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Junnan Li,1– 4,* Wenjuan Peng,1– 4,* Yuting Zhang,1– 4 Shunai Liu,1– 4 Ming Han,1– 4 Rui Song,2,4 Yuanyuan Zhang,1– 4 Ronghua Jin,1– 4 Xi Wang1– 4 1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Beijing Institute of Infectious Disease, Beijing, 100015, People’s Republic of China; 4National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ronghua Jin; Xi Wang, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email ronghuajin@ccmu.edu.cn; xiwang@ccmu.edu.cnBackground: To compare the clinical characteristics of symptoms and laboratory findings across SARS-CoV-2 variants (Wild-type, Alpha, Delta, Omicron) and assess the effectiveness of COVID-19 vaccines in preventing symptoms and laboratory abnormalities.Methods: We conducted a retrospective cohort study of individuals with SARS-CoV-2 infection at Beijing Ditan Hospital, Capital Medical University. Patients were grouped by the SARS-CoV-2 variant (Wild-type, Alpha, Delta, Omicron) based on whole-genome sequencing. Thirteen symptoms and 22 laboratory indices were compared across variants, and Omicron patients were further analyzed by vaccination status with generalized estimating equations (GEE) model.Results: One thousand four hundred and thirteen participants were included for the analysis as following: Wild-type group (N=322), Alpha group (N=67), Delta group (N=98), and Omicron group (N=926). Omicron patients showed the highest proportion (30.1%) of respiratory symptoms across groups. Patients displayed normal laboratory manifestation, except for inflammatory markers, coagulation function index and glucose. Meanwhile, the Omicron variant was featured by higher inflammatory biomarkers (serum amyloid A protein [SAA] and C-reactive protein [CRP]). In addition, Omicron patients with three or more vaccine doses had fewer symptoms and higher values of SAA and CRP compared to those with fewer than three doses. Results of GEE showed, when compared with ≤ 1 vaccine dose, red blood cell count, white blood cell count, neutrophil count, platelet count, haemoglobin, and C-reactive protein in patients with ≥ 3 doses of vaccine significantly increased; while aspartic transaminase, creatine kinase, blood urea nitrogen, activated partial thromboplastin time, prothrombin time and thrombin time dramatically decreased, respectively.Conclusion: Omicron variant resulted in abnormal inflammatory response. Individuals with three or more vaccine doses are more likely to experience fewer symptoms and have stronger protection against the virus. This study highlights key differences in symptom onset and laboratory profiles across SARS-CoV-2 variants, reinforcing the importance of three vaccine doses in providing strong protection against the Omicron variant.Keywords: COVID-19, clinical characteristics, vaccines, variants

Xianjun Xiao,1,&ast; Peiwen Xue,1,&ast; Xiangyun Yan,2,&ast; Yanqiu Li,2,&ast; Yunzhou Shi,2 Haiyan Qin,2 Di Qin,2 Wei Cao,2 Zihao Zou,2 Lu Wang,2 Rongjiang Jin,1 Ying Li,2 Junpeng Yao,2 Juan Li1,3 1School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 3Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, Sichuan, 611135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Yao; Juan Li, Email yjp@cdutcm.edu.cn; 785939016@qq.comBackground: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research.Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness.Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of − 22%, − 24.9%, and − 24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of − 21.7% and − 23.7%, respectively.Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs’ potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.Keywords: urticaria, short-chain fatty acids, gut microbiota, gut-skin axis, Mendelian randomization

