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Xiao-tian Nan,1,* Ma-chao Li,1,* Tong-yang Xiao,2,* Hai-can Liu,1,* Shi-qiang Lin,3 Wei Wang,1 Cheng Qian,4 Hao Hang,1 Gui-lian Li,1 Xiu-qin Zhao,1 Kang-Lin Wan,1 Li-li Zhao1 1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, 100013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-li Zhao, Email zhaolili@icdc.cnObjective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates.Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance.Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates.Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.Keywords: ethambutol, multidrug-resistant tuberculosis, embB, ubiA, mutations, minimum inhibitory concentration

Jingnan Zhao,1 Chengyu Qian,2 Youqiao Jiang,1,3 Wangrui He,1 Wenhua Wu1 1Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029, People’s Republic of China; 2Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Young Scientific Research and Innovation Team, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, Jiangxi, 330029, People’s Republic of ChinaCorrespondence: Wangrui He, Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, No. 555, Beijing East Road, Nanchang, Jiangxi, 330029, People’s Republic of China, Email jxcdccbs@126.comPurpose: In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates.Patients and Methods: A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions.Results: About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in rpoB (57.9%), Ser315Thr in katG (74.1%), Met306Val in embB (40.0%), Lys43Arg in rpsL (75.0%), Ala90Val in gyrA (32.8%) were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%.Conclusion: MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.Keywords: Mycobacterium tuberculosis, drug resistant, whole-genome sequencing, genetic diversity, transmission dynamics

Shan Chen,1 Jie Zhang,1 Chengjia Qian,2 Xiaowei Qi,3 Yong Mao,1 Tingxun Lu1 1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of China; 2Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of ChinaCorrespondence: Tingxun Lu, Department of Oncology, Affiliated Hospital of Jiangnan University, 1000, Hefeng Road, Wuxi, 214122, Jiangsu, People’s Republic of China, Email lutingxun@163.comPurpose: We aim to investigate the clinical significance of dynamic changes in the lymphocyte-to-monocyte ratio (LMR) and neutrophil-lymphocyte ratio (NLR) in peripheral blood at different time points combined with CEA in the prediction of postoperative-recurrence-in-patients with colorectal cancer (CRC).Patients and Methods: This study collected 357 patients with stage I–III CRC between 2016 and April 2018. The dynamic changes from preoperative to postoperative LMR (p-LMR-p) and NLR (p-NLR-p) were analyzed using COX regression for multivariate analysis. Logistic regression was used to investigate whether the dynamic changes from post-treatment to pre-end of follow-up LMR (p-LMR-f) and NLR (p-NLR-f) were independent risk factors for CRC recurrence and to construct a predictive model. Internal validation using bootstrapping was performed to validate the discrimination ability of the model. The models’ discriminative effect, calibration degree, and clinical utility were assessed.Results: In both the total cohort and the adjuvant therapy group, the dynamic changes of p-LMR-p (High-High vs Low-Low: p=0.006; HR:2.210, 95% CI: 1.256– 3.890) were found to be independent prognostic factors for recurrence-free survival (RFS) in CRC patients. Additionally, logistic regression analysis revealed that N stage, CEA, LMR of pre-end of follow-up (f-LMR), and p-LMR-f were independent risk factors for CRC recurrence. In the total cohort, the p-LMR-f had an area under the curve (AUC) of 0.704, with a sensitivity of 64% and a specificity of 75.3%. By combining p-LMR-f with CEA, a predictive model was constructed, which showed an AUC of 0.913 (0.986– 0.913) in the total cohort and an AUC of 0.924 (0.902– 0.924) in the adjuvant therapy group during internal validation using bootstrapping.Conclusion: Dynamic changes in LMR can be used to predict the prognosis of CRC and serve as a biomarker for predicting CRC recurrence. Combined with CEA, it can improve the predictive performance for detecting CRC recurrence.Keywords: colorectal cancer, postoperative recurrence, predictive model, inflammatory markers

Bin Cao,1,2,* Xiaokaiti Mijiti,3,* Le-Le Deng,2,4 Quan Wang,3 Jin-Jie Yu,1,2 Aiketaguli Anwaierjiang,5 Chengyu Qian,2,6 Machao Li,2 Dan-Ang Fang,2,6 Yi Jiang,2 Li-Li Zhao,2 Xiuqin Zhao,2 Kanglin Wan,2 Haican Liu,2 Guilian Li,2 Xiuqin Yuan1 1School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China; 2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 4National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, 848000, People’s Republic of China; 6Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiuqin Yuan; Guilian Li, Email wtjysh@126.com; liguilian@icdc.cnBackground: Ethionamide (ETH), a structural analogue of isoniazid (INH), is used for treating multidrug-resistant tuberculosis (MDR-TB). Due to the common target InhA, INH and ETH showed cross-resistance in M. tuberculosis. This study aimed to explore the INH and ETH resistant profiles and genetic mutations conferring independent INH- or ETH-resistance and INH-ETH cross-resistance in M. tuberculosis circulating in south of Xinjiang, China.Methods: From Sep 2017 to Dec 2018, 312 isolates were included using drug susceptibility testing (DST), spoligotyping, and whole genome sequencing (WGS) to analyze the resistance characteristics for INH and/or ETH.Results: Among the 312 isolates, 185 (58.3%) and 127 (40.7%) belonged to the Beijing family and non-Beijing family, respectively; 90 (28.9%) were INH-resistant (INHR) with mutation rates of 74.4% in katG, 13.3% in inhA and its promoter, 11.1% in ahpC and its upstream region, 2.2% in ndh, 0.0% in mshA, whilst 34 (10.9%) were ETH-resistant (ETHR) with mutation rates of 38.2% in ethA, 26.2% in inhA and its promoter, and 5.9% in ndh, 0.0% in ethR or mshA; and 25 (8.0%) were INH-ETH co-resistant (INHRETHR) with mutation rates of 40.0% in inhA and its promoter, and 8% in ndh. katG mutants tended to display high-level resistant to INH; and more inhA and its promoter mutants showed low-level of INH and ETH resistance. The optimal gene combinations by WGS for the prediction of INHR, ETHR, and INHRETHR were, respectively, katG+inhA and its promoter (sensitivity: 81.11%, specificity: 90.54%), ethA+inhA and its promoter+ndh (sensitivity: 61.76%, specificity: 76.62%), and inhA and its promoter+ndh (sensitivity: 48.00%, specificity: 97.65%).Conclusion: This study revealed the high diversity of genetic mutations conferring INH and/or ETH resistance among M. tuberculosis isolates, which would facilitate the study on INHR and/or ETHR mechanisms and provide clues for choosing ETH for MDR treatment and molecular DST methods in south of Xinjiang, China.Keywords: cross-resistance, ethionamide, isoniazid, mutation, Mycobacterium tuberculosis

