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Chen Wang,1,* Chunyan Peng,2,* Leping Ning,3,* Xueping Qiu,1 Kaisong Wu,4 Na Yang,1 Bingyu Jin,1 Yue Zhao,1 Fang Zheng1 1Center for Gene Diagnosis, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Laboratory Medicine, Taihe hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China; 4Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang Zheng, Center for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, People’s Republic of China, Tel +86-27-67813233, Fax +86 27 67813497, Email zhengfang@whu.edu.cnPurpose: SARS-CoV-2 is extremely infectious, and the incidence of nosocomial infection is conceivably high. We aimed to develop and validate a nomogram to assist monitoring nosocomial SARS-CoV-2 infection in hospitalized patients.Patients and Methods: There were 437 COVID-19 hospitalized cases and 420 negative inpatients enrolled from two hospitals in Hubei province, China. We compared the demographic and clinical characteristics of participants between the two groups. Then, LASSO regression and logistic regression were applied to build a nomogram for SARS-CoV-2 infection prediction in the development cohort. Our nomogram was assessed by area under the curve (AUC), calibration curve, decision curve (DCA) and clinical impact curve analysis (CICA).Results: After LASSO regression filtration, eleven laboratory indicators were correlated with SARS-CoV-2 infection. Then, we integrated these features and constructed a nomogram, which showed a high AUC 0.863 (95% CI: 0.834– 0.892) in the development cohort with a sensitivity of 80.41% and specificity of 77.38% and 0.813 (95% CI: 0.760– 0.866) in validation cohort with a sensitivity of 82.98% and specificity of 70.43%. The calibration plot displayed that the predicted outcomes were in good concordance with the actual observations. DCA and CICA further showed a larger clinical net benefit.Conclusion: We constructed and validated a nomogram that integrated eleven laboratory indexes to assist monitoring of nosocomial SARS-CoV-2 infection in hospitalized patients. Our nomogram is remarkably informative for clinical practice, which will be helpful for preventing SARS-CoV-2 further transmission in hospital and avoiding nosocomial infection.Graphical Abstract: Keywords: COVID-19, nomogram, nosocomial SARS-CoV-2 infection, machine learning

Despite high hepatitis B (HBV) prevalence among people of Vietnamese ethnicity in Australia and elsewhere, there is limited research on levels of HBV knowledge and factors associated with such knowledge. The aim of this study was to examine HBV knowledge and associated demographic and attitudinal factors among people of Vietnamese ethnicity in Australia. People of Vietnamese ethnicity (n = 966) were recruited through community events and social media groups to complete online surveys measuring HBV knowledge, attitudes towards HBV, levels of mistrust in Western medicine, and demographic characteristics. Findings of this study indicate that levels of knowledge are mixed, with gaps in knowledge related to transmission and treatment of the virus. Those with greater knowledge of HBV tended to be older, have higher levels of formal education, have been tested for HBV, and know someone living with HBV. Those with lower levels of knowledge tended to have more negative attitudes towards the virus and greater levels of mistrust in Western medicine. Given that health literacy is connected to effective communication from health providers, we suggest that there is a need for the development of health promotion and education resources targeted at people of Vietnamese ethnicity and translated into Vietnamese. We propose that such resources be developed in consultation with Vietnamese communities and health providers to ensure that they are culturally appropriate and sensitive to people of Vietnamese ethnicity living in Australia. [ABSTRACT FROM AUTHOR]

Zhi Yang,1– 3 Peng Duan,2 Weihong Li,2 Ronghui Nie,2,3 Xiaoyang Lou,2,4 Lina Wang,2 Kexia Wu,2 Jiang Liu,2 Ping Tu,2 Xiaoyang Lai1 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang, 330000, Jiangxi, People’s Republic of China; 3Jiangxi Medical College of Nanchang University, Nanchang, 330036, Jiangxi, People’s Republic of China; 4Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoyang Lai Tel +86 13607916298Email 1640852510@qq.comObjective: We investigated the relationship between thyroid hormones and the risk of diabetic kidney disease (DKD) progression.Methods: A total of 452 patients with type 2 diabetes were included, and a cross-sectional analysis was performed. Urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to diagnose persistent albuminuria and stage chronic kidney disease, respectively. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline was used to describe the risk of DKD progression (low, moderate, and high or very high risks).Results: The DKD group had higher levels of thyroid-stimulating hormone (TSH) and lower levels of free triiodothyronine (FT3) and free thyroxine (FT4) than the non-DKD group. The prevalence of thyroid dysfunction in the DKD group was significantly higher than in the non-DKD group, especially the prevalence of subclinical hypothyroidism. FT3 levels decreased gradually with the deterioration of DKD. TSH levels increased with an increasing KDIGO category. FT3 and FT4 levels were negatively correlated with serum creatinine levels and ACR, and positively correlated with eGFR. Contrastingly, TSH was positively correlated with ACR, and negatively correlated with eGFR. After adjustment, an increase in FT3 levels significantly reduced the risk of DKD [odds ratio, OR (95% confidence interval, CI)=0.58 (0.42– 0.79)] and DKD progression [ORs (95% CIs)=0.65 (0.45– 0.93) for the moderate risk group and 0.50 (0.33– 0.74) for the high or very high-risk group, using the low-risk group as a reference]. FT3 levels below 4.30 pmol/L in men and 3.99 pmol/L in women were the cut-off points for an increased risk of DKD progression.Conclusion: Low FT3 level is an independent risk factor for DKD and DKD progression. FT3 ≤ 4.30 pmol/L in men and ≤ 3.99 pmol/L in women will greatly increase the risk of kidney disease progression in patients with type 2 diabetes.Keywords: thyroid hormone, prognosis of chronic kidney disease, type 2 diabetes mellitus

Huifang Huang,1 Kunhai Wu,2 Lufei Chen,2 Xiaomei Lin1 1Intensive Care Unit, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Blood Transfusion Department, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Kunhai Wu; Lufei Chen Tel +86 13906921205; +86 13705032570Fax +86 591-87555474Email 315084702@qq.Com; 502108678@qq.ComObjective: We aimed to evaluate whether the systemic inflammatory response index (SIRI) and platelet lymphocyte ratio (PLR) are associated with ovarian malignancy and their diagnostic value. Design: This retrospective study compared SIRI, PLR, cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 199 (CA199), A carcinoma embryonic antigen (CEA) and alpha fetal protein (AFP) of the two groups in Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University from January 2018 to December 2020, divided into two groups based on pathological results, including 85 with ovarian malignancy who met the study criteria and 85 patients with benign ovarian tumors were randomly selected as control group.Results: 1) SIRI and PLR in benign ovarian tumor group were lower than those in ovarian malignancy group; 2) SIRI and PLR in ovarian malignant tumor low stage group were lower than those in the high stage group; 3) In ovarian malignancies, SIRI and PLR were positively associated with CA125 (the correlation coefficient r = 0.251, p = 0.021; r = 0.251, p = 0.020;) but showed no correlation with CA153.Conclusion: The study shows that SIRI and PLR are both convenient and associated with ovarian malignancy. SIRI and PLR can be used to help the differentiation of benign and malignant ovarian tumors and can also be used in the markers of ovarian malignant tumors roughly staging.Keywords: ovarian malignancy, SIRI, PLR