Yiqi Xiong,1,&ast; Wenying Qiao,2,3,&ast; Tingting Mei,1,&ast; Kang Li,4 Ronghua Jin,2,3 Yonghong Zhang1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Changping Laboratory, Beijing, 102206, People’s Republic of China; 4Research center for biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Zhang, Interventional therapy center for oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, Tel +86-13810108505, Email zhangyh@ccmu.edu.cn Ronghua Jin, National center for infectious diseases, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, Tel +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: The aim of our study was to investigate the relationship between albumin-bilirubin (ALBI) grade and recurrence in patients who underwent TACE sequential ablation. We developed and validated a nomogram to predict low levels of ALBI patients’ recurrence.Patients and Methods: A total of 880 patients undergoing TACE combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were retrospectively enrolled, including 415 patients with L-ALBI (≤-2.6) and 465 patients with high levels (>-2.6) of ALBI (H-ALBI). L-ALBI patients were randomized in a 7:3 ratio into the training cohort (N=289) and validation cohort (N=126). Multivariate Cox regression followed by random survival forest was carried out to identify independent risk factors for prediction nomogram construction. An examination of nomogram accuracy was performed using the C-index, receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) curves. According to the nomogram, the patients were divided into low-risk, intermediate-risk, and high-risk groups. Kaplan-Meier (KM) curves were applied to compare the difference in recurrence-free survival (RFS) among the three groups.Results: The median RFS in L-ALBI patients was significantly longer than the H-ALBI patients (40.8m vs 20.1m, HR:1.71, 95% CI:1.44– 2.04, P< 0.0001). The nomogram was composed of five variables, such as age, Barcelona Clinic Liver Cancer (BCLC) stage, globulin, gamma-glutamyl transferase to lymphocyte ratio (GLR), and international normalized ratio (INR). The C-index (0.722 and 0.731) and 1-, 3-, and 5-year AUCs (0.725, 0.803, 0.870, and 0.764, 0.816, 0.798) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves demonstrated good consistency and good clinical utility. There were significant differences in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).Conclusion: L-ALBI Patients who underwent TACE combined ablation had better recurrence-free survival than patients with H-ALBI. The nomogram developed and validated in our study had good predictive ability in recurrence for L-ALBI patients.Keywords: hepatocellular carcinoma, HCC, ablation, nomogram, recurrence, albumin-bilirubin, ALBI

Wenying Qiao,1– 3,&ast; Yiqi Xiong,1,&ast; Kang Li,4 Ronghua Jin,2,3 Yonghong Zhang1,5 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Changping Laboratory, Beijing, 102206, People’s Republic of China; 4Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Beijing Research Center for Respiratory Infectious Diseases, Beijing, 100006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Zhang, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel +86-13810108505, Email zhangyh@ccmu.edu.cn Ronghua Jin, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, People’s Republic of China, Tel +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence.Patients and Methods: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥ 30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram.Results: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P< 0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).Conclusion: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.Keywords: hepatocellular carcinoma, HCC, transcatheter arterial chemoembolization, TACE, ablation, nomogram, recurrence

Xiaomeng Tang,1– 4,&ast; Qi Wang,2– 4,&ast; Ronghua Jin,2– 4 Caixia Hu1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caixia Hu, Interventional therapy center for oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13811395702, Email hucaixia1217@126.com Ronghua Jin, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Early diagnosis is crucial for improving prognosis. Elderly HCC patients often have underlying liver diseases such as chronic hepatitis and cirrhosis, leading to impaired liver function and suboptimal liver reserve. Radiofrequency ablation (RFA) has rapidly become one of the most important methods for treating early-stage hepatocellular carcinoma (EHCC) due to its advantages, including minimal trauma, short operation time, less intraoperative bleeding, quick postoperative recovery, cost-effectiveness, and few postoperative-complications. However, the prognostic model for early recurrence after local ablation in elderly EHCC patients has not been widely evaluated. We have developed a prognostic model for the recurrence of local RFA in elderly EHCC patients. This is expected to provide a new early warning system for preventing early recurrence in elderly EHCC patients, prolonging patient’s life, and improving overall quality of life.Methods: In this study, we included 661 EHCC patients who underwent local ablation, dividing them into a Primary cohort and a Validation cohort in a 7:3 ratio. We characterized the cohorts and utilized the primary cohort to develop a prognostic nomogram model for recurrence after local ablation in elderly EHCC patients. Additionally, the validation cohort was used to assess the potential of the nomogram as a non-invasive biomarker for post-ablation recurrence in EHCC.Results: The user-friendly nomogram incorporates common clinical variables including gender, BCLC stage, tumor number, tumor size, red blood cell (RBC), gamma-glutamyl transferase (GGT), and prothrombin time activity (PTA). The nomogram constructed using the identified seven variables exhibits robust discriminatory capabilities, favorable predictive performance, and noteworthy clinical utility.Conclusion: We developed a user-friendly nomogram based on the BCLC stage classification, which may provide prognostic assessments for elderly EHCC patients at 1, 3, and 5 years post-RFA.Keywords: hepatocellular carcinoma, elderly, radiofrequency ablation, EHCC, relapse, prognostic model

