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Zihui Yuan,* Chao Du,* Yun You,* Jian Wang Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Wang, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +11-86-15902735929, Email jianwang1030@126.comPurpose: Iliac limb occlusion (ILO) is a serious complication of endovascular abdominal aneurysm repair (EVAR). This study aimed to identify predictive factors for ILO derived from aortoiliac morphology, endovascular procedure-related parameters, and aneurysmal remodeling characteristics.Patients and Methods: Patient demographics, pre-EVAR anatomical characteristics of the aneurysm, endovascular procedure details, and post-EVAR aneurysmal remodeling outcomes were analyzed and compared using univariate analysis. Statistically significant factors were subsequently subjected to Cox regression and Kaplan–Meier analyses.Results: Between January 2013 and April 2022, 66 patients were included in this study. Fourteen patients presented with ILO and were compared with 52 control patients with patent endograft limb over at least 1-year of follow-up. The tortuosity indices of the common iliac artery (CIA) and endograft iliac limb to vessel oversizing were significantly larger in the ILO group than in the patent endograft limb group. The CIA index of tortuosity ≥ 1.08, and endograft iliac limb to vessel oversizing ≥ 18.8% were independent predictors for ILO. During the follow-up of all patients, the proximal aortic neck and CIA diameters increased, aneurysm sac diameter decreased, and aortic neck and aortic length increased. The aortoiliac length increased over time in patients with patent endograft limb but not in patients with ILO. A change in the lowest renal artery-left iliac bifurcation distance ≦0.07 mm increased the risk of ILO.Conclusion: ILO is predisposed to occur when the CIA index of tortuosity ≥ 1.08 and endograft iliac limb to vessel oversizing ≥ 18.8% are present. Significant aortoiliac remodeling, including proximal aortic neck dilatation, neck straightening, aneurysmal sac regression, iliac artery enlargement, and aortic lengthening, occurs after EVAR. Aortoiliac elongation was observed in patients with patent endograft limb, but not in patients with ILO. ILO was associated with a change in the lowest renal artery–left iliac bifurcation from the postoperative measurements ≦ 0.07 mm.Keywords: abdominal aortic aneurysm, endovascular abdominal aneurysm repair, iliac limb occlusion, aortoiliac anatomy, aneurysmal remodeling, oversizing, aortoiliac tortuosity

Kai Qiu,1,2 Jiaqi Lu,1 Hebing Guo,1 Chunjing Du,1 Jingyuan Liu,1 Ang Li3 1Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Intensive Care Medicine, Liangxiang Hospital of Beijing Fangshan District, Beijing, People’s Republic of China; 3Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jingyuan Liu; Ang Li, Beijing Ditan Hospital, Capital Medical University, #8 Jing Shun East St Chaoyang, Beijing, 100015, People’s Republic of China, Email dtyyicu@ccmu.edu.cn; liang@ccmu.edu.cnObjective: We performed a comparative analysis of respiratory function and hemodynamics among patients with Acquired Immunodeficiency Syndrome (AIDS)-associated respiratory failure and those with non-AIDS-associated respiratory failure.Methods: Data were collected from critically ill patients diagnosed with Acquired Immunodeficiency Syndrome who were admitted to the Intensive Care Unit (ICU) of Beijing Ditan Hospital, affiliated with Capital Medical University, between January 1, 2019, and December 31, 2019. We simultaneously gathered data from non-AIDS patients admitted to the ICU of Beijing Liangxiang Hospital within the same timeframe. A comparative study was performed to analyze clinical data from these two patient groups, encompassing parameters related to respiratory mechanics and hemodynamic indicators.Results: A total of 12 patients diagnosed with Acquired Immunodeficiency Syndrome (AIDS) and experiencing respiratory failure, along with 23 patients with respiratory failure independent of AIDS, were included in our study. Subsequently, a comparative analysis of clinical information was conducted between the two patient cohorts. Our findings demonstrate non-statistically significant differences between the two patient groups when assessing various indicators, encompassing peak airway pressure, plateau pressure, mean pressure, compliance, oxygenation index, and arterial partial pressure of carbon dioxide (P> 0.05). Additionally, the comparison of multiple indicators encompassing mean arterial pressure, central venous pressure, cardiac output index, intrathoracic blood volume index, global end-diastolic volume index, extravascular lung water content, and pulmonary vascular permeability index revealed no statistically significant differences between the two patient groups (P> 0.05). Ultimately, the Galileo respiratory system was utilized to assess the pressure-volume (P-V) curve of the experimental cohort, revealing a consistent and seamless trajectory devoid of noticeable points of inflection.Conclusion: No statistically significant differences were found in the respiratory function and hemodynamic profiles between patients diagnosed with AIDS presenting respiratory failure and those experiencing respiratory failure unrelated to AIDS. Additionally, the pressure-volume curve of individuals diagnosed with AIDS presenting respiratory failure displayed a seamless and uninterrupted trajectory devoid of discernible points of inflection. Hence, there might be constraints when utilizing P-V curve-based adjustments for positive end-expiratory pressure (PEEP) during mechanical ventilation in individuals diagnosed with AIDS presenting respiratory failure.Keywords: acquired immunodeficiency syndrome, acute respiratory failure, respiratory function, hemodynamics, pressure-volume curve

Suyang Zheng,1,* Dong Li,1,2,* Qingbai Liu,1,3 Cheng Tang,1 Wenhao Hu,1,4 Shengshan Ma,1,5 Yan Xu,1,6,7 Yong Ma,8 Yang Guo,8 Bo Wei,1 Chuanlin Du,9 Liming Wang1,6,7 1Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Trauma Center, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Department of Orthopedics, Lianshui People’s Hospital of Kangda College Affiliated to Nanjing Medical University, Huai’an, Jiangsu Province, People’s Republic of China; 4Department of Orthopedics, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu Province, People’s Republic of China; 5Department of Sports Medicine, The First People’s Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu Province, People’s Republic of China; 6Key Laboratory of Additive Manufacturing Technology, Institute of Digital Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 7Cartilage Regeneration Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 8Laboratory of New Techniques of Restoration and Reconstruction of Orthopedics and Traumatology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of China; 9Department of Orthopedics, Ganyu District People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liming Wang; Chuanlin Du, Tel +86-25-5227-1000 ; +86-518-8621-2626, Fax +86-25-5226-9924 ; +86-518-8622-5984, Email wlmnjsy@outlook.com; chuanlindu@foxmail.comPurpose: This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes.Methods: In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules.Results: Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration.Conclusion: These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.Graphical Abstract: Keywords: subchondral bone, surface modification, bio-ink, scaffold, hydrogel

