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Junjuan Li,1,* Yue Tian,2,* Qi Qin,2,* Zhaolei Ding,1 Xue Zhao,3 Wei Tan1 1Department of Respiratory Medicine, The First Affiliated Hospital of Weifang Medical University/Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 2School of Clinical Medicine, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Weifang Medical University/Weifang People’s Hospital, Weifang, 261000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Tan, Department of Respiratory Medicine, Weifang People’s Hospital, 151 Guangwen Street, Weifang, Shandong Province, 261000, People’s Republic of China, Email 13863659099@126.com Xue Zhao, Department of Laboratory Medicine, Weifang People’s Hospital, 151 Guangwen Street, Weifang, Shandong Province, 261000, People’s Republic of China, Email 42281870@qq.comPurpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention.Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine–indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff’s base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG.Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV‐vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G−) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated.Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.Keywords: cationic, mild photothermal, photodynamic, NO gas, antibacterial

Junya Zhou,1 Qingzhu Qin,1 Songge Chen,1 Hongmei Zhang2 1Department of Cardiology, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Nursing, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Hongmei Zhang, Department of Nursing, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15699930876, Email zhang_hongmei2023@yeah.netAbstract: In intensive care units, patients are often restrained to ensure their safety, with physical restraints being the most commonly used method. However, physical restraints compromises the patient’s freedom, health and comfort, and nurses often face moral dilemmas when deciding whether to use physical restraints. This article examines physical restraints through the four universal principles of autonomy, beneficence, non-maleficence and justice. Through these principles, the authors will critically explore whether the physical restraints of patients by nurses is ethical in practice and what moral issues exist. This paper also explores conflicts and moral dilemmas for nurses in this context. Finally, suggestions are made on changes to education and clinical practice.Keywords: physical restraints, ethical dilemmas, ethics

Yulin Chen,1 Yi Zhang,2 Jianjun Wang,3 Xiong Cai,1 Junzhang Chen,1 Xiaobo Min,1 Yunjie Xu,1 Qi Qin,1 Chidan Wan1 1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Engineering Research Center of Tumor-Targeted Biochemotherapy, Wuhan, 430030, People’s Republic of China; 3Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Qi Qin; Chidan Wan, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email qinqi8441@163.com; wcdwhxhgdwk@163.comBackground: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment.Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities.Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine.Conclusion: Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine. Keywords: liver cancer, drug-loaded microparticles, tumor immune microenvironment, tumor vaccine

Qiuying Qin,1,2,&ast; Xiaoxuan Kou,1,2,&ast; Yuanyuan Zheng,1,2 Fei Zhou,1,2 Xiaoyong Zhang,1,2 Hongyan Liu1,2 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Zhang; Hongyan Liu, Email xiaoyzhang@smu.edu.cn; liuhongyan205628@163.comPurpose: In recent years, a new therapeutic approach, known as immune checkpoint blockade (ICB), has been proposed as approach to improve outcomes in patients with intermediate stage (Barcelona Clinic Liver Cancer, BCLC B) or advanced stage (BCLC C) hepatocellular carcinoma (HCC). Unfortunately, only a select patients can benefit from ICB. Hence, biomarkers that can predict the success and survival of treatment are still necessary.Patients and Methods: Between 2018 to 2021, 132 patients received ICB treatment for intermediate or advanced stage HCC. Based on the early kinetics of C-reactive protein (CRP), the patients were classified into three groups. The study endpoints were progression-free survival (PFS) and overall survival (OS).Results: Our findings support the predictive power of early CRP kinetics in determining immunotherapy response for intermediate or advanced HCC. Objective response rates (ORR) were found in 41.2% of CRP flare-responders, 13.3% of CRP responders, and 3.5% of CRP non-responders (p< 0.001). Disease control rates (DCR) in the three groups were substantially different (p< 0.001). The improved PFS and OS were strongly correlated with the early kinetics of CRP. Compared to CRP non-responders, CRP responders, especially CRP flare-responders, had significantly longer PFS (median PFS: CRP flare-responders: 11.6 months vs CRP responders: 5.2 months vs CRP non-responders: 2.3 months, p< 0.001).Conclusion: The CRP flare response robustly predicts the immunotherapy response and outcomes in patients with HCC. Early CRP kinetics may be an inexpensive, easily implemented and non-invasive biomarker to anticipate response to ICB therapy in intermediate or advanced HCC, with the potential to optimize treatment monitoring.Keywords: hepatocellular carcinoma, C‐reactive protein kinetics, CRP flare response, immune checkpoint blockade, biomarker, immunotherapy

