Search

Yue Wang,&ast; Liyan Chu,&ast; He Li, Yingjie Du, Shanshan Wang, Ying Liu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Email guyanwang2006@163.comPurpose: The aim of this study was to determine whether preoperative video distraction reduces the incidence of emergence delirium in preschool children under general anesthesia with sevoflurane.Patients and Methods: In this prospective randomized controlled study, children aged 3– 6 years were randomized to receive either video distraction (Group V) or common clinical practice (Group C) from arrival at the holding area to induction of anesthesia. The primary outcome was the incidence of emergence delirium. Preoperative anxiety scores, assessed by the simple modified Yale Perioperative Anxiety Scale, were also collected.Results: A total of 160 patients were included in our study. The children in Group V (n=80) exhibited a significantly lower incidence of emergence delirium than did those in Group C (n=80) (12.5% vs 35.0%; RR 0.36, 95% CI 0.19, 0.69; P =0.0008). The maximum Pediatric Anesthesia Emergence Delirium score in Group V was significantly lower than that in Group C (3.0 vs 5.0; mean difference − 2.64, 95% CI: − 4.12, − 1.16; P=0.0003). The simple modified Yale Perioperative Anxiety Scale scores at separation from parents and the onset of inhalation induction in Group V were significantly lower than those in Group C (36.4 ± 9.9 vs 48.2 ± 16.7; mean difference 11.92, 95% CI 7.25, 16.59; P< 0.0001 and 41.5 ± 15.9 vs 59.7 ± 21.5; mean difference 18.11, 95% CI 11.76, 24.47; P< 0.0001).Conclusion: Preoperative video distraction reduces the incidence of emergence delirium in preschool children who undergo strabismus surgery under general anesthesia with sevoflurane.Keywords: emergence delirium, anxiety, children, preschool

Yu Chen,1 Ru Gao,1 Honghui Liu,1 Maoyu Ye,1 Ling Chu,2 Tiansheng Wang1 1Department of Otolaryngology-Head and Neck Surgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Pathology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Tiansheng Wang, Department of Otolaryngology-Head and Neck Surgery, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha, People’s Republic of China, Email 600923@csu.edu.cnBackground: Individuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology.Methods: We recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated.Results: We identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P< 0.05), and serum MRC1 (AUC=0.742, P< 0.001) and MMP2 (AUC=0.766, P< 0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P< 0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P< 0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils.Conclusion: Circulating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.Keywords: chronic rhinosinusitis with nasal polyps, endotype, eosinophilic, proteomics

Ziwen Ma,1,&ast; Liming Chu,1,&ast; Yan Zhang,1,&ast; Fang Lu,2 Yun Zhu,1 Fei Wu,1 Zhiping Zhang1 1Department of Obstetrics and Gynecology, Shanghai Pudong New Area Healthcare Hospital for Women and Children, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Shanghai Forth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Zhang, Email zzpdr@126.comPurpose: The aim of this study was to investigate the relationship between gestational diabetes mellitus (GDM) and Chemerin by analyzing chemerin levels in peripheral blood and cord blood, and chemerin mRNA and its protein expression in placenta and adipose tissue.Methods: A case-control study was conducted in 110 women with GDM and 110 controls without GDM who received regular prenatal services and delivered at Shanghai Pudong New Area Healthcare Hospital for Women and Children from June 2019 to December 2020.Results: The age, pre-pregnancy weight, pre-pregnancy BMI, antepartum BMI, TG/HDL ratio and TG levels in pregnant women with GDM were significantly higher than those in women without GDM, and HDL levels were significantly lower than those in the normal group. Chemerin in the umbilical cord blood of the GDM group was significantly higher than in that of the normal group, but there was no difference in chemerin levels in peripheral blood. In the two groups, the chemerin concentration in peripheral blood was significantly higher than that in umbilical cord blood (P< 0.001). The Chemerin mRNA and protein expression levels in the placenta and adipose tissue of pregnant women in the GDM group were significantly higher than those in the normal group (P < 0.001). In the GDM group, the expression of chemerin protein in adipose tissue was significantly higher than that in placental tissue. Regression analysis showed that the expression level of chemerin protein in placental tissue and adipose tissue was positively correlated with the risk of GDM.Conclusion: Elevated chemerin is closely related to the risk of GDM, and the placenta may be an important secretion of chemotactic factor sources in addition to adipose tissue and participate in the development of GDM.Keywords: chemerin, GDM, placenta, adipose