Chunjing Du,1,&ast; Siyuan Yang,2,&ast; Chuansheng Li,1 Pan Xiang,1 Lin Pu,1 Jingyuan Liu1 1Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyuan Liu; Lin Pu, Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Street, Chaoyang District, Beijing, 100015, People’s Republic of China, Tel +86 108432682; +86 108432966, Email dtyyicu@ccmu.edu.cn; pulin1103@ccmu.edu.cnIntroduction: Information regarding the clinical course of COVID-19 patients with liver injury is very limited, especially in severe and critical patients. The objective of this study was to describe the characteristics and clinical course of liver function in patients admitted with severe and/or critical SARS-CoV-2 infection, as well as explore the risk factors that affect liver function in the enrolled COVID-19 patients.Methods: Information on clinical characteristics of 63 severe and critical patients with confirmed COVID-19 was collected. Data on patients’ demographics, laboratory characteristics, laboratory examination, SARS-CoV-2 RNA results and liver test parameters were acquired and analyzed.Results: The incidence of abnormal aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the critical group was significantly higher than in the severe group (respectively 81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, p < 0.05). The time for liver function parameters to reach their extremes was approximately 2– 3 weeks after admission. The independent factors associated with liver injury were patients with invasive ventilators, decreased percentages of neutrophils, lymphocytes and monocytes, and sequential organ failure assessment (SOFA) score ≥ 2 (p < 0.05).Conclusion: Abnormal liver tests are commonly observed in severe and critical patients with COVID-19. Severe patients infected by SARS-CoV-2 should be closely observed and monitored the liver function parameters, particularly when they present with independent risk factors for liver injury.Keywords: abnormal liver tests, coronavirus disease 2019, COVID-19, liver injury, pneumonia, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2

Jianbing Wu,1,&ast; Jie Zhang,1,&ast; Qiangli Xie,2 Xiaohuan He,3 Zhangchao Guo,1 Bo Zheng,4 Sisong Wang,5 Qiumei Yang,6 Chunfu Du1 1Department of Neurosurgery, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 2Department of Cardiovascular Medicine, Chengdu Qingbaijiang District People’s Hospital, Chengdu, 610300, People’s Republic of China; 3Department of the Fifth Dispatched Outpatient, The General Hospital of Western Theater Command, Chengdu, 610083, People’s Republic of China; 4Department of Neurology, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 5Department of Neurosurgery, the Chengdu 363 Affiliated Hospital of Southwest Medical University, Chengdu, 610041, People’s Republic of China; 6Department of Geriatrics, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfu Du, Department of Neurosurgery, Ya’an People’s Hospital, 358 Chenghou Road, Ya’an, Sichuan, 625000, People’s Republic of China, Tel +86-835-2862065, Email 1012036559@qq.comPurpose: Neuroinflammation is considered a critical pathological process in various central nervous system (CNS) diseases and is closely related to neuronal death and dysfunction. Bergaptol is a natural 5-hydroxyfurocoumarin found in lemon, bergamot and other plants. Some studies have confirmed its anti-cancer, anti-inflammatory and anti-atherogenic functions, indicating that it may have significant medicinal value. In this study, we investigated the potential effect of Bergaptol in vitro and in vivo neuroinflammatory models.Methods: Mice were injected with LPS (40 μg/kg) into the hippocampal CA1 region and then injected intraperitoneally with Bergaptol (10, 20 and 40 mg/kg) once a day for two weeks. In addition, to verify the effect of Bergaptol on BV2 cells, Bergaptol with different concentrations (5, 10 and 20 μg/mL) was firstly incubated for 1 hour, then LPS with a concentration of 1 μg/mL was added and incubated for 23 hours.Results: Bergaptol treatment significantly improved the cognitive impairment induced by LPS. In addition, Bergaptol significantly inhibited the reduction of dendritic spines and the mRNA level of inflammatory factors (TNF-α, IL-6 and IL-1β) in hippocampal induced by LPS. In vitro, Bergaptol inhibited the production of TNF-α, IL-6 and IL-1β from LPS-treated BV-2 cells. In addition, Bergaptol treatment significantly reduced the phosphorylation levels of JAK2, STAT3 and p65 in LPS-stimulated BV-2 cells.Conclusion: In conclusion, our results suggest that Bergaptol alleviates LPS-induced neuroinflammation, neurological damage and cognitive impairment by regulating the JAK2/STAT3/P65 pathway, suggesting that Bergaptol is a promising neuroprotective agent.Keywords: Bergaptol, neuroinflammation, LPS, JAK2/STAT3/p65

Yuanfei Bao,1,&ast; Yao Zhang,2,&ast; Chaopin Du,1 Yan Ji,1 Yiwei Dai,1 Wei Jiang3 1Department of Neurology, Affiliated Nantong Hospital 3 of Nantong University, Nantong, 226000, People’s Republic of China; 2Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 3Department of Neurology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Jiang, Department of Neurology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, No. 68 Zhongshan Road, Wuxi, 214000, People’s Republic of China, Tel/Fax +86 0510-68562222, Email jianghaot1986@163.comBackground and Purpose: This study aimed to investigate the relationship between malnutrition and early neurological deterioration (END) in elderly patients with acute ischemic stroke in China.Methods: We used the registry data in the Third Affiliated Hospital of Nantong University and Nanjing Brain Hospital from June 2019 to January 2021. Malnutrition risk was evaluated by controlling nutritional status score (CONUT), geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) score, respectively. END was defined as an increment of at least two points in the total NIHSS score within three days after admission. We evaluated the relationship between malnutrition and END with multivariable logistic regression models and reclassification indexes.Results: A total of 732 elderly patients with first-ever acute ischemic stroke were included in the study. 243 patients developed END. 5.7%, 21.4%, 4.6% patients were classified as moderate to severe malnutrition by CONUT, GNRI and PNI, respectively. Malnutrition was associated with the risk of END for CONUT (odds ratio [OR], 1.210; 95% confidence interval [CI] 1.092– 1.341; P < 0.001), for GNRI (OR, 0.943; 95% CI, 0.919– 0.967; P < 0.001), and for PNI (OR, 0.936; 95% CI, 0.908– 0.965; P < 0.001) in multivariable logistic regression models using the back-ward selection method. The discriminative ability was 0.763 (95% CI, 0.727– 0.798) for CONUT, 0.769 (95% CI, 0.733– 0.805) for GNRI and 0.769 (95% CI, 0.733– 0.805) for PNI after adjusting for confounders. Besides, adding malnutrition indexes into models made the prediction of END more accurate.Conclusion: Malnutrition was associated with END in elderly Chinese patients with acute ischemic stroke.Keywords: malnutrition, ischemic stroke, elderly, early neurological deterioration