Xiaohua Zhang,1,&ast; Xinguo Liu,2,&ast; Qiongxiang Ye,2 Xunbao Wang,2 Jinjun Chen,2 Zhiyong Wang,2 Pengfei Zhao,2 Baozhou Tao,2 Guoping Xu,2 Wanfeng Xu,2 Kan Wu,2 Yao Xiao,3 Li Yang,1 Junqiang Tian,1 Juan Wang,1 Zhilong Dong,1 Zhiping Wang1 1Institute of Urology, Lanzhou University Second Hospital; Key Laboratory of Gansu Province for Urological Diseases; Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu Province, People’s Republic of China; 2Department of Urology, Susong County People’s Hospital, Susong, Anhui Province, People’s Republic of China; 3Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Wang Email wangzplzu@163.comObjective: To compare the analgesic efficacy and safety of acupuncture and lornoxicam in acute renal colic (ARC).Design, Setting, Participant: A randomized, double-blind, parallel-controlled, single-centered trial was conducted at Susong County People’s Hospital from October 2019 to November 2020. Eighty-four patients with ARC were randomly divided into lornoxicam group (Group L) and acupuncture group (Group A). Group A was treated with acupuncture at Sanyinjiao (SP6), Yinlingquan (SP9) and normal saline, and Group L was treated with sham acupuncture at SP6, SP9 and lornoxicam.Main Outcome Measures: Visual analogue scale (VAS) scores and adverse reactions such as nausea and dizziness were recorded within 5, 10, 15, 20 and 40 minutes after treatment. The main outcome of this study was the short-term effective (STE) rate, the secondary outcome was the onset time, and the safety index was incidence of adverse reactions.Results: A total of 80 patients completed this study, including 41 patients (21 males and 20 females) in Group L and 39 patients (21 males and 18 females) in Group A. Group A exhibited lower scores versus group L after treatment (P < 0.05). The overall STE of group L was 61.00% (25/41), significantly lower than group A [84.62% (33/39)] (P < 0.001). There was no difference in the incidence of adverse reactions between group A [2.6% (1/39)] and group L [7.3% (3/41)] (P = 0.616). The ordered logistic regression analysis showed patients receiving acupuncture therapy are more likely to be cured [OR = 2.887, 95% CI: (1.190, 7.000), P = 0.019].Conclusion: Acupuncture at SP6, SP9 and intramuscular injection of lornoxicam can effectively and safely relieve ARC, but the former has faster and better analgesic effect. Moreover, the incidence of adverse reactions was similar between the two treatments. This acupuncture therapy is recommended as a complementary therapy for ARC.Keywords: acupuncture, lornoxicam, renal colic, analgesia

Kelun Wu,1– 3 Chuan He,1– 3 Yue Wu,1– 3 Xiaojie Zhou,1– 3 Pan Liu,1– 3 Wei Tang,1,3 Mei Yu,1,2 Weidong Tian1– 3 1State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610065, Sichuan, People’s Republic of ChinaCorrespondence: Mei YuState Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaEmail yumei925@hotmail.comWei TangDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaTel/Fax +86-28-85503499Email mydrtw@vip.sina.comPurpose: Small extracellular vesicles (sEV) play an irreplaceable role in cell–cell communication. However, sEV in solution aggregate with each other during preservation, leading to impairment of the structures, contents, and functions of sEV. Therefore, there is a need to develop an optimal preservation method that combines high recovery rate, low cost, convenience, and easy-transportation in one. In this study, a new preservation strategy different from the cryopreservation or lyophilization was developed by reducing sEV particles aggregation.Methods: The sEV were encapsulated in thermoresponsive gelatin methacryloyl (GelMA) hydrogels at 4°C to reduce particles aggregation during the reversible cross-linking process. The sEV movement was visualized in different mediums and particles’ number, size, structure and protein of 28 days preserved sEV were compared to fresh sEV. Human umbilical vein endothelial cells (HUVEC) and rat adipose-derived stromal stem cells (rASC) were isolated and cultured with fresh and preserved sEV to test the cellular response. A mice subcutaneous model was adopted to detect controlled release and angiogenesis ability of preserved sEV.Results: Through particles tracks visualization, GelMA hydrogels significantly decreased the sEV movement. After 28 days preservation in GelMA at 4°C, the particles number, size, structure and protein of sEV were similar to fresh sEV. In vitro, preserved sEV had the same ability to promote cell proliferation, migration and angiogenesis as fresh sEV. In vivo, preserved sEV-GelMA could artificially regulate the absorptivity of GelMA hydrogels and controlled released sEV for therapeutic application, and preserved sEV encapsulated in GelMA significantly promoted angiogenesis in mice.Conclusion: Our results demonstrated that sEV encapsulated in GelMA could be a novel strategy for long-term preservation of sEV for therapeutic application.Keywords: small extracellular vesicles, particle track visualization, preservation, controlled release, aggregation, gelatin methacryloyl hydrogel

Kunhai Wu,1 Lufei Chen,1 Huifang Huang2 1Blood Transfusion Department, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, Fujian, People’s Republic of China; 2Intensive Care Unit, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Huifang HuangIntensive Care Unit, Fujian Provincial Maternity and Children’s Hospital, Fuzhou, Fujian, People’s Republic of ChinaTel +86 13906913057Fax +86 591-87555474Email 190596715@qq.comPurpose: The study aimed to analyse the clinical effect of homotype ET method and compatible ET method in neonates with hyperbilirubinemia caused by non-blood-group antibodies (non-blood-group antibodies refers to due to cause other than blood-group antibodies) as well as to provide relevant reference materials for clinical diagnosis and treatment in Fuzhou city.Patients and Methods: Between January 2011 and December 2020, a total of 125 neonates, who were admitted to the Sentinel hospital of Fuzhou city, Fujian Provincial Maternity and Children’s Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into homotype ET (n=32) and compatibility ET (n=93) treatment groups. We analysed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count before and after ET; retrospectively analysed the neonates’ clinical data; and compared findings between the 2 groups.Results: The homotype ET group and the compatible ET group showed higher STB, SIB, and platelet levels before ET and decreased levels of the same after ET; the difference was statistically significant (P< 0.001). Compared with the compatible ET group, the decreases in STB, SIB, and platelet count in the homotype ET group showed no significant difference (P> 0.05).Conclusion: ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically, and the effects of homotype and compatible ET are similar.Keywords: hyperbilirubinemia, exchange transfusion, neonate, homotype, compatibility