Chenjing Qian,1,* Qiuling Wu,1,* Zhixuan Ruan,2 Fang Liu,1 Weiming Li,1 Wei Shi,1 Ling Ma,3 Danyue Peng,1 Hua Yin,1 Lan Yao,1 Zixuan Li,1 Mei Hong,1,4 Linghui Xia1 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Faculty of Natural, Mathematical and Engineering Sciences, King’s College, London, UK; 3Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Hong; Linghui Xia, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan, Hubei Province, People’s Republic of China, Tel +8613037137937 ; +8618627733999, Email hmxh@hust.edu.cn; linghuixia@hust.edu.cnBackground: Bloodstream infection (BSI) due to carbapenem-resistant organisms (CROs) has emerged as a worldwide problem associated with high mortality. This study aimed to evaluate the risk factors associated with mortality in HM patients with CROs BSI and to establish a scoring model for early mortality prediction.Methods: We conducted a retrospective cohort study at our hematological department from January 2018 to December 2021, including all HM patients with CROs BSI. The outcome measured was death within 30-day of BSI onset. Survivor and non-survivor subgroups were compared to identify predictors of mortality. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors and develop a nomogram.Results: In total, 150 HM patients were included in the study showing an overall 30-day mortality rate of 56%. Klebsiella pneumonia was the dominant episode. Cox regression analysis showed that pre-infection length of stay was > 14 days (score 41), Pitt score > 4 (score 100), mucositis (score 41), CAR (The ratio of C-reactive protein to albumin) > 8.8 (score 57), early definitive therapy (score 44), and long-duration (score 78) were positive independent risk predictors associated with 30-day mortality, all of which were selected into the nomogram. Furthermore, all patients were divided into the high-risk group (≥ 160 points) or the low-risk group based on the prediction score model. The mortality of the high-risk group was 8 times more than the low-risk group. Kaplan-Meier analysis showed that empirical polymyxin B therapy was associated with a lower 30-day mortality rate, which was identified as a good prognostic factor in the high-risk group. In comparison, empirical carbapenems and tigecycline were poor prognostic factors in a low-risk group.Conclusion: Our score model can accurately predict 30-day mortality in HM patients with CROs BSI. Early administration of CROs-targeted therapy in the high-risk group is strongly recommended to decrease mortality.Keywords: carbapenem-resistant organisms, predictive model, nomogram, hematological malignancies, bloodstream infection

Mengxin Xu,1 Changrui Qian,2 Huaiyu Jia,1 Luozhu Feng,3 Shiyi Shi,1 Ying Zhang,3 Lingbo Wang,1 Jianming Cao,3 Tieli Zhou,1 Cui Zhou1 1Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, People’s Republic of China; 2School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Medical Laboratory Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Tieli Zhou; Cui Zhou, Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325035, People’s Republic of China, Tel +86 0577 8668 9885, Email wyztli@163.com; ZHOUCUI0826@163.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to human public health. Ceftazidime–avibactam (CZA) is currently one of the few effective antibiotics for carbapenem-resistant Enterobacteriaceae (CRE).Methods and Results: Here, we analyzed two longitudinal Klebsiella pneumoniae clinical isolates (FK8578, FK8695) that were isolated from an ICU patient during antimicrobial treatment. Broth microdilution method, whole-genome sequencing (WGS) and comparative genomic analysis were used to elucidate the dynamics and mechanisms of antibiotic resistance. String test, quantification of capsule, biofilm inhibition test and Galleria mellonella (G. mellonella) infection model were used to explore the changes in virulence of the two clinical isolates. During antibiotic treatment, CRKP FK8578 underwent a series of drug resistance and virulence changes, including CZA resistance, carbapenem susceptibility and virulence attenuation. The results of WGS showed that mutation of blaKPC-2 to blaKPC-33 was responsible for the change of drug resistance phenotype between FK8578 and FK8695. pLVPK-like virulence plasmid without siderophore synthesis operon was identified in the two strains. On the other hand, the loss of hypermucoviscosity phenotype in the FK8695 strain may be related to a single nucleotide deletion of the rmpA gene, which would further lead to a decrease in virulence. Virulence results showed that compared with FK8578, FK8695 was negative in the string test, with decreased capsular production, smaller amounts of biofilm formation and higher survival rate of G. mellonella.Conclusion: This is the first report of CZA resistance and decreased virulence in ST11 CRKP strains during antimicrobial treatment. It is urgent to monitor CZA resistance and timely adjust anti-infective treatment strategies.Keywords: ceftazidime–avibactam, carbapenem-resistantKlebsiella pneumoniae, whole-genome sequencing, hypermucoviscosity, pLVPK-like plasmid, virulence attenuation

Ma-Chao Li,1,* Xiao-Yue Wang,1,* Tong-Yang Xiao,2,* Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutation

Nongzhang Xu,1,&ast; Jianwei Wan,1,&ast; Cuihong Wang,1 Jiatao Liu,2 Chenqai Qian,1 Hongyang Tan3 1Department of Pharmacy, Shanghai University of Medicine and Health Science Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Clinical Research Center for Mental Disorders, Chinese-German Institute of Mental Health Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyang Tan, Clinical Research Center for Mental Disorders, Chinese-German Institute of Mental Health, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86-18321133996, Email tanhongyang2013@163.comPurpose: Trimethylamine N-oxide (TMAO) is a metabolite of phosphatidylcholine in red meat and other diets, which is associated with cardiovascular and other diseases. The aim of this study is to evaluate the associations of serum TMAO with mild cognitive impairment (MCI) in the Chinese type 2 diabetes mellitus (T2DM) population.Materials and Methods: A total of 253 hospitalized T2DM patients and 150 healthy controls were included in this cross-sectional study. Montreal Cognitive Assessment (MoCA) assessed the cognition function, and the 253 T2DM patients were divided into 74 subjects with MCI and 179 with non-MCI. Demographic data and biochemical test results were evaluated. Serum TMAO level was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).Results: A higher serum TMAO level was observed in T2DM patients compared with the healthy controls (P < 0.001). Among all T2DM patients, the MCI group (n = 74) showed higher serum TMAO levels than the non-MCI group. Spearman correlation test showed that TMAO levels were significantly positively correlated with age (r = 0.147, P = 0.019), body mass index (BMI) (r = 0.153, P = 0.015), diabetes duration (r = 0.160, P = 0.011), HbA1c (r = 0.138, P = 0.029), triglyceride (TG) (r = 0.138, P = 0.029), creatinine (r = 0.184, p = 0.003), hs-CRP (r = 0.243, P < 0.001), and were negatively correlated with HDL-C (r = − 0.144, P = 0.022), BDNF (r = − 0.165, p = 0.009), and MoCA (r = − 0.386, P < 0.001) score (all P < 0.05). Multivariable Logistic regression identified high serum TMAO level as a significant independent factor of MCI in the T2DM patients (OR = 1.404, 95% CI = 1.255– 1.571; P < 0.001).Conclusion: Our study showed that T2DM patients with MCI have elevated serum TMAO levels.Keywords: trimethylamine N-oxide, type 2 diabetes mellitus, mild cognitive impairment, Montreal Cognitive Assessment, healthy control

Xinran Gu, Guangyi Xu, Chen Qian, Saichao Chang, Dandan Deng School of Business Administration, South China University of Technology, Guangzhou, People’s Republic of ChinaCorrespondence: Chen Qian, School of Business Administration, South China University of Technology, Tianhe District, Guangzhou, People’s Republic of China, Email 201710105492@mail.scut.edu.cnPurpose: Prior work suggests that responsibility is negatively associated with employee procrastination behavior. Based on the conservation of resources (COR) theory, we suggest this view is oversimplified and propose that procrastination can be induced when employees have congruent job and family responsibilities via the mediating effect of emotional exhaustion.Methods: This is a quantitative study of the configurational approach. Survey data were collected from 323 employees at two stages in southern Chinese internet enterprises in September 2020. A randomized cluster sample was used and an anonymous self-assessment questionnaire was distributed to all selected respondents (employees). Samples involved different departments, and the procrastination phenomenon is more significant among them. SPSS20.2 and MPLUS 8.3 software and Response Surface Analysis Strategy were used to test the hypotheses.Results: The data analysis results indicated that: a) employee procrastination behavior is higher when employees’ job responsibility and family responsibility are congruent than the incongruent configurations. b) Procrastination is lower when job-family dyads are congruent at high levels of responsibility compared the low levels. c) Procrastination decreases as employees’ job and family responsibilities become more discrepant (ie, incongruent); employees with low job-high family responsibilities procrastinate more than those with high job-low family responsibilities. d) Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Conclusion: Drawing on the conservation of resources theory, we proposed a model clarifying how varying combinations of job and family responsibilities affect employee procrastination behavior. The results showed that there are significant differences in the impact of different job-family responsibility combinations on employee procrastination behavior. Employee procrastination behavior is higher when employees’ job-family responsibility are congruent than the incongruent configurations. Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Keywords: job-family responsibilities congruence, emotional exhaustion, employee procrastination behavior, conservation of resources theory, configurational approach

