Search

Shuai Guo,1,* Zhaoting Gong,1,* Xiaona Sun,2 Fei Gao,1 Xiang Li,1 Xiaolin Zu,1 Chao Qu,1 Hongliang Zhang,3 Hai Gao1 1Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Laizhou City People’s Hospital, Laizhou, People’s Republic of China; 3Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai Gao, Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China, Email gaohai1221@mail.ccmu.edu.cn Hongliang Zhang, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email 13810694497@163.comBackground: Ischemic cardiomyopathy (ICM) significantly contributes to global disease burden, while the role of ferroptosis in ICM remains underexplored.Methods: We identified differentially expressed ferroptosis-related genes (DEFRGs) by analyzing the GSE57338 dataset and cross-referencing with FerrDb. Consensus clustering was then used to identify ferroptosis-associated clusters within the ICM samples. A ferroptosis-specific predictive signature was developed using the least absolute shrinkage and selection operator (LASSO) method and validated with the GSE5406 dataset. Additionally, quantitative real-time PCR (qRT-PCR) experiments were performed to validate the 11 feature genes in a rat ICM model.Results: We identified 15 DEFRGs in GSE57338, which distinguished two patient clusters with distinct ferroptosis gene expression, pathway enrichment profiles, and metabolic characteristics. All DEFRGs were upregulated in cluster 2. Potential therapeutic targets were also identified for different ICM patient clusters. The 11-gene predictive signature (TXNRD1, STEAP3, STAT3, SCL2A1, PLIN2, NQO1, NNMT, IL33, ENPP2, ARRDC3, ALOX5) showed robust predictive power in both training and validation sets. High-risk patients exhibited increased infiltration of CD8+ T cells, CD4+ naïve T cells, M0/M1 macrophages, and resting mast cells, along with significant enrichment in epithelial mesenchymal transition and interferon responses. Low-risk patients had higher infiltration of regulatory T cells and monocytes. Results of qPCR analysis confirmed the bioinformatic analysis, validating the expression of the 11 feature genes in the rat ICM model.Conclusion: We identified two ferroptosis-related clusters in ICM patients and developed a predictive signature based on ferroptosis-related genes. Our findings highlight the importance of ferroptosis in ICM and offer new insights for its diagnosis and treatment.Keywords: ischemic cardiomyopathy, ferroptosis, bioinformatics analysis, predictive signature

Kaixin Wang,1 Lingfei Yang,2 Qingsheng Li,2 Xuan Yang,1 Ziyi Chen,2 Yongyan Zhou,3 Yanjie Jia,1 Zhe Gong1 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Electrocardiogram, Zhoukou Center Hospital, Zhoukou, People’s Republic of ChinaCorrespondence: Yanjie Jia; Zhe Gong, The First Affiliated Hospital of Zhengzhou University, Department of Neurology, Postal FfCode 450052, No. 1 Jianshe East Road, Zhengzhou, People’s Republic of China, Email jiayanjie1971@aliyun.com; gongzhe1415@163.comBackground: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes.Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed.Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol.Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.Keywords: cerebral ischemia, chronic ethanol exposure, pericytes, TLR4, NLRP3 inflammasome

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Zheng Gong,1,&ast; Fengzhi Su,2,&ast; Xiaoyu Kang,1 Yuling Zhong,1 Yubo Xie3 1Department of Anesthesiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo Xie, Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, 6th Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-13977121557, Email xybdoctor@163.comBackground: To study the related factors of frailty and quality of life in elderly patients after spinal surgery.Methods: The anxiety, depression, frailty, and quality of life of all patients were assessed by the Anxiety screening scale (GAD-7), Depression screening scale (PHQ-9), Frailty screening scale (FRAIL), and European five-dimensional health scale (EQ-5D-5L) 1 day before surgery (DAY-0). A numeric rating scale (NRS) was used to evaluate patients’ pain during activities on the 1st day (POD-1), 3rd day (POD-3), and 30th day (POD-30) after operation. FRAIL scale and EQ-5D-5L were used to evaluate patients’ frailty and quality of life on POD-30 and 90th day (POD-90) after the operation.Results: There were significant differences in age, body mass index (BMI), preoperative serum albumin level (ALB), and NRS score on POD-1 between the two groups (P< 0.05). Age and PHQ-9 score were positively correlated with EQ-5D-5L score (P< 0.05, r Age=0.245, rPHQ-9=0.217), and preoperative ALB level was negatively correlated with EQ-5D-5L score (P< 0.05, r ALB=− 0.274).Conclusion: The older the age, the larger the BMI and the higher the NRS score on the first day after surgery, the more prone to frailty in elderly patients after spinal surgery; The older age and the lower the preoperative ALB level, the worse the quality of life in elderly patients after spinal surgery.Keywords: elderly patients, spinal surgery, frailty, quality of life

Fangmin Gong,1 Zhuliu Gong,1 Haimeng Liu,2 Pei Yi,1 Yuhan Jia,3 Jingwen Zhuang,1 Jilin Shu,1 Xincheng Huang,4 Yibo Wu5 1College of Literature and Journalism Communication, Jishou University, Jishou, People’s Republic of China; 2College of Minority Preparatory Education, Jishou University, Zhangjiajie, People’s Republic of China; 3Office of the Party and Administration, Hebei Academy of Fine Arts, Shijiazhuang, People’s Republic of China; 4School of Economics and Management, Beijing Institute of Graphic Communication, Beijing, People’s Republic of China; 5School of Public Health, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Haimeng Liu, Zhangjiajie Campus, Jishou University, Dayongqiao Street, Ziwu Road, Yongding District, Zhangjiajie, Hunan Province, 427000, People’s Republic of China, Tel +86 15074328922, Email Liu.Haimeng@outlook.com Yibo Wu, Peking University School of Public Health, No.38 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 18810169630, Email bjmuwuyibo@outlook.comPurpose: To explore the relationship between adolescents’ problematic Internet use and loneliness and the mediating roles of social support and family communication.Methods: A questionnaire survey of 2483 adolescents aged 12– 17 years in 148 cities in China was conducted using the Problematic Internet Use Scale, the Collaborative Social Support Scale, the Family Communication Scale, and the Loneliness Scale. The data were statistically analyzed by SPSS 26.0 and validated by AMOS 28.0. Structural equation modelling (SEM) was conducted to test the effects of problematic Internet use on adolescents’ loneliness and the mediating effects of perceptions of social support and family communication.Results: There was a significant positive effect of adolescents’ problematic Internet use on loneliness (B-0.471, P< 0.001), and the mediating effects of perceptual social support (0.003, 0.012) and family communication (0.008, 0.019) were found to play a chain effect between adolescents’ problematic Internet use and loneliness, respectively. Use and feelings of loneliness played a chain mediating role (0.002, 0.006).Conclusion: This study identified the effects of adolescent problematic Internet use on loneliness and its mechanism of action, emphasized the importance of social support and family communication, and provided practical insights for improving family parenting styles and preventing and intervening in adolescent loneliness problems.Keywords: problematic internet use, adolescents, loneliness, perceived social support, family communication