Shuangli Zhu,1 Shiyu Li,1 Ming Yi,1 Ning Li,2 Kongming Wu1,2 1Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of ChinaCorrespondence: Ning LiDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of ChinaTel +86-371-65587805Email lining97@126.comKongming WuDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-27-69378414Email wukm_lab@163.comAbstract: Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids can be used as biomarkers for cancer diagnosis or assessment of prognosis. Tumor-derived microvesicles can also be deployed to reverse drug resistance of tumor regenerative cells, or to deliver chemotherapeutic drugs and oncolytic adenovirus for the treatment of cancer patients. This review summarizes the general characteristics of tumor-derived microvesicles, focusing on their biological characteristics, their involvement in tumor progression, and their clinical applications.Keywords: tumor-derived microvesicles, metastasis, drug resistance, cancer vaccine, cancer

Wenhui Zhong,1,&ast; Chunyu Zhou,2,&ast; Lufei Chen,1 Zhenna Wang,3 Hongxing Lin,1 Kunhai Wu,1 Sujiao Zhang4 1Clinical Laboratory, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Nursing Department, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 3Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenhui ZhongClinical Laboratory, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, No. 18 Daoshan Road, Fuzhou, 350001, Fujian, People’s Republic of ChinaEmail 289492316@qq.comPurpose: This study assessed the prognostic value of red blood cell distribution width (RDW) and cancer antigen 125 (CA125) in predicting the prognosis of endometrial cancer (EC) patients.Patients and Methods: In this study, we included 525 patients with EC between January 2013 and January 2019. Demographic and clinical indicators were collected, and the receiver operating characteristics curve (ROC) and cutoff values were calculated between the early and advanced stages of EC. Independent risk factors associated with EC prognosis were assessed using Cox regression analyses and the Kaplan–Meier method.Results: Compared to women in the early stage of EC, women with advanced stage had significantly elevated RDW coefficient of variation (RDW-CV) and CA125 levels and lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (both P < 0.05). Consequently, RDW-CV and CA125 were found to be independent risk factors for EC by using ROC curve and multivariate logistic regression analysis. The survival analysis curve was used to assess the diagnostic value of RDW-CV, CA125, and their combination in the prognosis of EC. The results showed that patients with high expression of RDW-CV and CA125 had worse overall survival than those with low expression. Moreover, multivariate Cox regression analysis indicated that RDW-CV+CA125=2 was an independent prognostic factor.Conclusion: These findings suggest that CA125 combined with RDW-CV has a good prognostic value for EC. Thus, the RDW-CV+CA125 score is a promising prognostic marker for the clinical decision-making process regarding EC outcomes.Keywords: CA125, RDW-CV, endometrial cancer, prognosis

Yanxiang Shao,1,&ast; Xiang Tu,1,&ast; Yang Liu,1,&ast; Yige Bao,1 Shangqing Ren,1,2 Zhen Yang,1,3 Xu Hu,1 Kan Wu,1 Hao Zeng,1 Qiang Wei,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18980601428Email xiangli87@hotmail.comObjective: To investigate the predictive factors of lymph node metastasis (LNM) and evaluate the usefulness of prediction nomograms.Methods: This study included 300 patients diagnosed with penile squamous cell carcinoma at West China Hospital (WCH) of Sichuan University (Chengdu, China) and 412 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis was performed on these cohorts to investigate the predictive factors of LNM. We evaluated a recently developed prediction nomogram for LNM, which was established based on the National Cancer Database (NCDB). Moreover, we developed a novel nomogram using cases from the WCH for the prediction of lymphatic metastasis.Results: Logistic analysis identified that younger age at diagnosis, invasion of the penis body, poorer pT stage, cN stage, nuclear grade and the presence of lymph vascular invasion (LVI) were significantly correlated with LNM in WCH cases; however, only race, poorer T stage and cN stage were significantly associated with LNM among the cases from the SEER. Multivariate analysis demonstrated that younger age, poorer T stage, cN stage and nuclear grade were independent predictors of LNM. Receiver operating characteristic curve analysis of WCH cases showed that the tumor T stage 8th edition has better area under the curve than 7th stage (0.672 vs 0.636, respectively). Moreover, well AUC was seen in external validation of NCDB nomogram in WCH cohorts and SEER series (0.833 vs 0.795). The new nomogram included the aforementioned independent predictors and the bootstrap-corrected concordance was 0.876.Conclusion: Younger diagnose age, poorer pT stage, cN stage, nuclear grade and LVI were the most important predictors of LNM in patients with penile cancer. 8th T stage performed better than 7th version in predicting LNM. NCDB nomogram has some application values in both WCH and SEER cases, and our novel model further improved the predictive accuracy.Keywords: penile cancer, lymph node metastasis, prediction model, nomogram, SEER

Shifei Yao,1,2 Nanning Luo,1,2 Jiaoyang Liu,1,2 He Zha,1 Yuanhang Ai,1,2 Juan Luo,1,2 Shi Shi,3 Kaifeng Wu1,2 1Department of Laboratory Medicine, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of China; 2Scientific Research Center, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of China; 3Department of Laboratory Medicine, The Fourth People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of ChinaCorrespondence: Kaifeng WuDepartment of Laboratory Medicine/Scientific Research Center, Zunyi Medical University Third Affiliated Hospital/The First People’s Hospital of Zunyi, Zunyi, 563000, Guizhou, People’s Republic of ChinaTel +86 85123116548Email kiphoonwu@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined.Methods: We did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis.Results: At baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6– 119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8– 55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1– 1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4– 689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P= 0.008) and inversely with sICAM-1 (r= − 0.609, P= 0.021) and aspartate aminotransferase levels (r= − 0.560, P= 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment.Conclusion: The present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.Keywords: COVID-19, PGRN, soluble adhesion molecules, pathogenesis, biomarker

