Search

Luo-Gang Ding,1,* Xiang Ji,2,* Yue-Yue Liu,3,* Min Shi,1 Jian-Da Li,1 Fei Liu,1 Yu-Yu Zhang,1 Jiang Yu,1 Jia-Qiang Wu1 1Shandong Key Laboratory of Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Shandong Microbial Engineering, College of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 3Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan, 250100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Qiang Wu; Jiang Yu, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China, Email yujiang_2213@163.com; wujiaqiang2000@sina.comBackground: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection.Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe.Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival.Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.Keywords: crystal porous materials, microenvironment-responsive, controlled release, fluorescence imaging, diagnosis and therapy

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Yu-Yun Zhang,1 Wei Li,2 Yu Sheng,1 Qun Wang,3,&ast; Fang Zhao,4,&ast; Ying Wei4 1School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Endocrinology, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Endocrinology and Metabolism Department, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Endocrinology, China-Japan Friendship Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Sheng, School of Nursing, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 33 Badachu Road, Shijingshan District, Beijing, People’s Republic of China, Tel +86 138 1069 1298, Email shengyupumc2020@163.comPurpose: To address the prevalence of diabetes distress (DD) and its correlators in adults with type 2 diabetes.Patients and Methods: During 2021 and 2022, we conducted a cross-sectional study in three Class A tertiary comprehensive hospitals in China, and received 947 participants who completed a printed survey covering DD, demographic, diabetic, physiological, and psychosocial factors. We used Jonckheere-Terpstra, chi-square, and Fisher’s exact tests to assess intergroup differences between different levels of DD. We used ordinal logistic regression analysis to analyze correlators of DD further.Results: The prevalence of DD was 34.64%. In univariate analysis, those with lower satisfaction with financial status, longer durations of diabetes, more complications, higher glycemia, more severe insomnia, treatment by medications only, poorer lifestyle interventions, fewer self-care activities, more types and frequencies of insulin injections, and spending more money and time on treatment were susceptible to DD. Type D personality, negative illness perceptions, negative coping styles, and psychological effects of major life events were related to higher DD. Hope, self-efficacy, positive coping styles, and social support can reduce DD. In ordinal logistic regression analysis, hypoglycemic episode (β=− 1.118, p=0.019, “have hypoglycemic” as reference) and Brief Illness Perception Questionnaire (β=0.090, p< 0.001) were significant positive correlators for DD, while diet intervention (β=0.803, p=0.022, “have diet intervention” as reference), money spent on diabetes treatment (β

Cheng-Yi Hu,1 Wen-Shuai Cui,1 Yi Lei,1 Yu-Wen Tang,1 Yan-Yan Zhang,1 Qi-Min Su,1 Fang Peng,2 Yun-Fei Zeng,1 Jia-Lin Song,1 Cheng-Na Luo,1 Yan Zhou,1 Xin-Yan Li,1 Zhu-Xiang Zhao1 1Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Critical Care Medicine, the Third Affiliated Hospital of Guang Zhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhu-Xiang Zhao, Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510515, People’s Republic of China, Email zhaozhuxiang@126.comPurpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19).Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization.Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among “severe patients”, the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P< 0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P> 0.05), length of stay (P> 0.05), or hospital costs (P> 0.05).Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.Keywords: azvudine, nirmatrelvir/ritonavir, COVID-19, SARS-CoV-2