Xiaoyan Jiang,1,&ast; Fang Deng,1,2,&ast; Shunli Rui,1 Yu Ma,1 Min Wang,1 Bo Deng,1 Hongyan Wang,1 Chenzhen Du,1 Bing Chen,2 Xiuhua Yang,3 Johnson Boey,4 David G Armstrong,5 Wuquan Deng,1 Xiaodong Duan6 1Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, Chongqing, 400014, People’s Republic of China; 2Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, 400038, People’s Republic of China; 3Department of Lower Extremity Surgery, NO.1 Orthopedics Hospital of Chengdu, Chengdu City, 610000, Sichuan, People’s Republic of China; 4Department of Podiatry, National University Hospital, 169608, Singapore; 5Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA; 6Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng, Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, No. 1 Jiankang Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +86 23 63692185, Email wuquandeng@cqu.edu.cn Xiaodong Duan, Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email duanxiaodong2032@sina.comObjective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p< 0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p< 0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p< 0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p< 0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p< 0.05).Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.Keywords: gait, balance, diabetic peripheral neuropathy, risk assessment, wearable biomechanical system

In this work, the interdiffusion coefficient and atomic mobility for the fcc Ag-Cu-Mg phase at 1073 K were investigated by combining diffusion couple experiments and calculations. Based on the experimental composition profiles, the diffusion coefficients at the intersections of the diffusion paths were calculated using the Matano-Kirkaldy method. Using the thermodynamic descriptions available in the literature, the atomic mobilities for the fcc Ag-Cu-Mg phase were automatically optimized by numerical inverse method integrated with the CALTPP (CALculation of ThermoPhysical Properties) program. Moreover, the obtained atomic mobilities were confirmed to be reliable by good agreements between the model-simulated and the measured composition profiles. In addition, three-dimensional surfaces were presented for the interdiffusion coefficient, activation energy, and frequency factor. The presently obtained atomic mobilities can be incorporated into the diffusion database for Ag-based alloys, which can contribute to microstructure simulation and materials design.

Xi Zhang,1,&ast; Hongyan Wang,1,&ast; Chenzhen Du,1 Xiaoyun Fan,2 Long Cui,3 Heming Chen,4 Fang Deng,5 Qiang Tong,6 Min He,7 Mei Yang,8 Xingrong Tan,9 Lin Li,10 Zerong Liang,11 Yaqin Chen,12 Deqing Chen,13 David G Armstrong,14 Wuquan Deng1 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing University, Chongqing, People’s Republic of China; 2Department of Endocrinology, Hospital for Occupational Diseases of Chongqing, Chongqing, People’s Republic of China; 3Department of Endocrinology, Armed Police Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Endocrinology, Ankang Central Hospital, Ankang, Shaanxi, People’s Republic of China; 5Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, People’s Republic of China; 6Department of Endocrinology, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 7Department of Endocrinology, The People’s Hospital of Shapingba District, Chongqing, People’s Republic of China; 8Department of Endocrinology, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China; 9Department of Endocrinology, The 9th People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 10Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 11Department of Endocrinology, Chongqing Red Cross Hospital, People’s Hospital of Jiangbei District, Chongqing, 400020, People’s Republic of China; 12Department of Endocrinology, The People’s Hospital of Shizhu, Chongqing, People’s Republic of China; 13Department of Endocrinology, The People’s Hospital of Rongchang, Chongqing, People’s Republic of China; 14Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng Email wuquandeng@cqu.edu.cnBackground: Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy’s clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions.Methods: A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy.Results: Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up.Conclusion: Patients’ adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.Keywords: custom-molded offloading footwear, high-risk diabetic foot, patient adherence

Ruolin Mao,1,&ast; Zilong Liu,1,&ast; Yunfeng Zhao,2,&ast; Chunlin Du,3,&ast; Jintao Zhou,4,&ast; Qian Wang,5,&ast; Jinchang Lu,3 Lei Gao,1 Bo Cui,1 Yuan Ma,1 Tieying Sun,6 Lei Zhu,1,7 Zhihong Chen1 1Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University. Shanghai Institute of Respiratory Disease, Shanghai, People’s Republic of China; 2Department of Respiratory Disease, Punan Hospital, Pudong New Area, Shanghai, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Taicang Hospital Affiliated with Soochow University, Taicang, Jiangsu, People’s Republic of China; 5Department of Respiratory Medicine, Jing’an District Zhabei Central Hospital, Shanghai, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Chen;Tieying Sun Tel +86-21-64041990-2445; +86-10-85132266Fax +86-21-64187165; +86-10-65132969Email chen.zhihong@zs-hospital.sh.cn; suntieying@126.comBackground: Early diagnosis and proper management of a large number of chronic obstructive pulmonary disease (COPD) patients are great challenges for the Chinese health care system. Although tiered medical services have been promoted by the Chinese government since 2015, they have not been ideally implemented for COPD diagnosis and management.Patients and Methods: We designed a cross-sectional study. Eligible COPD patients (n = 648) and physicians (n = 161) were consecutively recruited from 8 hospitals in different tiers in China. COPD characteristics and treatments were compared among hospitals in different tiers. Multivariate logistic regression was performed to identify risk factors associated with airflow limitation, symptoms and acute exacerbation.Results: The PFT rate at first diagnosis was 99%, 69.4% and 29.9% in teaching, second-tier and community hospitals (P < 0.001). Only approximately 10.9%, 1.7% and 9.6% and 21.8%, 6.9% and 32% of COPD patients received influenza or pneumococcal vaccines (P < 0.001). The proportion of patients who did not use inhaled drugs or had irregular inhalation was 2%, 24.6% and 78.8% (P < 0.001). Education level (RR-1 = − 41.26%, P = 0.007), FEV1%pred (RR-1 = − 2.76%, P < 0.001), and influenza vaccination in the last year (RR-1 = − 64.53%, P = 0.006) were all negatively correlated with COPD acute exacerbation (AE). COPD duration (RR-1 = 131.73%, P = 0.009), AE (RR-1 = 151.39%, P < 0.001), and COPD Assessment Test (CAT) scores (RR-1 = 3.82%, P = 0.019) were all positively correlated with COPD airflow limitation severity.Conclusion: Differences exist in the diagnosis, treatment and management of COPD among different tiers of hospitals in China. Teaching hospitals can manage COPD patients relatively well. There are still some gaps compared with developed countries.Keywords: stable chronic obstructive pulmonary disease, tiered medical system, airflow limitation, symptoms, acute exacerbation