Dapeng Hu,1,2 Junwen Huang,1 Wenqu Zhao,1 Maosheng Xu,1 Yanyan Ma,1 Zhaoqian Gong,1 Qian Zhang,1 Haijin Zhao1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, NanFang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Emergency Medicine, Dalian Municipal Friendship Hospital, Dalian, Liaoning, 116001, People’s Republic of ChinaCorrespondence: Haijin Zhao, Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel/Fax +86-2062787112, Email zhjin@smu.edu.cnPurpose: Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department.Patients and Methods: The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated.Results: A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR < 0.755, exacerbation history, PaO2 < 60mmHg, PaCO2 > 50 mm Hg, hypoalbuminemia and age ≥ 80 was developed to predict death risk and showed good performance.Conclusion: During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.Keywords: eosinophil, COPD, eosinophil to platelet ratio, emergency department

Shaodan Zhou,1 Yishuang Wen,1 Chao Liu,1 Jian Zhong,1 Manli Liang,1 Yu Wu,2 Sirao Lv,1 Zhuowei Gong,1 Dayuan Lao,1 Taiyan Li,1 Ting Lu,1 Jingqun Tang,1 Xuean Mo,1 Wen Huang1 1Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2University of Pittsburgh School of Medicine, Pittsburgh, PA, USACorrespondence: Wen Huang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356504, Fax +86-771-5350031, Email hwen1229@163.comPurpose: With the adjustment of prevention strategies in December 2022, coronavirus disease 2019 (COVID-19) became widely prevalent in China. This study is aimed to describe the clinical characteristics of myasthenia gravis (MG) patients with COVID-19 and identify risk factors of exacerbation in MG patients with COVID-19 in Guangxi.Patients and Methods: A total of 489 MG patients and 587 control subjects in Guangxi during the COVID-19 pandemic were enrolled in this case–control study. After contacting the participants, the clinical data of MG patients and the control group were analyzed. The clinical characteristics of MG patients with COVID-19 were described. Multivariable logistic regression analysis was used for discovering independent risk factors of MG exacerbation in the patients with MG and COVID-19.Results: A total of 311 (75.30%) MG patients and 428 (72.91%) control subjects were infected with COVID-19, and 64.31% of MG patients with COVID-19 were women. The median age at the time of interview was 41 (IQR: 28, 54) years old, and median onset age was 36 (IQR: 24, 51), both of which were lower than those in MG patients without COVID-19. MG duration was 24 (IQR: 9, 72) months. About 44.69% of patients were generalized MG (GMG). About 11.90% of MG patients with COVID-19 showed severe COVID-19 symptoms and the duration of symptomatic COVID-19 was 9.57 ± 6.79 days, higher than those in the control group. About 35.69% MG patients with immunosuppressive drugs were infected with COVID-19, which is higher than those in the non-infected MG patients (21.57%). A total of 120 (38.59%) MG patients with COVID-19 had comorbidities. About 21 (20.19%) of the 104 MG patients without vaccination showed severe COVID-19 symptoms. Multivariable logistic regression analysis showed that baseline MG activities of daily living profile (MG-ADL, OR 1.280, 95% CI: 1.010– 1.621, p = 0.041), duration of COVID-19 (OR 1.158, 95% CI: 1.100– 1.220, p < 0.001), GMG (OR 2.331, 95% CI: 1.228, 4.426, p = 0.010), and lack of COVID vaccination (OR 2.075, 95% CI: 1.152, 3.738, p = 0.015) were independent factors of exacerbation in MG patients with COVID-19.Conclusion: MG patients with immunosuppressive drugs, younger onset, longer MG duration, or comorbidities are more susceptible to COVID-19. The baseline MG-ADL, duration of symptomatic COVID-19, GMG, and lack of COVID-19 vaccination are independent risk factors of exacerbation in MG patients with COVID-19.Keywords: myasthenia gravis, COVID-19, exacerbation, vaccination, clinical characteristics

Zhuowei Gong, Dayuan Lao, Fang Huang, Sirao Lv, Fengping Mao, Wen Huang Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Wen Huang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356504, Email hwen1229@163.comPurpose: Disturbance of consciousness is common in patients with severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, little is known about it. This study aimed to analyze the clinical manifestations and prognostic factors of anti-NMDAR encephalitis with disturbance of consciousness.Methods: In this retrospective study, the clinical features, treatment results, and long-term outcomes of anti-NMDAR encephalitis patients with disturbance of consciousness were analyzed, and multivariate logistic regression was used to analyze the factors affecting their prognosis.Results: In the group with disturbance of consciousness, the incidences of seizures, involuntary movements, pulmonary infection, mechanical ventilation, intensive care unit (ICU) admission, neutrophil-lymphocyte ratio (NLR), abnormal cerebrospinal fluid index, plasma exchange, and immunosuppressive therapy were higher than those in the group without disturbance of consciousness (all P< 0.05). During the follow-up period (median: 36 months, range: 12– 78 months), the modified Rankin scale (mRS) score, the maximum mRS score during hospitalization, the mRS score at discharge, and the mRS score at 12 months after discharge were higher in the disturbance of consciousness group (all P < 0.001). However, there was no significant difference in long-term outcomes and recurrence between the two groups. Multivariate logistic regression analysis showed that mechanical ventilation, elevated IgG index, and delayed immunotherapy were independent risk factors for poor outcomes in patients with anti-NMDAR encephalitis with disturbance of consciousness at 12 months (odds ratio: 22.591, 39.868, 1.195). The receiver operating characteristics (ROC) curve analysis showed that the area under the curve (AUC) of mechanical ventilation, elevated IgG index, and delayed immunotherapy was 0.971 (95% CI=0.934– 1.000, P< 0.001).Conclusion: Mechanical ventilation, elevated IgG index, and delayed immunotherapy may be the influencing factors of poor prognosis of anti-NMDAR encephalitis patients with disturbance of consciousness. Although their condition is relatively serious, most patients with anti-NMDAR encephalitis with disturbance of consciousness will achieve favorable long-term outcomes after long-term treatment.Keywords: anti-NMDAR encephalitis, disturbance of consciousness, severity of disease, prognosis

