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Xing Wei,1 Xinyi Wei,2 Xiaotong Yu,1 Feifei Ren1 1Department of Psychology, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2College of Engineering, Northeastern University, Boston, MA, USACorrespondence: Feifei Ren, Department of Psychology, Qingdao University, No. 308 Ningxia Road, Qingdao, People’s Republic of China, Tel +86-13165021997, Email renfeifei@qdu.edu.cnPurpose: Economic pressure has become an important source of stress for employees. However, the conclusions regarding the relationship between financial stress and employees’ work behavior are not consistent. The present study explored the relationship between financial stress and employee job performance with a Chinese sample and further explored how and when financial stress influenced job performance.Samples and Methods: The present study investigated five distinct companies operating in diverse sectors using a convenience sampling technique. Three hundred and twenty-one employees were recruited. Financial Stress, Job Performance, Work Engagement, and Emotional Exhaustion were measured for this investigation. The mediation effect was tested using a four-step procedure. The analysis of the moderated mediation model was performed using Hayes’s PROCESS macro for SPSS.Results: The results found financial stress was positively related to job performance, and work engagement mediated the positive relationship between financial stress and job performance. In addition, emotional exhaustion moderated the mediating process between financial stress, work engagement, and job performance. Specifically, the beneficial effect of financial stress on work engagement disappeared when emotional exhaustion was high. Besides, a high level of emotional exhaustion weakened the positive relationship between work engagement and job performance.Conclusion: Financial stress plays a motivating role in employees’ job performance in China. Work engagement is a key factor between financial stress and job performance. Notably, the positive effect of financial stress and work engagement on job performance is contingent upon the individual’s level of emotional exhaustion. These results might explain the inconsistency of the effect of financial stress in previous research. Moreover, this finding suggests that emotional factors may not only be the result of stress but can also influence its effects.Keywords: financial stress, job performance, work engagement, emotional exhaustion, moderated mediation model

Yixin Liu,1 Feifei Ren,1 Shan Li,1 Xiangchen Li,1 Dongyan Shi,2 Zhiqing Zhang1 1Department of Pharmacy, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Clinical Laboratory, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Zhiqing Zhang, Department of pharmacy, the Second Hospital of Hebei Medical University, 215, Heping Road, Xinhua District, Shijiazhuang, Hebei, People’s Republic of China, Email 26500007@hebmu.edu.cn Dongyan Shi, Department of clinical laboratory, the Second Hospital of Hebei Medical University, 215, Heping Road, Xinhua District, Shijiazhuang, Hebei, People’s Republic of China, Email shidongyan73@126.comObjective: To define the antifungal activity of n-butylphthalide alone or in combination with fluconazole in Candida glabrata and Candida tropicalis.Methods: The antifungal activity of n-butylphthalide alone and in combination with fluconazole was investigated by the classical broth microdilution method and the time-killing curve method. The QRT-PCR method was used to determine gene expressions changes of mitochondrial respiratory chain enzymes, drug efflux pumps and drug target enzymes in Candida glabrata and Candida tropicalis after n-butylphthalide treatment.Results: The MIC values of n-butylphthalide against Candida glabrata and Candida tropicalis ranged from 16 to 64 μg·mL-1. The FICI value of the combination of n-butylphthalide and fluconazole against drug-resistant Candida glabrata and Candida tropicalis ranged from 0.5001 to 0.5315 with partial synergism. Time-killing curves showed that 256 μg·mL-1 n-butylphthalide significantly inhibited the growth of drug-resistant colonies of Candida glabrata and Candida tropicalis, and 128 μg·mL-1 n-butylphthalide combined with 1 μg·mL-1 fluconazole had an additive effect. N-butylphthalide could alter the expression of mitochondrial respiratory chain enzymes COX1, COX2, COX3, and CYTB genes in Candida glabrata and Candida tropicalis (P< 0.05) and downregulate the expression of the drug efflux pump genes CDR1 and CDR2 in drug-resistant Candida glabrata to 3.36% and 3.65%, respectively (P< 0.001), but did not affect the drug target enzyme ERG11 in drug-resistant Candida tropicalis.Conclusion: N-butylphthalide had antifungal activity against Candida glabrata and Candida tropicalis. N-butylphthalide improved the activity of fluconazole against drug-resistant Candida glabrata by affecting the expression of mitochondrial respiratory chain enzyme genes and reversing the high expression of drug efflux pump genes CDR1 and CDR2.Keywords: n-butylphthalide, fluconazole, drug resistance, Candida glabrata, Candida tropicalis, potentiation