Wenying Qiao,1– 5,&ast; Shugui Sheng,1– 3,&ast; Junnan Li,1– 3,&ast; Ronghua Jin,1– 4 Caixia Hu5 1Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Changping Laboratory, Beijing, People’s Republic of China; 5Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Jin, Beijing Key Laboratory of Emerging Infectious Diseases, BeijingDitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ronghuajin@ccmu.edu.cn Caixia Hu, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China, Email hucaixia1217@126.comPurpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS).Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell’s concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes.Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification.Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.Keywords: hepatocellular carcinoma, HCC, nomogram, LASSO regression, random survival forest, RSF, overall survival, OS

Wenying Qiao,1– 3,&ast; Jiashuo Li,2,&ast; Qi Wang,2,&ast; Ronghua Jin,2,3 Honghai Zhang1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Di’tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Changping Laboratory, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Jin, Beijing Di’tan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cn Honghai Zhang, Interventional therapy center for oncology, Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13260398697, Email haiyuer@yeah.netPurpose: Although alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) have a certain predictive ability for the prognosis of hepatocellular carcinoma (HCC), there are still some cases of aggressive recurrence among patients with AFP and DCP double-negative HCC (DNHC) after local ablation. However, prediction models to forecast the prognosis of DNHC patients are still lacking. Thus, this retrospective study aims to explore the prognostic factors in DNHC patients and develop a nomogram to predict recurrence.Patients and methods: 493 DNHC patients who underwent the local ablation at Beijing You’an Hospital between January 1, 2014, and December 31, 2022, were enrolled. A part that was admitted from January 1, 2014, to December 31, 2018, was designated to the training cohort (n = 307); others from January 1, 2019, to December 31, 2022, were allocated to the validation cohort (n = 186). Lasso regression and Cox regression were employed with the aim of screening risk factors and developing the nomogram. The nomogram outcome was assessed by discrimination, calibration, and decision curve analysis (DCA).Results: Independent prognostic factors selected by Lasso-Cox analysis included age, tumor size, tumor number, and gamma-glutamyl transferase. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training and validation groups (0.738, 0.742, 0.836, and 0.758, 0.821) exhibited the excellent predicted outcome of the nomogram. Calibration plots and DCA plots suggest desirable calibration performance and clinical utility. Patients were stratified into three risk groups by means of the nomogram: low-risk, intermediate-risk, and high-risk, respectively. There exists an obvious distinction in recurrence-free survival (RFS) among three groups (p< 0.0001).Conclusion: In conclusion, we established and validated a nomogram for DNHC patients who received local ablation. The nomogram showed excellent predictive power for the recurrence of HCC and could contribute to guiding clinical decisions.Keywords: hepatocellular carcinoma, nomogram, prognosis, local ablation, alpha-fetoprotein, des-gamma-carboxyprothrombin