Zhichao Gong, Yi Guo, Xiaowei Liu, Kun Ai, Wu Li, Jiangshan Li College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jiangshan Li, College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642, Fax +8673188458187, Email 292463008@qq.com; Wu Li, College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642, Fax +8673188458187, Email 272434694@qq.comAbstract: Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.Keywords: tuina, neck pain, CiteSpace, VOSviewer, knowledge graph analysis

Chunxia Shi, Pan Cao, Yukun Wang, Qingqi Zhang, Danmei Zhang, Yao Wang, Luwen Wang, Zuojiong Gong Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Zuojiong Gong, Department of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Email zjgong@163.comAbstract: PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis

Zhou Liu,1,* Xiubing Hang,1,* Tao Yan,1 Wenwen Chu,1 Zhen Gong,1 Yanyan Liu,2– 4 Yuanyuan Dai,5 Min Yang,6 Jiabin Li,2– 4 Qiang Zhou1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Laboratory Medicine, Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China; 6Department of Intensive Care, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Yang, Department of Intensive Care, The Second Affiliated Hospital of Anhui Medical University, Furong Road No. 678, Hefei, Anhui, 230032, People’s Republic of China, Email yangmin@ahmu.edu.cn Qiang Zhou, Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Furong Road No. 678, Hefei, People’s Republic of China, Email Zhouqiang_ahmu@126.comPurpose: To establish and evaluate a simple disk stacking plus micro-elution (DSE) method that can be routinely performed to rapidly detect the synergistic effect between aztreonam (ATM) and ceftazidime/avibactam (CZA) against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).Methods: The DSE method was established, and a total of 32 MBL-producing CRE isolates collected from multiple centers were tested for ATM-CZA synergy. The results obtained after 8 h of incubation were compared with those obtained by a reference checkerboard assay (CBA) after 18~24 h. Reproducibility experiments were completed on three separate days.Results: The reproducibility study showed that the results of the DSE method were precise. Compared with CBA, the DSE method exhibited excellent performance, with 92.8% sensitivity, 100.0% specificity 93.8% categorical agreement, 0.0% very major error, 0.0% major error, and 6.2% minor error over three days of testing.Conclusion: The DSE method is a simple, rapid and practical method for ATM-CZA combination testing. Further evaluation should be completed to improve its clinical application.Keywords: aztreonam, ceftazidime/avibactam, metallo-β-lactamases, Enterobacterales, antimicrobial combinations, clinical method

Zhichao Gong, Wu Li, Jiangshan Li College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jiangshan Li; Wu Li, College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642 ; +86 13574851647, Fax +8673188458187, Email 292463008@qq.com; 272434694@qq.com

Yanni He,1,* Meijun Zhou,1,* Sushu Li,1,* Zheli Gong,2 Fei Yan,3 Hongmei Liu1 1Department of Ultrasound, Institute of Ultrasound in Musculoskeletal Sports Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 2Department of Ultrasound, The People’s Hospital of Hunan Province, Changsha, 410061, People’s Republic of China; 3CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongmei Liu, Department of Ultrasound, Institute of Ultrasound in Musculoskeletal Sports Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China, Tel/Fax +86-19924270557, Email hongmeiliu3@163.com Fei Yan, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China, Tel/Fax +86-755-86392284, Email fei.yan@siat.ac.cnBackground: Angiogenesis plays an important role in endometrial receptivity, determining the response of the endometrium to the blastocyst at the early stage of embryo implantation. During the application of assisted reproduction technologies, it is very important to evaluate the status of uterine angiogenesis before deciding on embryo implantation. Targeted microbubbles (MBs)-based ultrasound molecular imaging (UMI) can noninvasively detect the expression status of biomarkers at the molecular level, thereby being a potential diagnosis strategy for various diseases and their therapeutic evaluation.Methods: The iRGD-lipopeptide (DSPE-PEG2000-iRGD) conjugate was prepared with iRGD peptides and DSPE-PEG2000-maleimide through the Michael-type addition reaction. Then, the magnetic iRGD-modified lipid-polymer hybrid MBs (Mag-iLPMs) were prepared with the double-emulsification-solvent-evaporation method. Magnetic targeting of Mag-iLPMs was confirmed under the microscope, followed by a rectangular magnet. Next, the in vitro targeted binding of MBs to murine brain-derived endothelial cells.3 (bEnd.3) and human umbilical vein endothelial cells (HUVEC) were evaluated. The ratio of MBs binding to bEnd.3 and HUVEC at the same field was also compared. For in vivo studies, bolus injections of targeted or control MBs were randomly administrated to non-pregnant or pregnant rats on day 5. Then, the uteri were imaged using a VisualSonics Vevo 2100 ultrasound system (Fujifilm VisualSonics Inc., Ontario, Canada) equipped with a high-frequency transducer. Ultrasonic imaging signals were acquired from Mag-iLPMs, and compared with Mag-LPMs, iLPMs, and LPMs.Results: The Mag-iLPMs showed excellent performance in ultrasound contrast imaging and binding affinity to target cells. Using the magnetic field, 10.5- and 12.47-fold higher binding efficiency to bEnd.3 and HUVEC were achieved compared to non-magnetic iLPMs, respectively. Significantly enhanced UMI signals were also observed in the uteri of rats intravenously injected pregnant rats (6.58-fold higher than rats injected with iLPMs).Conclusion: We provided a powerful ultrasonic molecular functional imaging tool for uterine angiogenesis evaluation before embryonic implantation.Keywords: endometrial receptivity, ultrasound molecular imaging, αvβ3 integrin