Haoran Lu,1,&ast; Rou Zhao,2,&ast; Qianqian Qin,3 Liyong Tang,1 Guodong Ma,1 Baoyu He,2 Jing Liang,2 Li Wei,2 Xutong Wang,2 Qingli Bie,2 Xuning Wang,4 Bin Zhang2,5 1Department of Hepatobiliary Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 3Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of General Surgery, The Air Force Hospital of Northern Theater PLA, Liaoning, People’s Republic of China; 5Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhang, Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China, Tel +86 186 0647 3594, Fax +86 537 2213030, Email zhb861109@163.comBackground: Hepatocellular carcinoma (HCC) is one of the most common type of cancers, but there is still a lack of known biomarkers for the effective diagnosis or prognosis of HCC. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a substrate of protein kinase C, which was located in the cell plasma membrane. The purpose of our study was to evaluate the role of MARCKS in HCC.Methods: The role of MARCKS in HCC was explored by bioinformatics and experiment.Results: We demonstrated that MARCKS expression was significantly elevated in HCC datasets of TCGA. MARCKS was up-regulated in tumor sample in HCC. Functional enrichment indicated that MARCKS-related differentially expressed genes (DEGs) were mainly enriched in cell junction tissue, response to growth factors and cell population proliferation. Tumor and ECM-receptor interactions related pathways were enriched by the KEGG. MARCKS expression in HCC patients was higher in females, younger individuals, and those at worse clinical stages. Cox regression analysis showed that MARCKS expression was a risk factor for overall survival and disease-specific survival of patients.Conclusion: MARCKS was up-regulated in HCC, may play a crucial role in HCCs, and has prognostic value for clinical outcomes.Keywords: myristoylated alanine-rich C-kinase substrate, HCC, TCGA, prognostic value

Xi Zhang, Mingfang Zhu, Jia Zhou, Shuhui Wu, Juan Liu, Qiuyan Qin Department of Dermatology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Mingfang Zhu, Department of Dermatology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 233 Cai E North Road, Kaifu District, Changsha, People’s Republic of China, Tel +86-13907317358, Fax +86-0731-84917727, Email 20153203@stu.hnucm.edu.cnAbstract: The folliculitis decalvans (FD) and lichen planopilaris (LPP) phenotypic spectrum combines biphasic features of FD and LPP. It is characterized by successive or concomitant occurrence of pustules, crusts, follicular tufts, perifollicular erythema, perifollicular scales, and cicatricial alopecia and includes mixed histologic features of both FD and LPP. Here, we report the case of a 33-year-old female patient with a 30-year history of FD-LPP phenotypic spectrum lesions.Keywords: primary cicatricial alopecia, biphasic features, pustules, perifollicular erythema, follicular tufts

Yayuan Liu,1,&ast; Lizhi Lu,1,&ast; Xuemin Cheng,1 Qixiong Qin,1 Yunfei Wei,2 Dacheng Wang,3 Haihua Li,4 Guohui Li,5 Hongbin Liang,6 Shengyu Li,7 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Province, People’s Republic of China; 3Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, 536000, Guangxi Province, People’s Republic of China; 4Department of Neurology, Fusui County People’s Hospital, Chongzuo, 532100, Guangxi Province, People’s Republic of China; 5Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, 543002, Guangxi Province, People’s Republic of China; 6Department of Neurology, Cenxi People’s Hospital, Cenxi, 543200, Guangxi Province, People’s Republic of China; 7Department of Neurology, The Affiliated Wuming Hospital of Guangxi Medical University, Nanning, 530100, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530000, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnPurpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke.Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden’s J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors.Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051– 1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002– 1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628– 3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index.Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.Keywords: independent risk factors, carcinoembryonic antigen, D-dimer, neutrophil count