Wenying Qiao,1– 3,&ast; Zibo Fan,2,&ast; Qi Wang,2,&ast; Ronghua Jin,2,3 Caixia Hu1 1Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Changping Laboratory, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caixia HuInterventional Therapy Center for Oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13811395702, Email hucaixia1217@126.comRonghua JinBeijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: We first aimed to compare the prognostic difference between the application of Contrast-enhanced computed tomography (CECT) and Non-enhanced computed tomography (NECT) in hepatocellular carcinoma(HCC) patients with early-stage immediately after ablation. We secondly propose to explore the risk factors for recurrence in patients undergoing CECT, and then develop a nomogram.Patients and Methods: Clinical data were collected from 711 patients who received TACE combined with ablation from January 1, 2015, to December 31, 2022, at Beijing Youan Hospital. According to the imaging methods applied after ablation, patients were categorized into the CECT group and the NECT group and then were compared by Kaplan-Meier (KM) curves. Lasso regression is used to screen risk factors for recurrence and the nomogram was plotted. Finally, discrimination, calibration plot, and decision curve analysis (DCA) were used to measure the performance of the nomogram.Results: The KM curve indicates that recurrence-free survival (RFS) was longer in the CECT group than in the NECT group (HR =0.759, 95% CI 0.606– 0.951, P=0.016). Six variables were selected to construct the nomogram. 1-, 3-, and 5-year area under the curves (AUCs) (0.867, 0.731, 0.773 and 0.896, 0.784, 0.773) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the two groups in the training and validation cohorts (P< 0.001).Conclusion: We demonstrated that HCC patients who underwent CECT evaluation after ablation had a better prognosis, making this evaluation method highly recommended for guiding clinical management.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, contrast-enhanced computed tomography, recurrence-free survival, risk factors

Qiuling Tong,1,2 Yu Yao,3 Yanhuo Xia,4 Zhibo Chen,2 Gangze Ji,2 Liuzhu Chen,2 Rujun Jin,2 Wanli Dong1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, Ningbo First Hospital, Ningbo, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Wanli Dong, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +8651265223637, Fax +8657755579318, Email wanlidong23@163.comObjective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA).Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann–Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test.Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores.Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.Keywords: migraine without aura, patent foramen ovale, clinical features, closure treatment

Qian Feng,1 Liang-Jie Tang,2 Ding-Hai Luo,3 Ying Wang,1 Nan Wu,1 Hao Chen,1 Meng-Xia Chen,1 Lei Jiang,4 Rong Jin1,5 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Taizhou, 317000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 5Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Rong JinDepartment of Gastroenterology, Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaEmail jinrongjrjr@163.comLei JiangCentral Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaTel +86-577-55579127Fax +86-577-55578999Email jiangleistone79@163.comPurpose: Hyperuricemia and metabolic syndrome (MetS) have been shown to correlate with prognosis in patients with malignant tumors. The present study evaluated the relationship between preoperative hyperuricemia and MetS in colorectal cancer (CRC) patients and analyzed the effect of this combination on prognosis within 5 years.Patients and Methods: The study enrolled patients who had undergone radical CRC resection at three independent medical centers from January 2014 to December 2016. Patients were preoperatively categorized into four groups, those with hyperuricemia alone (H), those with MetS alone (MS), those with MetS-related hyperuricemia (MSH), and those with neither condition (control [C] group). The disease-free survival (DFS) and overall survival (OS) rates of these four groups were compared.Results: The study population consisted of 1271 patients, with 114, 201, 101, and 855 patients categorized into the H, MS, MSH and C groups, respectively. Preoperative MetS was found to be significantly associated with hyperuricemia (P < 0.001). Multivariate Cox regression analysis showed that MetS-related hyperuricemia (hazard ratio [HR] = 2.728; P < 0.001) and MetS alone (HR = 1.631; P < 0.001) were independent predictors of death, whereas simple hyperuricemia was not (P > 0.1). Relative to the C group, the MSH group had the highest rate of tumor recurrence or metastasis (HR = 5.103, P < 0.001), followed by the MS (HR = 2.231, P < 0.001) group. In contrast, prognosis did not differ significantly in the H and C groups (P > 0.1). MetS was significantly associated with poor prognosis, with MetS-related hyperuricemia resulting in a significantly poorer prognosis. In contrast, hyperuricemia alone had no effect on the long-term prognosis of CRC patients.Conclusion: This study highlights the prognostic importance of MetS-related hyperuricemia on the survival of patients with CRC.Keywords: colorectal cancer, metabolic syndrome, hyperuricemia, prognosis