Haizhe Jin,1 Meng Xiao,2 Zibo Gong,3 Yinan Zhao4 1Department of Industrial Engineering, School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 2School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 3Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 4Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Zibo Gong, Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, People’s Republic of China, Email gongzibomed@163.com Yinan Zhao, Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China, Email zhaoyinan1616@yahoo.co.jpBackground: COVID-19 has brought greater workload pressures to the medical field, such as medical staff being required to wear personal protective equipment (PPE). While PPE can protect the safety of staff during the pandemic, it can also accelerate the accumulation of fatigue among operators.Objective: This study explores the influence of different protection states on the mental fatigue of nurses.Methods: In this study, 10 participants (5 males and 5 females) were randomly selected among applicants to monitor mental fatigue during the nurses’ daily work in four different PPE states (low temperature and low protection; low temperature and high protection; high temperature and low protection; high temperature and high protection). The NASA subjective mental fatigue scale was used for subjective evaluation. Reaction time, attention concentration, attention distribution, memory, and main task completion time were used for objective evaluation.Results: The results demonstrated a significant difference in the effects of different protection states on mental fatigue. The state of high temperature and high protection had the greatest influence on mental fatigue, the state of low temperature and low protection had the least, and states of high (low) temperature and low (high) protection had intermediate effects on mental fatigue. Furthermore, the correlation between the subjective and objective fatigue indices was analyzed using a multiple regression model.Conclusion: This study clarified the influence of different protection states on the mental fatigue of nurses, and verified that nurses require more time and energy to complete the same work as before under high protection states. It provides a basis for evaluating the mental fatigue of nurses in the unique period of the COVID-19 pandemic and specific ideas for optimizing the nursing process.Keywords: COVID-19, personal protective equipment, mental fatigue, experimental research, nurse

ZhaoHui Xu,1,2,&ast; Hui Qu,1,2,&ast; YanYing Ren,1 ZeZhong Gong,1,2 Hyok Ju Ri,1,2 Fan Zhang,1,&ast; Shuai Shao,1 XiaoLiang Chen,1 Xin Chen1 1Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Graduate School of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Chen, Tel +86 17709872266, Email chenxincjz@gmail.comBackground: The E2 factor (E2F) family of transcription factors is dysregulated in numerous cancer types and may play a vital role in the development of various malignancies. However, to our knowledge, the specific function of each of the E2Fs and their relation to the disease prognosis of colorectal cancer (CRC) patients remain unknown.Materials and Methods: We used different publicly available databases and tools, such as ONCOMINE, GEPIA2, UALCAN, cBioPortal, Kaplan–Meier plotter, Metascape, and TIMER analysis, to do an in silico exploration of the potential roles of E2Fs in CRC.Results: In our analyses, we found a downregulation of E2F2 expression and an upregulation of E2F1 and E2F3-8 expression in CRC tissues compared to normal controls. These findings were consistent with our subgroup analysis using the different clinicopathological features of CRC patients. Furthermore, overexpression of E2F3 and E2F4 were significantly correlated with worse overall survival (OS) in colon cancer patients. Meanwhile, low levels of E2F2 resulted in a shorter OS in rectal cancer patients. The E2F family members had varying degrees of genetic alterations with the highest alteration rate observed in E2F1 (23%). Interestingly, a moderate positive express correlation had been found in the following E2F family members: E2F1 with E2F4, E2F2 with E2F7, E2F2 with E2F8, and E2F7 with E2F8. In addition, spearman analysis revealed that E2Fs have a strong positive correlation with the critical oncogenes in CRC patients. Lastly, the expression of E2Fs was significantly associated with the infiltration of six immune cells.Conclusion: In this study, we found that E2F2, E2F3, and E2F4 have the potential to be novel prognostic biomarkers in CRC. The role of these E2F family members in disease pathology may be related to their functions in cell cycle regulation, therapeutic resistance, immune cell infiltration, and epithelia-to-mesenchymal transition. Further studies are required to validate our results; however, our findings may help provide a foundation for broadening our understanding of CRC pathology.Keywords: colorectal cancer, E2F, biomarkers, prognosis, bioinformatics

Yufeng Lin,1 Kaiyuan Wang,2 Daowen Ji,1 Zhongying Gong,1 Zhiyun Wang1 1Department of Neurology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 2Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Zhiyun Wang; Zhongying Gong, Department of Neurology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, 300192, People’s Republic of China, Tel +86 22-23626600, Fax +86 22-23626600, Email 13820585625@163.com; 13212121250@163.comPurpose: To investigate the correlation between plasma levels of high mobility group protein N1 (HMGN1) and the severity of neurological deficits and prognosis in patients with acute cerebral infarction (ACI).Patients and Methods: The plasma HMGN1 levels of 108 patients with ACI were detected by ELISA. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) were used to assess the neurological impairment and outcomes of these patients, respectively. The correlation between HMGN1 levels and clinical parameters was analyzed.Results: The plasma HMGN1 levels of patients with ACI were positively correlated with their NIHSS and mRS scores. Patients with the large artery atherosclerosis (LAA) subtype in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification had higher plasma HMGN1 levels than patients with other subtypes.Conclusion: HMGN1 levels are positively correlated with the severity of ACI and could be used to predict the prognosis of these patients. HMGN1 can be used as a biological marker and potential target for clinical assessment and therapy of ACI.Keywords: high mobility group protein N1, alarmins, cerebral infarction, neurologic examination

Zhihong Gong,1 Jinghui Zhang,1– 3 Jianmei Hou,1,4 Shujie Chen,1 Zixin Hu,1 Xiaoya Kong,1 Guiyuan Ma,1 Lingxia Luo1,5 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Thoracic Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Emergency Medicine, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinghui ZhangTeaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, 87 Xiangya St, Kaifu District, Changsha, 410008, Hunan, People’s Republic of ChinaTel +86 15874032339Email zhangjh-1206@163.comBackground and Aim: Drug extravasation is one of the most common complications of intravenous therapy, which can lead to severe tissue injury if inappropriately treated. This study analyzes the current situation of extravasation and the risk factors affecting the severity of extravasation to provide a theoretical basis for carrying out prospective research, reducing the severity of drug extravasation, and strengthening the management of drug extravasation.Materials and Methods: We retrieved the data on extravasation from January 2016 to December 2020 from the hospital’s safe infusion management system. We used nonparametric tests to assess the differences in the severity of drug extravasation among each variable and performed a multivariate analysis using multivariate ordered logistic regression.Results: Extravasation occurred in 0.038% (263/694,043) of patients, including 203 cases of mild extravasation (77.2%), 57 cases of moderate extravasation (21.7%), and 3 cases of severe extravasation (1.1%). The main diseases of the patients with extravasation were cancer (24.7%), neurological-related diseases (19.4%), circulatory-related diseases (14.8%), and digestive-related diseases (14.1%); the main extravasated drugs were hypotonic or hypertonic drugs (31.9%) and contrast media (27.8%); the infusion tools of extravasation were indwelling needles (92.0%) and steel needles (8.0%). The multi-factor analysis showed that close to joints, patients’ age ≤ 6 or age > 65, cancer, neurological-related diseases, circulatory-related diseases, antineoplastic agents, hypotonic or hypertonic drugs and strong acid or alkali drugs were independent risk factors for more severe extravasation. The nurses’ age and first identified by nurse were nurse-related factors that influenced the severity of drug extravasation.Conclusion: To prevent the occurrence of drug extravasation and reduce its severity, the nurses should strengthen the learning of emergency plans related drug extravasation, strengthen inspections of high-risk patients. Besides, the managers should strengthen the risk warning management of high-risk extravasated drugs.Keywords: extravasation, risk factors, retrospective cohort study, the severity level