Yan Wu,1– 3,&ast; Shuaifeng Liu,4,&ast; Liuxi Chu,1– 3 Quan Zhang,5,6 Jin Yang,3,7 Shan Qiao,5 Xiaoming Li,5 Yuejiao Zhou,4 Huihua Deng,1– 3 Zhiyong Shen4 1Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 2Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing, People’s Republic of China; 3Institute of Child Development and Education, Research Center for Learning Science, Southeast University, Nanjing, People’s Republic of China; 4Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, People’s Republic of China; 5Department of Health Promotion, Education and Behavior, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 6College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA; 7Department of Preventive Medicine, School of Public Health, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huihua Deng, Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, No. 2 Sipailou, Nanjing, 210096, People’s Republic of China, Tel +86 25 8379 5664, Fax +86 25 8379 3779, Email dengrcls@seu.edu.cn Zhiyong Shen, Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, No. 18 Jinzhou Road, Nanning, 530028, People’s Republic of China, Tel +86 771 251 8838, Email shenzhiyong99999@sina.comBackground: Hair antiretroviral concentrations are an objective and non-invasive measure of adherence to long-term antiretroviral therapy (ART) and can further predict virologic outcomes among people living with HIV/AIDS (PLWH). Zidovudine, one of the mainstream antiretrovirals in China, has been verified to have high reliability in adherence assessment, especially for its hair concentrations. However, data are limited in its predicting virologic outcomes. Therefore, this study aimed to characterize whether hair zidovudine concentrations can predict virologic suppression among Chinese PLWH compared with hair lamivudine concentrations and two self-reported measures, the overall frequency of adherence behaviors and percentage adherence.Methods: This cross-sectional study randomly recruited 564 PLWH currently treated with zidovudine, lamivudine, and other ART agents (efavirenz, nevirapine, or lopinavir/ritonavir) in Guangxi, China. Hair antiretroviral concentrations were determined using the LC-ESI+-MS/MS method. Receiver operating characteristic (ROC) curves were used to estimate the optimal classification thresholds of hair concentrations of zidovudine and lamivudine, and the two self-reported measures. Based on those optimal classification thresholds, logistic regression was used to examine whether those four adherence measures can predict virologic suppression (HIV-1 RNA < 200 copies/mL).Results: ROC curves demonstrated good classification performance for association with virologic suppression of zidovudine with the optimal threshold at 58 pg/mg and lamivudine at 255 pg/mg but no self-reported measures. PLWH with hair zidovudine concentrations > 58 pg/mg had an adjusted odds ratio (aOR) of 43.191 (95% confidence interval (CI) = 10.171‒183.418, p < 0.001) for virologic suppression. Hair lamivudine concentrations were also associated with virologic suppression (aOR = 10.656, 95% CI = 3.670‒30.943, p < 0.001). However, two self-reported measures did not predict virologic suppression (aORs = 1.157 and 2.488, ps > 0.149).Conclusion: Hair zidovudine concentrations can be served as an alternative tool for clinically predicting virologic suppression among PLWH in China.Keywords: hair antiretroviral concentrations, zidovudine, virologic suppression, PLWH, LC-MS/MS

Tianyan Ding1,2 &ast;, Cantong Liu1,2 &ast;, Binliang Huang,1,2 Lingyu Chu,1,2 Laifeng Wei,1,2 Yiwei Lin,1,2 Yun Luo,1,2 Biao Zhang,1,2 Chaoqun Hong,3 Yiwei Xu,1,2 Yuhui Peng1,2 1Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 2Precision Medicine Research Center, Shantou University Medical College, Shantou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiwei XuDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, 515041, Guangdong, People’s Republic of ChinaFax +86-754-8856-0352Email yiwei512@126.comYuhui Peng Email pengyuhui666@163.comBackground: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is a component of the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC), and the parameters for survival prediction are not clear yet. Our study aimed to construct a survival prediction nomogram for ESCC with NCRT followed by surgery.Methods: We analyzed hematological parameters and related-derivative indexes from 122 ESCC patients treated with NCRT followed by surgery. Univariate and multivariate Cox survival analyses were performed to identify independent prognostic factors to establish a nomogram and predict overall survival (OS). The predictive value of the nomogram for OS was evaluated by the concordance index (C-index), decision curve analysis (DCA), the clinical impact curve (CIC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The pretreatment nutritional candidate, prognostic nutrition index, inflammation-related absolute monocyte count and TNM staging were entered into the nomogram for ESCC with NCRT followed by surgery. The C-index of the nomogram for OS was 0.790 (95% CI = 0.688– 0.893), which was higher than that of TNM staging (0.681; 95% CI = 0.565– 0.798, P = 0.026). The DCA, CIC, NRI, and IDI of the nomogram showed moderate improvement in predicting survival. Based on the cut point calculated according to the constructed nomogram, the high-risk group had poorer OS than that of the low-risk group (P < 0.05).Conclusion: A novel nomogram based on nutrition- and inflammation-related indicators might help predict the survival of ESCC treated with NCRT followed by surgery.Keywords: esophageal squamous cell carcinoma, neoadjuvant chemoradiotherapy, surgery, nomogram, survival, prognosis