Mingdi Zhang, Kejin Wu, Peng Zhang, Yiran Qiu, Fang Bai, Hongliang Chen Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongliang ChenDepartment of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, People’s Republic of ChinaTel/Fax +86-21-33189900Email 13671852284@163.comBackground: To summarize the regulatory role of mRNA-miRNA-lncRNA network associated with endocrine therapy resistance (ETR) in breast cancer.Methods: We analyzed the differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) in long-term estrogen-deprived (LTED) estrogen receptor (ER)-positive breast cancer cells (LTED MCF7) (modeling relapse on endocrine therapy) and MCF7 cells in the presence of estrogen (E2) (modeling a patient at primary diagnosis) by mining GSE120929 and GSE120930 datasets. The mRNA-miRNA-lncRNA network was constructed by multiple bioinformatic tools. The prognosis of genes from the network was validated in breast cancer patients with following systemic treatment (endocrine therapy) by GEPIA, Kaplan–Meier plotter and UALCAN database.Results: Totally, 769 DEGs, 33 DEMs, and 10 DELs were selected. The mRNA-miRNA-lncRNA network was established including 60 mRNA nodes, 6 miRNA nodes and 3 lncRNA nodes. A significant module containing 3 nodes and 3 edges was calculated based on the mRNA-miRNA-lncRNA network. The hub genes in the network are ABCG2, ESR1 and GJA1. ESR1/miR-130b-3p/HOTAIR are significantly correlated with the prognosis of breast cancer patients with endocrine therapy.Conclusion: This study provides a novel ETR-related mRNA-miRNA-lncRNA network. Further, we suggest that ESR1/miR-130b-3p/HOTAIR may be promising targets for clinical treatment of endocrine therapy-resistant breast cancer.Keywords: endocrine therapy resistance, breast cancer, bioinformatic analysis, mRNA-miRNA-lncRNA network, GEO

Qian Xu,1 Kang Wu,2 Yi Yang,2 Rui Chang,1 Hua Qiu,2 Yingying Wang,1 Tao Lin,2 Chaowei Fu,1 Yue Chen,3 Na Wang,1 Xiaonan Ruan2 1School of Public Health, Fudan University, Pudong Preventive Medicine Research Institute of Fudan University, Shanghai, 200032, People’s Republic of China; 2Pudong New Area Center for Disease Control and Prevention, Pudong Preventive Medicine Research Institute of Fudan University, Shanghai, 200136, People’s Republic of China; 3School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, CanadaCorrespondence: Na WangSchool of Public Health, Fudan University, Pudong Preventive Medicine Research Institute of Fudan University, No. 130, Dongan Road, Xuhui District, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86 21-54237455Email na.wang@fudan.edu.cnXiaonan RuanPudong New Area Center for Disease Control and Prevention, Shanghai, 200136, People’s Republic of ChinaTel/Fax +86 21-50342409Email xnruan@pdcsc.sh.cnPurpose: Poor sleep quality and pain were common and had been proved as an important influenced factor of quality of life for patients with COPD. The association of sleep quality with pain has been observed in other population but remains unclear in mild patients with COPD from a community setting.Methods: A cross-sectional study was conducted to include eligible mild patients with COPD in Pudong New District of Shanghai. A structured questionnaire was used to collect general and clinical information for the patients. The Chinese version of Pittsburgh Sleep Quality Index (PSQI) and the short form of McGill Pain Questionnaire (SF-MPQ) was used to assess sleep quality and intensity of pain. Logistic regression was performed to test the association between sleeping quality and pain intensity.Results: Two hundred and sixty-four patients with COPD, with an average age of 64 years (SD 5.78 years), were enrolled, and of 52% were women. Seventy-one (26.9%) participants reported at least one exacerbation during the past year. About 28.2% of the patients were classified as having poor sleep quality. Sleep quality was significantly associated with PRI score (adjusted odds ratio (ORad)=2.16, 95% CI: 1.16– 4.00) and PPI rank (ORad=1.90, 95% CI: 1.08– 3.34). People with daytime disturbance were more likely to have pain (ORad =2.03, 95% CI: 1.18– 3.50).Conclusion: Poor sleep quality was common in mild patients with COPD in community and was associated with higher pain intensity. Pain may involve an impairment of sleep quality.Keywords: sleep, pain, chronic obstructive pulmonary disease, Pittsburgh sleep quality index, SF-MPQ

Yanxiang Shao,1,&ast; Thongher Lia,1,&ast; Yaohui Wang,1,&ast; Kan Wu,1 Xu Hu,1 Yang Liu,1 Shuyang Feng,1 Shangqing Ren,1,2 Zhen Yang,1,3 Sanchao Xiong,1 Weixiao Yang,1 Qiang Wei,1 Hao Zeng,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People’s Republic of ChinaEmail xiangli87@hotmail.comObjective: To evaluate the prognostic factors of penile cancer and the utility of prognostic models.Methods: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models.Results: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results.Conclusion: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.Keywords: penile cancer, TNM stage, survival, nomogram, external validation

Yuanyuan Huang,1,* Yongjie Zhou,2,* Yi Wei,1 Lingyun Zeng,2 Jiezhi Yang,3 Yi Li,2 Xiuli Song,4 Hehua Li,1 Hongbo He,1 Ting Li,1 Kai Wu,5 Mingzhe Yang,1 Fengchun Wu,1,6,7 Yuping Ning,1,7 Xiangyang Zhang1,8 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, People’s Republic of China; 2Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 3Department of Psychiatry, Shenzhen Health Development Research Center, Shenzhen, People’s Republic of China; 4Clinical Psychology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 5Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (scUT), Guangzhou, People’s Republic of China; 6Department of Psychiatry, Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 7The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 8CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuping NingDepartment of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), 36 Mingxin Road, Liwan District, Guangzhou, 510370, People’s Republic of ChinaEmail ningjeny@126.comXiangyang ZhangCAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of ChinaEmail zhangxy@psych.ac.cnBackground: During the outbreak of coronavirus disease 2019 (COVID-19), occupational differences were recognized with respect to psychological issues, but there are no reports regarding the insomnia and anxiety comorbidities and their related factors among the general public and medical staff. Our study aimed to compare the prevalence of anxiety and anxiety with insomnia, as well as the relationship between different psychological symptoms between the two groups.Methods: A total of 605 medical staff and 1091 public respondents were assessed through an online questionnaire survey, including the 7-item Insomnia Severity Index (ISI), the somatization subscale of Symptom Checklist 90-Revised (SCL-90-R), and the 7-item Generalized Anxiety Disorder scale (GAD-7).Results: Compared with the general public, medical staff had a higher incidence of anxiety (45.5% vs 32.4%). The incidence of insomnia in anxious participants was 52.7% in medical staff and 44.6% in the general public, and the difference was significant (p < 0.05). The GAD-7 score and somatization subscore of the SCI-90 were independently associated with insomnia among anxiety participants in both groups (all p < 0.001).Conclusion: Our findings suggest that during the epidemic period of COVID-19, medical staff experienced more anxiety and anxiety with insomnia. Somatization, anxiety and insomnia are highly correlated among medical staff and the general public.Keywords: somatic symptom, anxiety, insomnia, medical staff, COVID-19