Yan-Yan Zhang,1,2,&ast; Qiao-Xian Zhang,3,&ast; Jun-Ting Li,1 Yan Wang,1 Ze-Hao Zhuang,4,5 Jia-Yuan Zhuang1 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Department of Nursing, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Endoscopy Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ze-Hao Zhuang, Endoscopy Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China, Tel +8613178032412, Email zehaozhuang@fjmu.edu.cn Jia-Yuan Zhuang, School of Nursing, Fujian Medical University, No. 1 Xueyuan Road, Fuzhou, Fujian, People’s Republic of China, Tel +8613860669060, Email jiayuanz@fjmu.edu.cnPurpose: To explore the effects of the clinical pathway on the outcomes of patients with non-variceal upper gastrointestinal bleeding.Materials and Methods: Randomized controlled trial. The study was conducted in two medical centers in China from 1 June 2022 to 31 December 2022. Patients with a diagnosis of non-variceal upper gastrointestinal bleeding who provided written informed consent were consecutively assigned to the intervention group. The patients in the intervention group were treated using the clinical pathway, while the control group received routine care and follow-up. Time, cost, complications, and prognostic indicators were analyzed. Intentional-to-treat analysis and per-protocol analysis were used for data analysis.Results: A total of 114 eligible patients with non-variceal upper gastrointestinal bleeding were randomly divided into two groups and included in the intention-to-treat analysis. In addition, 106 patients were included in the per-protocol analysis. The median age of the 106 patients was 57 years (range, 18– 92 years) and 83.0% were male. There were no significant differences between groups regarding the baseline characteristics. The intervention group demonstrated a statistically significantly shorter length of stay, lower hospital cost (ie, cost during hospitalization, cost in the emergency room, and cost in the ward), significantly fewer cases of complications, and a higher level of patient satisfaction when compared with the control group. There was no significant difference between the two groups in the rates of transfusion, repeat endoscopy, rebleeding readmission, and mortality.Conclusion: The implementation of the clinical pathway for patients with non-variceal upper gastrointestinal bleeding may help improve patient outcomes and satisfaction.Trial Registration Number: ChiCTR2200060316.Registration Link: https://www.chictr.org.cn/.Keywords: clinical pathway, medical-nursing integration model, non-variceal upper gastrointestinal bleeding, patient, outcomes

Su-Fei Pan,&ast; Shi-Mei Huang,&ast; Lian Xie, Yuan-Yuan Zhang, Yu-Rong Tang, Xiao-Zhen Wang Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Zhen Wang, Department of Clinical Laboratory, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying District, Dongying, Shandong, 257034, People’s Republic of China, Tel +86-18654610519, Email xiaozhenwang007@163.comAbstract: Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.Keywords: fungi, fungal infections, infectious diseases, Scedosporium, abscesses, voriconazole

Xiao-Pei Hou,1 Yan-Yang Zhang,1 Hong-Feng Zhang,1 Shan Wang,1 Yun-Li Xing,1 Hong-Wei Li,2 Ying Sun1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ying Sun, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, No. 95 of Yong’an Road, Xicheng District, Beijing, People’s Republic of China, Tel +86-010-63137740, Email ysun15@163.comPurpose: Many older patients with acute myocardial infarction (AMI) have impaired ability for activities of daily living (ADL). Impaired ADL leads to poor prognosis in elderly patients. The Global Registry of Acute Coronary Events (GRACE) score is widely used for risk stratification in AMI patients but does not consider physical performance, which is an important prognosis predictor for older adults. This study assessed whether the Barthel Index (BI) score combine the GRACE score would achieve improved one-year mortality prediction in older AMI patients.Patients and Methods: This single-center retrospective study included 688 AMI patients aged ≥ 65 years who were divided into an impaired ADL group (BI ≤ 60, n = 102) and a normal ADL group (BI > 60, n = 586) based on BI scores at discharge. The participants were followed up for one year. Cox survival models were constructed for BI score, GRACE score, and BI score combined GRACE score for one-year mortality prediction.Results: Patients had a mean age of 76.29 ± 7.42 years, and 399 were men (58%). A lower BI score was associated with more years of hypertension and diabetes, less revascularization, longer hospital stays, and higher one-year mortality after discharge. Multivariable Cox regression analysis identified BI as a significant risk factor for one-year mortality in older AMI patients (HR 0.977, 95% CI, 0.963– 0.992, P = 0.002). BI (0.774, 95% CI: 0.731– 0.818) and GRACE (0.758, 95% CI: 0.704– 0.812) scores had similar predictive power, but their combination outperformed either score alone (0.810, 95% CI: 0.770– 0.851).Conclusion: BI at discharge is a significant risk factor for one-year mortality in older AMI patients, which can be better predicted by the combination of BI and GRACE scores.Keywords: older adults, acute myocardial infarction, Barthel Index, GRACE, prognosis