Xiaoyuan Qian,1 Junlai Wan,2 Can Qian,3 Jiaqiao Zhang1 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Traditional Chinese Medicine and Rheumatology, Southwest Hospital, Army Military Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jiaqiao ZhangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei Province, People’s Republic of ChinaEmail medzjq@163.comPurpose: Although papillary renal cell carcinoma (pRCC) is the second common renal malignant tumor, the current understanding of pRCC is poor. This study aims to explore the clinicopathological features and prognostic factors of pRCC.Methods: From August 2007 and August 2017, 87 patients diagnosed with pRCC by postoperative pathology were enrolled. The clinicopathological features between type1 pRCC and type2 pRCC were compared by Chi-square test, Fisher’s exact test, or t-test. The Kaplan–Meier method was performed to estimate progression-free survival (PFS). Univariate and multivariate cox regression models were used to verify the prognostic factors.Results: Of the 87 cases, the median tumor diameter was 5.3cm. Twenty-nine patients were diagnosed with type1 pRCC and 58 patients with type2 pRCC. According pathological stage, 59 (67.8%) cases were in pT1 stage, 19 (21.8%) in pT2 stage, and 9 (10.4%) in pT3 stage. WHO/ISUP pathological grade revealed that 56 (64.4%) patients were in grade I, 17 (19.5%) in grade II, 7 (8.05%) in grade III, and 7 (8.05%) in grade IV. The median follow-up time was 57.0months, and the 1-, 3-year PFS was 95.4%, and 80.8%, respectively. For type1 and type2 pRCC, 3-years PFS was 93.0% and 74.9%, respectively. Survival of type1 pRCC was better than that of type2 (P= 0.027). Patients with late pT stage, lymph node metastasis, distant metastasis, high pathological grade, and large size exhibited worse survival. pTNM stage, pathological grade, and tumor types were potentially related to prognosis for PFS. However, an independent prognostic factor affecting PFS was not found in multivariate regression models. For patients with the pT1 stage, nephron-sparing surgery (NSS) and radical nephrectomy (RN) did not affect the PFS, ignoring tumor types (P=0.45).Conclusion: Type2 pRCC is more than type1 pRCC and has an advanced TNM stage and a higher pathological grade. For patients with pRCC with the pT1 stage, the outcome of NSS is not inferior to that of RN.Keywords: papillary renal cell carcinoma, clinical features, pathological features, prognosis

Xin Yang, Jun Fan, Yingzhi Wu, Jie Lin, Chongling Qian, Jing Li Department of Laboratory Medicine, Kongjiang Hospital, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Xin YangDepartment of Laboratory Medicine, Kongjiang Hospital, No. 480 Shuangyang Road, Yangpu District, Shanghai, 200093, People’s Republic of ChinaTel/Fax +86 2165434597 Ext8136Email xinyang_2021@21cn.comObjective: To investigate the clinical value of sodium dodecyl sulfate–agarose gel electrophoresis (SDS-AGE) of urinary proteins combined with several biochemical indices in the detection of hypertensive nephropathy.Material and Methods: In this study, 210 patients with hypertensive nephropathy were recruited as the kidney disease group, 100 patients with simple hypertension were recruited as the hypertension group, and another 100 healthy participants were recruited as the control group. We conducted SDS-AGE of urinary proteins and urinary microalbumin (mAlb), β2-microglobulin (β2-MG), retinol-binding protein (RBP), serum cystatin C (CysC), blood urea nitrogen (BUN), and creatinine tests at the same time.Results: The results showed that the urinary mAlb levels in the hypertension group and hypertensive nephropathy group were higher than in the control group (P< 0.05). The biochemical index detection results showed that β2-MG, RBP, serum CysC, BUN, and creatinine were higher in the hypertensive nephropathy group than in the control group and hypertension group (P< 0.05). The total positive rates of urinary protein SDS-AGE and urinary mAlb, urinary β2-MG, blood CysC, blood RBP, BUN, and creatinine in 210 patients with essential hypertension nephropathy were 100.0%, 98.6%, 32.8%, 98.6%, 21.0%, 2.0%, and 20%, respectively. The total positive rate of SDS-AGE urinary protein was higher than that of the other six biochemical indices.Conclusion: SDS-AGE of urinary proteins, combined with urinary mAlb, β2-MG, serum CysC, RBP, BUN, and creatinine, could improve the detection sensitivity, which would be helpful for the early and accurate diagnosis of kidney damage.Keywords: hypertension, kidney damage, sodium dodecyl sulfate–agarose gel electrophoresis, urinary mAlb, β2-MG, serum CysC, RBP, BUN, pathological proteinuria

Xi Lin,1,2 Junwan Lu,1,2 Changrui Qian,1,2 Hailong Lin,1– 3 Qiaoling Li,1– 3 Xueya Zhang,1– 3 Hongmao Liu,1– 3 Zhewei Sun,1,2 Danying Zhou,1,2 Wei Lu,1,2 Mei Zhu,4 Hailin Zhang,2,3 Teng Xu,5 Kewei Li,1,2 Qiyu Bao,1– 3 Li Lin2,3 1Key Laboratory of Medical Genetics of Zhejiang Province, Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Institute of Biomedical Informatics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3The Second Affiliated Hospital and Children’s Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 4Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China; 5Institute of Translational Medicine, Baotou Central Hospital, Baotou, 014040, People’s Republic of ChinaCorrespondence: : Li LinThe Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of ChinaTel +86-577-88002134Email linli97@126.comQiyu BaoInstitute of Biomedical Informatics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of ChinaTel/Fax +86-577-86699398Email baoqy@genomics.cnPurpose: An increasing frequency of antibiotic resistance has been observed in both clinical and environmental Aeromonas hydrophila isolates in recent years. However, there are still very few in-depth studies regarding the role of plasmids in the antibiotic resistance of A. hydrophila. Hence, we investigated the molecular and functional characterization of a multidrug-resistant plasmid encoding an NDM-like metallo-β-lactamase, AFM-1, in the clinical A. hydrophila isolate SS332.Methods: The minimum inhibitory concentrations (MICs) of 24 antibiotics against A. hydrophila SS332 were measured by the agar dilution method. The genome of A. hydrophila SS332 was sequenced with PacBio and Illumina platforms. Six plasmid-borne antimicrobial resistance genes were chosen for cloning, including blaAFM-1, blaOXA-1, msr(E), mph(E), aac(6ʹ)-Ib10, and aph(3ʹ)-Ia. Phylogenetic analysis, amino acid sequence alignment, and comparative genomic analysis were performed to elucidate the active site requirements and genetic context of the blaAFM-1 gene.Results: A. hydrophila SS332 showed high levels of resistance to 15 antibiotics, especially those with MIC levels at or above 1024 μg/mL, including ampicillin, cefazolin, ceftriaxone, aztreonam, spectinomycin, and roxithromycin. Six plasmid-borne resistance genes from A. hydrophila were verified to be functional in E. coli DH5α. AFM-1 shared 86% amino acid identity with NDM-1 and showed resistance to ampicillin, cefazolin, cefoxitin, and ceftazidime. In addition, the blaAFM-1 gene was associated with three different novel ISCR19-like elements, designated ISCR19-1, ISCR19-2 and ∆ISCR19-3, which may be involved in the acquisition and mobilization of the blaAFM-1 gene.Conclusion: Our investigation showed that plasmid-borne resistance genes can contribute to antibiotic resistance in A. hydrophila SS332. A novel blaNDM-like gene, blaAFM-1, was verified to be functional and associated with novel ISCR19-like elements. This fact indicated the risk of spread of blaAFM-1 genes and ISCR19-like elements.Keywords: Aeromonas hydrophila, whole-genome sequencing, plasmid-borne resistance genes, blaAFM-1, ISCR19-like elements