Xiushuai Shang,1,2 Liaoran Zhang,2 Rilong Jin,1 Hu Yang,1 Hairong Tao2 1Department of Orthopedics Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Hairong TaoShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of ChinaTel +86-13761221256Email doctorthr@163.comObjective: Pain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes’ NGF level, affecting OA pain.Methods: Primary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17β-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels.Results: We found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1β-stimulated or TGF-β 1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07± 0.1 fold).Conclusion: We showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β 1 or IL-1β. MEK-ERK signaling is involved in this process.Keywords: osteoarthritis, pain, estrogens, nerve growth factor

Yubo Wang,1,* Rui Han,1,* Qiushi Wang,2 Jie Zheng,1 Caiyu Lin,1 Conghua Lu,1 Li Li,1 Hengyi Chen,1 Rongbing Jin,3 Yong He1 1Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong HeDepartment of Respiratory Medicine, Daping Hospital, Army Medical University, 10# Changjiangzhilu Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel +86-2368757791Fax +86-2368700970Email heyong@tmmu.edu.cnRongbing JinDepartment of Nuclear Medicine, Daping Hospital, Army Medical University, 10# Changjiangzhilu Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel +86-2368757641Email jinrb99@126.comPurpose: To investigate the potential of maximum standardized uptake value (SUVmax) in predicting epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients.Methods: Clinical data of 311 NSCLC patients who had undergone both EGFR mutation test and 18F-FDG PET/CT scans between January 2013 and December 2017 at our hospital were retrospectively analyzed. Patients were sub-grouped by their origin of SUVmax. Univariate and multivariate analyses were performed to investigate the association between clinical factors and EGFR mutations. Receiver operating characteristic curve (ROC) analysis was performed to confirm the predictive value of clinical factors. In vitro experiments were performed to confirm the correlation between EGFR mutations and glycolysis.Results: EGFR-mutant patients had higher SUVmax than the wild-type patients in both primary tumors and metastases. In the multivariate analysis, SUVmax, gender and histopathologic type were determined as independent predictors of EGFR mutation status for patients whose SUVmax were obtained from the primary tumors; while for patients whose SUVmax were obtained from the metastases, SUVmax, smoking status and histopathologic type were regarded as independent predictors. ROC analysis showed that SUVmax of the primary tumors (cut off > 10.92), not of the metastases, has better predictive value than other clinical factors in predicting EGFR mutation status. The predict performance was improved after combined SUVmax with other independent predictors. In addition, our in vitro experiments demonstrated that lung cancer cells with EGFR mutations have higher aerobic glycolysis level than wild-type cells.Conclusion: SUVmax of the primary tumors has the potential to serve as a biomarker to predict EGFR mutation status in NSCLC patients.Keywords: non-small cell lung cancer, epidermal growth factor receptor, SUVmax, receiver operating characteristic curve

Miaomiao Li,1,* Juntao Hu,2,* Riming Jin,3,* Hongxia Cheng,1 Huaping Chen,4 Limin Li,4 Kun Guo1 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China; 2Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of First Surgery, the Third Affiliated Hospital, NAVY Medical University, Shanghai, People’s Republic of China; 4Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun GuoLiver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Building 19, No. 180, Fenglin Road, Shanghai 20032, People’s Republic of ChinaTel +86-21-54237962Fax +86-21-54237959Email guo.kun@zs-hospital.sh.cnBackground: To date, aberrated lipid metabolism has been recognized as an important feature of hepatocellular carcinoma (HCC); however, it remains poorly defined. As a large member of the low-density lipoprotein receptor family, LRP1B plays a pivotal role in maintaining lipid homeostasis. Here we investigated the expression feature of LRP1B in HCC and elucidated its effects on lipid metabolism of HCC cells.Materials and Methods: LRP1B expression in HCC cells and tumor tissues was respectively examined by quantitative PCR, Western blotting and immunohistochemistry. Crispr-cas9 RNA inference and CRISPRa transcription activation system were used to downregulate and upregulate LRP1B expression, respectively. Oil red O staining, DiD staining combined with flow cytometry and transmission electron microscopy were used to evaluate the lipid content in HCC cells. Overall survival (OS) and time to recurrence (TTR) were calculated; meanwhile, Kaplan–Meier and the Cox proportional hazards model were used to assess the prognosis of HCC patients.Results: In contrast to inactivation expression in a majority of cancers, LRP1B showed predominantly strong expression in HCC. LRP1B knockdown induced the decrease of intracellular lipid content, downregulated expressions of lipid synthesis-related enzymes and upregulated expressions of β-oxidation-related enzymes as well as activated the AMPK signaling. Moreover, HSF1 directly regulated the transcription of LRP1B and was involved in LRP1B-mediated lipid metabolism in HCC; meanwhile, the combination of LRP1B knockdown and HSF1 inhibition suppressed synergistically the proliferation of HCC cells. In addition, simultaneous expression of HSF1 and LRP1B was an independent prognostic factor for HCC patients.Conclusion: Altogether, the study reveals a novel unique role of LRP1B in HCC by serving as a mediator in lipid metabolism, which provides an insight for making explorable therapeutic strategies for HCC.Keywords: hepatocellular carcinoma, lipid metabolism, LRP1B, HSF1, prognosis