Dan Yu, Wenhan Huang, Min Sheng, Shan Zhang, Hang Pan, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin Tang, Department of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of China, Tel +86 23 63693878, Fax +86 23 62888265, Email hopetang@hospital.cqmu.edu.cnPurpose: Inflammation triggers a metabolic shift in macrophages from oxidative phosphorylation to glycolysis, a phenomenon known as the Warburg effect. This metabolic reprogramming worsens inflammation and cascades into organ damage. Angiotensin-(1-7) [Ang-(1-7)], a small molecule, has demonstrated anti-inflammatory properties. This study investigates whether Ang-(1-7) mitigates inflammation in LPS-induced macrophages and septic mice by regulating the Warburg effect in immune metabolism.Methods: The study induced macrophages with LPS in vitro and measured inflammatory factors using ELISA and Western blot. Key enzymes in glycolysis, mitochondrial respiratory complexes, and citrate pathway key molecules were assessed using Western blot and qRT-PCR. Mitochondrial membrane potential (MMP), lactate, and ATP were measured using assay kits. In vivo, a mouse model of sepsis induced by LPS was used. Kidney tissues were examined for pathological and mitochondrial ultrastructural alterations. The levels of inflammatory factors in mouse serum, glycolysis and citrate pathway-related molecules in the kidney were assessed using qRT-PCR, Western blot, and immunofluorescence techniques. Additionally, MMP, lactate, and ATP in the kidney were measured using assay kits.Results: In vitro experiments demonstrated that Ang-(1-7) inhibited the levels of inflammatory factors in LPS-treated RAW264.7 cells. It also reduced the expression of key glycolytic enzymes HK2, PFKFB3, and PKM2, as well as lactate levels. Additionally, it decreased intracellular citrate accumulation, enhanced mitochondrial respiratory complexes I and III, and ATP levels. Ang-(1-7) alleviated MMP damage, modulated citrate pathway-related molecules, including SLC25A1, ACLY, and HIF-1α. In vivo experiments showed that Ang-(1-7) lowered glycolysis levels in septic mice, improved mitochondrial ultrastructure and function, mitigated inflammation and renal tissues damage in septic mice, and suppressed the expression of key molecules in the citrate pathway.Conclusion: In conclusion, Ang-(1-7) can regulate the Warburg effect through the citrate pathway, thereby alleviating inflammation in LPS-induced macrophages and septic mice.Keywords: Ang-(1-7), macrophage, sepsis, Warburg effect, glycolysis, citrate

Hong-Liang Jia,1 Jian Gao,2 Feng Ren,2 Yaping Ma1 1Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of ChinaCorrespondence: Yaping Ma, Department of Pediatrics, Affiliated Hospital of Jiangnan University, No. 1000 of Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86 510-68089896, Email mayp987@163.comObjective: We retrospectively analysed related clinical data to determine the influencing factors to better prevent and treat children’s respiratory tract infection.Methods: The study participants were children with respiratory tract infection who had sputum cultured in our hospital between 2014 and 2021. Sputum samples were extracted using negative suction pressure and sent to the hospital microbiological laboratory for testing. The testing results were analysed.Results: A total of 4610 sputum samples were collected, and 508 positive samples were detected. The positive rate of pathogenic bacteria was 11.02%. Escherichia coli infection was more common in male patients (11.11%), whereas Haemophilus influenzae infection was more common in female patients (17.54%); the infection rates of these 2 bacteria are increasing annually. There were 304 (59.84%) strains of gram-negative bacteria, 172 (33.86%) strains of gram-positive bacteria and 32 (6.3%) strains of fungi. In children between 0 and 3 years old, the proportions of gram-negative bacteria were significantly higher than those of gram-positive bacteria in 2016– 2017, 2018– 2019 and 2020– 2021 (p

Ren F, Shrestha C, Shi H, et al. Onco Targets Ther. 2020;13;9419-9428. At the authors request, we, the Editor and Publisher of the journal OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from another article authored by the first author, Fang Ren. Specifically, The image for Figure 4H, OVCAR-8, miR-421 mimics, has been duplicated with an image for Figure 4F, MDA-MB-231, anti-miR-374a, from Zhang J, He Y, Yu Y, et al. Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. Cancer Med. 2018;7:3351–3362. https://doi.org/10.1002/cam4.1576. In addition, images for Figure 5D, Lenti-NC group and Lenti-miR-421, Ki-67 have been duplicated. The authors responded to our queries but were unable to provide a satisfactory explanation for the duplicated images or provide satisfactory data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and we, the editor and publisher, agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Juanru Wei,1,&ast; Cong Zhang,2,&ast; Wei Ma,1 Juncheng Ma,1 Zhenzhen Liu,1 Fucai Ren,1 Ning Li1 1School of Pharmacy, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Li; Fucai Ren, School of Pharmacy, Anhui Medical University, No. 81 Meishan Road Shushan District, Hefei, 230032, People’s Republic of China, Tel/Fax +86-5516-516-1115, +86-5516-517-2133, Email 1993500019@ahmu.edu.cn; renfucai@ahmu.edu.cnPurpose: The drug resistance of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae has become more and more serious, and it is urgent to seek new antibacterial drugs. In this study, Thesium chinense Turcz. extracts were tested for its potential antibacterial activities.Methods: T. chinense powder was extracted with 5 solvents of different polarity (ethyl alcohol, petroleum ether, ethyl acetate, n-butyl alcohol and double distilled water), and their antibacterial activities were tested. The Broth dilution method was used to evaluate the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of highly active plant extracts with a concentration of 1g/mL. The inhibitory activity of this extract on biofilm formation was investigated. Afterwards, we investigated its effect on the transcriptome of S. aureus.Results: The ethanol extract coded as BRY, only inhibited S. aureus, whereas the ethyl acetate extract coded as BY2 showed inhibitory effect on all the tested bacteria. The MIC of BRY on S. aureus was 128 mg/mL, and the MBC was 512 mg/mL. The MIC of BY2 against S. aureus, S. pneumoniae, S. pyogenes and H. influenzae were 8 mg/mL, 4 mg/mL, 4 mg/mL, and 4 mg/mL, respectively. The MBC of BY2 for these four bacteria ranged from 4 to 256 mg/mL. Mechanism studies have shown that BRY and BY2 have an impact on anti-formation of biofilms at MIC concentrations. Transcriptome sequencing results showed that 531 genes were up-regulated and 340 genes showed down-regulated expression in S. aureus after BY2 treatment.Conclusion: BY2 has a broader antibacterial spectrum than BRY. Meanwhile, the inhibitory effect of BY2 on S. aureus is better than BRY. The mechanism of BY2 against S. aureus may relate to its inhibition of ribosome synthesis, restriction of key enzymes of citric acid cycle, decrease of pathogenicity and influence on biofilm formation. The results confirmed that BY2 was the main antibacterial part of T. chinense, which can be used as a source of antibacterial agents.Graphical Abstract: Keywords: plant extract, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, antibacterial