Yanbo Sun,1,* Jing Luo,2,* Chuan Qian,3,* Lan Luo,3 Manqi Xu,1 Haiyan Min,3 Yunyun Cen1 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First People’s Hospital of Qujing, Qujing, 655000, People’s Republic of China; 3The Second Department of Infection, Yunnan Provincial Infectious Disease Hospital, Kunming, 650301, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunyun CenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374 of Yunnan-Burma Road, Kunming City, Yunnan Province, 650101, People’s Republic of ChinaTel +86-871-63402778Fax +86-871-65361017Email drcenyunyun@163.comHaiyan MinThe Second Department of Infection, Yunnan Provincial Infectious Disease Hospital, Shi’an Highway in Kunming, Kunming City, Kunming, Yunnan Province, 650301, People’s Republic of ChinaTel/Fax +86-871-68728053Email min_haiy23an@126.comObjective: Many studies have suggested that indexes of nutritional status, such as body mass index (BMI), serum albumin (ALB), serum pre-albumin (PA), and hemoglobin, may be used as risk factors for the prognosis of HIV or lymphoma. Therefore, this study aimed to retrospectively analyze and explore the value of nutritional status in the prognostic assessment of patients with AIDS-related lymphoma (ARL).Methods: In this retrospective study, the clinical data of 69 patients with ARL were collected. All patients had a definite diagnosis of non-Hodgkin lymphoma by pathological examination and met the requirements of the Hematopoietic and Lymphocytic Tissue Tumor Classification (2016) established by the World Health Organization. Patients who did not receive standard chemotherapy, those with incomplete medical records, and those with an unclear pathological diagnosis were excluded. The patients were divided into two groups (survival and death) according to the prognostic outcome, and their clinical characteristics and prognoses were discussed by relevant statistical methods.Results: During the three-year follow-up period, 20 (28.99%) patients died, and 49 (71.01%) survived. The one-year cumulative survival rate was 78.26%. A univariate analysis found that the prognosis was associated with the International Prognostic Index (IPI) score, BMI, ALB, PA, and CD4 T lymphocyte count. The Cox risk proportional regression analysis showed that the IPI score, BMI, and PA were the independent risk factors for survival; their combination had a greater ability to forecast the clinical outcome (area under the curve = 0.874, P < 0.001).Conclusion: In this study, at the time of the visit, the patients with ARL tended to be in the advanced stages of disease and, therefore, at high risk of mortality. Therefore, their nutritional status might be of great value to the prognostic assessment. The combination of BMI, PA, and IPI scores could be used for risk stratification and better screening of high-risk patients.Keywords: AIDS-related lymphoma, body mass index, pre-albumin, prognostic factor, retrospective analysis

Chengsi Qian1 *,* Yan Sun2 *,* Jun Jiang1 1Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang Province, People’s Republic of China; 2Department of Cardiology, Zhejiang Rongjun Hospital, Jiaxing, 314001, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Jiang Email leiyanci13712@163.comBackground: Coronary heart disease (CHD) is the most common cardiovascular disease which greatly threatens the health of middle-aged and elderly people.Objective: To explore the correlations of epicardial adipose tissue (EAT) thickness with right common carotid artery elasticity and intima-media thickness (IMT) in middle-aged and elderly patients with CHD by ultrasound.Methods: A total of 132 patients diagnosed with CHD by coronary angiography (CAG) from February 2019 to August 2020 were enrolled and divided into single-vessel disease group (n=38), double-vessel disease group (n=52), and three-vessel disease group (n=42), and 52 healthy subjects were selected as control group. Their general data, biochemical indices, EAT thickness, right common carotid artery elasticity indices, and IMT were compared. The correlations of EAT thickness with right common carotid artery elasticity indices and IMT were studied by Pearson’s analysis. The predictive values of EAT thickness and IMT for CHD were analyzed by receiver operating characteristic curves.Results: With increasing number of diseased branches, EAT thickness, stiffness parameters β (β), strain elastic modulus (Ep), pulse wave velocity β (PWV-β) and IMT increased, arterial compliance (AC) decreased (P< 0.05), but argumentation index (AI) did not change significantly. EAT thickness had significant positive correlations with β, Ep, PWV-β and IMT, negative correlation with AC, and no significant correlation with AI. The areas under the curves of EAT thickness and IMT for predicting CHD were 0.806 and 0.784, respectively.Conclusion: EAT thickness is significantly correlated with right common carotid artery elasticity and IMT in middle-aged and elderly patients with CHD, and EAT thickness and IMT have high predictive values. The three indices are crucial for CHD diagnosis.Keywords: ultrasound, coronary heart disease, epicardial adipose tissue, right common carotid artery elasticity, intima-media thickness

Ying Chen, Wei-li Wang, Wei Zhang, Yun-tao Zhang, Sa-xiao Tang, Ping-ping Wu, Lei Zeng, Chao Qian, Ting-bo Liang Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of ChinaCorrespondence: Ting-bo LiangDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of ChinaTel +86-571-87236688Fax +86-571-87236739Email liangtingbo@zju.edu.cnBackground: There is an increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infection after liver transplantation (LT). Improved understanding of the risk factors and outcomes of CRE infections can help us to develop effective preventive strategies and even guide early treatment of high-risk LT patients.Methods: This was a retrospective study involving all Chinese adult patients who underwent LT between December 2017 and September 2019 in our center. We analyzed the possible risk factors and outcomes associated with CRE infections in the first 30 days post-LT.Results: A total of 387 patients underwent LT. Among them, 26 patients (6.7%) developed CRE infections within 30 days after transplantation. Patients with CRE infections had significantly lower 30-day and 180-day survival rates (80.8% vs 96.4%, p< 0.001; 51.5% vs 92.4%, p< 0.001). Multivariate analysis identified that intraoperative blood loss equal to or more than 1500 mL (odds ratio [OR], 3.666; 95% confidence interval [CI], 1.407– 9.550; p=0.008), CRE rectal carriage within 30 days post-LT (OR, 5.516; 95% CI, 2.113– 14.399; p=0.000), biliary complications (OR, 3.779; 95% CI, 1.033– 13.831; p=0.045) and renal replacement therapy for more than 3 days (OR, 3.762; 95% CI, 1.196– 11.833; p=0.023) were independent risk factors for CRE infections within 30 days post-LT.Conclusion: CRE infections within 30 days post-LT were associated with worse outcomes. Intraoperative blood loss equal to or more than 1500 mL, CRE rectal carriage within 30 days post-LT, biliary complications and renal replacement therapy for more than 3 days were independent risk factors of CRE infections after LT.Keywords: carbapenem-resistant Enterobacteriaceae, liver transplantation, infections, immunosuppression, mortality, risk factors