Xiaoyan Huang,1– 3,* Yingyi Kuang,1– 3,* Qiyuan Qin,1– 3,* Miaomiao Zhu,1– 3 Yanjiong He,1– 3 Zixu Yuan,1– 3 Huaiming Wang,1– 3 Qinghua Zhong,1,2,4 Qi Guan,1– 3 Hui Wang,1– 3,* Tenghui Ma,1– 3,* Xinjuan Fan1,2,5,* 1Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 4Department of Endoscopic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 5Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinjuan FanDepartment of Pathology, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email fanxjuan@mail.sysu.edu.cnTenghui MaDepartment of Colorectal Surgery, Sun Yat-sen University Sixth Affiliated Hospital, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, People’s Republic of ChinaFax +86 20-38737621Email matengh@mail.sysu.edu.cnBackground: Chronic radiation intestinal injury (CRII) is the most common complication after pelvic malignancy radiation. Once hemorrhagic CRII patients suffer from lower extremity deep venous thrombosis (LE-DVT), hemostasis and anticoagulation therapy will be adopted simultaneously, but the treatment strategy is a paradox, as the condition is extremely intractable and serious. The aim of this study was to investigate the prevalence of and risk factors for LE-DVT in CRII patients and explore the treatment of hemorrhagic CRII patients with LE-DVT.Methods: This was a retrospective study, and a total of 608 hospitalized CRII patients after pelvic radiotherapy were included from November 2011 to October 2018. Univariate and multivariate analyses were conducted to investigate the potential risk factors for LE-DVT in CRII patients. Furthermore, the treatment of hemorrhagic CRII patients with LE-DVT was explored.Results: Among the CRII patients, 94 (15.5%) were with suspicious symptoms of LE-DVT in the lower limbs, and 32 (5.3%) were diagnosed with LE-DVT. Among the patients with LE-DVT, 65.6% (21/32) had bleeding simultaneously, and 29 (90.6%) had anemia with 24 (75.0%) having moderate to severe anemia. Multivariate analysis showed that a recent surgical history (≤ 6 months) (OR = 5.761, 95% CI: 2.506∼ 13.246, p < 0.001), tumor recurrence or metastasis (OR = 3.049, 95% CI: 1.398∼ 6.648, p = 0.005) and the hemoglobin (Hb) level (OR = 0.960, 95% CI: 0.942∼ 0.979, p < 0.001) were significantly associated with the development of LE-DVT. ROC curve analysis showed that the AUC of the merged risk score of the independent risk factors was 0.822 (95% CI: 0.789∼ 0.852), and the optimal Hb cutoff was 82.5 g/L. After colostomy, obvious bleeding remission was rapidly found in 84.6% of hemorrhagic CRII patients with LE-DVT.Conclusion: The prevalence of LE-DVT in hospitalized CRII patients was 5.3%. A recent surgical history, tumor recurrence or metastasis and a lower Hb level were independently associated with LE-DVT development in CRII patients. Colostomy could be a good choice for intractable hemorrhagic CRII patients with LE-DVT.Keywords: chronic radiation intestinal injury, lower extremity deep venous thrombosis, pelvic malignancy radiation, risk factor, colostomy, hemorrhagic