Yida Li,1,2,&ast; Liqing Zou,1,2,&ast; Li Chu,1,2 Luxi Ye,1,2 Jianjiao Ni,1,2 Xiao Chu,1,2 Tiantian Guo,1,2 Xi Yang,1,2 Zhengfei Zhu1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengfei Zhu; Xi YangDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People’s Republic of ChinaTel +86-18017312901; +8617321296901Fax +86-2164175242Email fuscczzf@163.com; ntgeorge@qq.comBackground: Radiation-induced lung injury (RILI) is a main threat to patients who received thoracic radiotherapy. Thus, understanding the molecular mechanism of RILI is of great importance. Circular RNAs (circRNAs) have been found to act as a regulator of multiple biological processes, and the circRNA-microRNA (miRNA)-mRNA axis could play an important role in the signaling pathway of many human diseases including radiation injury.Methods: First, the circRNA and miRNA of RILI in a mouse model were investigated. The mice received 12 Gy of thoracic irradiation, and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA sequencing (RNA-seq) compared with normal lung tissues. Then, Gene Ontology analysis of the target mRNAs of the significantly differently expressed circRNAs was performed.Results: In the irradiated group, inflammatory changes in lungs were observed; 21 significantly up-regulated and 33 down-regulated significantly miRNAs were identified (p < 0.05). Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated in the irradiated group [log2 (fold change) > 1 or < − 1, p< 0.05]. These differentially expressed miRNAs took part in a series of cellular processes, such as positive regulation of alpha-beta T-cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B-cell receptor signaling pathway. The differentially expressed circRNAs were related to Th1 and Th2 differentiation pathways, and the predicted mRNAs were verified.Conclusion: This study revealed immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs such as circRNA5229, circRNA544, and circRNA3340, could benefit the treatment of RILI.Keywords: circRNA, miRNA, radiation-induced lung injury, T cell proliferation

Jiali Yang,1,&ast; Zhixia Jia,1,&ast; Zhigang Xiao,1 Jing Zhao,2 Ye Lu,2 Li Chu,3 Hui Shao,1,2 Lin Pei,1,2 Shaodan Zhang,4 Yuan Chen4 1School of Integrated Traditional Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Hebei Key Laboratory of Turbidity, Hebei Academy of Chinese Medicine Sciences, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaodan Zhang; Lin PeiPaediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaTel/Fax +86 13653115066; +86 13831190309Email 13653115066@163.com; peilin13831190309@126.comPurpose: This study aims to evaluate the beneficial effects of anti-epileptic mechanisms of baicalin (BA) on cognitive dysfunction and neurodegeneration in pentylenetetrazol (PTZ)-induced epileptic rats.Methods: First, PTZ-induced epileptic rats were administered intraperitoneally a sub-convulsive dose of PTZ (40 mg/kg) daily, and the seizure susceptibility (the degree of seizures and latency) was evaluated using Racine’s criterion. Then, classical behavioral experiments were performed to test whether BA ameliorated cognitive dysfunction. Neurodegeneration was assessed using Fluoro Jade-B (FJB), and NeuN staining was used to determine whether BA offered a neuroprotective role. After BA had been proven to possess anti-epileptic effects, its possible mechanisms were analyzed through network pharmacology. Finally, the key targets for predictive mechanisms were experimentally verified.Results: The epileptic model was successfully established, and BA had anti-epileptic effects. Epileptic rats displayed significant cognitive dysfunction, and BA markedly ameliorated cognitive dysfunction. Further, we also discovered that BA treatment mitigated neurodegeneration of the hippocampus CA3 regions, thereby ameliorated cognitive dysfunction of epileptic rats. Subsequent network pharmacology analysis was implemented to reveal a possible mechanism of BA in the anti-epileptic process and the TLR4/MYD88/Caspase-3 pathway was predicted. Finally, experimental studies showed that BA exerted an anti-epileptic effect by activating the TLR4/MYD88/Caspase-3 pathway in PTZ-induced epileptic rats.Conclusion: In conclusion, BA had a protective effect against PTZ-induced seizures. BA improved cognitive dysfunction and exerted a neuroprotective action. The anti-epileptic effects of BA may be potentially through activation of the TLR4/MYD88/Caspase-3 pathway.Keywords: baicalin, pentylenetetrazol, epilepsy, cognitive dysfunction, network pharmacology, TLR4/MYD88/Caspase-3