Weihua Zhang,1,2,* Na Zhu,3,* Jianbo Lai,1,4 Jingjing Liu,1,5 Chee H Ng,6 Jun Chen,3 Chao Qian,1,7 Yanli Du,1 Chanchan Hu,1,4 Jingkai Chen,1,4 Jianbo Hu,1,4 Zhong Wang,1,4 Hetong Zhou,1,4 Yi Xu,1,4 Yiru Fang,3 Chuan Shi,8– 11 Shaohua Hu1,4 1Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of China; 2Department of Psychiatry, Taizhou Second People’s Hospital, Taizhou 317200, People’s Republic of China; 3Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, People’s Republic of China; 4The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou 310003, People’s Republic of China; 5Department of Psychiatry, Wenzhou Kangning Hospital, Wenzhou 325000, People’s Republic of China; 6The Melbourne Clinic Department of Psychiatry, University of Melbourne, Melbourne, Victoria 3052, Australia; 7Department of Psychiatry, The Seventh Shaoxing People’s Hospital, Shaoxing 312000, People’s Republic of China; 8Department of Psychological Assesssment, Peking University Sixth Hospital, Beijing 100191, People’s Republic of China; 9Peking University Institute of Mental Health, Beijing 100191, People’s Republic of China; 10NHC Key Laboratory of Mental Health, Beijing 100191, People’s Republic of China; 11National Clinical Research Center for Mental Disorders, Beijing 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru FangShanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, People’s Republic of ChinaEmail yirufang@aliyun.comShaohua HuDepartment of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder Management of Zhejiang Province, 79 Qing Chun Road, Hangzhou 310003, People’s Republic of ChinaEmail dorhushaohua@zju.edu.cnPurpose: The THINC-integrated tool (THINC-it) as a brief screening tool can assesses cognitive impairment in patients with major depressive depression (MDD). Here, we aim to evaluate the reliability and validity of the THINC-it in a bipolar depression (BD-D) group in comparison with a healthy control (HC) group.Materials and Methods: Both groups were matched according to age, gender, years of education, and IQ. All participants completed the THINC-it test, including Spotter, Symbol Check, Codebreaker, Trails, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). The concurrent validity and internal consistency of the THINC-it test were analyzed, and 30 healthy controls were randomly sampled to retest THINC-it to verify the reliability of the THINC-it retest. The correlation between THINC-it and Hamilton Depression Scale (HAMD-17) and Sheehan Disability Scale (SDS) was also analyzed.Results: Fifty-eight patients with BD-D and 61 HCs were included for final analysis. There were significant mean difference (MD) standard errors (SE) between two groups in PDQ-5-D, Spotter and Codebreaker (all P< 0.01), Trails (P=0.015). There was no significant difference in Symbol Check (MD (SE)=− 0.01 (0.18), P=0.938; 95% CI=− 0.38 to 0.35). The Cronbach’s α of PDQ-5-D was 0.640. The intraclass correlation coefficient (ICC) was between 0.440 and 0.757. The highest concurrent validity was PDQ-5-D (r=0.812, P< 0.001). PDQ-5-D was positively correlated with HAMD-17 and SDS score (P< 0.01). The objective test had no significant correlation with HAMD-17 and SDS scores (P> 0.05).Conclusion: This study found that THINC-it can accurately present the cognitive impairment of patients with BD-D. It can be potentially applied in assessing the cognitive function of patients with BD-D although Symbol Check may not accurately reflect the level of cognitive function. The concurrent validity and retest reliability are lower than expected, we need to further increase the sample size to study.Keywords: bipolar depression, BD-D, major depressive depression, MDD, THINC-it, cognitive function, reliability, validity

Cui-juan Qian1 ,* Zhu-rong Xu1 ,* Lu-yan Chen,1 Yi-chao Wang,2 Jun Yao1 1Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, People’s Republic of China; 2Department of Medical Laboratory, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zhejiang 318000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Yao Email yaojuntzu@yeah.netBackground: LncRNA dysregulation is implicated in esophageal squamous cell carcinoma (ESCC) progression; However, the precise role and function of lncRNA MAFG-AS1 in ESCC remains unknown.Materials and Methods: Expressions of MAFG-AS1, miR-765, PDX1, GLUT1 and LDH-A were detected via qRT-PCR or/and Western blot in ESCC tissues and cell lines. CCK-8, transwell and glycolysis assays were used to investigate the effects of MAFG-AS1 on ESCC cell proliferation, migration, invasion and aerobic glycolysis after knockdown or overexpression of MAFG-AS1, and bioinformatics analyses, RNA pull-down and dual luciferase reporter systems were applied to investigate the interaction between MAFG-AS1, miR-765 and PDX1.Results: MAFG-AS1 was significantly up-modulated in ESCC tissues and cell lines. MAFG-AS1 significantly accelerated ESCC cell proliferation, migration, invasion and aerobic glycolysis. MAFG-AS1 competitively adsorbed miR-765, while miR-765 negatively modulated the expression of PDX1. miR-765 and PDX1 participated in the promotive effects of MAFG-AS1 on cell migration, invasion and aerobic glycolysis in ESCC cells.Conclusion: Our research indicates that the MAFG-AS1/miR-765/PDX1 axis accelerates ESCC cell proliferation, migration, invasion and aerobic glycolysis.Keywords: ESCC, MAFG-AS1, aerobic glycolysis, miR-765, PDX1

Yiling Yang,1,* Qiang Zhou,2,* Huiwen Pan,2 Liming Wang,1,3 Cheng Qian4 1Department of Oncology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, People’s Republic of China; 3Department of Respiratory, Xuhui Hospital-Affiliated Hospital of Zhongshan Hospital of Fudan University, Shanghai 200032, People’s Republic of China; 4Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liming Wang; Cheng Qian Email wanglim1130@126.com; qian.cheng@zs-hospital.sh.cnPurpose: The aim of this study was to screen the predisposed population and explore possible interactions between genetic polymorphisms and risk factors involved in the tumorigenesis and progression of ESCC (esophageal squamous cell carcinoma), in hope of identifying possible therapeutic targets along the way.Patients and Methods: Cases (1043) and controls (1315) were enrolled to evaluate the possible association between MAP3K1 SNPs and ESCC risk. Subgroup analyses include MAP3K1 variants, gender, age, smoking and drinking status.Results: Among all three single locus polymorphisms of MAP3K1, only the heterozygote genotype of rs702689 AG is shown to be associated with increased risk for developing ESCC (OR=1.272, 95% confidence interval=1.061– 1.525, p=0.009). Moreover, stratified analysis results observed altered susceptibility among patients with exposure to risk factors combined with certain genetic variant to ESCC.Conclusion: This study reveals that MAP3K1 rs702689 AG genotype might facilitate the tumorigenesis in ESCC, particularly among women, patients who were over 63y and those who never drink nor smoke.Keywords: single nucleotide polymorphism, esophageal cancer