Maojian Chen,1,* Chanchan Xiao,2,* Wei Jiang,3 Weiping Yang,4 Qinghong Qin,1 Qixing Tan,1 Bin Lian,1 Zhijie Liang,5 Changyuan Wei1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Microbiology and Immunology, School of Medicine and Public Health, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 3Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 4Department of Ultrasound Diagnosis, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 5Department of Gland Surgery, The Fifth Affiliated Hospital of Guangxi Medical University & The First People’s Hospital of Nanning, Nanning, Guangxi 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyuan WeiDepartment of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 0771 5308593Email changyuanwei@gxmu.edu.cnBackground: As a natural compound extracted from a variety of hot peppers, capsaicin has drawn increasing attention to its anti-cancer effects against multiple human cancers including breast cancer. FBI-1 is a major proto-oncogene negatively regulating the transcription of many tumor suppressor genes, and plays a vital role in tumorigenesis and progression. However, whether FBI-1 is involved in capsaicin-induced breast cancer suppression has yet to be ascertained. This study aimed to investigate the effects of capsaicin on proliferation and apoptosis and its association with FBI-1 expression in breast cancer.Methods: CCK-8 and morphological observation assay were employed to detect cell proliferation. Flow cytometry and TUNEL assay were conducted to detect cell apoptosis. RNA interference technique was used to overexpress or silence FBI-1 expression. qRT-PCR and/or Western blot analysis were applied to detect the protein expression of FBI-1, Ki-67, Bcl-2, Bax, cleaved-Caspase 3, Survivin and NF-κB p65. Xenograft model in nude mice was established to assess the in vivo effects.Results: Capsaicin significantly inhibited proliferation and induced apoptosis in breast cancer in vitro and in vivo, along with decreased FBI-1, Ki-67, Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Furthermore, FBI-1 overexpression obviously attenuated the capsaicin-induced anti-proliferation and pro-apoptosis effect, accompanied with the above-mentioned proteins reversed, whereas FBI-1 silencing generated exactly the opposite response. In addition, as a target gene of FBI-1, NF-κB was inactivated by p65 nuclear translocation suppressed with capsaicin treatment, which was perceptibly weakened with FBI-1 overexpression or enhanced with FBI-1 silencing.Conclusion: This study reveals that FBI-1 is closely involved in capsaicin-induced anti-proliferation and pro-apoptosis of breast cancer. The underlying mechanism may be related to down-regulation of FBI-1-mediated NF-κB pathway. Targeting FBI-1 with capsaicin may be a promising therapeutic strategy in patients with breast cancer.Keywords: capsaicin, breast cancer, proliferation, apoptosis, FBI-1, NF-κB

Zhen Huang,* Qixing Tan,* Qinghong Qin, Qinguo Mo, Changyuan Wei Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinguo Mo; Changyuan WeiDepartment of Breast Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning 530021, People’s Republic of ChinaTel +86-771-5308593; + 86-771-5308593Fax +86-771-5312000Email qgmo135@263.net; weichangyuan@gxmu.edu.cnPurpose: The efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer.Materials and Methods: Women with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients.Results: Two hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤ 3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival.Conclusion: Surgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.Keywords: stage IV breast cancer, surgery, survival

Zhen Huang,* Qinghong Qin,* Longjie Xia,* Bin Lian, Qixing Tan, Yinghua Yu, Qinguo Mo Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinguo MoDepartment of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, No. 71 Hedi Road, Nanning 530021 Guangxi Province, People’s Republic of ChinaTel +86-771-530859Email qgmo135@263.netObjective: To investigate the association between the recurrence score (RS) obtained by Oncotype DX 21-gene test and long non-coding RNA (lncRNA) MALAT1 expression in early and estrogen receptor-positive (ER+) breast cancer.Materials and Methods: The Oncotype DX 21-gene test and MALAT1 expression detection were performed in tumor samples from 76 ER+ and early breast cancer patients with the Surplex liquid chip. The RS value was calculated based on the expression of total 21 genes. The level of MALAT1 was measured in both tumor tissue and para-tumor tissue, and relatively quantified with an internal control gene. Mann–Whitney U-test or Kruskal–Wallis test were used to analyze the association between MALAT1 level and different clinical pathological characteristics, including age, tumor stage, disease grade, lymph node status, Ki-67 expression, and progesterone receptor (PR) status. The association between the RS and different characteristics was analyzed by Wilcoxon rank-sum test. Correlation between two parameters was analyzed by Spearman’s rank correlation analysis.Results: The expression of MALAT1 was more abundant in tumor tissue (2.992 ± 2.256) than that in adjacent normal tissue (1.641± 1.438, Z=− 2.594, p= 0.009), and it was not correlated with any clinical pathological characteristics. According to the old criteria for RS stratification, 52.7% of patients were in low risk (RS< 18), 36.8% of patients were in medium risk (18≤RS≤ 30), and 10.5% of patients were in high risk (RS> 30). While under the new criteria, 18.4% were in low risk group (RS< 11), 63.2% were in a medium risk group (11≤RS≤ 26), and 18.4% were in a high risk group (RS> 26). The Oncotype DX 21-gene results only correlated with Ki-67 expression under both new and old criteria, and it was not related with other cancer characteristics. The expression of lncRNA MALAT1 was significantly correlated with the Oncotype DX 21-gene results under the old criteria.Conclusion: MALAT1 is a novel breast cancer biomarker independent of tumor stage, disease grade and lymph node status. MALAT1 level is associated with the Oncotype DX 21-gene RS value. Therefore, combination of MALAT1 and the Oncotype DX 21-gene test may be used to predict prognosis in ER+ and early stage breast cancer.Keywords: Oncotype DX 21-gene test, MALAT1, long non-coding RNA; lncRNA, breast cancer, risk of recurrence