Mingcheng Huang,1,* Keping Wu,1,* Shan Zeng,2,* Wenfen Liu,1 Tianjiao Cui,1 Zhiqing Chen,1 Lian Lin,1 Dongying Chen,3 Hui Ouyang1 1Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, ShenZhen, Guandong, People’s Republic of China; 2Department of Rheumatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guandong, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongying Chen; Hui Ouyang Email chendy3@mail.sysu.edu.cn; ouyh23@mail.sysu.edu.cnBackground: The aggressive phenotype of fibroblast-like synoviocytes (FLSs) is essential in the synovitis and bone destruction in rheumatoid arthritis (RA). Punicalagin is a natural polyphenol extracted in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumor properties suggesting it may be a potent drug for RA therapy. However, there is paucity of information on its effect in RA.Objective: To investigate the effects of punicalagin on synovial inflammation and bone destruction in RA.Methods: FLSs were isolated from synovial tissue of RA patients. The mRNA levels were evaluated by quantitative real-time PCR. Western blot was used for protein level measurements. The secretion of pro-inflammatory cytokines and metalloproteinases (MMPs) was detected by ELISA assays. Edu staining assays were carried out to investigate the proliferation of FLSs. Cell migration was assessed by Boyden chambers, wound scratch assays and F-actin staining in vitro. The intracellular translocation of nuclear factor kappa B (NF-κB) was investigated using immunofluorescence. The effects of punicalagin in vivo were measured by using collagen-induced arthritis (CIA) mice.Results: Punicalagin treatments significantly reduced the TNF-α induced expressions of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17A) and MMPs (MMP-1 and MMP-13) of RA FLSs. Punicalagin also suppressed the proliferation and migration of RA FLSs. Moreover, punicalagin (50mg/kg/d) alleviated arthritis severity and bone destruction, and decreased serum IL-6 and TNF-α in CIA mice. Further mechanism studies indicated that punicalagin blocked NF-κB activation via suppressing phosphorylation of IKK and IkBα, and preventing the translocation of 65.Conclusion: Our findings suggested that punicalagin might be one of natural therapeutic compounds for relieving RA progress via suppressing FLSs inflammation and migration through modulating NF-κB pathways.Keywords: rheumatoid arthritis, punicalagin, fibroblast-like synoviocytes, migration, pro-inflammatory cytokines

Qiuzhen Lin,1– 4 Ousseina Bonkano,1– 5 Keke Wu,1– 4 Qiming Liu,1– 4 Toure Ali Ibrahim,5 Ling Liu1– 4 1Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, People’s Republic of China; 3Modern Cardiovascular Disease Clinical Technology Research Center of Hunan Province, Changsha, People’s Republic of China; 4Cardiovascular Disease Research Center of Hunan Province, Changsha, Hunan, 410011, People’s Republic of China; 5Department of Cardiovascular and Internal Medicine Niger, Niamey Amirou Boubacar Diallo National Hospital, Abdou Moumouni University, Niamey, NigerCorrespondence: Ling LiuDepartment of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, #139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaFax +86-73185295407Email feliuling@csu.edu.cnBackground: Atypical chest pain in some outpatients could derive from mental disorders. It is necessary for them to have a preliminary emotional assessment in the outpatient department of Cardiology before psychiatric outpatient visits.Methods: This study included 122 Chinese outpatients with atypical chest pain in the department of Cardiology. They accepted routine examinations, including treadmill test, and were judged by the three-question method as highly likely to have emotional disorders. Then, a standard questionnaire package containing the Chinese version of the seven-item scale for General Anxiety Disorder (GAD-7), Self-rating Anxiety Scale (SAS), the nine-item Patient Health Questionnaire (PHQ-9) and Self-rating Depression Scale (SDS) was administered to evaluate anxiety and depression.Results: The percentages of anxiety evaluated by GAD-7 and SAS were 62.3% and 26.2%, respectively. Analogously, the assessment by PHQ-9 showed a significantly higher percentage of depression than that by SDS (61.5% vs 29.5%) (P < 0.05). Kappa analysis showed that the consistency between GAD-7 and SAS, or that between PHQ-9 and SDS was not very good. About 73% outpatients suffered from emotional disorders, presenting as anxiety/depression evaluated by GAD-7 and PHQ-9. Furthermore, sleep disorders accounted for more than 80% of patients with mental disorders. Finally, the suicidal tendency of depression patients was about 17% that should not be ignored.Conclusion: Compared with SAS and SDS, GAD-7 and PHQ-9 detected more participants with emotional disorders in the Chinese outpatients with atypical chest pain, indicating that GAD-7 and PHQ-9 could be briefly well-validated tools to screen emotional disorders in the outpatient department of Cardiology before psychiatric visits.Keywords: depression, anxiety, screen, atypical chest pain

Xiao Xiao,1 Zhiwen Tan,2 Min Jia,3 Xiaoli Zhou,1 Kemei Wu,3 Yanbing Ding,1 Wenjing Li3 1Department of Encephalopathy, Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Institute of Traditional Chinese Medicine), Wuhan City, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of China; 3Department of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of ChinaCorrespondence: Wenjing LiDepartment of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Avenue, Enshi, 445000, Hubei Province, People’s Republic of ChinaTel +86 13597789520Fax +86 718 8263395Email 13597789520@163.comBackground: Parkinson’s disease (PD) is a prevalent neurodegenerative disease. Long noncoding RNA small molecule RNA host gene 1 (SNHG1) has been reported to play critical roles in Parkinson’s disease (PD) progression. The study aimed to further elucidate the mechanism of SNHG1 in PD pathogenesis.Methods: The levels of SNHG1, miR-125b-5p and mitogen-activated protein kinase 1 (MAPK1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell viability and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of Caspase-3 or Caspase-9 was measured using a Caspase-3 or Caspase-9 Assay Kit. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were gauged by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to identify the relationship between miR-125b-5p and SNHG1 or MAPK1. The MPTP-induced PD mouse was used as an in vivo model of PD and MPP+-treated SK-N-SH and MN9D cells were used as in vitro models of PD.Results: SNHG1 and MAPK1 were significantly up-regulated while miR-125b-5p was down-regulated in the MPTP-induced PD mouse model and MPP+-induced PD cell models. SNHG1 silence or miR-125b-5p overexpression protected against MPP+-evoked apoptosis, oxidative stress and inflammation in SK-N-SH and MN9D cells. Moreover, SNHG1 acted as a molecular sponge of miR-125b-5p, and the protective impact of SNHG1 silence on MPP+-evoked cell damage was reversed by miR-125b-5p inhibition. Furthermore, MAPK1 was a functional target of miR-125b-5p and its overexpression attenuated the effects of miR-125b-5p restoration in MPP+-triggered cell injury. In addition, the behavioral changes in MPTP-induced PD mouse in vivo model were relieved by SNHG1 silence.Conclusion: SNHG1 knockdown exerted neuroprotective effects in MPP+-evoked cytotoxicity through regulating the miR-125b-5p/MAPK1 axis both in human and mouse PD cell models, highlighting a possible target for PD therapy.Keywords: Parkinson’s disease, SNHG1, miR-125b-5p, MAPK1, cytotoxicity