Chuangkun Li,1,2,* Weiwen Liang,1,2,* Lili Chu,1,* Yingqi Wei,1,2 Xiusen Qin,1,2 Zifeng Yang,1,2 Wentai Guo,1,2 Hui Wang,1,2 Huaiming Wang,1,2 Rongkang Huang1,2 1Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huaiming WangDepartment of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People’s Republic of ChinaEmail wanghm7@mail.sysu.edu.cnRongkang HuangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86-134-8021-8647Email huangrk3@mail.sysu.edu.cnPurpose: Anastomotic leakage after rectal cancer surgery in elderly patients is a critical challenge. Many risk factors have been found and many interventions tried, but anastomotic leakage in elderly patients remains difficult to deal with. This study aimed to create a nomogram for predicting anastomotic leakage after rectal surgery in elderly rectal cancer patients with dysfunctional stomata.Methods: We collected data from 326 consecutive elderly patients with dysfunctional stomata after rectal cancer surgery at the Sixth Affiliated Hospital, Sun Yat-Sen University from January 2014 to December 2019. Risk factors of anastomotic leakage were identified with multivariate logistic regression and used to create a nomogram. Predictive performance was evaluated by the area under the receiver-operating characteristic (ROC) curve.Results: American Society of Anesthesiologists score ≥ 3, male sex, and neoadjuvant radiotherapy were identified as significantly associated factors that could be combined for accurate prediction of anastomotic leakage on multivariate logistic regression and development of a nomogram.The area under the ROC curve for this model was 0.645. The C-index value for this model was 0.645, indicating moderate predictive ability of the risk of anastomotic leakage.Conclusion: The nomogram showed good ability to predict anastomotic leakage in elderly patients with rectal cancer after surgery, and might be helpful in providing a reference point for selection of surgical procedures and perioperative treatment.Keywords: nomogram, rectal cancer, anastomotic leakage, elderly patients

Bin Zheng,1,* Yakun Yang,1,* Jinghan Li,1 Jing Li,1 Saijie Zuo,1 Xi Chu,2 Shan Xu,3 Donglai Ma,1 Li Chu1,4 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Hebei Province Hospital of Chinese Medicine, Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donglai Ma; Li ChuSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of ChinaTel/Fax +86 311 89926719Email mdl_hebei@aliyun.com; chuli0614@126.comPurpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism.Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.Keywords: magnesium isoglycyrrhizinate, arsenic trioxide, cardiotoxicity, Nrf2, TLR4/NF-κB

Jingshuai Wang,1,* Xuemin Gu,1,* Yiqin Ouyang,1 Lei Chu,1 Mengjiao Xu,1 Kun Wang,2 Xiaowen Tong1 1Obstetrics and Gynecology Department, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China; 2Cancer Center, Shanghai East Hospital of Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun Wang Jimo Road 150, Pudong New District, Shanghai, People’s Republic of ChinaEmail 001wangkun@tongji.edu.cnXiaowen Tong Xincun Road 389, Putuo District, Shanghai, People’s Republic of ChinaEmail Xiaowen_tong@hotmail.comPurpose: Although the neutrophil membrane (NM)-based nanoparticulate delivery system has exhibited rapid advances in tumor targeting stemmed from the inherited instinct, the antitumor effect requires further improvement due to inefficient cellular internalization in the absence of specific interactions between NM-coated nanoparticles and tumor cells.Methods: Herein, we fabricated drug-paclitaxel loaded NM camouflaging nanoparticles (TNM-PN) modified with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), favorable for the cellular internalization.Results: The results showed that TNM-PN exerted a significant cytotoxicity to tumor cells by TRAIL-mediated endocytosis and strong adhesion to inflamed endothelial cells in vitro. Due to TRAIL modification as well as the adhesive interactions between neutrophil and inflamed tumor vascular endothelial cells, tumors in TNM-PN group exhibited almost 2-fold higher fluorescence intensities than that of NM camouflaging nanoparticles and 3-fold higher than that of bare nanoparticles, respectively. Significant tumor inhibition and survival rates of mice were achieved in TNM-PN group as a consequence of prolonged blood circulations to 48 h and preferential tumor accumulations, which was ascribed to targeting adhesion originated from NM to immune evasion and subsequent excellent cellular internalization.Conclusion: The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.Keywords: neutrophil membrane camouflaging, nanoparticulate delivery, tumor targeting, cellular internalization, antitumor therapy