Zhihuan Zhang, Wenhan Huang, Feifeng Ren, Lei Luo, Jun Zhou, Mengxue Tian, Zhongjie Wang, Dandan Chen, Lin Tang Department of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin Tang, Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Email hopetang@163.comPurpose: To explore the risk factors for thrombi occurring in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and establish a risk prediction model to better predict the risk of thrombosis in patients with AAV.Patients and Methods: We retrospectively analyzed 117 AAV patients who had been hospitalized in The Second Affiliated Hospital of Chongqing Medical University between October 2010 and December 2021. For all patients, we recorded demographic characteristics and clinical data, analyzed the risk factors for thrombosis in AAV patients and then developed a risk prediction model.Results: Stepwise logistic regression analysis indicated that a high complement C3 level, a high BVAS score and a high Padua score were independent risk factors for thrombosis in AAV patients. According to multivariate analysis, a predictive model for thrombus risk was successfully established; the area under the ROC curve(AUC) was 0.803 (95% CI: 0.716– 0.890) and the maximum Youden index, sensitivity and specificity were 0.487, 59.0% and 89.7%, respectively.Conclusion: A high complement C3 level, high BVAS score, and a high Padua score were shown to be independent risk factors for thrombosis in AAV patients. We developed a risk prediction model based on these three risk factors that could predict the risk of thrombosis in AAV patients to some extent.Keywords: antineutrophil cytoplasmic antibody, thromboembolism, risk factors, risk prediction model

Jin-Bao Ma,1 Ling-Cheng Zeng,2 Fei Ren,1 Li-Yun Dang,1 Hui Luo,1 Yan-Qin Wu,1 Xin-Jun Yang,1 Rong Li,1 Han Yang,3 You Xu1 1Department of Drug-Resistance Tuberculosis, Xi’an Chest Hospital, Xi’an, People’s Republic of China; 2Xi’an Center for Disease Control and Prevention, Xi’an, People’s Republic of China; 3Department of Clinical Laboratory, Xi’an Chest Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Fei Ren; You Xu, Department of Drug-resistance tuberculosis, Xi’an Chest Hospital, West Section of HangTian Avenue, Yanta District, Xi’an, People’s Republic of China, Email doc.renfei@163.com; xuyou7575@126.comBackground: Long-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known.Methods: This was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi’an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression.Results: Of the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age > 40 years (OR = 3.25, 95% CI = 2.12– 4.98), male sex (OR = 2.53, 95% CI = 1.52– 4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11– 2.61), whereas poor treatment outcome risk factors were age > 40 years (OR = 5.51, 95% CI = 2.52– 12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45– 7.51), and smear-positive (OR = 4.0, 95% CI = 1.47– 10.8).Conclusion: In Xi’an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.Graphical Abstract: Keywords: tuberculosis, multidrug-resistant, treatment outcomes, risk factors, China

Lichuan Zeng,1,&ast; Qu Wang,2,&ast; Haodong Liao,1,&ast; Fengchun Ren,1 Yudong Zhang,1 Jian Du,3 Huaqiang Liao,1 Mingguo Xie,1 Wenbin Wu3 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingguo Xie, Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email 767030837@qq.com Wenbin Wu, Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, People’s Republic of China, Email wwb1201@vip.sina.comPurpose: We aimed to investigate the prevalence of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and the clinical–radiological correlation in transient ischemic attack (TIA) patients.Materials and Methods: We performed a retrospective analysis of TIA patients who had undergone magnetic resonance imaging (MRI) within 24 h of symptom onset. Two independent neuroradiologists investigated the presence of FVHs, large-artery severe stenosis or occlusion (LASO) in magnetic resonance angiograms, and the nature of factors associated with FVH.Results: A total of 207 patients were enrolled in this study. FVHs were detected in 42 (20.3%) patients, in whom atrial fibrillation (AF) was confirmed in 25 (59.5%) cases and LASO was confirmed in 30 (71.4%) cases. The corresponding figures were 33 (20.0%) and 10 (6.1%), respectively, for the 165 FVH-negative patients. Logistic regression analysis showed that time from symptom onset to MRI (odds ratio [OR] = 0.82, 95% CI 0.76– 0.97, p = 0.042), previous stroke (OR = 2.95, 95% CI 1.58– 6.74, p = 0.002), AF (OR = 5.83, 95% CI 2.24– 9.46, p < 0.001), and LASO (OR = 4.28, 95% CI 2.96– 10.28, p < 0.001) were independently associated with FVH. Overall, the sensitivity and specificity of FVH for predicting LASO were 0.75 and 0.93, respectively, and the positive predictive value, negative predictive value, and accuracy were 0.71, 0.94, and 0.89, respectively. The area under the receiver operating characteristic curve was 0.839. FVH-positive TIA patients with LASO had less AF (14 [46.7%] versus 11 [91.7%], p = 0.019) and longer times from symptom onset to MRI (6.8 ± 2.8 h versus 4.8 ± 1.3 h, p = 0.004) than those without LASO.Conclusion: The presence of FVH could be an important marker in TIA patients. Many factors, including LASO, AF, and time from symptom onset to MRI, are associated with the detection of FVH.Keywords: FLAIR vascular hyperintensity, hyperintense vessel, transient ischemic attack, magnetic resonance imaging