Guangzhen Qu, Dong Wang, Weiyu Xu, Kai Wu, Wei Guo Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Wei Guo Email guowei@ccmu.edu.cnBackground: Although many studies have confirmed the correlation between inflammation-based or nutritional markers and postoperative complications in patients undergoing colorectal cancer surgery, their correlation after undergoing pancreaticoduodenectomy (PD) remains unclear.Methods: We retrospectively reviewed the clinical data of patients who underwent PD in Beijing Friendship hospital between 2018 and 2020. Univariate analysis, multivariate analysis, and receiver operating characteristic curve (ROC) were performed. We assessed the preoperative modified Glasgow Prognostic Score (mGPS), C-reactive protein/albumin ratio (CAR), C-reactive protein (CRP), postoperative Glasgow Prognostic Score (poGPS), CRP on postoperative day 3 (POD3) and CAR on POD3. The optimal cut-off values were determined by performing logistic regression analysis.Results: Of the 172 patients who underwent PD, 74 (43.0%) developed complications, of whom 27 (15.7%) had clinically relevant postoperative pancreatic fistulas (CR-POPF) and 36 (20.9%) had positive drainage fluid cultures. Elevated levels of preoperative mGPS (P< 0.001), poGPS (P< 0.001), CRP (P< 0.001) and CAR on POD3 were associated with postoperative complications. CRP on POD3 (OR=1.028, 95% CI=1.017– 1.039, P< 0.001) was an independent risk factor associated with postoperative complications in both univariate and multivariate analyses. CAR on POD 3 showed the largest area under the curve (AUC=0.883, P< 0.001). Compared with CAR< 4.86, CAR ≥ 4.86 on POD3 was associated with a higher probability of complications (85.5% vs 14.6%, P< 0.001), especially CR-POPF (33.3% vs 4.9%, P< 0.001), intra-abdominal infection (36.2% vs 10.7%, P< 0.001) with a positive drainage fluid culture.Conclusion: CAR, an inflammatory response-based marker, can effectively predict early postoperative complications in patients undergone PD.Keywords: C-reactive protein, albumin, Glasgow Prognostic Score, pancreaticoduodenectomy, complications prediction

Kexin Wu,1,2 Zhencheng Xiong,3,4 Yasuo Ding1,2 1Postgraduate School, Dalian Medical University, Dalian, People’s Republic of China; 2Department of Neurosurgery, Taizhou People’s Hospital, Taizhou, People’s Republic of China; 3Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China; 4Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yasuo DingDepartment of Neurosurgery, Taizhou People’s Hospital, Taizhou, People’s Republic of ChinaEmail doctordys@126.comAbstract: Thrombectomy is superior to intravenous thrombolysis for patients with large vessel occlusion in acute ischemic stroke, but nearly half of the patients still experience poor functional outcomes. Elevated blood pressure (BP) is widely observed in acute ischemic stroke, and BP may be one of the modifiable parameters that can potentially influence the outcomes; however, only observational studies exist to support current guidelines, and the recommended range for BP after thrombectomy is too wide to meet the clinical requirement. Randomized controlled trials are therefore needed to better understand the relationship between BP and outcomes after thrombectomy. In this review, we introduce the current management of BP after thrombectomy and several aspects of postthrombectomy BP management that should be resolved in future clinical trials.Keywords: acute ischemic stroke, mechanical thrombectomy, blood pressure, hypertension, outcomes

Ruthenium nanoparticles stabilised by an amine‐modified Ordered Mesoporous Silica Immobilized Ionic Liquid (OMSIIL) are efficient catalysts for the partial reduction of nitrobenzene to hydrazobenzene with 100 % selectivity as well as the complete reduction to aniline. High selectivity for the partial reduction of nitrobenzene to hydrazobenzene was obtained when the reaction was conducted in ethanol with 0.5 mol% catalyst and NaBH4 as the hydrogen donor whereas aniline was obtained as the sole product in water when dimethylamine borane (DMAB) was used as the hydrogen donor. Interestingly, while a range of electron poor nitroarenes were reduced to the corresponding hydrazoarene with high selectivities and good conversions, nitroarenes substituted with electron donating groups resulted in complete reduction to the aniline. Composition‐time profiles suggest that reductions conducted in ethanol with sodium borohydride occur via the condensation pathway while those conducted in water using dimethylamine borane as the hydrogen source may well go via the direct pathway. This is the first example of the selective reduction of nitrobenzene to hydrazobenzene using a ruthenium nanoparticle‐based catalyst and the initial TOF of 320 mol nitrobenzene converted mol Ru−1 h−1 for the partial reduction of nitrobenzene to hydrazobenzene is markedly higher than previous literature reports. A study of the catalyst performance as a function of the surface modification revealed that each component has a direct and dramatic effect on the efficacy as RuNPs stabilised by COK‐12 modified with imidazolium‐based ionic liquid and a primary amine gave the highest conversion while selective removal of either component or replacement of the primary amine with a tertiary amine resulted in a marked reduction in efficiency. [ABSTRACT FROM AUTHOR]

To investigate the perforating characteristics of Zr-based bulk metallic glass fragments against thin steel target, ballistic experiments were carried out to measure ballistic the limit velocities of fragments perforating against different thicknesses of targets. The fragments were driven by a 57 mm one-stage light gas gun to impact the thin steel target. The numerical model of Zr-based bulk metallic glass fragments perforating against thin steel target was established using Autodyn2D commercial software, and the perforating process and perforating mechanism were analyzed by numerical simulation. The semi-empirical model to predict the ballistic limit velocity was fitted. An energy model for calculating the residual velocity of a fragment was derived based on the conservation of energy. The theoretical results of the semi-empirical model and the energy model are in good agreement with experiment results and simulation results. And the energy model has good applicability without fitting the parameters for different target thicknesses. [ABSTRACT FROM AUTHOR]

We have investigated space and astrophysical phenomena in nonrelativistic laboratory plasmas with long high-power lasers, such as collisionless shocks and magnetic reconnections, and have been exploring relativistic regimes with intense short pulse lasers, such as energetic ion acceleration using large-area suspended graphene. Increasing the intensity and repetition rate of the intense lasers, we have to handle large amounts of data from the experiments as well as the control parameters of laser beamlines. Artificial intelligence (AI) such as machine learning and neural networks may play essential roles in optimizing the laser and target conditions for efficient laser ion acceleration. Implementing AI into the laser system in mind, as the first step, we are introducing machine learning in ion etch pit analyses detected on plastic nuclear track detectors. Convolutional neural networks allow us to analyze big ion etch pit data with high precision and recall. We introduce one of the applications of laser-driven ion beams using AI to reconstruct vector electric and magnetic fields in laser-produced turbulent plasmas in three dimensions. [ABSTRACT FROM AUTHOR]