ZhaoHui Xu,1,2 Hui Qu,1,2 YanYing Ren,1 ZeZhong Gong,1,2 Hyok Ju Ri,1– 3 Fan Zhang,1 XiaoLiang Chen,1 WanJi Zhu,1 Shuai Shao,1 Xin Chen1 1Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 2Dalian Medical University, Dalian, People’s Republic of China; 3Department of Colorectal Surgery, The Hospital of Pyongyang Medical College, Pyongyang, 999093, People’s Republic of KoreaCorrespondence: Xin Chen Tel +86 17709872266Email chenxincjz@gmail.comBackground: The coronavirus disease 2019 (COVID-19) pandemic is ravaging the world. To date, there are no standard therapies available to cure the disease. Consequently, research on COVID-19 vaccines is booming. This report aimed to assess the research trends of the global COVID-19 vaccines.Methods: The relevant publications on the COVID-19 vaccines were searched in the Web of Science Core Collection Database (WOSCC) database from December 2019 to 11 August 2021. The VOSviewer1.6.16 was used to assess the co-authorship, co-occurrence, citation of countries, institutions, authors, journals, and hotspot keywords. The HistCiteTM (http://www.histcite.com/) software was used to calculate the total local citation score (TLCS) and total global citation score (TGCS) of each variable and generate the citation historiography graph of COVID-19 vaccine development using the citation time series analysis method.Results: A total of 5070 studies authored by 21,151 researchers and published by 1364 different journals were eventually included in this study. The bulk of the retrieved studies were original articles (n = 2401, 47.36%). Among these studies, 1204 (23.75%) were published in 2020. A total of 3863 (76.19%) were published in 2021 and 4295 (84.71%) were open access. The highest number of studies was conducted in the USA, followed by England, China, and Germany. The main partners of the USA were China, England, and Canada. The University of Maryland (TLCS: 1618, TGCS: 2991) and Prof. Ugur Sahin from the University Medical Center of the Johannes Gutenberg University (TLCS: 1397, TGCS: 2407) were the most cited institution and author, respectively. The vaccines featured the highest number of papers, with 294 publications (TLCS: 0, TGCS: 1226). The most cited journal was the New England Journal of Medicine (TLCS: 3310, TGCS: 5914), with an impact factor (IF) of 91.245. The related topics included the following six aspects: attitudes towards vaccination, immunoinformatics analysis, clinical research, effectiveness and side effects, and the public management of vaccines. The timing diagram revealed that the research hotspots focused on the side effects of vaccines and public attitude towards vaccination.Conclusion: This novel comprehensive bibliometric analysis can help researchers and non-researchers to rapidly identify the potential partners, landmark studies, and research topics within their domains of interest. Through this study, we hope to provide more data to combat the COVID-19 pandemic.Keywords: bibliometric analysis, COVID-19, vaccines

Zhen Gong,1 Li Xia,1 Rune Xu,1 Min Luo,1 Hongxiang Deng,1 Zhiping Kang,1 Leping Liu,1 Yaqing Liu,1 Fangjie Zhang,2 Jian Shi1 1Department of Rheumatology, Yiyang Central Hospital, Yiyang, Hunan, People’s Republic of China; 2Department of Emergency Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Fangjie ZhangDepartment of Emergency Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 15116256248Email zhangfj@csu.edu.cnJian ShiDepartment of Rheumatology, Yiyang Central Hospital, No. 118 Kangfu North Road, Yiyang, Hunan, 413000, People’s Republic of ChinaTel +86 18607371607Email 408739063@qq.comPurpose: The purpose of the study was to retrospectively analyze the effects of febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition and febuxostat treatment alone on uric acid levels and acute flares in gout patients.Patients and Methods: We retrospectively analyzed gout patients who were treated from February 2016 to December 2020. Patients were divided into a control group (febuxostat treatment alone) or a combined group (febuxostat combined with arthroscopic surgery). We recorded and analyzed clinical data including age, sex, body mass index, comorbidities, lesion affected joints, acute flare times, medications history, febuxostat side effects, arthroscopic complications, and serum creatinine and uric acid levels changes.Results: There were 80 patients in the control group and 93 patients in the combined group. At the beginning of treatment, the combined group had significantly higher disease severity (higher serum uric acid levels and more acute gout flare times). Arthroscopy was performed in 61 knees and 38 ankles, and 86 joints showed crystals deposition. Compared with baseline, follow-up results showed that serum creatinine significantly decreased in the combined group, and serum uric acid and acute gout flare times significantly decreased in both groups (all p < 0.05). In the comparison between the two groups at the follow-up endpoint, acute gout flare times did not differ significantly (p > 0.05), however, serum creatinine and uric acid levels were lower in the combined group compared with those in the control group (ps < 0.05).Conclusion: Febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition or tophi had a superior effect on lowering uric acid levels and acute flare times in gout patients than did febuxostat alone.Keywords: arthroscopy, febuxostat, crystal deposition, tophi, gout