Chengxin Shi,1,* Fengli Yue,2,* Feiyu Shi,1 Qian Qin,1 Lizhao Wang,1 Guanghui Wang,1 Lijun Mu,1 Dan Liu,1 Yaguang Li,1 Tianyu Yu,1 Junjun She1 1Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China; 2College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun SheDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-17765856985Email shejunjun@mail.xjtu.edu.cnBackground: Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids – selenocysteine and selenocystine – on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD.Methodology: C57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis.Results: Selenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids.Conclusion: We found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.Keywords: Inflammatory bowel diseases, colitis, selenium-containing amino acids, selenocysteine, selenocystine, oxidative stress, inflammation

Sn doped and BiOI coupled dual modified Bi2WO6 photocatalytic material was prepared using hydrothermal route. The phase composition, morphology, surface area, elemental composition and oxidation state, as well as optical properties, were comprehensively characterized. Take the methylene blue (MB) as the model pollutant for photodegradation to estimate the photocatalytic property of the synthesized material. The prepared Bi2WO6- based composite material shows a flower-like structure assembled from nanosheets, with a surface area of 45.3 m²/g and a bandgap width of 2.41 eV, enabling visible light responsiveness. The synergistic effect of Sn doping and BiOI coupling modification enhances the photocatalytic performance. The Sn-BiOI/Bi2WO6 photocatalytic composite material shows excellent photocatalytic activity, with complete degradation of MB after 40 minutes of illumination, and a first-order reaction rate constant (k) of 0.102 min-1. Experimental evidence suggests that photoinduced holes are the main active species. [ABSTRACT FROM AUTHOR]

Suzhen Fan,1,* Shujun Zhao,1,* Xiang Gao,1 Qiaohong Qin,1 Yan Guo,1 Zhongfu Yuan,2 Min Zhang,1 Qing Liu,1 Hongyu Li1 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyu LiDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front Street, Erqi, Zhengzhou, Henan 450052, People’s Republic of ChinaEmail fkzlzdsys@163.comBackground: A growing number of studies have identified that circular RNAs (circRNAs) play a vital role in the progression of various tumors. However, the underlying functions and mechanisms of circRNAs in cervical cancer have not been clarified.Methods: qRT-PCR was used to detect the level of circGSE1 in cervical cancer tissues and matched normal tissues. In vitro cell wound healing, transwell migration and invasion assays were employed to assess the effects of circGSE1 on cell mobility. The pull-down, luciferase reporter, RIP and rescue assays were performed to evaluate the interaction between circGSE1and miR-138-5p and the regulation of miR-138-5p on Vimentin.Results: We found that circGSE1 was significantly higher in cervical cancer tissues than that in matched normal tissues. Further analyses revealed that the level of circGSE1 was positively correlated with tumor differentiation, FIGUREO stage, depth of stromal invasion, lymph node metastasis and infiltration of parauterine organ. Kaplan–Meier survival analysis showed that high circGSE1 predicted worse overall survival and disease-free survival. Down-regulated circGSE1 evidently inhibited cell migration and metastasis of cervical cancer, while up-regulated circGSE1 significantly promoted cell migration and metastasis. The pull-down, luciferase reporter and RIP assays revealed that circGSE1 directly bound to and sponge miR-138-5p. MiR-138-5p inhibited the expression of Vimentin through directly binding to 3ʹUTR of Vimentin mRNA. In addition, miR-138-5p suppressed cell migration and invasion through inhibiting Vimentin expression, and circGSE1 promoted cell migration and invasion through sponging miR-138-5p and enhancing Vimentin expression.Conclusion: CircGSE1 promotes the progression and may act as a novel diagnostic biomarker for disease progression of cervical cancer.Keywords: circGSE1, miR-138-5p, Vimentin, cervical cancer, migration and metastasis