Yanshuang Liu,1,2,* Yingran Liang,3,* Bin Zheng,3 Li Chu,3 Donglai Ma,3 Hongfang Wang,3 Xi Chu,4 Jianping Zhang2,5 1Department of Diagnostics, School of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 5Department of Pharmacology, School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi ChuThe Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, People’s Republic of ChinaTel/Fax +86 311 86095324Email chux2014@126.comJianping ZhangSchool of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of ChinaTel/Fax +86 311 89926719Email zhangjianping14@126.comPurpose: Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats.Methods: Rats were pretreated with 25 or 50 mg/kg crocetin 6 h prior to treating with 5 mg/kg ATO to induce hepatic injury daily for 7 days.Results: Treatment with crocetin attenuated ATO-induced body weight loss, decreases in food and water consumption, and improved ATO-induced hepatic pathological damage. Crocetin significantly inhibited ATO-induced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) increases. Crocetin prevented ATO-induced liver malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Crocetin abrogated the ATO-induced decrease of catalase (CAT) and superoxide dismutase (SOD) activity. Crocetin was found to significantly restore the protein levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). Furthermore, crocetin promoted the expression of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADP(H): quinone oxidoreductase 1 (NQO1).Conclusion: These findings suggest that crocetin ameliorates ATO-induced hepatic injury in rats. In addition, the effect of crocetin might be related to its role in antioxidant stress, as an anti-inflammatory agent, and in regulating the Nrf2 signaling pathway.Keywords: crocetin, arsenic trioxide, hepatotoxicity, oxidative stress, inflammation, Nrf2 signaling pathway

Zhifeng Zhao, 1,* Miaomiao Liu, 1,* Yuanyuan Zhang, 1 Yingran Liang, 1 Donglai Ma, 1 Hongfang Wang, 1 Zhihong Ma, 2 Shengjiang Guan, 2 Zhonglin Wu, 3 Xi Chu, 3 Yue Lin, 2 Li Chu 1, 4 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of China; 2School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of China; 3The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li ChuSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of ChinaEmail chuli0614@126.comYue LinSchool of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of ChinaTel/Fax +86 311 89926718Email yuelin8992@126.comPurpose: Monoammonium glycyrrhizinate (MAG) is an aglycone of glycyrrhizin that is found in licorice and is often used clinically as an injection to treat liver diseases. However, the effect of MAG injection on cardiac function and its possible cellular mechanisms remain unclear. We explored the protective effects of MAG against myocardial ischemic injury (MII) induced by isoproterenol (ISO), as well as the cellular mechanisms via molecular biology techniques and patch-clamp recording.Methods: A rat model of myocardial ischemia injury was induced by administering ISO (85 mg/kg) subcutaneously for 2 consecutive days. ECG, cardiac functional parameters, CK and LDH levels, SOD and GSH activities, MDA concentration, histological myocardium inspection, mitochondria ultrastructure changes, intracellular calcium concentrations were observed. Influences of MAG on ICa-L and contraction in isolated rat myocytes were observed by the patch-clamp technique.Results: MAG reduced damage, improved cardiac morphology, inhibited oxidative stress, decreased the generation of reactive oxygen species, and decreased intracellular Ca 2+ concentration. Exposure of the rats’ ventricular myocytes to MAG resulted in a concentration-dependent reduction in L-type calcium currents (ICa-L). MAG reduced ICa-L in a consistent and time-dependent fashion with a semi-maximal prohibitive concentration of MAG of 14 μM. MAG also shifted the I-V curve of ICa-L upwards and moved the activation and inactivation curves of ICa-L to the left.Conclusion: The findings indicate that MAG injection exerts a protective influence on ISO-induced MII by inhibiting oxidative stress and regulating Ca 2+ homeostasis by ICa-L.Keywords: cardiopretection, reactive oxygen species, calcium influx, isoproterenol, calcium concentration