Yi Zhao, Haojie Xie, Chunyang Pan, Yaobing Yao, Zhe Gong, Yanfei Li, Yanjie Jia Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yanjie JiaDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, 1st Jian She East Road, Zhengzhou, 450052, People’s Republic of ChinaTel +86-135 13802916Email jiayanjie1971@zzu.edu.cnPropose: To investigate the clinical characteristics and potential risk factors of the first onset of cerebral hemorrhage in patients with occult malignant tumors.Patients and methods: In this retrospective study, 23 patients with occult malignant tumors with the first onset of cerebral hemorrhage were enrolled in the tumor group, and 92 patients without occult tumors in the same period were enrolled in the control group. There were no statistical differences in age and sex between both groups by propensity score matching. Collected clinical data included age, sex, smoking history, drinking history, hypertension history, diabetes history, past medical history, routine blood tests, neutrophil-to-lymphocyte ratio (NLR), liver and kidney function, fasting blood glucose level, coagulation function, tumor markers, imaging examinations, National Institute of Health stroke scale (NIHSS) score on admission, modified Rankin Scale (mRS) score 90 days after intracerebral hemorrhage and final mRS score.Results: Compared with the control group, the tumor group had fewer patients with hypertension (52.2% vs 81.5%, P< 0.05), and the NLR was significantly decreased in the tumor group (2.74 vs 5.46, P< 0.05). The tumor group had a greater number of patients with the bleeding sites located in the lobar regions (43.5% vs.19.6%, P< 0.05) and a higher coagulation dysfunction (52.2% vs 29.3%, P< 0.05) than the control group. Multivariate logistic regression analysis revealed that no history of hypertension (OR: 3.141, 95% CI: 1.107– 8.916), lobar cerebral hemorrhage (OR: 3.465 95% CI:1.172– 10.243), and coagulation dysfunction (OR: 3.176, 95% CI: 1.131– 8.913) were independent predictors of occult tumors, and the receiver operating characteristic (ROC) curve showed that the area under the curve of the three-index combined diagnosis was 0.748, C-statistic analysis also showed the same result.Conclusion: No history of hypertension, lobar cerebral hemorrhage, and coagulation dysfunction may be predictors of the risk of occult malignancies in patients with cerebral hemorrhage.Keywords: cerebral hemorrhage, clinical features, malignant tumor, risk factors

ZhaoHui Xu, Hui Qu, YanYing Ren, ZeZhong Gong, Hyok Ju Ri, Xin Chen Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of ChinaCorrespondence: Xin Chen Tel +86 17709872266Email chenxincjz@gmail.comAbstract: Colorectal cancer (CRC) is a major health burden worldwide, and thus, optimised diagnosis and treatments are imperative. E2F transcription factors (E2Fs) are a family of transcription factors consisting of eight genes, contributing to the oncogenesis and development of CRC. Importantly, E2Fs control not only the cell cycle but also apoptosis, senescence, DNA damage response, and drug resistance by interacting with multiple signaling pathways. However, the specific functions and intricate machinery of these eight E2Fs in human CRC remain unclear in many respects. Evidence on E2Fs and CRC has been scattered on the related regulatory genes, microRNAs (miRNAs), and competing endogenous RNAs (ceRNAs). Accordingly, some drugs targeting E2Fs have been transferred from preclinical to clinical application. Herein, we have systemically reviewed the current literature on the roles of various E2Fs in CRC with the purpose of providing possible clinical implications for patient diagnosis and prognosis and future treatment strategy design, thereby furthering the understanding of the E2Fs.Keywords: E2Fs, colorectal cancer, proliferation, apoptosis, drug resistance

Yao Wang,* Xun Li,* Qian Chen, Fangzhou Jiao, Chunxia Shi, Maohua Pei, Luwen Wang, Zuojiong Gong Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuojiong Gong; Luwen WangDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of ChinaEmail zjgong@163.com; wangluw8253@163.comBackground: The glycolysis pathway of M1 macrophages is a key factor affecting the inflammatory response. The aim of this article is to investigate the role of histone deacetylase 6 (HDAC6) in the M1 macrophage glycolysis pathway during acute liver failure (ALF).Methodology: Targeted metabolomics for quantitative analysis of energy metabolites technology was used to detect the characteristics of energy metabolism for 8 ALF patients and 8 normal volunteers. The ALF mice model was intervened with HDAC6 inhibitor ACY-1215. iTRAQ/TMT quantitative proteomics was used to detect protein expression in livers in different mice groups. The liver function, energy metabolites, M1 macrophages, cytokines, and pathological structure, DDX3X, NLRP3 and DNMT1 in liver tissue were detected. The changes of the above molecules were verified in cell groups.Results: ALF patients and mice have significant energy metabolism disorders, accompanied by activation of M1 macrophages. After the intervention of ACY-1215, the activated M1 macrophages and cytokines levels in the mouse liver were reduced. The levels of IDH1, MDH1, and ATP were significantly increased. The expression of DDX3X increased, while the expression of NLRP3 and DNMT1 decreased. ACY-1215 could reduce the model cell apoptosis level and inflammatory response, and improve energy metabolism. It could also promote the expression of DDX3X, and inhibit the expression of NLRP3 and DNMT1.Conclusion: ACY-1215 could inhibit the activation of M1 macrophages by improving the glycolytic pathway through regulating DNMT1 and DDX3X/NLRP3 signals to alleviate ALF.Keywords: HDAC6, M1 macrophage, metabolic reprogramming, acute liver failure

Yue Zheng,* Zijian Gong,* Jian Chen, Yao Lin, Yufang Liu Dermatology Department, Third Affiliated Hospital of Sun-Yat Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue ZhengDermatology Department, Third Affiliated Hospital of Sun-Yat Sen University, Guangzhou 510630, People’s Republic of ChinaEmail benbenzhu-11@163.comBackground: COVID-19 can affect various organ systems including the skin. Cutaneous manifestations of COVID-19 in infected patients are poorly characterized.Objective: To summarize retrospectively the skin features of COVID-19 infection and to analyze the skin rash incidence rate, clinical onset time, cutaneous manifestations, pathological characteristics and relationship with the novel coronavirus pneumonia severity.Methods: The literature up to Sep 20, 2020, were searched and analyzed. Information on clinical features including skin manifestations, disease severity, stage and onset day, and cutaneous pathological characteristics was extracted. Data were analyzed using descriptive non-parametric statistics. For categorical data, the number and percentage of patients are presented. A Spearman correlation test was used to analyze the associations between rash type, rash onset and severity of COVID-19. All statistical analysis was performed with IBM SPSS software (version 20) using two-tailed tests. P values < 0.05 were considered statistically significant.Results: Twenty-three cases of COVID-19 patients with cutaneous manifestations from seven reports were collected. Inflammatory dermatosis, skin vasculitis and vascular dermatosis were the main lesion types of COVID-19 patients. Microvascular and endothelial cell injury, perivascular lymphocytic infiltrate, thrombosis, extremely dilated vessels and prominent deposits of C5b-9 were the main dermatologic pathological changes. The onset day analysis showed that out of 19 patients, 63.2% of cutaneous manifestations were within 10 days, 21.1% in 10– 20 days and 15.8% were 20 days after the time the patient presented with COVID-19 main symptoms. Spearman rho analysis found no correlation between skin rash type, onset day and COVID-19 severity.Conclusion: COVID-19 induced skin changes are one of the manifestations of immune responses to the novel coronavirus. Clinical and pathological characteristics were identified as dermal inflammatory reactions and/or skin vascular injury. External or systematic use of anti-inflammatories, protection of blood vessels and circulation-improving medicines should be considered in the skin treatments for novel coronavirus pneumonia patients.Keywords: COVID-19, skin manifestations, diagnosis, treatment