Anti‐dipolarization fronts (ADFs), characterized by the rapid increase of the negative magnetic field Bz component, are typically formed at the leading edge of the tailward reconnection jets in the Earth's magnetotail. To date, the electron‐scale current structures, which govern the energy conversion at ADFs, are still barely understood due to the lack of high‐resolution measurements. Here, using Magnetospheric Multiscale mission, we for the first time report a tailward ADF associated with strong field‐aligned current (FAC). The FAC appears at the leading part of the ADF and its densities can reach about 200 nA/m2, which is significantly larger than those reported before. Such current is primarily contributed by the electron flow, which also forms electron beam distribution in the anti‐parallel direction. Significant energy conversion (E⋅ J, E is electric field and J is current density) is also observed at the ADF, which is mainly contributed by the FAC and the fluctuating electric fields. This study makes essential steps toward understanding the current system and the energy conversion at the ADF in the Earth's magnetotail. Plain Language Summary: Dipolarization fronts (DFs) and anti‐dipolarization fronts (ADFs) are the leading edge of the reconfigured magnetic field after reconnection, expanding earthward and tailward from the reconnection site respectively. The field‐aligned current (FAC) at DFs play crucial roles in global mass transport and energy conversion during substorm and they have been widely studied by in situ observation and simulation. However, the FAC at ADFs and the corresponding energy conversion have not been studied so for. Here, for the first time, we report an ADF associated with strong FAC using high‐resolution data from the MMS mission. We investigate the detailed features of the currents, electron distribution functions, electric fields and energy conversion at the ADF. This study shed light on how strong FAC drive energy conversion at ADFs. Key Points: We for the first time report a tailward anti‐dipolarization front (ADF) associated with strong field‐aligned current (FAC)The FAC is primarily carried by electrons and can reach ∼200 nA/m2, which is even stronger than the FACs reported in earthward Dipolarization frontsThe strong FAC and fluctuating electric fields can drive significant energy conversion at the ADF [ABSTRACT FROM AUTHOR]

Mi Zhang,1 Wei Zhao,2 Shanshan Liu,1 Haichuan Liu,1 Liang Liu,2 Qiling Peng,2 Chengyou Du,1 Ning Jiang3 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2School of Basic Medical Science, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Pathology, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Chengyou Du; Ning Jiang Email duchengyou@126.com; jiangning@cqmu.edu.cnBackground: The H/ACA small nucleolar ribonucleoprotein (snoRNP) gene family, including GAR1 ribonucleoprotein (GAR1), NHP2 ribonucleoprotein (NHP2), NOP10 ribonucleoprotein (NOP10), and dyskerin pseudouridine synthase 1 (DKC1), play important roles in ribosome biogenesis. However, the potential clinical value of the H/ACA snoRNP gene family in hepatocellular carcinoma (HCC) has not yet been reported.Methods: Bioinformation databases were used to analyze the expression and roles of the H/ACA snoRNP gene family in HCC. Survival analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment pathway (KEGG) analyses were performed using R software. Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation between the expression of the H/ACA snoRNP gene family and immune infiltration in HCC. Finally, immunohistochemistry and Western blotting were performed to verify the protein expression of the H/ACA snoRNP gene family in HCC tissues and adjacent tissues.Results: The expression of the H/ACA snoRNP gene family was significantly increased in HCC samples compared to normal tissues, and the area under the curve (AUC) of GAR1, NHP2, NOP10, and DKC1 was 0.898, 0.962, 0.884, and 0.911, respectively. Increased expression of the H/ACA snoRNP gene family was associated with poor prognosis in HCC patients (Hazard Ratio, HR = 1.44 [1.02– 2.04], 1.70 [1.20– 2.40], 1.53 [1.09– 2.17], and 1.43 [1.02– 2.03], respectively; log-rank P = 0.036, 0.003, 0.014, 0.039, respectively). GO and KEGG analyses showed that co-expressed genes were primarily enriched in ribosome biogenesis. In addition, upregulated expression of H/ACA snoRNP gene family was related to the infiltration of various immune cells and multiple T cell exhaustion markers in HCC patients. Immunohistochemical analysis and Western blotting showed that the protein expression of H/ACA snoRNP gene family was higher in HCC tissues than in adjacent tissues of clinical samples.Conclusion: H/ACA snoRNP gene family expression was higher in HCC tissues than in normal or adjacent tissues and was highly associated with poor prognosis of HCC patients and, therefore, has the potential to serve as diagnostic and prognostic biomarkers for HCC.Keywords: hepatocellular carcinoma, H/ACA snoRNP gene family, diagnosis, prognosis, biomarker

Hui Zhang1 &ast;, Dandan Chen2 &ast;, Nianqi Cui,3 Ping Zou,4 Jing Shao,2 Xiyi Wang,5 Yichi Zhang,6 Jiao Du,6 Chunxue Du,6 Guanglan Zhou,6 Deyi Zheng6 1Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 2Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 3The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4School of Nursing, Nipissing University, Toronto, Ontario, Canada; 5Shanghai JiaoTong University, School of Nursing, Shanghai, People’s Republic of China; 6Department of Burn and Plastic Surgery, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deyi ZhengDepartment of Burn and Plastic Surgery, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of ChinaTel +86 13984826262Email deyizheng@126.comBackground: Despite a flood of research on job satisfaction, few studies have examined how and why social support influences job satisfaction. This study aimed to explore how social support has an indirect effect on job satisfaction by examining its impact on emotional exhaustion and anxiety symptoms among residents of the physicians standardized residency training program in China.Methods: This cross-sectional study adopted questionnaires to collect data from residents in the standardized residency training program in China. The PROCESS macro for SPSS based on ordinary least-squares regression and the bootstrap method was used. The indirect effect of social support was examined using bootstrapping procedures. A serial multiple mediation model was examined in which social support was associated with job satisfaction via emotional exhaustion and anxiety symptoms.Results: There were 269 residents who provided usable data for the analysis. The mean age of residents was 25.98 years old. Close to half (52%) of the participants were female. The total indirect effect of social support on job satisfaction was significant (ab=0.21, SE=0.05, CI=0.12 to 0.32). The specific indirect effect 1 (social support→emotional exhaustion→job satisfaction) was significant (a1b1=0.12, SE=0.04, CI=0.05 to 0.19). The specific indirect effect 2 (social support→anxiety symptoms→job satisfaction) was significant (a2b2=0.07, SE=0.03, CI=0.02 to 0.13).The specific indirect effect 3 (social support→emotional exhaustion→anxiety symptoms→job satisfaction) was also found to be significant through both optimism and work engagement (a1a3b2=0.03, SE=0.01, CI=0.01 to 0.05).Conclusion: It seems critical for hospital management to develop a supportive work environment to improve the effects of emotional exhaustion and anxiety symptoms and to provide sufficient support to improve job satisfaction among residents in standardized residency training programs.Keywords: residents, social support, emotional exhaustion, job satisfaction, anxiety symptoms, standardized residency training programs