Ting Guo,1– 3,* Qinxue Shen,1– 3,* Zhiguo Zhou,4 Jinhua Li,1– 3 Wei Guo,1– 3 Wenlong He,1– 3 Yunnian Wang,5 Zhi Xiang,6 Peng Huang,7 Nanyang Zeng,8 Qingwu Qin,1– 3 Ping Chen,1– 3 Hong Luo,1– 3 Hong Peng1– 3 1Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central-South University, Changsha, Hunan, People’s Republic of China; 3The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The Traditional Chinese Medicine Hospital of Liling, Zhuzhou, Hunan, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Huaihua, Huaihua, Hunan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, The Central Hospital of Zhuzhou, Zhuzhou, Hunan, People’s Republic of China; 8Department of Infectious Disease, The Lvkou People’s Hospital of Zhuzhou, Zhuzhou, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong PengDepartment of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, No. 139 Renmin Middle Road, Changsha, Hunan 410011, People’s Republic of ChinaTel +86 13807494486Email penghong66@csu.edu.cnPurpose: To summarize the clinical features and effective therapy of severe COVID-19 patients.Patients and Methods: In this retrospective, multicenter study, the medical records of COVID-19 patients in Hunan, from January 21, 2020 to February 19, 2020 were reviewed.Results: Of the 350 COVID-19 patients, 13.7% were severe cases. On admission, compared with non-severe patients, more severe patients had a neutrophil/lymphocyte ratio > 3 (58.3% vs 33.8%, P=0.001), D-dimer > 1 mg/L (41.7% vs 13.6%, P< 0.0001), higher level of CRP (39.1 mg/L, IQR18.1– 75.9 vs 13.4 mg/L, IQR5.0– 32.8, P< 0.0001), and multiple pneumonia on CT (77.1% vs 18.2%, P< 0.0001). All severe patients received oxygen support. 95.8% of them received antivirals, and the most frequent therapy was lopinavir and ritonavir plus human interferon-α 2b. Moxifloxacin was used in 70.8% severe patients. The total dosage of methylprednisolone sodium succinate was 640 mg (IQR 360– 960) in severe patients, and the duration of use was 8.5 days (IQR 6.8– 11.3). The total dosage of immunoglobulin was 80 g (IQR, 60– 140) in severe patients, and the duration was 8.0 days (IQR, 6.0– 11.5). As of March 15, 2020, 95.8% of the severe patients had been discharged and only two deaths occurred.Conclusion: The rate of severe cases and mortality of COVID-19 in Hunan are lower than those in Wuhan. In addition to antivirals and oxygen support, timely interventions including corticosteroids, immunoglobulin, and antibiotics, contribute to improving the prognosis of severe COVID-19 patients.Keywords: coronavirus disease 2019, SARS-CoV-2, severe disease, corticosteroid, immunoglobulin

Fan S, Zhao S, Gao X, et al. Onco Targets Ther. 2020;13:13371-13386. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised following the authors request to replace several western blot and cell migration and invasion images in Figures 2, 4 and 6. The authors were unable to provide a satisfactory explanation for why the images required replacing, nor were they able to provide original data that could adequately verify the findings. The Editor determined the reported findings were unreliable and requested for the article to be retracted. The authors were notified of this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