Zixuan Gong,1,* Xiaoyu Chen,2,* YueChao Zhang,3,* Cheng Liu,4 Zhibing Wang,5 Xiaoyan Xu,6 Jun Zhu,7 Tongqing Xue4 1Department of Urology, Jiangsu Provincial People’s Hospital, Nanjing, Jiangsu Province, 211166, People’s Republic of China; 2Department of Radiology, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian 223001, Jiangsu Province, People’s Republic of China; 3Department of Pharmacy, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 4Department of Interventional Radiology, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 5Department of Radiology, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 6Department of Drug, Huaian Hospital, Huaian 223200, Jiangsu Province, People’s Republic of China; 7Department of Interventional Radiology, The Third People’s Hospital of Yancheng, Yancheng 224001, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tongqing Xue; Jun Zhu Tel +86 51785938616; +86 51581606203Email rrolp240bv@163.com; zhujun320634@163.comBackground: Much evidence unveils the significance of long non-coding RNAs (lncRNAs) in diverse cancers. This study was designed to clarify the function and mechanism of lncRNA GATA6 antisense RNA 1 (GATA6-AS1) in the progression of non-small cell lung cancer (NSCLC).Methods: GATA6-AS1, miR-543 and Raf kinase inhibitor protein (RKIP) mRNA expressions were detected by qRT-PCR. Chi-square test was adopted to analyze the relationship between GATA6-AS1 expression and the clinicopathological parameters of NSCLC patients. NSCLC cells H1299 and H460 cells were used as overexpression or knockdown models, respectively, and cell proliferation and metastasis were determined by CCK-8 and Transwell assays. RKIP, E-cadherin, N-cadherin, STAT3, p-STAT3 expressions in NSCLC cells were detected by Western blot. The targeting relationship between GATA6-AS1 and miR-543 was confirmed by dual-luciferase reporter assay.Results: GATA6-AS1 was significantly lowly expressed in NSCLC tissues and cell lines, and its low expression level was significantly correlated with larger tumor size and positive lymph node metastasis. GATA6-AS1 overexpression inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition of NSCLC cells, while GATA6-AS1 knockdown caused the opposite effects. Mechanistically, it was confirmed that GATA6-AS1 impeded NSCLC cell proliferation and metastasis by adsorbing miR-543 and up-regulating the expression of RKIP.Conclusions: As a tumor suppressor, GATA6-AS1 participates in suppressing the progression of NSCLC by modulating the miR-543/RKIP axis.Keywords: NSCLC, GATA6-AS1, miR-543, RKIP, proliferation, metastasis

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

For the modelling and determination of the Earth’s external gravity potential as well as its second-order radial derivatives in the space near sea surface, the surface layer integral method was discussed in the paper. The reasons for the applicability of the method over sea surface were discussed. From the original integral formula of disturbing potential based on the surface layer method, the expression of the radial component of the gravity gradient tensor was derived. Furthermore, an identity relation was introduced to modify the formula in order to reduce the singularity problem. Numerical experiments carried out over the marine area of China show that, the modi-fied surface layer integral method effectively improves the accuracy and reliability of the calculation of the second-order radial gradient component of the disturbing potential near sea surface.

For the calculation of gravity disturbance in the Earth’s external gravity field, the Stokes-Pizzetti integral is a commonly used method. However, when the target point approaches the Earth’s surface, such problems as singularity and discontinuity arise due to the Stokes kernel structure itself. To settle the problems, firstly the reason for singularity and discontinuity was discussed, and then modification was made to the integral formula, by which the singularity at the surface point is eliminated. Finally the non-singular integral formulas for the calculation of disturbing gravity were derived. In numerical experiments, an area in China was selected to test the modified formula. Numerical results show that the modified formula performs much better than classical Stokes-Pizzetti integral formula when dealing with the calculation of the radial component of gravity disturbance near the Earth’s surface.

Zhenxing Gong,1 Chao Shan,1 Haizhen Yu2 1Department of Business Administration, School of Business, Liaocheng University, Liaocheng 252000, People’s Republic of China; 2Technical Reconnaissance Department, Liaocheng Public Security Bureau, Liaocheng 252000, People’s Republic of ChinaCorrespondence: Zhenxing GongDepartment of Business Administration, School of Business, Liaocheng University, No. 1 Hunan Road, Dongchangfu District, Liaocheng 252000, People’s Republic of ChinaTel +86 1 890 635 0166Email zxgong118@163.comBackground: For companies, employee creativity is vital to gaining competitive business advantages. Research regarding creativity has focused on contextual factors such as feedback, but results of studies on the relationship between feedback and creativity are inconsistent; further, only a handful of studies have been carried out from the perspective of coworkers. In this study, we aimed to analyze the association between the coworker feedback environment and creativity, to test the mediating role of feedback monitoring in this relationship and to test the moderating role of self-motivation among employees in China.Methods: A coworker feedback environment survey, a coworker feedback monitoring questionnaire, a self-motivation scale and a creativity scale were used. The staff submitted 264 questionnaires, of which 235 (74.6%) were completed by the participants. Among the respondents in the sample, 132 (56.2%) were men, and 103 (43.8%) were women. The mean age is 30 and age range from 24–49. Mplus 7.11 software was used to perform descriptive analysis, Spearman’s correlation analysis, mediating analysis and moderation analysis.Results: Coworker feedback environment was positively associated with creativity (β=0.60, p

Shuangshuang Zeng,1,2,* Zhijie Xu,3,* Xiang Wang,1,2 Wanli Liu,1,2 Long Qian,1,2 Xi Chen,1,2 Jie Wei,1,2 Minwen Zhu,1,2 Zhicheng Gong,1,2 Yuanliang Yan1,21Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China; 2Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of ChinaCorrespondence: Zhicheng Gong; Yuanliang YanDepartment of Pharmacy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan, People’s Republic of ChinaTel +86 7 318 432 7306Email gongzhicheng@csu.edu.cn yanyuanliang@csu.edu.cn*These authors contributed equally to this workPurpose: To describe trends and correlation between antibacterial exposure and bacterial resistance from hospitalized patients in a hospital in southern China.Patients and methods: This study used hospital-wide data regarding antimicrobial resistance and consumption between January 1, 2014 and December 31, 2018. Antibacterial consumption was expressed as antimicrobial use density (AUD). The changes in trends and associations between antibacterial utilization and resistance were analyzed using linear regression and time series analysis.Results: The total AUD of all antimicrobials decreased year by year (50.66 in 2014 vs 44.28 in 2018, P=0.03). The annual use of antimicrobials, such as penicillins, monobactams, aminoglycosides, macrolides, and lincosamides, significantly decreased (P