Xinxin Li,1,* Dongming Guo,1,* Lingyu Chu,2 Yiteng Huang,3 Feiran Zhang,1 Wei Li,1 Juntian Chen1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, People’s Republic of China; 3Department of Health Care Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juntian ChenDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou 515041, Guangdong Province, People’s Republic of ChinaTel/Fax +86 754 8890 5256Email 13809846668@163.comPurpose: To evaluate the diagnostic value of combining the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) or lymphocyte–monocyte ratio (LMR) with carcinoembryonic antigen (CEA) in patients with colorectal cancer (CRC).Patients and methods: The diagnostic performance of inflammatory makers and CEA was evaluated in cohort 1 (664 patients with CRC, 336 patients with colorectal polyps and 664 healthy controls) and validated in cohort 2 (87 patients with CRC and 87 healthy controls) by using receiver operating characteristic curve analysis.Results: In cohort 1, the NLR, PLR and CEA levels were significantly higher, while the LMR was markedly lower in patients with CRC than in healthy controls. The PLR and LMR were significantly associated with invasion depth and lymph node metastasis. Moreover, significant differences in the PLR and LMR were observed between patients with stage I/II CRC and healthy or polyp controls and those with stage III/IV CRC. Using the NLR, PLR or LMR with CEA resulted in a significantly larger area under the curve (AUC) than any of them used alone. Combining the PLR and LMR with CEA exhibited the best diagnostic value for CRC (AUC=0.892). The AUCs of this combination were 0.864 and 0.783 for distinguishing stage I/II CRC from healthy and polyp controls, respectively. When we used the same cut-off values to assess the diagnostic ability of these markers in cohort 2, similar results were observed, and the PLR, LMR and CEA combination also showed the highest accuracy (AUC=0.936).Conclusion: Combining inflammatory cell ratios with CEA could improve the diagnostic efficacy for CRC patients. The combination of the PLR and LMR with CEA might be a valuable indicator in the early detection and monitoring of CRC patients.Keywords: colorectal cancer, neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, lymphocyte–monocyte ratio, carcinoembryonic antigen, diagnosis

Yigang Wang,1 Binrong Wang,1 Junnan Liang,2 Caixia Cui,3 Chang Ying,1 Fang Huang,4 Buyun Ma,1 Xiumei Zhou,1 Liang Chu21College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China; 2Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People’s Republic of China; 4Department of Pathology, Zhejiang Provincal People’s Hospital, Hangzhou 310014, People’s Republic of ChinaBackground: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC).Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models.Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice.Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.Keywords: laryngocarcinoma, oncolytic virus, ZD55-TRAIL, doxorubicin

Zhang Y, Zhou J, Yang C, et al. Int J Nanomedicine. 2016;11:1119–1130. The authors have advised due to an error at the time of figure assembly, Figure 4 on page 1124 is incorrect. The correct Figure 4 is shown in Download Article. Page 1126, Table 1, the authors have advised a mistake was made in calculating the Drug loading content (DLC) in the manuscript. The correct Table 1 is shown in Download Article. The authors apologize for these errors and advise it does not affect the results of the paper. Read the original article

Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P

Feng Han,1,* Rong Hu,2,* Hua Yang,1 Jian Liu,1 Jianmei Sui,1 Xin Xiang,1 Fan Wang,1 Liangzhao Chu,1 Shibin Song1 1Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, 2Department of Histology and Embryology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China *These authors contributed equally to this work Background: We conducted this meta-analysis based on eligible trials to investigate the relationship between phosphatase and tensin homolog (PTEN) genetic mutation and glioma patients’ survival. Methods: PubMed, Web of Science, and EMBASE were searched for eligible studies regarding the relationship between PTEN genetic mutation and glioma patients’ survival. The primary outcome was the overall survival of glioma patient with or without PTEN genetic mutation, and second outcome was prognostic factors for the survival of glioma patient. A fixed-effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies. Results: Nine cohort studies, involving 1,173 patients, were included in this meta-analysis. Pooled results suggested that glioma patients with PTEN genetic mutation had a significant shorter overall survival than those without PTEN genetic mutation (hazard ratio [HR] =2.23, 95% confidence interval [CI]: 1.35, 3.67; P=0.002). Furthermore, subgroup analysis indicated that this association was only observed in American patients (HR =2.19, 95% CI: 1.23, 3.89; P=0.008), but not in Chinese patients (HR =1.44, 95% CI: 0.29, 7.26; P=0.657). Histopathological grade (HR =1.42, 95% CI: 0.07, 28.41; P=0.818), age (HR =0.94, 95% CI: 0.43, 2.04; P=0.877), and sex (HR =1.28, 95% CI: 0.55, 2.98; P=0.564) were not significant prognostic factors for the survival of patients with glioma. Conclusion: Current evidence indicates that PTEN genetic mutation is associated with poor prognosis in glioma patients. However, this finding is derived from data in observational studies, potentially subject to selection bias, and hence well conducted, high-quality randomized controlled trials are warranted. Keywords: glioma, PTEN genetic mutation, meta-analysis