Chen Du, Xiujuan Chen Reproductive Medicine Center, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010050, People’s Republic of ChinaCorrespondence: Xiujuan ChenReproductive Medicine Center, Affiliated Hospital, Inner Mongolia Medical University, 1 North Pass Street, Hohhot, Inner Mongolia, 010050, People’s Republic of ChinaTel + 86-471-3451651Email chenxh546@163.comBackground: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Evidence indicates that genetic and environmental factors contribute to the pathogenesis of PCOS. The molecular basis of PCOS is not well understood.Methods: Whole-genome RNA sequencing was performed on single oocyte at the germinal vesicle (GV) stage from females with normal ovulation and females with PCOS. All subjects were women from Mongolia undergoing intracytoplasmic sperm injection in vitro fertilization (ICSI-IVF) who met the Rotterdam criteria for PCOS. Women with normal ovulation who were undergoing ICSI-IVF owing to male factor infertility were recruited as control subjects.Results: A total of 1313 differentially expressed genes were found by bio-informatics software in the GV oocytes of PCOS patients and compared with the control group. There were 367 upregulated and 946 downregulated genes (fold change > 2, false discovery rate < 0.01). When compared with the healthy controls, it was shown that the DEGs like VEGF, IGF, FADS1 et al were investigated as potential causes of PCOS oocytes. The DEGs were related to kinase activity, cell proliferation, gene regulation, and the signaling pathways of phosphatidylinositol 3-kinase, Hippo, and ECM-receptor pathway in patients with PCOS. In addition, the interconnected gene co-expression network was constructed by gene bionetwork analysis, indicating that ITGB5, ITGB3, and CAV2 were the core genes in regulating the module expression of DEGs in PCOS.Conclusion: RNA sequencing analysis demonstrated DEGs were linked to inflammation, cardiovascular disease, and lipid metabolism in the GV oocytes of women with PCOS. We hypothesize that ITGB5, ITGB3, and CAV2 may be involved in metabolic disorders associated with the different phenotypes of PCOS.Keywords: polycystic ovarian syndrome, PCOS, RNA-seq, oocyte, transcriptional regulation

Jianhua Zhang, Chuang Du, Linfeng Zhang, Yan Wang, Yingying Zhang, Jingruo Li Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, 450000, People’s Republic of ChinaCorrespondence: Jingruo LiDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou City, Henan Province, 450000, People’s Republic of ChinaEmail jingruolihenan@163.comBackground: This study aimed to explore the biological functions of G-quadruplex-forming sequence containing lncRNA (GSEC) in triple negative breast cancer (TNBC).Methods: The expression of GSEC in TNBC tissues was evaluated by qRT-PCR. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell proliferation was evaluated by 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were evaluated by Transwell assay. Gain- and loss-function assays were performed to assess the biological functions of GSEC in TNBC. The interactions between GSEC, miR-202-5p and AXL were determined by luciferase report assay and RNA immunoprecipitation (RIP) assay. In addition, a nude mouse xenograft model was used to confirm the oncogenic role of GSEC in TNBC.Results: GSEC was significantly upregulated in TNBC tissues and cancer cell lines, and high level of GSEC was associated with advanced tumor stage, positive lymph-node metastasis and the poor prognosis of TNBC patients. Knockdown of GSEC effectively inhibited TNBC cell proliferation, invasion and migration in vitro. GSEC regulated the expression of AXL by directly sponging miR-202-5p. Downregulation of miR-202-5p attenuated GSEC knockdown-induced inhibition on TNBC cell proliferation, invasion and migration in vitro. Meanwhile, overexpression of AXL obviously reversed the inhibitory effects of miR-202-5p mimics in TNBC progression in vitro.Conclusion: GSEC functioned as a potential oncogene and promoted AXL-mediated TNBC progression by sponging miR-202-5p, which might be a novel diagnostic and therapeutic target for TNBC.Keywords: TNBC, GSEC, miR-202-5p, AXL

Hui Zhang,1,* Yi Zhao,2,* Ping Zou,3 Shuanghong Lin,2 Shaoyu Mu,4 Qiansu Deng,5 Chunxue Du,1 Guanglan Zhou,1 Jiang Wu,2 Lu Gan2 1Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, 550002, Guizhou, People’s Republic of China; 2Department of Nursing, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, People’s Republic of China; 3Department of Scholar Practitioner Program, School of Nursing, Nipissing University, Toronto, M6J 3S3, Ontario, Canada; 4Department of Nursing, Nursing College of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 5Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuanghong LinDepartment of Nursing, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, People’s Republic of ChinaTel +8618771059373Email 18771059373@163.comBackground: Little is known about the associated factors with organizational citizenship behavior among Chinese nurses combating COVID-19. The aim of the present study was to investigate the relationships between autonomy, optimism, role conflict, work engagement, and organizational citizenship behavior based on moderated mediation models among Chinese nurses combating COVID-19.Methods: This cross-sectional study was performed on a sample of 368 nurses supporting the COVID-19 epidemic in Wuhan Leishenshan Hospital, China. According to the Job Demands-Resources model, two moderated mediation models were tested, in which autonomy/optimism was associated with organizational citizenship behavior through work engagement, when role conflict served as a moderator.Results: This current study found the mediating effect of work engagement and the moderating effect of role conflict on the relationship between autonomy/optimism and organizational citizenship behavior among nurses. Of note, nurses working in the COVID-19 epidemic viewed role conflict as challenge job demands rather than hindrance job demands.Conclusion: Based on the findings, organizational citizenship behavior can be affected by work engagement and role conflict. Nursing management is suggested to put emphasis on work engagement and role conflict among nurses supporting the COVID-19 epidemic.Keywords: the job demands-resources model, autonomy, optimism, organizational citizenship behavior, nurses, COVID-19