Hehua Li,1,* Yaping Zhang,2,3,* Honggang Wang,4 Jing Liang,4 Yongjie Zhou,2,3 Yuanyuan Huang,1 Tianyi Zhai,1 Qiong Yang,1 Mingzhe Yang,1 Yuping Ning,1,5 Hongbo He,1 Kai Wu,6 Fengjuan Chen,7 Fengchun Wu,1,5,8 Xiangyang Zhang1,9 1Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Research Center for Psychological and Health Sciences, China University of Geosciences, Wuhan, People’s Republic of China; 3Affiliated Wuhan Mental Health Center, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, People’s Republic of China; 4Qingdao Mental Health Center, Qingdao University, Qingdao, People’s Republic of China; 5The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 6Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology (scUT), Guangzhou, People’s Republic of China; 7Department of Medical, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 8Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 9CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengchun WuInstitute of Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Liwan District, Guangzhou 510370, People’s Republic of ChinaEmail 13580380071@163.comXiangyang ZhangInstitute of Psychology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, People’s Republic of ChinaEmail zhangxy@psych.ac.cnBackground: The pandemic of coronavirus disease 2019 (COVID-19) has posed a threat to global health. Increasing studies have shown that the mental health status of health professionals is very poor during the COVID-19 epidemic. At present, the relationship between somatic symptoms and symptoms of anxiety of health professionals during the COVID-19 has not been reported. The purpose of this study was to explore the frequency of somatic symptoms and its related factors in health professionals with symptoms of anxiety during COVID-19 in China.Methods: A total of 606 health professionals were assessed online with the Chinese version of the 7-item Generalized Anxiety Disorder (GAD-7) scale, 7-item Insomnia Severity Index (ISI) and the somatization subscale of Symptom Checklist 90 (SCL-90).Results: The percentage of symptoms of anxiety, somatic symptoms and insomnia in all health professionals was 45.4%, 12.0%, and 32%, respectively. The frequency of somatic symptoms in health professionals with symptoms of anxiety was 22.9%. The SCL-90 somatization subscale score was significantly positively correlated with history of somatic diseases, GAD-7 score and ISI score in participants with symptoms of anxiety.Conclusion: During the COVID-19, symptoms of anxiety, insomnia, and somatic symptoms are commonly observed in health professionals. Insomnia and symptoms of anxiety are independently associated with somatic symptoms of health professionals with symptoms of anxiety.Keywords: somatic symptoms, coronavirus disease 2019, health professionals, frequency, related factors

Hua Ye,1,2 Wende Li,3 Kefeng Wu,1,2 Yi Liu,1,2 Yingnian Lv,1,2 Yuzhen Zhu,1,2 Hui Luo,1,2 Liao Cui1,2 1Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Institute of Marine Biomedical Research, Guangdong Medical University, Zhanjiang, People’s Republic of China; 3Guangdong Laboratory Animals Monitoring Institute, Zhanjiang, Guangdong 524023, People’s Republic of ChinaCorrespondence: Hua YeGuangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, 2 Wenming East Road, Zhanjiang 524023 Guangdong Province, People’s Republic of ChinaEmail yehua339@hotmail.comIntroduction: Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) are pivotal regulators involved in the pathogenesis of cancer; however, the molecular mechanism of LINC00339 in colorectal cancer (CRC) remains unclear.Methods: The quantitative real-time polymerase chain reaction for the expression of LINC00339 and miR-378a-3p and Western blots for MED19 were performed. A dual-luciferase assay was used to investigate the interaction between LIN00339 and miR-378a-3p, as well as between miR-378a-3p and MED19. Cell proliferation was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and 5-ethynyl-2ʹ-deoxyuridine (EdU) assay. The cell cycle was analyzed by propidium iodide staining followed by flow cytometry analysis. The wound-healing and transwell invasion assays were used to evaluate cell migration and invasion.Results: The expression of LINC00339 was significantly upregulated in CRC cells and tissues, and high LINC00339 expression indicated an advanced tumor stage. Further experiments demonstrated that SP1 activated LINC00339 expression by binding to its promoter region. Luciferase activity and RNA pull-down assays demonstrated a direct interaction between LINC00339 and miR-378a-3p. miR-378a-3p expression was decreased in CRC samples and negatively correlated with LINC00339 expression in tumors. Gain- and loss-of-function assays indicated that LINC00339 contributed to cell proliferation, cell cycle progression, migration, and invasion, while miR-378a-3p reversed these effects. Furthermore, cotransfection of wild-type MED19 3ʹ-UTR reporters and miR-378a-3p significantly reduced luciferase activity. MED19 mRNA and protein expression was inhibited and enhanced by miR-378a-3p and LINC00339, respectively. MED19 overexpression reversed the effect of miR-378a-3p on cellular processes. Moreover, LINC00339 promoted tumor growth in vivo and induced epithelial–mesenchymal transition (EMT) and activated the Wnt/β-catenin signaling pathway in cells.Conclusion: Our findings demonstrate the regulatory role of the SP1/LINC00339/miR-378a-3p/MED19 axis in CRC tumorigenesis and provide novel insight into the molecular mechanism underlying CRC.Keywords: LINC00339, ceRNA, miR-378a-3p, MED19, colorectal cancer

Wei W, Mo X, Yan L, et al. Cancer Manag Res. 2020;12:15—30. The authors have advised there are errors in Figures 3 and 5. Figure 3, page 24. The key in parts B and C have the labels of “823-Si-circRNA_0005039” and “7901-SicircRNA_0005039” which should read “823-SicircRNA_104433” and “7901-Si-circRNA_104433”, respectively. The correct Figure 3 is shown below. Figure 5, page 26. The Y axis in part E has the label of “The relative expression of miR-593-5p” which should read “The relative expression of miR-497-5p”. The correct Figure 5 is shown below. Read the original article