The effect of MgO content on the viscosity of blast furnace slag bearing high Al2O3 was studied under laboratory conditions. The viscosity of slag was determined by rotation method. The research results indicate that when the Al2O3 content in blast furnace slag is 17 % -18 %, the MgO content in blast furnace slag should be controlled at 10 %. When the Al2O3 content is 19 %, the MgO content should be controlled at 11 %, and the binary basicity of the slag should be controlled at around 1,10. This type of blast furnace slag has a lower melting point and better fluidity. The purpose of reducing the MgO content in the slag can be achieved by reducing the MgO content in sintered ore, that is, the MgO content in sintered ore should be controlled at 2,0 %-2,5 %. [ABSTRACT FROM AUTHOR]

Maojian Chen,1,* Wei Jiang,2,* Chanchan Xiao,3 Weiping Yang,4 Qinghong Qin,1 Anyun Mao,1 Qixing Tan,1 Bin Lian,1 Changyuan Wei1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 3Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China; 4Department of Ultrasound Diagnosis, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyuan Wei Department of Breast SurgeryGuangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 771 5308593Email changyuanwei@gxmu.edu.cnPurpose: This study is aimed to investigate the combined treating efficacy of sodium butyrate and docetaxel on proliferation and apoptosis of the lung adenocarcinoma A549 cell line based on Gli1 regulation in vitro and in vivo.Materials and Methods: RNA interference method was used to overexpress Gli1 in A549 cells. Cells were treated with varying concentrations of sodium butyrate, docetaxel or both in combination. CCK-8, colony formation assay, Hoechst 33258 staining, flow cytometry and TUNEL assay were employed to detect proliferation, cell cycle and apoptosis. qRT-PCR and Western blot analysis were applied to detect the mRNA and protein expression of Gli1. In vivo tumorigenicity was detected by tumor transplantation in nude mice. Downstream protein levels of Gli1 were detected using Western blot assay.Results: It was found that sodium butyrate or docetaxel alone, respectively, inhibited proliferation and promoted apoptosis of A549 cells in vitro and in vivo, while the combination of the two generated significantly higher responses, which were also effective in another lung adenocarcinoma cell line H1299. Furthermore, the combined therapy had an additive effect in suppressing Gli1 expression and regulating the expression of its downstream proteins that involve in proliferation, cell cycle and apoptosis of A549 cells in vitro and in vivo, including decreased protein expression of Ki-67, CDK1, CDK2, Cyclin D1, Bcl-2 and Survivin, and increased protein expression of Cyclin A, p21, Bax and cleaved-Caspase 3. On the other hand, Gli1 overexpression perceptibly reversed the above-mentioned additive effect in vitro and in vivo.Conclusion: This study demonstrates that the combined therapy of sodium butyrate and docetaxel additively inhibits proliferation and promotes apoptosis of A549 lung adenocarcinoma cells via suppressing Gli1 expression in vitro and in vivo. Targeting Gli1 by the combined therapy may provide new insights into the therapeutic management of patients with lung adenocarcinoma.Keywords: sodium butyrate, docetaxel, lung adenocarcinoma, A549, Gli1