Xue C, He Y, Hu Q, et al. Cancer Manag Res. 2018;10:5101–5112. We, the Editors and Publisher of Cancer Management and Research, have retracted the published article. Concerns were raised about the integrity of the data in the article following the author’s request to correct images in Figures 2 and 3. It was found images from these figures had been duplicated within the article and with those from another article. Specifically, The images for Figure 2D, GBC-SD, NC and PIM1-siRNA, have been duplicated with the images for Figure 3C, GBC-SD, NC and NOZ, PIM1-siRNA, respectively. The images for Figure 2D, NOZ, NC, have been duplicated with the images from Figure 5d, Hep3B, PLK-4 from Bao J, Yu Y, Chen J, et al. MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway. Cell Death Dis. 2018;9:1045. https://doi.org/10.1038/s41419-018-1020-0. When approached for an explanation, the authors were cooperative and provided some original data for their study, however, the provided data was not satisfactory, and the results could not be adequately verified. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Jun Zhou, Wenhan Huang, Feifeng Ren, Lei Luo, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, People’s Republic of ChinaEmail tanglin1217@163.comObjective: The aim of our study was to elucidate the potential prognostic factors in anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive patients.Methods: We divided anti-MDA5-positive patients into death and survival groups. The differences in clinical characteristics were analyzed.Results: A total of 56 cases were included. The death group comprised 10 (17.9%) cases, and the survival group comprised 46 (82.1%) cases. Median age of the death group was greater than the survival group, 59.50 years vs 39.25 years, p< 0.05. The death group had lower lymphocyte count and albumin and higher erythrocyte sedimentation rate, ferritin and lactate dehydrogenase initially (p< 0.05, respectively). Ground-glass opacity on chest computed tomography was found more often in the death group (p< 0.05), in which there was an absence of honey-combed shadow initially. The diagnosis of interstitial pneumonia with autoimmune features was higher in the death group than the survival group (70% vs 13%, p< 0.05). The median dose of maximum daily methylprednisolone in the death group (160 mg/d) was higher than that in the survival group (48 mg/d) (p< 0.05).Conclusion: Advanced age, low lymphocyte count and albumin, and increased levels of inflammatory markers may portend poor prognosis in anti-MDA5-positive patients. Extra-large doses of glucocorticoid may have no additional benefit in these patients.Keywords: anti-melanoma differentiation-associated gene 5 antibody, interstitial lung disease, clinical manifestation, prognosis

Wenhan Huang, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaEmail hopetang@163.comObjective: Clinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+).Methods: Body-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University.Results: Plasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI.Conclusion: 1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.Keywords: anti-melanoma differentiation-associated gene 5 antibodies, anti-Ro-52 antibody, lipid, high-density lipoprotein, apolipoprotein A1

Hang Pan, Wenhan Huang, Zhongjie Wang, Feifeng Ren, Lei Luo, Jun Zhou, Mengxue Tian, Lin Tang Department of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 13795683033Fax +86 23 62888265Email hopetang@163.comPurpose: Angiotensin 1– 7 [Ang-(1-7)] has been identified as an important anti-inflammatory and anti-fibrotic factor. This study determined how the ACE2-Ang-(1-7)-Mas axis affected M1/M2 macrophage polarization and thus contributed to anti-inflammatory processes in the cecal ligation and puncture (CLP)-induced inflammation model.Materials and Methods: ELISA, western blotting, and qRT-PCR were used to verify that Ang-(1-7) decreased the expression of pro-inflammatory cytokines and increased anti-inflammatory cytokines. The differentiation of M1/M2 macrophages was assessed by flow cytometry for assessing the cell-surface markers, CD86 and CD206. The related key receptors and pathways were analyzed by Western blotting, qRT-PCR, and immunofluorescence. CLP-induced inflammatory mice models were used for in vivo studies. Hematoxylin and eosin and immunohistochemical and immunofluorescence staining protocols were used to analyze histological changes in the spleen, and the related key pathway proteins were analyzed by western blotting.Results: Ang-(1-7) decreased the expressions of the TNF-α and IL-6 pro-inflammatory cytokines and increased the expressions of the IL-4 and IL-10 anti-inflammatory cytokines. INOS and TNF-α, which represented M1 macrophage polarization, were decreased by Ang-(1-7). ARG1 and CD163, which represented M2 macrophage polarization, were increased by Ang-(1-7). Both Mas receptor and ACE2 are expressed on macrophages. Furthermore, the ACE2-Ang-(1-7)-MAS axis modulated macrophage polarization by ameliorating TLR4 expression and regulating the NF-кB and MAPK pathways. In addition, splenomegaly and macrophage infiltration were observed in the spleen of the CLP-induced mouse models and macrophages in the spleen suspension of CLP models were shifted to M1 phenotype and were effectively inhibited by Ang-(1-7) via the TLR4-mediated NF-кB and MAPK pathways, which could be partially rescued by A-779.Conclusion: Ang-(1-7) inhibited inflammatory responses in vivo and in vitro, and repressed macrophage polarization toward the M1 phenotype and promoted it toward the M2 phenotype, which provided new evidence for the anti-inflammation activity of the ACE2-Ang-(1-7)-MAS axis.Keywords: ACE2-Ang-(1‑7)-MAS axis, macrophage polarization, sepsis, NF-kB pathway, MAPK pathway