Jian-hua Zhou,1,* Zhi-xian Yao,2,* Zhong Zheng,2,* Jun Yang,1 Rui Wang,1 Shi-jie Fu,1 Xu-feng Pan,1 Zhi-hong Liu,2 Ke Wu2 1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-hua Zhou; Ke Wu Email drzhihuazhou@163.com; doctorwuke@sjtu.edu.cnBackground: The immune environment of lung cancer is complex, and the critical immune factors that promote lung cancer progression need to be explored. Granulocytic myeloid-derived suppressor cells (G-MDSCs) are regarded as immune suppressing cells. However, they also promote tumor progression through other ways, which needs to be explored further. Therefore, we sought to study the regulatory mechanisms underlying the cancer promoting function of G-MDSCs in lung cancer.Methods: G-MDSCs were isolated from lung cancer tissues using flow cytometry. Exosomes were separated from the G-MDSCs supernatant by ultracentrifugation and verified using flow cytometry, Western blot, and transmission electron microscopy (TEM). RNA sequencing was used to identify the differential miRNAs and genes. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results. The proliferation rate was assessed using the CCK-8 assay. Lentiviral vectors were used to alter the expression of the miRNAs and genes to analyze their effects on lung cancer progression.Results: G-MDSCs secreted more exosomes in the lung cancer tissues, which promoted cancer progression by accelerating proliferation. Micro RNA-143-3p (miR-143-3p) increased in G-MDSCs derived exosomes and downregulated integral membrane protein 2B (ITM2B) by targeting the 3ʹ-untranslated region (UTR) region. Overexpression of miR-143-3p enhanced proliferation by inhibiting transcription of ITM2B to activate the PI3K/Akt signaling pathway, which can be blocked by deguelin. This phenomenon was further confirmed by accelerated tumor growth and worse prognosis in mice.Conclusion: The key findings of this study highlight the potential of the G-MDSC-derived exosomes and the miR-143-3p/ITM2B axis as therapeutic targets and clinical indicators of lung cancer.Keywords: G-MDSCs, exosomes, miRNA-143-3p, ITM2B, proliferation, lung cancer

Kai Wu,1,* Qiong Feng,2,* Liang Li,1 Yanfei Xiong,3 Shihong Liu,4 Jie Liu,1 Qing Wu1 1Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang 300006, People’s Republic of China; 2Nursing School, Nanchang University, Nanchang 300006, People’s Republic of China; 3Department of Orthopedics, Jingan Hospital, Yichun 330600, People’s Republic of China; 4Jingan Hospital of Traditional Chinese Medicine, Yichun 330600, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Wu Email wuqing18186@126.comIntroduction: The long-noncoding RNA PCAT6 plays an important regulatory role in the development of several cancers. However, the expression pattern and underlying mechanisms of PCAT6 in osteosarcoma (OS) are yet unknown.Methods: We used real-time PCR to measure PCAT6 expression in 106 tumor pairs and corresponding non-tumor tissues from OS patients. Statistical analyses were applied to evaluate the prognostic value and associations of PCAT6 expression with clinical parameters. Furthermore, the PCAT6 was silenced with siRNA in OS cells. Moreover, phenotype of PCAT6 silenced OS cells was measured using colony formation, CCK-8, cell migration and invasion assay. Finally, the molecular mechanism of PCAT6/miR-143-3p/ZEB1 axis in OS progression was explored.Results: The expression level of PCAT6 in OS tissues was significantly elevated as compared with that in the adjacent normal bone tissues and that high PCAT6 expression closely correlated with the malignant phenotype and poor survival among patients with OS. Multivariate analyses revealed PCAT6 overexpression as an independent prognostic factor for the poor outcome of patients with OS. Functional assay results demonstrated that the knockdown of PCAT6 expression notably suppressed the proliferation, migration, and invasion of OS cells. An elevated PCAT6 level aggravated the malignant phenotype of OS cells via ZEB1 expression upregulation. Mechanistic studies revealed that PCAT6 could sponge endogenous miR-143-3p and inhibit its activity, resulting in an increase in ZEB1 level. Finally, we demonstrated that the tumour-promoting role of PCAT6 in OS was dependent on the regulation of the miR-143-3p/ZEB1 axis.Conclusion: These findings highlight the potential role of PCAT6, which could serve as a valuable prognostic indicator for patients with OS.Keywords: osteosarcoma, PCAT6, ZEB1, miR-143-3p

Limin Zhou,1,* Haojun Wu,2,* Xiang Gao,2,* Xiaoyan Zheng,1 Hang Chen,2 Hailong Li,1 Jun Peng,1 Weichong Liang,1 Wenxing Wang,1 Zuocheng Qiu,3 Anjaneyulu Udduttula,3 Kefeng Wu,1 Lin Li,4 Yuyu Liu,1 Yanzhi Liu1,3 1Guangdong Key Laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong 524023, People’s Republic of China; 2Department of Orthopaedics, Stem Cell Research and Cellular Therapy Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, People’s Republic of China; 3Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China; 4School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence : Yanzhi Liu Email liuyanzhi02@163.comYuyu Liu Email liuyuyu77@163.comAim: Nonunion is a major complication in fracture repair and remains a challenge in orthopaedics and trauma surgery. In this study, we aimed to evaluate the effectiveness of treatment of nonunion with a large radial defect using a bone-targeting liposome-encapsulated salvianic acid A (SAA-BTL)-incorporated collagen sponge and further elucidate whether the effects were closely related to histone deacetylase 3 (HDAC 3)-mediated endochondral ossification in nonunion healing process.Methods: Fifteen New Zealand female rabbits were randomly divided into three groups. Segmental radius critical size defects (15 mm) were created via surgery on both the forelimbs of the rabbits. The SAA-BTL/SAA/saline-incorporated collagen sponges were implanted into the defects in the three groups, respectively, for four weeks of treatment. X-ray imaging, micro-computed tomography (CT) analysis, histology, and immunofluorescence analysis (HDAC3, collagen II, VEGFA, and osteocalcin) were performed to determine the effects of the treatments. In addition, a short interfering RNA was applied to induce HDAC3 knockdown in the chondrogenic cell line ATDC5 to investigate the roles of HDAC3 and SAA intervention in endochondral ossification in nonunion healing.Results: X-ray imaging and micro-CT results revealed that SAA-BTL-incorporated collagen sponges significantly stimulated bone formation in the nonunion defect rabbit model. Furthermore, immunofluorescence double staining and histology analysis confirmed that SAA-BTL significantly increased the expression of P-HDAC3, collagen II, RUNX2, VEGFA, and osteocalcin in vivo; accelerated endochondral ossification turnover from cartilage to bone; and promoted long bone healing of nonunion defects. ATDC5 cells knocked down for HDAC3 showed significantly decreased expression of HDAC3, which resulted in reduced expression of chondrogenesis, osteogenesis, and angiogenesis biomarker genes (Sox9, Col10a1, VEGFA, RUNX2, and Col1a1), and increased expression of extracellular matrix degradation marker (MMP13). SAA treatment reversed these effects in the HDAC3 knockdown cell model.Conclusion: SAA-BTL can improve nonunion healing through the regulation of HDAC3-mediated endochondral ossification.Keywords: nonunion, fracture, HDAC3, endochondral ossification, bone-targeting liposome, salvianic acid A