Ning Sun,1,2 Chunxia Yang,1 Xiaoting He,1,3 Zhifen Liu,1 Sha Liu,1 Xinrong Li,1 Yanfang Wang,1 Ruihua Jin,2 Kerang Zhang1 1Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Nursing College of Shanxi Medical University, Taiyuan, People’s Republic of China; 3University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Ruihua Jin; Kerang Zhang Email jrh_xy@163.com; atomsxmu@vip.163.comBackground: Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD.Methods: First, we analyzed miR-34c-5p expression in 48 cases of MDD and 54 healthy controls in a Chinese population using qRT-PCR. We assessed the relationship between the level of miR-34c-5p expression and cognitive performance by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test (TMT). Second, in order to characterize allelic effects of miR-34b/c on cognitive performance in MDD patients, we performed genetic association analysis of single-nucleotide polymorphism (SNP) loci of the MIR34B/C genes with cognitive function in a second group consisting of 531 MDD patients and 267 healthy controls.Results: We found a significant negative correlation between the level of miR-34c-5p expression and both the language and delayed memory index scores in patients with MDD. We also found a significant positive correlation between the level of miR-34c-5p expression and the time required to complete tests A and B of the TMT. The interaction between the rs2187473 genotype and the disease was significant for both immediate memory and delayed memory. In the patient group, the rs2187473 CC genotype was significantly associated with higher performance on immediate memory (F = 6.683, p < 0.05) and delayed memory tasks (F = 4.221, p < 0.05).Conclusion: Our findings suggest that changes in miR-34c expression level have important impacts on cognitive function in patients with MDD. In particular, the polymorphism rs2187473 is a potential genetic risk factor for cognitive function in MDD, which may be of clinical use.Keywords: major depressive disorder, MDD, microRNA-34c, single-nucleotide polymorphism, cognitive function

Lu Zhou,1 Yanqing Le,1 Jieyu Tian,2 Xia Yang,2 Rong Jin,3 Xiaoyan Gai,1 Yongchang Sun1 1Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China; 2Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 3Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China Background and purpose: Cigarette smoke (CS) induces alveolar destruction through overproduction of proteinases including matrix metalloproteinase (MMP)-9 by alveolar macrophages (AMs). Receptor activator of nuclear factor-κB ligand (RANKL) functions in immune regulation and cytokine secretion; whether it is involved in CS-induced MMP-9 expression is unknown. The purpose of our study was to investigate the expression and functional role of RANKL pathway in MMP-9 production pertaining to the pathogenesis of COPD. Materials and methods: We first localized RANKL and its receptor RANK in the lungs of mice exposed to long-term CS exposure. Next, we studied RANKL and RANK expression under CS extract (CSE) stimulation in vitro. Lastly, we studied the in vitro biological function of RANKL in CS-induced production of MMP-9. Results: Both RANKL and RANK were highly expressed in AMs in CS-exposed mice, but not in the control mice. In vitro, CSE increased the expressions of RANKL and RANK in macrophages. AMs responded to CSE and RANKL stimulation by overexpressing MMP-9, and CSE-induced MMP-9 expression was partly blocked by using monoclonal anti-RANKL antibody. Conclusion: RANKL/RANK pathway mediates CS-induced MMP-9 expression in AMs, suggesting a novel mechanism for CS-associated emphysema. Keywords: COPD, receptor activator of nuclear factor-κB ligand, RANK, alveolar macrophages, MMP-9