Xiaoyuan Qian,1 Zhixian Wang,1 Jiaqiao Zhang,1 Qing Wang,1 Peng Zhou,1 Shaogang Wang,1 Bo Wang,1 Can Qian2 1Department of Urology Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Traditional Chinese Medicine and Rheumatology, Southwest Hospital, Army Military Medical University, Chongqing, ChinaCorrespondence: Shaogang WangTongji Hospital, 1095 Jiefang Avenue, Wuhan City, Hubei Province, People’s Republic of ChinaEmail sgwangtjm@163.comPurpose: Collecting duct carcinoma (CDC) is extremely rare and has high malignancy and poor prognosis. The purpose of this research is to explore the clinical characteristic, imaging, pathological diagnosis, treatment and prognostic outcome of CDCs.Materials and Methods: The clinical data of 12 CDC cases who had been surgically treated between August 2007 and August 2017 and verified the diagnosis of CDC by postoperative pathological and/or immunohistochemical staining (IHC) results were retrospectively analyzed, and related works of literature were reviewed. And Kaplan-Meier survival analysis was used to draw the survival curve and to calculate the survival rate and the median survival time.Results: According to the TNM stage system, 4 cases were in stage I, 2 in stage II,3 in stage III, and 3 in stage IV. On the computed tomograph and magnetic resonance imaging, CDC displayed that various shapes, unclear boundary and invasive growth into the renal parenchyma. Compared with small CDCs which did not change the contour of the kidney, large CDCs presented various imaging features. Microscopically, the typical morphology of CDCs was that collecting ducts or tubules were obviously infiltrated by tumor cells. A tubular, papillary, tubulopapillary or solid architectures with desmoplasia were often presented. And tumor cells had high-grade cytology or an infiltrative growth pattern. Necrosis of tumor cells also was common in many cases. The expression of biomarkers, such as PAX-8, INI-1, 34βE12, CK19, PAX-2, and vimentin, in most patients was detected by IHC. Eleven of all 12 cases received radical surgery, of whom 5 patients died 3– 11 months after surgery, and 1 case having undergone interventional embolization therapy died at 6 months after treatment due to multiple metastases. And 1 lost to contact. The overall 1-, 2-, and 5-year survival rates were 45.5%, 36.4%, and 8.8%, respectively, and the median survival time (MST) was 11 months.Conclusion: CDC has an aggressive clinical course, with a poor prognosis. The best way to treat CDC suspected by imaging examinations is radical surgery which can contribute to confirm the correct histopathological type. And post-operation follow-up is necessary.Keywords: collecting duct carcinoma, clinical characteristics, imaging, pathology, outcome

Jian Wang,1,2,* Teng Xu,3,4,* Jun Ying,1,* Wangxiao Zhou,1 Qianqian Chen,1 Changrui Qian,1 Xinyi Zhu,1 Kai Shen,1 Peizhen Li,1 Kewei Li,1 Qiyu Bao,1 Junwan Lu1,5 1Institute of Biomedical Informatics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Department of Laboratory Medicine, Ningbo First Hospital, Ningbo 315010, People’s Republic of China; 3Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 4Institute of Translational Medicine, Baotou Central Clinical Hospital of Inner Mongolia Medical University, Baotou 014040, People’s Republic of China; 5School of Medicine and Health, Lishui University, Lishui 323000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiyu Bao; Junwan LuInstitute of Biomedical Informatics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Chashan University Town, Ouhai District, Wenzhou 325035, People’s Republic of ChinaTel/Fax +86 577 86689779; +86 577 86689358Email baoqy@genomics.org.cn; lujunwan304041474@qq.comPurpose: The aim of this work was to identify a novel β-lactamase gene blaPAU-1 encoded on the plasmid of a clinical Pseudomonas aeruginosa isolate.Materials and methods: The clinical P. aeruginosa isolates were isolated from a hospital in southern China. Molecular cloning was performed to analyze the function of the resistance gene. The minimum inhibitory concentration (MIC) was determined by means of the agar dilution method to determine the antimicrobial susceptibilities of the strains. Whole-genome sequencing and comparative genomics analysis were performed to analyze the structures of the resistance gene-related sequences.Results: PAU-1 is a molecular class A, Bush-Jacoby group 2be enzyme which encoded 293 amino acids and shared 74% amino acid identity with a putative class A β-lactamase from Rhodoferax saidenbachensis. Cloned blaPAU-1 in Escherichia coli and P. aeruginosa conferred resistance to piperacillin and ampicillin, and elevated the MIC with a 2–3 dilution for some oxyimino-β-lactams in P. aeruginosa. The genetic environment of blaPAU-1 is tnpA-res-hp-relE-blaPAU-1-lysR, which is in accordance with the structure of a Tn3 transposon. Epidemiological investigation of blaPAU-1 in the same district did not show any evidences of molecular dissemination associated with this determinant.Conclusion: A novel class A β-lactamase gene, blaPAU-1, associated with the mobile genetic element was identified on a transferable plasmid in a clinical P. aeruginosa isolate. Strict surveillance for the emergence of the new determinant should be established and an effort should be made to block the dissemination of this determinant.Keywords: Pseudomonas aeruginosa, antimicrobial resistance, β-lactamase, PAU-1

Chunfa Qian,*,1 Bin Wang,*,2 Yuanjie Zou,*,1 Yansong Zhang,*,1 Xinhua Hu,*,1 Wenbo Sun,*,1 Hong Xiao,*,3 Hongyi Liu,1 Lei Shi21Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, People’s Republic of China; 3Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workBackground: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis.Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC.Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot.Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment.Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.Keywords: glioma stem cells, miR-145, demethoxycurcumin, proliferation, apoptosis

Qianliang Wang,1,* Hongzhen Ai,1,* Jinglin Liu,1,* Min Xu,2 Zhuang Zhou,1 Chen Qian,1 Ye Xie,1 Jun Yan1 1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; 2Department of Orthopedics, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China *These authors contributed equally to this work Background: Radicular pain, caused by a lesion or autologous nucleus pulposus (NP) implantation, is associated with alteration in gene expression of the pain-signaling pathways. lncRNAs have been shown to play critical roles in neuropathic pain. However, the mechanistic function of lncRNAs in lumbar disc herniation (LDH) remains largely unknown. Identifying different lncRNA expression under sham and NP-implantation conditions in the spinal cord is important for understanding the molecular mechanisms of radicular pain. Methods: LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. The mRNA and lncRNA microarray analyses demonstrated that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly altered at 7 days post operation. The expression patterns of several mRNAs and lncRNAs were further proved by qPCR.Results: LDH produced persistent mechanical and thermal hyperalgesia. A total of 19 lncRNAs was differentially expressed (>1.5-folds), of which 13 was upregulated and 6 was downregulated. In addition, a total of 103 mRNAs was markedly altered (>1.5-folds), of which 40 was upregulated and 63 downregulated. Biological analyses of these mRNAs further demonstrated that the most significantly upregulated genes in LDH included chemotaxis, immune response, and positive regulation of inflammatory responses, which might be important mechanisms underlying radicular neuropathic pain. These 19 differentially expressed lncRNAs have overlapping mRNAs in the genome, which are related to glutamatergic synapse, cytokine-cytokine receptor interaction, and the oxytocin-signalling pathway.Conclusion: Our findings revealed the alteration of expression patterns of mRNAs and lncRNAs in the spinal cord of rats in a radicular pain model of LDH. These mRNAs and lncRNAs might be potential therapeutic targets for the treatment of radicular pain. Keywords: lumbar disc herniation, spinal cord, radicular pain, lncRNA