Ya He,1,2 Zhihai Wang,1 Chuan Liu,1 Zhitao Gong,1 Yanshi Li,1 Tao Lu,1 Guohua Hu1 1Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Otolaryngology Head and Neck Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China Purpose: Several PCDH genes were shown to be downregulated or silenced in carcinomas and act as candidate tumor suppressor genes. However, the functions of PCDH17 in nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the PCDH17 promoter methylation status and its impact on the expression and functions of PCDH17 in NPC. Patients and methods: To determine the mRNA levels and promoter methylation status of PCDH17 in NPC cell lines as well as 42 NPC patient specimens, we performed reverse transcription PCR, methylation-specific PCR, and bisulfite genome sequencing. The effects of ectopic PCDH17 expression in NPC cell lines were determined by colony formation, cell proliferation, wound healing, in vitro human umbilical vein endothelial cells tube formation, migration, invasion, cell cycle, and apoptosis assays and an in vivo subcutaneous tumor model. Results: PCDH17 expression was almost absent or significantly reduced in 100% of the NPC cell lines (5/5). However, 5-aza-2′-deoxycytidine and trichostatin A treatment restored PCDH17 expression. Promoter methylation was involved in PCDH17 silencing. Ectopic expression of PCDH17 in silenced NPC cells reduced colony formation, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Conclusion: PCDH17 plays a tumor suppressor role in NPC. PCDH17 methylation may be a tumor-specific event and can be used as an epigenetic biomarker for NPC. Keywords: nasopharyngeal carcinoma, PCDH17, tumor suppressor gene, methylation, epigenetic inactivation

Gong Z, Chen X, Zhang Y, et al. Cancer Manag Res. 2020;12:9327–9338. The Editor and Publisher of Cancer Management and Research wish to publish an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. Read the original article

Jiachi Ma,1 Xiaowen Sun,2 Tiankang Guo,1 He Su,1 Quan Chen,1 Zhenqiang Gong,3 Jianbo Qi,3 Xiaodan Zhao3 1Department of General Surgery, Gansu Provincial People’s Hospital, LanZhou, 2Department of Dermatology, The First Hospital of Tianshui, Tianshui, 3Ningxia Medical University Graduate School of Medical Sciences, Surgical Oncology, Yinchuan, People’s Republic of China Purpose: This article investigates the relationship between cancer cells and stromal cells in carcinoma cell living microenvironment and elucidates the mechanism that interleukin-1 receptor antagonist (IL-1RA) blocks metastatic potential in colon cancer. Methods: Western blot and RT-PCR assay were used to determine the expression of hepatocyte growth factor (HGF) and IL-1α in colon carcinoma cells and stromal cells. Effect of IL-1RA and HGF on metastatic potential of colon cancer cells were examined by proliferation, invasion, and angiogenesis assays. The interactional role of IL-1RA and HGF were detected by ELISA assay, invasion, and angiogenesis assay making up a co-culture system consisting of stromal and colon cancer cells in cells living microenvironment.Results: IL-1α was expressed in human umbilical vein endothelial cells (HUVECs) and HT-29 and WiDr (colon cancer cell lines with higher liver metastatic potential). HGF was expressed only in fibroblast. HGF secretion from fibroblasts was significantly inhibited by IL-1RA (P

He Y, Wang Z, Liu C, et al. Cancer Manag Res. 2019;11:1601–1613. At the request of the authors, the Editor-in-Chief and Publisher of Cancer Management and Research wish toretract the published article. We were notified of some potential issues found in the electrophoresis images presented in Figure 1B and C of the published article. The authors were asked to provide the original, unedited images for these figures as well as the original, unedited images for the Western blots shown in Figures 3B and 5C. The authors responded and explained that the required raw data for the gel electrophoresis and Western blots images had been lost and asked to retract the article to maintain the principle of scientificintegrity. The authors wish to apologise for this error. 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

Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R) Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG) neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2) DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated). Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage-gated Na channels due to the chronic administration of these medications. For the first time, the present investigation explored the adaptations of this channel, which may contribute to the hyperexcitability of primary afferent nerves and hyperalgesia during these pathologic conditions. The results also suggest that neurophysiologic mechanisms of morphine tolerance and visceral hyperalgesia are related at the TTX-R Na+ channel.Keywords: TTX-resistant Na+ channel, neuroplasticity, visceral hyperalgesia, morphine tolerance, DRG

Expanding bound states in the continuum (BIC) beyond photonic crystal systems may enable broader applications benefiting from the unique properties of BIC states. We use photonic integrated circuit to realize a Fabry-Pérot BIC on a silicon chip. The devices consist of cascaded ring resonators with tunable resonance frequencies and phase delays. As a result, the BIC state is dynamically tuned with electrical I/O. We analyze the mechanism of the formation of BIC states in this waveguide system and point out the fundamental differences between the BIC states and electromagnetically induced transparency states in integrated photonics. The high transmission protected by the BIC state enables versatile optical filters, which are capable of independent control over switching, peak position, and quality factor. We also demonstrate the scalability of this platform. This integrated silicon photonic platform brings opportunities for practical BIC applications.

Laser-cooled and trapped atomic ions form an ideal standard for the simulation of interacting quantum spin models. Effective spins are represented by appropriate internal energy levels within each ion, and the spins can be measured with near-perfect efficiency using state-dependent fluorescence techniques. By applying optical fields that exert optical dipole forces on the ions, their Coulomb interaction can be modulated to produce long-range and tunable spin-spin interactions that can be reconfigured by shaping the spectrum and pattern of the laser fields in a prototypical example of a quantum simulator. Here the theoretical mapping of atomic ions to interacting spin systems, the preparation of complex equilibrium states, and the study of dynamical processes in these many-body interacting quantum systems are reviewed, and the use of this platform for optimization and other tasks is discussed. The use of such quantum simulators for studying spin models may inform our understanding of exotic quantum materials and shed light on the behavior of interacting quantum systems that cannot be modeled with conventional computers.