Rongbing Jin,1,* Jingjie Ge,2,* Ping Wu,2 Jiaying Lu,2 Huiwei Zhang,2 Jian Wang,3 Jianjun Wu,3 Xianhua Han,2 Weishan Zhang,2 Chuantao Zuo2,4 1Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China; 2PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China; 3Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; 4Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200433, China *These authors contributed equally to this work Purpose: We previously identified disease-related cerebral metabolic characteristics associated with Parkinson’s disease (PD) in the Chinese population using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging. The present study aims to assess data reproducibility and robustness of the metabolic activity characteristics across independent cohorts. Patients and methods: Forty-eight patients with PD and 48 healthy controls from Chongqing district, in addition to 33 patients with PD and 33 healthy controls from Shanghai district were recruited. Each subject underwent brain 18F-FDG PET/CT imaging in a resting state. Based on the brain images, differences between the groups and PD-related cerebral metabolic activities were graphically and quantitatively evaluated. Results: Both PD patient cohorts exhibited analogous cerebral patterns characterized by metabolic increase in the putamen, globus pallidus, thalamus, pons, sensorimotor cortex and cerebellum, along with metabolic decrease in parieto-occipital areas. Additionally, the metabolic pattern was highly indicative of the disease, with a significant elevation in PD patients compared with healthy controls (p

Encheng Bai,1,2,* Lehe Yang,1,* Youqun Xiang,2,* Wanle Hu,3 Caleb Li,4 Jiayuh Lin,5 Xuanxuan Dai,2 Guang Liang,1 Rong Jin,2 Chengguang Zhao1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, 2Department of Epidemiology, First Affiliated Hospital, 3Department of Coloproctology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Dublin Coffman High School, Dublin, OH, 5Department of Biochemistry and Molecular Biology, University of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA *These authors contributed equally to this work Background: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The poor prognosis of this disease highlights the urgent need to develop more effective therapies. Activation of the STAT3 represents a potential drug target for pancreatic cancer therapy. Currently, clinically available small-molecule inhibitors targeting STAT3 are lacking. Methods: Through bioassay screening and molecular docking, we identified a small molecule L61H46 that can potently target constitutive STAT3 signaling and kill human pancreatic cancer cells in vitro and in vivo. Results: L61H46 effectively reduced colony formation and the viability of pancreatic cancer cells in a dose-dependent manner with half-maximal inhibitory concentration (IC50) values in the range between 0.86 and 2.83 µM. L61H46 significantly inhibited STAT3 phosphorylation (Tyr705) and the subsequent nucleus translocation but did not downregulate STAT1 phosphorylation. Moreover, L61H46 demonstrated a potent activity in suppressing pancreatic tumor growth in BXPC-3 xenograft model in vivo. Furthermore, L61H46 showed no signs of adverse effects on liver, heart, and kidney cells in vivo. Conclusion: Collectively, our results suggest that L61H46 could be further optimized into a highly potent STAT3 inhibitor for the treatment of pancreatic cancer. Keywords: L61H46, STAT3, cancer therapy, interleukin-6, pancreatic cancer

Xiaoyan Wu,1 Lin Wang,1 Yining Qiu,1 Bingyu Zhang,1 Zhenhua Hu,2 Runming Jin1 1Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Pharmacy, Shanghai Jiao Tong University, Shanghai, China Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. Keywords: T cell acute lymphoblastic leukemia, IRAK1/4 inhibitor, ABT-737, Box-Behnken design and response surface methodology, PEG-PLGA

QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Bai E, Yang L, Xiang Y, et al. Cancer Manag Res. 2018;10:565–581. During the publication process there was an operator error that resulted in the Western blot images of Figures 5A and 5B on page 575 appearing spliced. Read the original article