Dongdong Zheng,1,* Caifeng Wan,1,* Hong Yang,2 Li Xu,1 Qi Dong,1 Chengrun Du,3 Jing Du,1 Fenghua Li1 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, People’s Republic of China; 3Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Du; Fenghua Li Email beautydujing@163.com; fenghua-li@163.comPurpose: The treatment of breast cancer is often ineffective due to the protection of the tumor microenvironment and the low immunogenicity of tumor cells, leading to a poor therapeutic effect. In this study, we designed a nano-theranostic platform for these obstacles: a photothermal effect mediated by a gold shell could remodel the tumor microenvironment by decreasing cancer-associated fibroblasts (CAFs) and promote the release of doxorubicin (DOX) from nanoparticles. In addition, it could realize photoacoustic (PA)/MRI dual-model imaging for diagnose breast cancer and targeted identification of Her2-positive breast cancer.Methods: Her2-DOX-superparamagnetic iron oxide nanoparticles (SPIOs)@Poly (D, L-lactide-co-glycolide) acid (PLGA)@Au nanoparticles (Her2-DSG NPs) were prepared based on a single emulsion oil-in-water (O/W) solvent evaporation method, gold seed growing method, and carbon diimide method. The size distribution, morphology, PA/MRI imaging, drug loading capacity, and drug release were investigated. Cytotoxicity, antitumor effect, cellular uptake, immunogenic cell death (ICD) effect, and targeted performance on human Her2-positive BT474 cell line were investigated in vitro. BT474/Adr cells were constructed and the antitumor effect of NPs on it was evaluated in vitro. Moreover, chemical-photothermal therapy effect, PA/MRI dual-model imaging, ICD effect induced by NPs, and tumor microenvironment remodeling in human BT474 breast cancer nude mice model were also investigated.Results: Nanoparticles were spherical, uniform in size and covered with a gold shell. NPs had a photothermal effect, and can realize photothermal-controlled drug release in vitro. Chemical-photothermal therapy had a good antitumor effect on BT474/Adr cells and on BT474 cells in vitro. The targeting evaluation in vitro showed that Her2-DSG NPs could actively target and identify Her2-positive tumor cells. The PA/MRI imaging was successfully validated in vitro/vivo. Similarly, NPs could enhance the ICD effect in vitro/vivo, which could activate an immune response. Immunofluorescence results also proved that photothermal effect could decrease CAFs to remodel the tumor microenvironment and enhance the accessibility of NPs to tumor cells. According to the toxicity results, targeted drug delivery combined with photothermal-responsive drug release proved that NPs had good biosafety in vivo. Chemical-photothermal therapy of Her2-targeted NPs has a good antitumor effect in the BT474 nude mice model.Conclusion: Our study showed that chemical-photothermal therapy combined with tumor microenvironment remodeling and immune activation based on the Her2-DSG NPs we developed are very promising for Her2-positive breast cancer.Keywords: tumor microenvironment remodeling, chemoimmunotherapy, photothermal effect, targeted nano-theranostic platform, dual-modal imaging

A better understanding of the distribution of suitable habitats of Larix kaempferi and its environmental constraints is crucial to know how global climate change will affect its growth and future dynamics. We simulated global suitable distribution areas of L. kaempferi under current and future climates, using different representative concentration pathway (RCP) scenarios, to evaluate the main factors affecting its geographical distribution. The results showed that under current climate conditions the suitable distribution areas of L. kaempferi are concentrated in Europe and Asia, followed by North America. The “Germany-Sweden-Britain” (19.42% of the total worldwide area) and “China-Japan-North Korea” (43.11%) regions are the cores for L. kaempferi distribution. The suitable distribution area for L. kaempferi is large in China (33.75% of the total area). The suitable distribution areas in Asia, Europe, and China decreased and shifted northward in the RCP scenarios. The main climatic factors affecting the distribution of L. kaempferi were the annual mean temperature, mean temperature of the coldest quarter, annual mean precipitation, and precipitation in the driest month. L. kaempferi could adapt or move to higher latitudes/altitudes to cope with climate change. Our results contribute to the introduction, cultivation, and management of L. kaempferi and potentially of other deciduous gymnosperms.

Chongtao Du,1,* Yuyang Feng,1,* Guizhen Wang,2 Zhiyuan Zhang,1 Huimin Hu,1 Yu Yu,1 Jiayang Liu,1 Lihao Qiu,1 Hongtao Liu,1 Zhimin Guo,3 Jing Huang,3 Jiazhang Qiu1 1Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, People’s Republic of China; 2College of Food Engineering, Jilin Engineering Normal University, Changchun 130052, People’s Republic of China; 3Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiazhang QiuCollege of Veterinary Medicine, Jilin University, No. 5333 Xi’an Road, Changchun 130062, People’s Republic of ChinaEmail qiujz@jlu.edu.cnJing HuangDepartment of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, People’s Republic of ChinaEmail huangj@jlu.edu.cnObjective: A colistin-resistant Escherichia coli strain isolated from dog feces was characterized in this study.Methods and Results: A multiplex PCR assay was used to detect the presence of colistin-resistant mcr genes; it was found that E. coli QDFD216 co-harbored the mcr-1 and mcr-3 genes. Whole-genome sequencing and further bioinformatics analysis revealed that E. coli QDFD216 belonged to serotype O176:H11, fimH1311 type and ST132. The resistance genes blaCTX-M-14, mdfA, dfrA3, acrA, acrB, tolc, and sul3 were present in the chromosome. The mcr-1.1 and mcr-3.7 genes were located in two plasmids of different incompatibility groups. mcr-1.1 was carried by a IncX4-type plasmid within an typical IS 26-parA-mcr-1.1-pap2 cassette, while mcr-3.7 was encoded by an IncP1-type plasmid with a genetic structure of TnAs2-mcr-3.7-dgkA-IS 26. No additional antibiotic resistance genes were carried by either plasmid.Conclusion: This is the first report of an E. coli isolate co-harboring a mcr-1.1-carrying IncX4 plasmid and a mcr-3.7-carrying IncP1 plasmid. The evolution and mechanism of mcr gene co-existence need further study to assess its impact on public health.Keywords: colistin resistance, whole-genome sequencing, mcr genes, mcr-1, mcr-3