Zhong-Han Fang,1,2 Hong-Lin Liao,1,2 Qing-Feng Tang,1,2 Ya-Jing Liu,1,2 Yan-Yan Zhang,1,2 Jiu Lin,1,2 Hao-Peng Yu,3 Cheng Zhou,4 Chun-Jie Li,1,5 Fei Liu,1,2,&ast; Jie-Fei Shen1,2,&ast; 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Liu; Jie-Fei Shen, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Email liufei.hxkq@scu.edu.cn; shenjiefei@scu.edu.cnBackground: Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear.Methods: In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery.Results: The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein–protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain.Conclusion: Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.Keywords: trigeminal neuropathic pain, non-coding RNAs, RNA-sequencing, trigeminal ganglion, trigeminal nerve injury, bioinformatics

Ying-Ying Zhang,1 Wen-Tao Tang,2 Hong Zhang,3 Jing Wang,3 Xiao-Xu Bai,3 Yan-Hui Liao,4 Nicola Robinson,1,5 Jian-Ping Liu1 1Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Pingyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 3Fangshan Hospital of Traditional Chinese Medicine Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, People’s Republic of China; 5Institute of Health and Social Care, London South Bank University, London, UKCorrespondence: Jian-Ping Liu, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email liujp@bucm.edu.cn; jianping_l@hotmail.comBackground: Smoking cessation is recommended as a key intervention for chronic obstructive pulmonary disease (COPD) smokers. However, in China, few COPD smokers quit successfully. The aim of this study was to explore in depth the barriers and facilitators for smoking cessation among smokers with COPD in China.Methods: A purposive sample of 32 hospitalized smokers with COPD were included, 17 ex-smokers and 15 current smokers, participated in the semi-structured interviews. Interviews were analyzed thematically and using a deductive approach guided by Capability, Opportunity, Motivation-Behavior (COM-B) framework.Results: Three inter-related themes were generated: smokers’ motivation was a prerequisite for quitting, maintaining capability to quit smoking, and opportunities that facilitated smokers to quit. Motivation to quit for most participants was activated by COPD-related symptoms, although they had a limited knowledge of COPD. Physical benefits from quitting and strong willpower were facilitators for maintaining quitting, while exposure to smoking environment and strong addiction to nicotine were frequent reasons for relapse. Most ex-smokers quit smoking by their own willpower rather than professionally delivered smoking cessation interventions. Smokers’ attitudes toward these interventions depended on their effectiveness and convenience. Very few participants had experienced pharmacotherapy or behavioral support from physicians. However, interviewees preferred auricular acupressure to pharmacotherapy.Conclusion: Motivation to quit among smokers with COPD was usually initiated by COPD-related symptoms. Physical benefits observed by quitting and strong willpower facilitated smoking cessation, while exposure to smoking environment and strong addiction to nicotine led to relapse. COPD smokers in China preferred auricular acupressure to pharmacotherapy.Keywords: chronic obstructive pulmonary disease, smoking cessation, tobacco, qualitative research, acupuncture

Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel

Yang-Xun Pan,1– 3,&ast; Xu-Qi Sun,1,2,&ast; Zi-Li Hu,1,2,&ast; Wa Xie,1,2 Ke-Xin Nie,4 Ai-Ping Fang,5 Ying-Yao Zhang,4 Yi-Zhen Fu,1,2 Jin-Bin Chen,1,2 Jun-Cheng Wang,1,2 Xin Wang,1,2 Yao-Jun Zhang,1,2 Dan-Dan Hu,1,2 Min-Shan Chen1,2 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Oncology-Pathology, Karolinska Institutet, Solna, 17165, Sweden; 4Real World Study Team, BaseBit.ai, Shanghai, 200050, People’s Republic of China; 5Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan-Dan Hu; Min-Shan ChenDepartment of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of ChinaTel +86-20-87343115; +86-20-87343117Fax +86-20-87343585; +86-20-8734358Email hudd@sysucc.org.cn; chenmsh@sysucc.org.cnBackground: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined.Patients and Methods: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately.Results: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P< 0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P< 0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits.Conclusion: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the “point-to-line” method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.Keywords: alpha-fetoprotein, des-gamma-carboxy prothrombin, hepatocellular carcinoma, clinical features