Min Yin,1,* Yi Jiang,1,* Changrui Qian,1 Fei Wu,1 Yuanyuan Ying,1 Chongyang Wu,1 Peizhen Li,1 Jun Ying,1 Kewei Li,1 Teng Xu,1 Qiyu Bao,1 Caixia Sun2 1Department of Microbiology and Immunology, School of Laboratory Medicine and Life Sciences/Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 2Nursing Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China *These authors contributed equally to this work Purpose: The aim of this work was to investigate the molecular characterization of a clinical Enterococcus casseliflavus strain with a resistance plasmid. Materials and methods: En. casseliflavus EC369 was isolated from a patient in a hospital in southern China. The minimum inhibitory concentration was found by means of the agar dilution method to determine the antimicrobial susceptibilities of the strains. Whole-genome sequencing and comparative genomics analysis were performed to analyze the mechanism of antibiotic resistance and the horizontal gene transfer of the resistance gene-related mobile genetic elements. Results: En. casseliflavus EC369 showed resistance to erythromycin, kanamycin, and streptomycin, but was susceptible to vancomycin, ampicillin, and streptothricin and other antimicrobials. There were six resistance genes (aph3′, ant6, bla, sat4, and two ermBs) carried by a transposon identified on the plasmid pEC369 and a complete resistance gene cluster of vancomycin and a tet (M) gene encoded on the chromosome. This is the first complete plasmid sequence reported in clinically isolated En. casseliflavus. The plasmid with the greatest sequence identity with pEC369 was the plasmid of Enterococcus sp. FDAARGOS_375, followed by the plasmids of Enterococcus faecium strains F12085 and pRE25, whereas the sequence with the greatest identity to the resistance genes carrying a transposon of pEC369 was on the chromosome of Staphylococcus aureus strain GD1677. Conclusion: The resistance profiles of En. casseliflavus EC369 might contribute to the resistance genes encoded on the plasmid. The fact that the most similar sequence to the transposon carrying resistance genes of pEC369 was encoded in the chromosome of a S. aureus strain provides insights into the mechanism of dissemination of multidrug resistance between bacteria of different species or genera through horizontal gene transfer. Keywords: Enterococcus casseliflavus, antimicrobial resistance, transposon, molecular characteristics, comparative genomics analysis

Chenyuan Zhu,1,2,* Yuting Lv,3,4,* Chao Qian,1,2,* Zihao Ding,3,5 Ting Jiao,1,2 Xiaoyu Gu,1,2 Eryi Lu,6 Liqiang Wang,3 Fuqiang Zhang1,2 1Department of Prosthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, 3State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 4College of Mechanical and Electronic Engineering, Shandong University of Science and Technology, Qingdao, People’s Republic of China; 5Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA, USA; 6Department of Stomatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The interaction between the material and the organism affects the survival rate of the orthopedic or dental implant in vivo. Friction stir processing (FSP) is considered a new solid-state processing technology for surface modification. Purpose: This study aims to strengthen the surface mechanical properties and promote the osteogenic capacity of the biomaterial by constructing a Ti-6Al-4V (TC4)/zinc (Zn) surface nanocomposites through FSP. Methods: FSP was used to modify the surface of TC4. The microstructures and mechanical properties were analyzed by scanning electron microscopy, transmission electron microscopy, nanoindentation and Vickers hardness. The biological properties of the modified surface were evaluated by the in vitro and in vivo study. Results: The results showed that nanocrystalline and numerous β regions, grain boundary a phase, coarser acicular α phase and finer acicular martensite α' appeared because of the severe plastic deformation caused by FSP, resulting in a decreased elastic modulus and an increased surface hardness. With the addition of Zn particles and the enhancement of hydrophilicity, the biocompatibility was greatly improved in terms of cell adhesion and proliferation. The in vitro osteogenic differentiation of rat bone marrow stromal cells and rapid in vivo osseointegration were enhanced on the novel TC4/Zn metal matrix nanocomposite surface. Conclusion: These findings suggest that this novel TC4/Zn surface nanocomposite achieved by FSP has significantly improved mechanical properties and biocompatibility, in addition to promoting osseointegration and thus has potential for dental and orthopedic applications. Keywords: nanocomposite, friction stir processing, nanocrystalline/ultrafine grained, bone marrow stromal cells, cell proliferation, osteogenic differentiation

A simple mechanical model is proposed to describe the dynamics system of the taut inclined cable excited by the deck vibration. Using Galerkin method, the dynamics system is simplified into a one-degree of freedom nonlinear system. Average method is used to obtain the average equations and bifurcation equation. Bifurcation maps are obtained and used to reveal the evolution mechanism of period-1 motion to period-2 motion. Several motion forms are discussed and evolution progress between different motions is studied. Several kinds of parametric resonance are revealed in various parameter regions. The conclusions indicate that the parametric resonance excited by the frequency ratio 3:2 is significant should be paid more attention.

Panshi Yan, Cheng Qian, Wenzhan Wang, Yi Dong, Guangming Wan, Yue Chen Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Background: This study was designed to examine the clinical effects of treating diabetic macular edema with an intravitreal injection of ranibizumab in combination with retinal photocoagulation.Methods: Sixty-two cases (75 eyes) with confirmed severe proliferative diabetic retinopathy or proliferative diabetic retinopathy in combination with macular edema were randomly divided into the observation group (37 eyes were given an intravitreal injection of ranibizumab combined with retinal photocoagulation) and the control group (38 eyes received retinal photocoagulation only). Vision, fundus condition, central macular thickness, and the macular leakage area were recorded before and after treatment.Results: The best-corrected visual acuity and macular leakage area were similar between the observation and control groups (P>0.05). The best-corrected visual acuity in the observation group was higher than that in the control group 3 and 6 months after treatment (P0.05). The central macular thickness of the observation group was lower than that in the control group 1, 3, and 6 months after treatment (P

Tao Ren,1–3,* Jinlu Shan,1,* Mengxia Li,1 Yi Qing,1 Chengyuan Qian,4 Guangjie Wang,5 Qing Li,1,3 Guoshou Lu,1 Chongyi Li,1 Yu Peng,1 Hao Luo,1 Shiheng Zhang,1 Yuxing Yang,1 Yi Cheng,1 Dong Wang,1 Shu-Feng Zhou31Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 2Department of Oncology, The Affiliated Hospital, North Sichuan Medical College, Sichuan, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 4Department of Oncology, The 97 Hospital of PLA, Jiangsu, 5Cancer Diagnosis and Treatment Center, Military District General Hospital of Chengdu Military Region, Sichuan, People’s Republic of China*These authors contributed equally to this workAbstract: AT-101 is a BH3 mimetic and pan-Bcl-2 inhibitor that has shown potent anticancer activity in non-small-cell lung cancer (NSCLC) in murine models, but failed to show clinical efficacy when used in combination with docetaxel in NSCLC patients. Our recent study has demonstrated that AT-101 enhanced the antitumor effect of cisplatin (CDDP) in a murine model of NSCLC via inhibition of the interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway. This study explored the underlying mechanisms for the enhanced anticancer activity of CDDP by AT-101. Our results show that, when compared with monotherapy, AT-101 significantly enhanced the inhibitory effects of CDDP on proliferation and migration of A549 cells and on tube formation and migration in human umbilical vein endothelial cells. AT-101 promoted the proapoptotic activity of CDDP in A549 cells. AT-101 also enhanced the inhibitory effect of CDDP on DNA repair and redox activities of apurinic/apyrimidinic endonuclease 1 (APE1) in A549 cells. In tumor tissues from nude mice treated with AT-101 plus CDDP or monotherapy, the combination therapy resulted in greater inhibition of angiogenesis and tumor cell proliferation than the monotherapy. These results suggest that AT-101 can enhance the antitumor activity of CDDP in NSCLC via inhibition of APE1 DNA repair and redox activities and by angiogenesis and induction of apoptosis, but other mechanisms cannot be excluded. We are now conducting a Phase II trial to examine the clinical efficacy and safety profile of combined use of AT-101 plus CDDP in advanced NSCLC patients.Keywords: AT-101, cisplatin, non-small-cell lung cancer, apurinic/apyrimidinic endonuclease 1, angiogenesis, tumor