Jiayang Liu1 ,* Zhiyuan Zhang1 ,* Yuyang Feng,1 Huimin Hu,1 Yu Yu,1 Lihao Qiu,1 Hongtao Liu,1 Zhimin Guo,2 Jing Huang,2 Chongtao Du,1 Jiazhang Qiu1 1Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, People’s Republic of China; 2Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiazhang Qiu; Chongtao DuKey Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, People’s Republic of ChinaEmail qiujz@jlu.edu.cn; duct@jlu.edu.cnBackground: The emergence and prevalence of plasmid-mediated colistin-resistant bacterial strains in recent years have raised great concerns in clinical medicine. It is urgently needed to develop a cheaper, faster, simpler, sensitive, and specific molecular detection method to identify and monitor the dissemination of the transferable resistant determinants.Methods and Results: Herein, eight pairs of primers were designed to set up a multiplex PCR method for the rapid and efficient determination of reported mcr genes. This assay can give results within 85 min (35 min for amplification and 50 min for electrophoresis). We validated the feasibility of this assay by testing the presence of mcr genes in 60 colistin-resistant isolates.Conclusion: Our multiplex PCR technique exhibits remarkable advantages in the light of clear identification, efficiency of amplification, as well as the time consuming for detection, and thus could be useful for the surveillance and epidemiological research of plasmid-mediated colistin resistance, particularly for the under-resourced laboratories.Keywords: multiplex PCR, colistin resistance, mcr genes

Chang M, Yan P, Zhang B, et al. Onco Targets Ther. 2019;12:9177–9187. At the authors request, the Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Following publication, the authors performed an STR analysis on the A172 cells used in the study and they were determined to be contaminated with HeLa cells. In addition, the authors were unable to provide adequate original data for their study and deemed the findings to be unreliable. The authors requested for the article to be retracted and the Editor agreed with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Shuangkuan Du,1 Pengjie Zhang,2 Wei Ren,1 Fan Yang,1 Chun Du1 1Department of Urology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, People’s Republic of China; 2The Center of Kidney Diseases and Hemodialysis, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, People’s Republic of ChinaCorrespondence: Pengjie Zhang Email ls6uhp@163.comBackground: The development of radioresistance remains the obstacle for prostate cancer (PCa) treatment. Here, we explored the role and potential mechanism of circular RNA zinc finger protein 609 (circ-ZNF609) in the radioresistance of PCa cells.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ-ZNF609, microRNA-501-3p (miR-501-3p) and hexokinase 2 (HK2) messenger RNA (mRNA). The viability, apoptosis, metastasis and radioresistance of PCa cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell assays and colony formation assay. The glycolytic rate was assessed through measuring the glucose consumption and lactate production using fluorescence-based glucose and lactate assay kits. The target interaction between miR-501-3p and circ-ZNF609 or HK2 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The protein level of HK2 was detected by Western blot assay. In vivo tumor growth assay was used to explore the role of circ-ZNF609 in the radioresistance of PCa in vivo.Results: Circ-ZNF609 was abnormally up-regulated in PCa tissues and cell lines. Circ-ZNF609 silencing hampered the viability, metastasis, radioresistance and promoted the apoptosis through suppressing cell glycolysis. MiR-501-3p was a direct target of circ-ZNF609, and si-circ-ZNF609-induced influence in PCa cells was partly alleviated by the addition of anti-miR-501-3p. MiR-501-3p functioned through directly interacting with and down-regulating HK2. HK2 was modulated by circ-ZNF609/miR-501-3p axis in PCa cells. Circ-ZNF609 silencing enhanced the radiosensitivity of PCa cells in vivo.Conclusion: Circ-ZNF609 promoted the progression and radioresistance of PCa cells through accelerating the glycolysis via miR-501-3p/HK2 axis, providing promising targets for improving the prognosis of PCa patients.Keywords: prostate cancer, circ-ZNF609, miR-501-3p, HK2, glycolysis, radioresistance

Jie Chen,* Jinggui Chen,* Bo Sun, Jianghong Wu, Chunyan Du Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunyan Du; Jianghong WuDepartment of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, 1205 Rm., 3# Bldg., 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaEmail chunyanfudan@126.com elite53@163.comBackground: Transcription factors (TFs) are key regulators which control gene expression during cancer initiation and progression. In the current study, we aimed to explore the proliferative function and clinical significance of TFs in gastric cancer (GC).Methods: Differential analysis was used to investigate the overall expression difference between normal and tumor tissues of each TF in TCGA-STAD cohort. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to confirm the mRNA expression of one cut homeobox 2 (ONECUT2) in GC tissues. Western blot analysis was conducted to confirm the protein knockdown efficiency. Cell counting, colony formation, and GC xenograft model assays were performed to confirm the proliferative function of ONECUT2 in GC cells. Gene set enrichment analysis (GESA) and qRT-PCR were conducted to confirm the affected signaling pathways and downstream targets of ONECUT2.Results: Our data indicated that a TF named ONECUT2 was highly expressed in GC and correlated with patients’ poor prognosis. Importantly, knockdown of ONECUT2 dramatically decreased GC cells proliferation, whereas overexpression of ONECUT2 promoted carcinogenesis in GC. Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed that the upregulating ONECUT2 induced the activation of Wnt signaling pathway and cell cycle regulation pathway. We further identified that ONECUT2 boosted gastric cancer cell proliferation through enhancing ROCK1 (Rho associated coiled-coil containing protein kinase 1) mRNA expression. High level of ROCK1 expression rescued proliferative behavior of ONECUT2-deficient GC cells.Conclusion: Our findings demonstrated that ONECUT2 promoted GC cells proliferation through activating ROCK1 expression at the DNA level, suggesting that ONECUT2-ROCK1 axis might be a potential therapeutic target in GC.Keywords: transcriptional factor, ONECUT2, ROCK1, gastric cancer, carcinogenesis