Li-Wei Shi,1,2 Zhi-Bo Zhao,3 Li Zhong,1 Jian Gao,1 Jian-Ping Gong,3 Hang Chen,4 Yu Min,4 Yi-Yin Zhang,5 Zhi Li4 1Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Department of Gastroenterology, Chongqing People’s Hospital, Chongqing 400010, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Department of Breast & Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 5Department of Anesthesiology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 401120, People’s Republic of ChinaCorrespondence: Zhi LiDepartment of Breast & Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing 400010, People’s Republic of ChinaTel +86 18883147602Email 393884358@qq.comBackground: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated.Materials and Methods: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan–Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo.Results: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo.Conclusion: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.Keywords: Rab40b, HCC, cell cycle, PI3K/AKT, cyclins, MMP2

Hui Chen,* Jing-Qiu Wei,* Yi-Wen Wang, Kun-Peng Zhou, Ying He, He Liu, Yue-Ying Zhang Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue-Ying Zhang Department of AnesthesiologyThe Affiliated Hospital of Xuzhou Medical University, Huaihai Western Road, Quanshan District, Xuzhou, Jiangsu 221004, People’s Republic of ChinaTel +86 138 1531 0789Email zyy0218@126.comPurpose: To investigate the effects of different doses of rocuronium on ischemia-reperfusion injury in skeletal muscle induced by tourniquet in patients undergoing elective unilateral total knee arthroplasty.Patients and Methods: A total of 90 patients undergoing elective unilateral knee arthroplasty under general anesthesia combined with femoral nerve block were randomly divided into 3 groups: normal saline group (group S), rocuronium 0.6 mg/kg group (group L), and rocuronium 1.2 mg/kg group (group H). The primary outcome was the expression of dystrophin in skeletal muscle at 60 min after ischemia. Secondary outcomes included the concentration of malondialdehyde (MDA) and neuronal nitric oxide synthase (nNOS) in blood at 5 min and 30 min after reperfusion. In addition, thigh girth at 24 h and 48 h after operation, the leaving bed time, the incidence of tourniquet-related hypertension and short-term (3 days after operation) complications (nausea and vomiting, swelling, blister, wound infection) and long-term (3 months after operation) complications (joint instability, stiffness, nerve paralysis, pain) were recorded.Main Results: The expression of dystrophin in the rocuronium group was higher than that in group S after ischemia (P < 0.05). The concentration of MDA in the rocuronium 1.2 mg/kg group was lower at 30 min after reperfusion (P < 0.05). There was no significant difference in nNOS among groups at each time point (P > 0.05). The change of thigh girth was the smallest in the rocuronium 1.2 mg/kg group after operation (P< 0.05). The leaving bed time was significantly earlier after operation in the rocuronium group than that in group S (P < 0.05).Conclusion: Rocuronium can protect skeletal muscle from ischemia-reperfusion injury induced by tourniquet. The mechanism may be related to the fact that rocuronium can reduce the loss of dystrophin in skeletal muscle and have the effects of anti-oxidation and anti-stress.Trial Registration: The study was registered at http://www.chictr.org.cn (ChiCTR1800019221, registered on 2018– 10-31).Keywords: ischemia-reperfusion injury, rocuronium, dystrophin, TKA