Yumin Zhang,1,* Junhui Zhou,2,* Cuihong Yang,1 Weiwei Wang,3 Liping Chu,1 Fan Huang,1 Qiang Liu,1 Liandong Deng,2 Deling Kong,3 Jianfeng Liu,1 Jinjian Liu1 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, 2Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, 3Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People’s Republic of China *These authors contributed equally in this work Abstract: Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. Keywords: core cross-linking, folic acid targeting, self-assembling, curcumin, drug delivery, micelles

Jianfeng Liu, Jinjian Liu, Hongyan Xu, Yumin Zhang, Liping Chu, Qingfen Liu, Naling Song, Cuihong YangTianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, People's Republic of ChinaAbstract: The poor aqueous solubility and low bioavailability of curcumin restrict its clinical application for cancer treatment. In this study, a novel tumor-targeting nanofiber carrier was developed to improve the solubility and tumor-targeting ability of curcumin using a self-assembled Nap-GFFYG-RGD peptide. The morphologies of the peptide nanofiber and the curcumin-encapsulated nanofiber were visualized by transmission electron microscopy. The tumor-targeting activity of the curcumin-encapsulated Nap-GFFYG-RGD peptide nanofiber (f-RGD-Cur) was studied in vitro and in vivo, using Nap-GFFYG-RGE peptide nanofiber (f-RGE-Cur) as the control. Curcumin was encapsulated into the peptide nanofiber, which had a diameter of approximately 10–20 nm. Curcumin showed sustained-release behavior from the nanofibers in vitro. f-RGD-Cur showed much higher cellular uptake in αvβ3 integrin-positive HepG2 liver carcinoma cells than did non-targeted f-RGE-Cur, thereby leading to significantly higher cytotoxicity. Ex vivo studies further demonstrated that curcumin could accumulate markedly in mouse tumors after administration of f-RGD-Cur via the tail vein. These results indicate that Nap-GFFYG-RGD peptide self-assembled nanofibers are a promising hydrophobic drug delivery system for targeted treatment of cancer.Keywords: nanofiber, tumor-targeting, self-assembling, curcumin, drug delivery

Hongjun Gao,2# Jinjian Liu,1# Cuihong Yang,1 Tangjian Cheng,2 Liping Chu,1 Hongyan Xu,1 Aimin Meng,1 Saijun Fan,1 Linqi Shi,2 Jianfeng Liu11Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People's Republic of China; 2Key Laboratory of Functional Polymer Materials, Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin, People’s Republic of China #These two authors contributed equally in the present workAbstract: Polyethylene glycol (PEG)-ylation is a widely used strategy to fabricate nanocarriers with a long blood circulation time. Further elaboration of the contribution of the surface PEGylation pattern to biodistribution is highly desirable. We fabricated a series of polyion complex (PIC) micelles PEGylated with different ratios (PEG2k and PEG550). The plasma protein adsorption, murine macrophage uptake, and in vivo biodistribution with iodine-125 as the tracer were systematically studied to elucidate the impact of PEGylation patterns on the biodistribution of micelles. We demonstrated that the PEGylated micelles with short hydrophilic PEG chains mixed on the surface were cleared quickly by the reticuloendothelial system (RES), and the single PEG2k PEGylated micelles could efficiently prolong the blood circulation time and increase their deposition in tumor sites. The present study extends the understanding of the PEGylation strategy to further advance the development of ideal nanocarriers for drug delivery and imaging applications.Keywords: drug delivery, PEGylation, mixed shell micelles, macrophage uptake, in vivo biodistribution