK-B10] induced the differentiation of murine pre-osteoblast MC3T3-E1 cells. In addition, two compounds [Isomyricitrin, HK-8; quercetin-8-(2’’-pyrrolidione-5”-yl)-3ʹ-O-β-D-glucopyranosid, HK-E3] suppressed osteoclastogenesis in murine Raw264.7 cells. HK-11 directly inhibited MM cells (ARP1 and H929) proliferation and induced G0/G1 cell cycle arrest, which may have involved the suppressing β-catenin protein, increasing expressions of IL-6 and TNF-α, as well as activating mature TGF-β 1 and some other metabolic pathways.Conclusion: These results of the present study indicated that the bio-active ingredients of HKC exerted protective effects on MM mouse survival through promoting osteoblastogenesis and suppressing osteoclastogenesis, thus improving the bone marrow microenvironment to inhibit MM cell proliferation.Keywords: Abelmoschus manihot L., Huangkui capsule, flavonoid extracts, multiple myeloma, osteoclast, osteoblast

Song Cao,1,2* Qingmei Li,3* Jingfeng Hou,1 Zhourui Li,1 Xinya Cao,1 Xiaohong Liu,4 Bangyong Qin11Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Department of Physiology, Zunyi Medical University, Zunyi 563000, People’s Republic of China *These authors contributed equally to this work Background: TRPM8 channel plays central roles in the sensitization of nociceptive transduction and is thought as one of the potential targets for the treatment of neuropathic pain. However, the specific molecular mechanisms are still less clear.Methods: Sciatic chronic constriction injury (CCI) rats were intrathecally administered with AMTB (TRPM8-selective antagonist) or PDTC (nuclear factor-kappa B (NF-κB) inhibitor). Cold-, thermal- and mechanical-pain thresholds were examined in CCI and sham-operated rats before and after intrathecal administration of AMTB or PDTC. Protein expression levels of TRPM8 and NF-κB p65, p-PKC/PKC value and p-PKA/PKA value in the CCI ipsilateral L4-6 dorsal root ganglions (DRGs) were analyzed. In addition, the co-expression of TRPM8 and NF-κB was evaluated in DRG.Results: Intrathecal injection of AMTB decreased the cold hypersensitivity and aggravated the thermal-hyperalgesia in the next 2 weeks after CCI surgery. The protein expression of TRPM8 and NF-κB p65 in the ipsilateral DRGs significantly increased after CCI surgery, which can be reversed by intrathecal administration of AMTB. The PKC, PKA, p-PKC/PKC and p-PKA/PKA values showed significantly increase after CCI surgery, while intrathecal AMTB administration offset the expression increase of PKC, p-PKC and p-PKC/PKC but PKA or p-PKA/PKA in the DRG. NF-κB inhibitor not only efficiently increased the cold-, thermal-pain threshold of CCI rats, but also enhanced AMTB’s anti-cold pain effect although exerted no anti-thermal hyperalgesia effect compared with TRPM8 blockade group. Immunofluorescence results showed co-expression of TRPM8 and NF-κB in DRG neurons.Conclusion: TRPM8 channels in DRGs participate in the pathogenesis of cold and thermal hyperalgesia (not mechanical allodynia) in rats with neuropathic pain, which could be regulated by PKC (not PKA) and NF-κB signaling. TRPM8 channel, PKC and NF-κB are potential targets for cold hyperalgesia treatment in neuropathic pain patients.Keywords: TRPM8, neuropathic pain, dorsal root ganglia, PKC, NF-κB

Jinxuan Hou,1,2,* Kun Zou,2,* Chaogang Yang,2 Xiaohua Leng,1 Yu Xu1,3 1Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; 3Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China *These authors contributed equally to this work Background: The aim of this meta-analysis was to assess the clinicopathological and prognostic significance of circulating tumor cells (CTCs) in patients with esophageal cancer (EC).Methods: We searched PubMed, EMBASE, Science Citation Index Expanded, Cochrane library (from inception to July 2018) with the keywords “esophageal cancer”, “circulating tumor cells”, “prognosis”, and “peripheral blood”. HR, risk ratio (RR), OR, and their 95% CIs were set as effect measures. All analyses were performed by STATA 12.0.Results: Eighteen studies were retrieved; CTC-positive patients were significantly associated with poor progression-free survival (PFS) (HR=2.61; 95% CI=2.08–3.28) and overall survival (OS) (HR=2.50; 95% CI=2.12–2.94). CTC-positive patients were also associated with high recurrence (OR=2.84; 95% CI=1.81–4.44) and poor response of chemoradiotherapy (RR=0.64; 95% CI=0.43–0.96). For clinicopathological characteristics, CTC-positive patients were significantly associated with TNM staging, depth of infiltration, regional lymph nodes metastasis, distant metastasis, lymphatic invasion, and venous invasion.Conclusion: The meta-analysis has confirmed the significant clinicopathological and prognostic value of CTC-positive patients for both PFS and OS in patients with EC. Keywords: esophageal cancer, CTCs, prognosis, meta-analysis