Lan Cui,1,* Wentao Liu,1,* Hao Liu,1 Qian Qin,1,2 Shuangxia Wu,1 Suqin He,1,3 Zhenya Zhang,4 Xinchang Pang,1 Chengshen Zhu1 1School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 2Bio & Soft Matter, Institute of Condensed Matter and Nanosciences, Universite Catholique de Louvain, Louvain-la-Neuve B-1348, Belgium; 3Henan Key Laboratory of Advanced Nylon Materials and Application, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 4Department of Chemistry, Changwon National University of Korea, Changwon-city, Gyeongnam-do 51140, Republic of Korea*These authors contributed equally to this workCorrespondence: Wentao Liu; Hao LiuSchool of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, Henan Province, People’s Republic of ChinaEmail wtliu@zzu.edu.cn; hliu@zzu.edu.cnBackground: Although pH and redox sensitiveness have been extensively investigated to improve therapeutic efficiency, the effect of disulfide bonds location and pH-triggered charge-reversal on cascade-targeting still need to be further evaluated in cancer treatment with multi-responsive nanoparticles.Purpose: The aim of this study was to design multi-responsive DOX@MSNs-COS-NN-CMC, DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS and systematically investigate the effects of disulfide bonds location and charge-reversal on the cancer cell specificity, endocytosis mechanisms and antitumor efficiency.Results: In vitro drug release rate of DOX@MSNs-COS-SS-CMC in tumor environments was 7-fold higher than that under normal physiological conditions after 200 h. Furthermore, the fluorescence intensity of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS was 1.9-fold and 1.3-fold higher than free DOX at pH 6.5 and 10 mM GSH. In addition, vesicular transport might be a factor that affects the uptake efficiency of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS. The clathrin-mediated endocytosis and endosomal escape of DOX@MSNs-COS-SS-CMC enhanced cellular internalization and preserved highly controllable drug release into the perinuclear of HeLa cells. DOX@MSNs-COS-SS-CMC exhibited a synergistic chemotherapy in preeminent tumor inhibition and less side effects of cardiotoxicity.Conclusion: The cascade-targeting of charge-reversal and disulfide bonds shielding would be a highly personalized strategy for cervical cancer treatment.Keywords: disulfide bonds, pH-triggered charge-reversal, redox sensitive, chitosan oligosaccharide, human cervical carcinoma therapy

Qiaoji Qin, Nan Lin, Huan Huang, Xuezhi Zhang, Xuelei Cao, Yongbin Wang, Peng LiEmergency Department, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, People’s Republic of ChinaBackground and purpose: Ginsenoside Rg1 (GS Rg1), as an important active substance of Panax ginseng, has been proven to have elaborate cardioprotective effects. The purpose of this study was to detect that GS Rg1 attenuates cardiac oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats (DM).Methods: Cardiac function was assessed by heart rate and blood pressure. Markers relevant to myocardial oxidative stress and antioxidant capacity, and inflammatory reaction factors were detected. The mRNA and protein expression were detected by RT-qPCR and Western blot, respectively.Results: GS Rg1 treatment significantly reduced the symptoms of cardiac hypertrophy and hypertension, and also decreased oxidative stress, inflammation response, NF-κB expression and NLRP3 inflammasome expression. GS Rg1 enhanced mitochondrial biogenesis by increasing PGC-1α, complex III and complex Ⅳ expression. GS Rg1 treatment significantly increased the expression of AMPK, Nrf2 and HO-1 in cardiac tissues.Conclusion: GS Rg1 exhibited protective effect against STZ-induced cardiac dysfunction, which is potentially associated with AMPK/Nrf2/HO-1 signal pathway.Keywords: Ginsenoside Rg1, oxidative stress, inflammation, AMPK, Nrf, HO-1

Lingling Yu,1,2 Wei Wang,1 Liang Li,2 Qingguang Qin,2 Yutian Yu,2 Kun Liu,2 Yufeng Zhao,2 Peijing Rong,2 Bing Zhu2 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 2Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China Background: The transmission of visceral nociception can be inhibited by electroacupuncture (EA) at the spinal level. However, relationships between current intensity and EA-induced analgesia are still lacking. This study compares the effects of different intensities of EA at local acupoints and heterotopic acupoints on nociceptive responses of spinal wide dynamic range (WDR) neurons induced by noxious colorectal distension (CRD). Materials and methods: Experiments were conducted on 40 Sprague Dawley rats anesthetized with 10% urethane. Discharges of WDR neurons in the L1–L3 segments of the dorsal horn of the spinal cord were recorded extracellularly by glass micropipettes. Different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, 2 Hz) were applied to contralateral “Zusanli” (ST 36) or “Neiguan” (PC 6), with either the same or different segmental innervation of the colon. Results: In local acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 0.5–8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 0.5–4 mA, but the inhibiting rate reached a plateau when EA exceeded 4 mA. In heterotopic acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 2–8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 2–6 mA. Further increase in the current beyond 6 mA also resulted in a plateau effect. Conclusion: Within a certain range, the nociceptive responses of dorsal horn neurons induced by CRD could be inhibited by EA in an intensity-dependent manner. Keywords: electroacupuncture, current intensity, wide dynamic range, colorectal distension