Lichuan Zeng,1 Huaqiang Liao,1 Fengchun Ren,1 Yudong Zhang,1 Qu Wang,2 Mingguo Xie1 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Mingguo Xie; Qu WangHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail 767030837@qq.com; 444028177@qq.comAbstract: Percutaneous computed tomography (CT)-guided transthoracic needle biopsy (TTNB) is a valuable procedure for obtaining tissue or cells for diagnosis, which is especially indispensable in thoracic oncology. Pneumothorax and hemoptysis are the most common complications of percutaneous needle biopsy of the lung. According to reports published over the past decades, pneumothorax incidence in patients who underwent TTNB greatly varies. The morbidity of pneumothorax after CT-guided TTNB depends on several factors, including size and depth of lesions, emphysema, the number of pleural surfaces and fissure crossed, etc. Attention to biopsy planning and technique and post-biopsy precautions help to prevent or minimize potential complications. Many measures can be taken to help prevent the progression of a pneumothorax, which in turn might reduce the number of pneumothoraces requiring chest tube placement. A multitude of therapeutic options is available for the treatment of pneumothorax, varying from observation and oxygen treatment, simple manual aspiration, to chest tube placement. When a pneumothorax develops during the biopsy procedure, it can be manually aspirated after the needle is retracted back into the pleural space or by inserting a separate needle into the pleural space. Biopsy side down positioning of the patient after biopsy significantly reduces the incidence of pneumothorax and the requirement of chest tube placement. Aspiration in biopsy side down position is also recommended for treating pneumothorax when simple manual aspiration is unsuccessful or delayed pneumothorax occurred. Chest tube placement is an important treatment strategy for patients with a large or symptomatic pneumothorax. Clinicians are encouraged to understand the development, prevention, and treatment of pneumothorax. Efforts should be made to reduce the incidence of pneumothorax in biopsy planning and post-biopsy precautions. When pneumothorax occurs, appropriate treatment should be adopted to reduce the risk of worsening pneumothorax.Keywords: pneumothorax, lung biopsy, aspiration, chest tube placement, computed tomography, CT

Feifei Ren,1 Rongjuan Guo2 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section, Fangxingyuan, Fangzhuang, Fengtai District, Beijing City, People’s Republic of ChinaTel/Fax +86 10-6768-9655Email 381160563@qq.comAbstract: Depression is a major disease that can affect both mental and physical health, limits psychosocial functioning and diminishes the quality of life. But its complex pathogenesis remains poorly understood. The dynamic changes of synaptic structure and function, known as synaptic plasticity, occur with the changes of different cellular microenvironment and are closely related to learning and memory function. Accumulating evidence implies that synaptic plasticity is integrally involved in the pathological changes of mood disorders, especially in depressive disorder. However, the complex dynamic process of synaptic plasticity is influenced by many factors. Here, we reviewed and discussed various factors affecting synaptic plasticity in depression, and proposed a specific framework named synaptic microenvironment, which may be critical for synaptic plasticity under pathological conditions. Based on this concept, we will show how we understand the balance between the synaptic microenvironment and the synaptic plasticity network in depression. Finally, we point out the clinical significance of the synaptic microenvironment in depression.Keywords: depression, synaptic plasticity, synaptic microenvironment, glia, influence factors

Fang Ren, Christina Shrestha, Huirong Shi, Fangfang Sun, Minghui Zhang, Yuan Cao, Gailing Li Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Fang RenDepartment of Gynecology, First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, People’s Republic of ChinaTel +8613849115866Email renfang@foxmail.comPurpose: The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms.Materials and Methods: Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated.Results: Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P< 0.05), and miR-421 expression was reduced in ovarian cancer tissue (P< 0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly.Conclusion: The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells.Keywords: ovarian cancer, KDM5A/RBP2, miR-421, progression