Rong Jin,1,3,* Yiqun Xia,1,2,* Qiuxiang Chen,1,2 Wulan Li,2,4 Dahui Chen,2 Hui Ye,2,5 Chengguang Zhao,2 Xiaojing Du,1,2 Dengjian Shi,2 Jianzhang Wu,2 Guang Liang2 1Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, 3Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, 4College of Information Science and Computer Engineering, Wenzhou Medical College, 5School of Basic Medical Sciences, Wenzhou Medical College, Wenzhou, People’s Republic of China *These authors contributed equally to this work Background: The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods: The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results: High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation and invasion, arrested the cell cycle, and induced apoptosis in vitro. Conclusion: The asymmetric mono-carbonyl analog of curcumin Da0324 exhibited significantly improved antigastric cancer activity. Da0324 may be a promising NF-κB inhibitor for the selective targeting of cancer cells. However, further studies are needed in animals to validate these findings for the therapeutic use of Da0324. Keywords: gastric cancer, anticancer drug, NF-κB inhibitor, asymmetric MACs, apoptosis, curcumin

Wu X, Wang L, Qiu Y, Zhang B, Hu Z, Jin R. Int J Nanomedicine. 2017;12:8025–8034.On page 8025, the first affiliation was listed as “Department of Pediatrics, Union Hospital, Tongji Medical College, University of Science and Technology, Wuhan” however it should have been “Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China”.Read the original article

Magnetic reconnection is a fundamental process known to play a crucial role in electron acceleration and heating, however, the mechanism of electron energization during reconnection is still not fully understood. This study introduces a novel electron acceleration mechanism in which electrons can be accelerated by secondary reconnection in the separatrix region. The secondary reconnection occurs in a thin current sheet resulted from the shear of the out‐of‐plane Hall magnetic fields of the primary magnetopause reconnection. It results in the intense electron energy fluxes toward the primary X‐line. This mechanism will likely be an important piece in the puzzle of particle acceleration by reconnection. Plain Language Summary: Magnetic reconnection is a fundamental process that plays a critical role in electron acceleration and heating. The separatrix region of magnetic reconnection, which distinguishes the inflow and outflow regions, is a crucial area in the particle acceleration of the reconnection process. However, previous studies mainly focused on the electron acceleration mechanism in the separatrix region under two‐dimensional reconnection, without considering the influence of the three‐dimensional structures. This paper reports, for the first time, the secondary reconnection occurring in the opposite Hall magnetic field in the three‐dimensional separatrix region of magnetopause primary reconnection. This secondary reconnection can accelerate and heat the inflow electrons of the primary reconnection, which provides important clues on how the particles are accelerated and heated by reconnection. Key Points: Secondary reconnection occurs between Hall magnetic fields in the separatrix region of the primary magnetopause reconnectionIntense electron enthalpy fluxes are injected toward the primary X‐line along the separatrixElectrons are accelerated by the secondary reconnection before being injected into the primary X‐line for further energization [ABSTRACT FROM AUTHOR]

Protein concentration (PC) is an essential characteristic of cells and organelles; it determines the extent of macromolecular crowding effects and serves as a sensitive indicator of cellular health. A simple and direct way to quantify PC is provided by brightfield‐based transport‐of‐intensity equation (TIE) imaging combined with volume measurements. However, since TIE is based on geometric optics, its applicability to micrometer‐sized particles is not clear. Here, we show that TIE can be used on particles with sizes comparable to the wavelength. At the same time, we introduce a new ImageJ plugin that allows TIE image processing without resorting to advanced mathematical programs. To convert TIE data to PC, knowledge of particle volumes is essential. The volumes of bacteria or other isolated particles can be measured by displacement of an external absorbing dye ("transmission‐through‐dye" or TTD microscopy), and for spherical intracellular particles, volumes can be estimated from their diameters. We illustrate the use of TIE on Escherichia coli, mammalian nucleoli, and nucleolar fibrillar centers. The method is easy to use and achieves high spatial resolution. [ABSTRACT FROM AUTHOR]