Tao Ren,1,2,* Jinlu Shan,1,* Yi Qing,1 Chengyuan Qian,1 Qing Li,1 Guoshou Lu,1 Mengxia Li,1 Chongyi Li,1 Yu Peng,1 Hao Luo,1 Shiheng Zhang,1 Weiwei Zhang,1 Dong Wang,1 Shu-Feng Zhou3 1Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China; 2Oncology Department, The Affiliated Hospital, North Sichuan Medical College, Nanchong, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work Abstract: AT-101, known as R-(–)-gossypol, is a potent anticancer agent, but its chemosensitizing effects remain elusive. The present study aimed to examine whether AT-101 could increase the sensitivity of non-small cell lung cancer A549 cells to cisplatin (CDDP) and the underlying mechanisms. We evaluated the efficacy of the sequential treatment with AT-101 and CDDP using both in vitro and in vivo models. Our results showed that as compared to AT-101 or CDDP monotherapy, or AT-101 plus CDDP concurrent treatment, the sequential treatment significantly inhibited cell proliferation and migration and induced tumor cell death. Moreover, the efficacy of the sequential treatment was also confirmed in a mouse A549 xenograft model. Our study revealed that AT-101 inhibited the reduced status of apurinic/apyrimidinic endonuclease 1 (APE1) and attenuated APE1-mediated IL-6/STAT3 signaling activation by decreasing IL-6 protein expression; suppressing the STAT3–DNA binding; and reducing the expression of the downstream antiapoptotic proteins Bcl-2 and Bcl-xL. In conclusion, AT-101 enhances the sensitivity of A549 cells to CDDP in vitro and in vivo through the inhibition of APE1-mediated IL-6/STAT3 signaling activation, providing a rationale for the combined use of AT-101 and CDDP in non-small cell lung cancer chemotherapy. Keywords: AT101, NSCLC, cisplatin, chemosensitivity, APE1, STAT3, nude mice, apoptosis

Jiangdong Sui,1,2 Mengxia Li,1 Chengyuan Qian,1 Shufeng Wang,3 Yi Cheng,1 Benjamin PC Chen,2 Dong Wang1 1Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China; 2Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Institute of Immunology, PLA, College of Basic Medical Sciences, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein possessing both DNA repair and redox regulatory activities. It has been shown that blocking redox function leads to genotoxic, antiangiogenic, cytostatic, and proapoptotic effects in cells. Therefore, the selective inhibitors against APE1’s redox function can be served as potential pharmaceutical candidates in cancer therapeutics. In the present study, we identified the biological specificity of the Chinese herbal compound tanshinone IIA (T2A) in blocking the redox function of APE1. Using dual polarization interferometry, the direct interaction between APE1 and T2A was observed with a KD value at subnanomolar level. In addition, we showed that T2A significantly compromised the growth of human cervical cancer and colon cancer cells. Furthermore, the growth-inhibitory or proapoptotic effect of T2A was diminished in APE1 knockdown or redox-deficient cells, suggesting that the cytostatic effect of T2A might be specifically through inhibiting the redox function of APE1. Finally, T2A pretreatment enhanced the cytotoxicity of ionizing radiation or other chemotherapeutic agents in human cervical cancer and colon cancer cell lines. The data presented herein suggest T2A as a promising bioactive inhibitor of APE1 redox activity. Keywords: tanshinone IIA, APE1, redox activity, multifunctional protein

Yinting Chen1, Weiwei Wang2, Guoda Lian1, Chenchen Qian1, Lingyun Wang1, Linjuan Zeng1, Chengde Liao3, Biling Liang4, Bing Huang5, Kaihong Huang1, Xintao Shuai21Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Kunming, 4Department of Radiology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 5Center of Animal Research, Zhongshan Ophthalmic Center Hospital of Sun Yat-sen University, Guangzhou, ChinaAbstract: An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFvCD44v6,-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFvCD44v6-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFvCD44v6-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.Keywords: tumor targeting, CD44 variant 6, nonviral vector, small interfering RNA, magnetic resonance imaging

The authors regret the following minor errors in the published article: In Section 2.1 (Materials), two chemicals, lead iodide and ethanol, were accidentally omitted from the list. The revised text should read:

Three dimensional epitaxially-fused colloidal quantum dot (QD) superlattices (epi-SLs) feature exceptional electronic coupling and spatial order and are promising systems for studying the emergence of delocalized states and mini-band charge transport in self-assembled solids. However, energy disorder arising from structural defects and aperiodicity has so far resulted in charge carrier localization and slow hopping transport. Detailed 3D structural characterization is critical for rationally improving epi-SL structural perfection to trigger the formation of mini-bands. Here, we analyze the 3D structure of a 120 × 38 nm disc-shaped region of a PbSe QD epi-SL using full-tilt high-angle annular dark-field electron tomography. The high spatial resolution of the tomographic reconstruction (0.65 nm) enables determination of the center-of-mass coordinates of all 1846 QDs in the sample as well as the size and shape of the thousands of epitaxial connections (necks) between the QDs. The tomogram reveals the detailed crystallography and internal positional disorder of the three SL grains that constitute this sample. A map of the neck network is used to quantify relationships between neck number (the number of necks each QD possesses), average neck diameter, QD location in the film, and the nearest neighbor inter-QD distance and distance distribution. We find a strong positive correlation between neck number and local spatial order, suggesting that future improvements in neck connectivity are likely to simultaneously enhance the overall structural perfection of the epi-SLs. A kinetic Monte Carlo model is employed to estimate the electron mobility of the tomography sample and assess the impact of grain boundaries on charge transport. Our electron tomography study establishes a baseline for the quantitative statistical analysis of structural defects in 3D QD epi-SLs.

Oriented attachment of nanocrystals is an important route to constructing epitaxially-connected nanocrystal superlattices for various applications. During oriented attachment of semiconductor nanocrystals, neck can be formed between nanocrystals and it strongly influences the properties of the resulting superlattice. However, the neck formation mechanism is poorly understood. Here, we use in situ liquid cell transmission electron microscopy to directly observe the initiation and growth of homoepitaxial necks between PbSe nanocrystals with atomic details. We find that neck initiation occurs slowly (~ 10 s) when two nanocrystals approach to each other within an edge-to-edge distance of 0.6 nm. During neck initiation, Pb and Se atoms defuse from other facets into the gap, forming “dynamic reversible” filaments. Once the filament (neck) width is larger than a critical size of 0.9 nm, it gradually (15 s) widens into a 3-nm-wide neck. The atomic structure of the neck is further obtained using ex situ aberration-corrected scanning TEM imaging. Neck initiation and growth mechanisms are elucidated with density functional theory calculations. Our direct unveiling of the atomic pathways of neck formation during oriented attachment shed light into the fabrication of nanocrystal superlattices with improved structural order and electronic properties. [Figure not available: see fulltext.].

A polyisoprene-sulfur (PIPS) copolymer and nano sulfur composite material (90 wt % sulfur) is synthesized through inverse vulcanization of PIP polymer with micrometer-sized sulfur particles for high-areal-capacity lithium sulfur batteries. The polycrystalline structure and nanodomain nature of the copolymer are revealed through high-resolution transmission electron microscopy (HRTEM). PIP polymer is also used as binders for the electrode to further capture the dissovlved polysulfides. A high areal capacity of ca. 7.0 mAh/cm2 and stable cycling are achieved based on the PIPS nanosulfur composite with a PIP binder, crucial to commercialization of lithium sulfur batteries. The chemical confinement both at material and electrode level alleviates the diffusion of polysulfides and the shuttle effect. The sulfur electrodes, both fresh and cycled, are analyzed through scanning electron microscopy (SEM). This approach enables scalable material production and high sulfur utilization at the cell level.