Pan Wang,1,* Honglin Zhao,1,* Qingchun Zhao,1,* Fan Ren,1 Ruifeng Shi,1 Xingyu Liu,1 Jinghao Liu,1 Hongyu Liu,2 Gang Chen,1 Jun Chen1,2 1Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Chen Email huntercj2004@yahoo.comBackground: The incidence of venous thromboembolism (VTE) is higher in patients with lung cancer. The aim of this study was to investigate the risk factors associated with postoperative VTE and explore the VTE predication capacity of D-dimer kinetics.Patients and Methods: Six hundred patients who had lung tumor surgery were analyzed retrospectively between January 2018 and August 2019, and venous ultrasound imaging and D-dimer examination before and after surgery were recommended to all operative patients. Of these 600 patients, 523 patients had venous thromboembolism after surgery, and 77 patients had not found. The general clinical data, postoperative prophylactic anticoagulant therapy, early systemic thromboprophylaxis, 50% increment of D-dimer, 100% increment of D-dimer, and perioperative (preoperative and days 1, 3, and 5 after surgery) D-dimer levels were collected. Logistic regression analysis was used to analyze the independent risk factors of postoperative VTE.Results: VTE developed in 77 (12.8%) patients. In a univariate analysis, age, surgical approach, tumor size, histology, postoperative preventive anticoagulation, postoperative limb compression therapy, postoperative hemostasis, duration of operation, early systemic thromboprophylaxis, 100% increment of D-dimer, preoperative and postoperative D-dimer level, intraoperative blood loss, and time spent in the hospital were significantly different between the thrombus group and nonthrombus group (P < 0.05). Multivariate analysis showed that age > 60 years (P = 0.006) and D-dimer level on 5 days after surgery (P =  0.000) were significant independent risk factors for VTE. Postoperative D-dimer was significantly higher than the preoperative level (P < 0.001). Postoperative D-dimer level was significantly different between benign and malignant tumor groups (P < 0.05) and between the thrombus group and nonthrombus group (P < 0.001). Preventive anticoagulation and limb compression therapy starting from the first day after surgery was statistically significant between the thrombus group and the nonthrombus group (P < 0.05).Conclusion: Continuous detection of D-dimer level after pulmonary tumor surgery combined with thrombotic-related risk factors can better evaluate the occurrence of VTE. Preventive anticoagulant therapy and limb compression therapy starting from the first day after surgery can effectively reduce the incidence of VTE.Keywords: anticoagulants, D-dimer, lung neoplasms, risk factors venous thromboembolism

Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of ChinaTel +86 1 861 137 7633Fax +86 1064286498Email dfguorongjuan@163.comPurpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrial

Saixu Huang, 1–3,* Zhiyong Huang, 1–3,* Zhiqin Fu, 3,* Yamin Shi, 3, 4 Qi Dai, 1, 2 Shuyan Tang, 3 Yongwei Gu, 3 Youfa Xu, 3 Jianming Chen, 3, 4 Xin Wu, 3 Fuzheng Ren 1, 2 1Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuzheng RenSchool of Pharmacy, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, People’s Republic of ChinaTel/Fax +86 21 6425 3255Email fzren@ecust.edu.cnXin WuShanghai Weier Biological Medicine Science and Technology Co. Ltd., No. 358, Tian Chen Road, Shanghai 201799, People’s Republic of ChinaTel/Fax +86 21 3119 8947Email xinwu007@126.comPurpose: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study.Methods: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection.Results: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 ± 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37°C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD 50 of Nimotop injection with no obvious toxicity or side effects.Conclusion: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.Keywords: nimodipine, nanoemulsion, pharmacokinetics, MCAO, LD50

Majority of practical multivariate statistical analysis and optimizations model interdependence among random variables in terms of the linear correlation. Though linear correlation is simple to use and evaluate, in several cases non-linear dependence between random variables may be too strong to ignore. In this paper, we propose polynomial correlation coefficients as simple measure of multi-variable non-linear dependence and show that the need for modeling non-linear dependence strongly depends on the end function that is to be evaluated from the random variables. Then, we calculate the errors in estimation resulting from assuming independence of components generated by linear de-correlation techniques, such as PCA and ICA. The experimental results show that the error predicted by our method is within 1% error compared to the real simulation of statistical timing and leakage analysis. In order to deal with non-linear dependence, we further develop a target-function-driven component analysis algorithm (FCA) to minimize the error caused by ignoring high order dependence. We apply FCA to statistical leakage power analysis and SRAM cell noise margin variation analysis. Experimental results show that the proposed FCA method is more accurate compared to the traditional PCA or ICA. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fei Ren,1,2 Weiwei Weng,1,2 Qiongyan Zhang,1,2 Cong Tan,1,2 Midie Xu,1,2 Meng Zhang,1,2 Lei Wang,1,2 Weiqi Sheng,1,2 Shujuan Ni,1,2 Dan Huang1,21Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of ChinaBackground: High serum levels of alpha-fetoprotein (AFP) are observed in some gastrointestinal cancers. However, primary AFP-producing colorectal cancer (CRC) is extremely rare and causes confusion among clinicians. In this study, we analyzed the clinicopathological features and clinical outcomes of AFP-producing CRC and provide a brief view of this rare carcinoma.Patients and methods: Twenty patients with AFP-producing CRC were enrolled at the Fudan University Shanghai Cancer Center from 2012 to 2015. Clinical information, including serum AFP and CEA levels, and outcomes were collected. Tumors were divided into three histologic types: the common adenocarcinoma (COM) type, mucinous adenocarcinoma type and hepatoid type (HPT). Immunohistochemical (IHC) staining of GPC3, Hepa-1, SALL4 and Arg-1 was performed. Additionally, mutations of the KRAS, NRAS and BRAF genes were examined. Finally, another 40 stage-matched patients with traditional CRC were enrolled as controls for survival analysis.Results: AFP-producing CRC was more likely to occur in males (60%) and arose mainly from the ascending (40%) and sigmoid (35%) colon. In addition, the majority of patients with AFP-producing CRC had poor differentiation (50%), advanced local invasion (80%) and lymph node (LN) metastasis (60%). Synchronous distant metastasis was commonly observed (35%). Interestingly, serum AFP levels were closely associated with LN metastasis. Histopathologically, the COM type was the most common pattern. In IHC staining, the HPT pattern was the most distinct due to high positivity rates of GPC3, Hepa-1 and Arg-1. One patient had mismatch repair deficiency, and another had a KRAS mutation. Patients with AFP-producing CRC had worse progression-free and overall survival than patients with traditional CRC.Conclusion: AFP-producing CRC has unique clinical and histopathological characteristics, showing an aggressive biological behavior and worse prognosis than traditional CRC.Keywords: AFP-producing colorectal cancer, clinicopathological features, serum AFP, prognosis