Bao Hai,1,* Xiaoyu Pan,1,* Chuanchao Du,1 Tianli Mao,1 Fei Jia,1 Yu Liu,1 Yunlong Ma,2 Xiaoguang Liu,1,2 Bin Zhu2 1Department of Orthopedics, Peking University Third Hospital, Beijing, People’s Republic of China; 2The Center for Pain Medicine, Peking University Third Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoguang LiuDepartment of Orthopedics, Peking University Third Hospital, North Garden Street No. 49, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 10 8226 5711Email xgliudoctor@163.comBin ZhuThe Center for Pain Medicine, Peking University Third Hospital, North Garden Street No. 49, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 10 8226 7368Email zhubin_ortho@126.comIntroduction: Chordoma is a malignant primary bone tumor that is found in the spine and skull. X-inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) is known to be involved in the development of various cancers, but its precise function and mechanism in human chordoma have not been elucidated. Here, we investigated the role of lncRNA XIST in chordoma progression.Methods: Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to determine lncRNA XIST expression in human chordoma tissues and matched-noncancerous tissues. Western blot was used to determine protein expression. Silencing and overexpression of lncRNA XIST were carried out by RNA interference (RNAi) and lentiviral transduction, respectively. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were employed to examine the effects of lncRNA XIST on growth of human chordoma cells. Lastly, the role of lncRNA XIST in vivo was explored using a xenograft model.Results: We found that lncRNA XIST expression was upregulated in chordoma and strongly correlated with poor patient prognosis. Moreover, lncRNA XIST promoted proliferation and inhibited apoptosis of chordoma cells. Mechanistically, upregulation of lncRNA XIST led to a decrease in miR-124-3p expression, thereby promoting the expression of the miR-124-3p target gene, inhibitor of apoptosis-stimulating protein of p53 (iASPP). Addition of miR-124-3p inhibitor or mimic reversed the effects induced by lncRNA XIST silencing or overexpression on chordoma cell proliferation. Lastly, using a xenograft mouse model, we found that silencing of lncRNA XIST decreased tumorigenicity in vivo, as shown by increased tumor cell apoptosis.Conclusion: Our findings demonstrate a key role for lncRNA XIST in chordoma progression by regulating miR124-3p/iAPSS pathway.Keywords: chordoma, lncRNA XIST, miR124-3p, iASPP, proliferation, apoptosis

In the literature, no detailed description is reported about how to detect if a miscibility gap exists in terms of interaction parameters analytically. In this work, a method to determine the likelihood of the presence of a miscibility gap in a binary substitutional solution phase is proposed in terms of interaction parameters. The range of the last interaction parameter along with the former parameters is analyzed for a set of self-consistent parameters associated with the miscibility gap in assessment process. Furthermore, we deduce the first and second derivatives of Gibbs energy with respect to composition for a phase described with a sublattice model in a binary system. The Al-Zn and Al-In phase diagrams are computed by using a home-made code to verify the efficiency of these techniques. The method to detect the miscibility gap in terms of interaction parameters can be generalized to sublattice models. At last, a system of equations is developed to efficiently compute the Gibbs energy curve of a phase described with a sublattice model.

Mingze Chang,1,2 Peng Yan,3 Bei Zhang,4 Gejuan Zhang,1 Juanhong Wang,5,6 Hanming Ge,1 Nannan Han,1 Chengxue Du,1 Wenzhen Shi,1 Ye Tian2 1Department of Neurology, Xi’an No. 3 Hospital, Xi’an 710021, People’s Republic of China; 2Department of Neurology, The Affiliated Hospital of Northwest University, Xi’an 710021, People’s Republic of China; 3The College of Life Sciences, Northwest University, Xi’an 710069, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Xi’an Medical University, Xi’an 710077, People’s Republic of China; 5Department of Pathology, Xi’an No.3 Hospital, Xi’an 710021, People’s Republic of China; 6Departments of Pathology, Xi’an Central Hospital, Xi’an 71000, People’s Republic of ChinaCorrespondence: Ye TianDepartment of Neurology, the Affiliated Hospital of Northwest University, 10 East Section of Fengcheng 3rd Road, Xi’an 710021, People’s Republic of ChinaTel +86-029-87268355Email tianye_xian@163.comBackground: Accumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated.Methods: The levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma.Results: We found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells.Conclusion: In summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.Keywords: miR-769-5p, glioma, KMT2A, tumor growth, apoptosis

Rong Yang,1 Yihe Wu,2,3 Linpeng Yao,1 Jinming Xu,2 Siying Zhang,1 Chengli Du,2 Feng Chen1 1Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China; 2Department of Thoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China; 3Department of Thoracic Surgery, The First Division Hospital of Xinjiang Corps, Aksu City 843000, Xinjiang Autonomous Region, China Purpose: This study investigated the perioperative risk factors of postoperative pulmonary complications (PPCs) after minimally invasive anatomic resection for lung cancer.Patients and methods: We retrospectively reviewed the data from medical records of 729 lung cancer patients undergoing minimally invasive anatomic lung resections between January 2017 and December 2017. Univariate and binary logistic regression analyses were performed to select the independent risk factors for PPCs during the patient’s postoperative hospitalization after surgery.Results: The incidence of PPCs was 24.8% (n=181/729). No patient died during the period of hospitalization. Logistic regression analysis revealed that body mass index (BMI) $24.0 kg/m2 (vs

Lu Di,1–3,* Kai Qian,2,4,* Chengrun Du,1,2 Chunying Shen,1,2 Ruiping Zhai,1,2 Xiayun He,1,2 Xiaoshen Wang,1,2 Tingting Xu,1,2 Chaosu Hu,1,2 Hongmei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 3Department of Oncology, Liyang People’s Hospital, Changzhou, Jiangsu 213000, China; 4Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China *These authors contributed equally to this work Background: Salivary duct carcinoma (SDC) is an extremely rare and highly malignant carcinoma, and surgical radical resection is the most effective therapy. However, there were quite a proportion of patients receiving non-radical resections, and how to treat them remained controversial. Thus, the aim of this study is to evaluate whether postoperative radiotherapy could be a salvage treatment of SDC in major salivary glands without radical operations.Patients and methods: We identified 40 pathologically diagnosed SDC patients who came to our hospital and did not receive radical operations. Thirty-three patients received at least one treatment (remedial operation, postoperative radiotherapy and chemotherapy), and seven patients only chose observation and received no further treatment. The prognostic indicators of the local–regional control (LRC) and distant disease-free survival were analyzed using the Kaplan–Meier methods and the Cox proportional hazards regression models.Results: Thirteen patients experienced local–regional recurrence or local progression, and distant metastases were observed in 15 patients. Through multivariate analysis, we found that postoperative radiotherapy was associated with better LRC, but this kind of treatment did not show significant efficacy in the prevention of distant metastasis.Conclusion: SDC is a rare, aggressive malignancy, and a substantial proportion of these patients experienced inadequate initial treatments. Although postoperative radiotherapy could not decrease distant metastases, it might help to improve LRC in patients with SDC. Keywords: salivary duct carcinoma, prognosis, non-radical resection, postoperative radiotherapy