Fangping Ren,1,* Tian Zhao,2,* Bing Liu,3 Lei Pan11Department of Respiratory, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 2Department of Clinical Laboratory, The 161st Hospital of PLA, Wuhan, 430010, People’s Republic of China; 3Department of Disease Control and Prevention, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to identify the prognostic value of blood neutrophil–lymphocyte ratio (NLR) in patients with advanced non-small-cell lung cancer (NSCLC) who received immune checkpoint blockade (ICB) therapy.Materials and methods: 147 advanced NSCLC patients were enrolled in this study from June 30, 2013, to August 30, 2017. Survival analysis used the Kaplan and Meier methodology. The mean follow-up time was 2.6 years. The phenotypic T cells subtypes were evaluated by flow cytometry.Results: Of these patients, receiver operating characteristic (ROC) curves analysis were used to confirm the cut-off value, and patients were stratified into NLR>2.5 (n=88) and NLR≤2.5 (n=59) groups. Survival analysis showed that patients with NLR≤2.5 had significantly favorable overall survival (OS) and progression-free survival (PFS) compared with patients with NLR>2.5. After stratified with the tumor mutational burden (TMB), we further found that patients with NLR≤2.5 had significantly favorable OS and PFS compared with patients with NLR>2.5 in the group of patients with TMB>10, while in group patients with TMB≤10, patients with NLR≤2.5 had no significantly favorable OS and PFS compared with patients with NLR>2.5. The CD3+ and CD8+/CD28+ T cell subsets were significantly increased in patients with NLR≤2.5 (P

Fan Ren,* Minghui Liu,* Xiaoqian Xu, Hongbing Zhang, Xin Li, Jinghao Liu, Jun Chen Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China *These authors contributed equally to this work Abstract: Lung cancer is one of the most common causes of cancer-related death. Most of them already have distant metastasis at the time of diagnosis, but ureteral metastasis is extremely rare. Herein, we reported a lung cancer patient with a metastatic lesion from lung cancer at the distal end of the ureter. The patient is a 61-year-old male diagnosed with invasive adenocarcinoma after the right upper lobe resection and system lymph node dissection surgery. After 12 months of surgery, during routine physical examination, lower abdominal enhanced computed tomography showed there was a soft mass with uneven continuous enhancement at the distal end of the ureter. After the surgery of ureter, the mass was histologically considered to be a metastatic lesion arising from the primary lung cancer. Keywords: non-small-cell lung cancer, ureteral metastasis, prognosis, treatment

Weiwei Zhu,1,2,* Hongqiang Li,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high incidence rate and poor prognosis. Enolase-1 (ENO1), a key glycolytic enzyme, has been implicated in the tumorigenesis of various cancers. However, its diagnostic value and clinical significance in HCC are unclear.Methods: Data of 374 HCC tissues and 50 nontumor tissues were retrieved from The Cancer Genome Atlas database, and the expression level of ENO1 mRNA in HCC was evaluated. In addition, a meta-analysis of 12 HCC cohorts deposited in the Gene Expression Omnibus database was conducted to determine ENO1 expression levels. The diagnostic power of ENO1 in distinguishing HCC tissues from non-HCC tissues was confirmed by receiver operating characteristic (ROC) curve analysis. A tissue microarray comprising 93 HCC specimens and 87 adjacent normal specimens was used to validate ENO1 expression, and its prognostic value in HCC was ascertained by Kaplan–Meier analysis and Cox regression models. In addition, the gene set enrichment analysis was performed to predict the molecular mechanism of ENO1 action in HCC.Results: ENO1 was overexpressed in HCC tissues and associated with worse outcomes in terms of overall survival (OS) (P

Yue Lu,1 Wenjun Jiang,1 Xin Wu,2 Saixu Huang,1 Zhiyong Huang,1 Yamin Shi,3 Qi Dai,1 Jianming Chen,2 Fuzheng Ren,1 Shen Gao4 1Shanghai Key Lab New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 4Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China Background: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). Methods: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7–plasmid DNA complex were examined. Results: The results demonstrated that the CRD-PEG-T7–plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG–plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. Conclusion: The results above indicatd that the CRD-PEG-T7–plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor. Keywords: arginine peptide, aspartic acid peptide, tumor targeting, DNA delivery, bone metastasis prostate cancer

Chen Xue,1,2,* Yuting He,1,2,* Qiuyue Hu,1,2 Yan Yu,1,2 Xiaolong Chen,1,2 Jianan Chen,1,2 Fang Ren,2 Juan Li,1,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1–3 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 3National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China *These authors contributed equally to this work Background: PIM1, a serine/threonine kinase, plays an essential role in tumorigenesis of multiple types of tumors. However, the expression pattern and functions of PIM1 in gallbladder cancer (GBC) remain largely unknown. Materials and methods: Immunohistochemistry, quantitative real-time PCR, and western blot analysis were performed to measure the expression of PIM1. Tissue microarray analysis was used to confirm the relationship between PIM1 expression and clinical outcomes of GBC patients. Finally, in vivo and in vitro functional studies were performed to detect the inhibition of PIM1 by RNAi or specific inhibitor in GBC cells. Results: We observed that PIM1 was dramatically overexpressed in GBC tissues, and its expression levels were positively related with clinical malignancies and a poor prognosis. Inhibition of PIM1 via RNAi or enzyme-specific inhibitor could suppress GBC cell proliferation, migration, and invasion both in vitro and vivo. Additionally, flow cytometry assays and cell cycle assays indicated that PIM1 inhibition promoted cell apoptosis and induced cell cycle arrest. Remarkably, inhibition of PIM1 could drive a metabolic shift from aerobic glycolysis to oxidative phosphorylation. We found that inhibition of PIM1 mechanistically reduced glucose consumption by regulating key molecules in aerobic glycolysis. Conclusion: PIM1 may serve as an oncogene in GBC and be involved in the regulation of glycolysis. PIM1 is a promising therapeutic target for the treatment of human GBC. Keywords: PIM1, gallbladder cancer, aerobic glycolysis, tumor progression

Zhu Y, Ren F, Zhu Y, et al. Nat Sci Sleep. 2020;12:1067–1074. The authors have advised that the name of last author on page 1067 is incorrect. Mingwen Zheng should be Minwen Zheng. The authors apologize for this error. Read the original article

Yuting He,1,2,* Chen Xue,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Gallbladder cancer (GBC) is a highly lethal disease and the most common biliary tract malignant tumor with poor prognosis. Accumulating evidence indicates that cluster of differentiation 44 (CD44) is overexpressed in several malignancies and has a crucial role in the development of cancer. However, its expression and function in GBC are unclear. The aim of this study was to explore CD44 expression and its role in GBC. Materials and methods: The expression of CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to confirm the relationship between CD44 expression and clinical outcomes of GBC patients. EDU assay, colony formation assay, cell migration and invasion assay were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with si-RNA. Results: CD44 was overexpressed and associated with poor outcomes in GBC patients. The univariate and multivariate analyses confirmed that elevated CD44 was an independent prognostic factor for the OS of GBC patients. Silencing CD44 could suppress the GBC cell proliferation, migration and invasion in vitro, as well as attenuated cancer stem cell functions. Conclusion: CD44 markedly correlated with aggressive tumor behaviors and contributed to the progression of GBC, which could represent a novel prognostic marker and potential therapeutic target for GBC patients. Keywords: CD44, gallbladder cancer, cancer stem cells, tumor progression

Yanhong Zheng,1 Yunlan Tang,2 Zhirong Bao,1 Hui Wang,1 Feng Ren,1 Mingxiong Guo,2 Hong Quan,1 Changzhong Jiang11Key Laboratory of Artificial Micro- and Nano-structures of the Ministry of Education and Center for Electronic Microscopy and Department of Physics, Wuhan University; 2College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaAbstract: Nanomaterials have an advantage in “personalized” therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration

Aluminum (Al) is the most abundant metal in the Earth’s crust and is not an essential element for plant growth. In contrast, nitrogen (N) is the most important mineral element for plant growth, but this non-metal is often present at low levels in soils, and plants are often N deficient. Aluminum toxicity is dominant in acid soils, and so plants growing in acid soils have to overcome both Al toxicity and N limitation. Because of low N-use efficiency, large amounts of N fertilizers are applied to crop fields to achieve high yields, leading to soil acidification and potential Al toxicity. Aluminum lowers plant N uptake and N-use efficiency because Al inhibits root growth. Although numerous studies have investigated the interactions between Al and N, a complete review of these studies was lacking. This review describes: (1) the link between plant Al tolerance and ammonium/nitrate (NH4+/NO3-) preference; (2) the effects of NH4+/NO3- and pH on Al toxicity; (3) the effects of Al on soil N transformations; and (4) the effects of Al on NH4+/NO3- uptake and assimilation by plants. Acid soils are characterized chemically by a relatively high ratio of NH4+ to NO3- and high concentrations of toxic Al. Aluminum-tolerant plants generally prefer NH4+ as an N source, while Al-sensitive plants prefer NO3-. Compared with NO3-, NH4+ increases the solubilization of toxic Al into soil solutions, but NH4+ generally alleviates Al phytotoxicity under solution culture because the protons from NH4+ compete with Al3+ for adsorption sites on the root surface. Plant NO3- uptake and nitrate reductase activity are both inhibited by Al, while plant NH4+ uptake is inhibited to a smaller degree than NO3-. Together, the results of numerous studies indicate that there is a synergistic interaction between plant Al tolerance and NH4+ nutrition. This has important implications for the adaptation of plants to acid soils that are dominated chemically by toxic Al as well as NH4+. Finally, we discuss how this knowledge can be used to increase plant Al tolerance and N-use efficiency in acid soils.