Guang-Yun Wang,1 Tie-Zheng Wang,1 Yuan-Yuan Zhang,1 Fang Li,1 Bo-Yang Yu,2 Jun-Ping Kou1 1State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of China; 2State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Resource and Development of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaCorrespondence: Jun-Ping KouState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaEmail junpingkou@cpu.edu.cnPurpose: Our previous studies have indicated that non-muscle myosin heavy chain IIA (NMMHC IIA) is involved in H2O2-induced neuronal apoptosis, which is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. However, the neuroprotective effect of NMMHC IIA inhibition with an adeno-associated virus (AAV) vector after transient middle cerebral artery occlusion (MCAO) and its role in caspases-3/ROCK1/MLC pathway remain blurred.Methods: Green fluorescent protein (GFP) and a small hairpin RNA targeting Myh9 (encoding NMMHC IIA) were cloned and packaged into the AAV9 vector. AAV-shMyh9 or control vector were injected into C57BL/6J mice four weeks prior to 60 min MCAO. Twenty-four hours after reperfusion, functional and histological analyses of the mice were performed.Results: In this study, AAV-shMyh9 was used to down-regulate NMMHC IIA expression in mice. We found that down-regulation of NMMHC IIA could improve neurological scores and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis, and this effect was partially attenuated when NMMHC IIA was inhibited by AAV-shMyh9. In addition, AAV-shMyh9 significantly reduced cerebral ischemic/reperfusion (I/R)-induced NMMHC IIA-actin interaction, caspase-3 cleavage, Rho-associated kinase1 (ROCK1) activation and myosin light-chains (MLC) phosphorylation.Conclusion: Consequently, we showed that AAV-shMyh9 inhibits I/R-induced neuronal apoptosis linked with caspase-3/ROCK1/MLC/NMMHC IIA-actin cascade, which has also been confirmed to be a positive feedback loop. These findings put some insights into the neuroprotective effect of AAV-shMyh9 associated with the regulation of NMMHC IIA-related pathway under ischemic attack and provide a therapeutic strategy for ischemic stroke.Keywords: NMMHC IIA, adeno-associated virus, ischemic stroke, apoptosis

Yan-Yan Zhang, Yan Li, Meng Qin, Yan Cai, Ying Jin, Ling-Ya Pan Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China Objectives: The aim of this study was to evaluate the factors associated with progress-free survival (PFS) and overall survival (OS) in patients with high-grade endometrial stromal sarcoma (HG-ESS). Patients and methods: A total of 40 patients were enrolled in this study at the Peking Union Medical College Hospital, Beijing, China, from 2006 to 2016. The study retrospectively analyzed clinical and pathological data, and associations of these variables with PFS and OS were evaluated. Results: The age of the patients at the time of diagnosis ranged from 16 to 73 years. Abnormal vaginal bleeding was the most commonly observed symptom. The tumor size ranged from 2 to 19 cm. The tumor locations were as follows: vulva (1 case), ovary (2 cases), broad ligament (2 cases), cervix (7 cases), and uterus (28 cases). A total of 34 (85%) and 6 (15%) patients underwent complete and ovarian preservation surgery, respectively. Notably, 33 (82.5%), 13 (32.5%), and 5 (12.5%) patients received adjuvant chemotherapy, radiation therapy, and hormone treatment, respectively. Lymph node dissection was performed in 15 (37.5%) patients (positive rate: 7.4%), 16 (40%) patients underwent omentectomy (positive rate: 10%), and 12 (30%) patients underwent peritoneal lavage cytology (positive rate: 0%). Eighteen (45%) patients had lymphovascular space invasion, 13 (32.5%) patients had uterine fibroids, and 11 (27.5%) patients were diagnosed with endometriosis. Moreover, the levels of CA125 in the serum were measured prior to and following treatment. The median PFS and OS were 9 and 24 months, respectively. Eventually, 29 (72.5%) patients experienced relapse and 19 (47.5%) patients expired due to the disease. Conclusion: Patients with advanced HG-ESS (stage II–IV) were associated with poor prognosis. The minimum value of CA125 and endometriosis were independent risk factors for PFS. The stage of disease, size of the tumor, minimum and average values of CA125, menopause, history of uterine leiomyoma, and endometriosis were independent risk factors for OS. The combination of surgery with radiotherapy and chemotherapy may improve the PFS of patients in the early stage of the disease. Keywords: high-grade endometrial stromal sarcoma, CA125, treatment, prognosis

Wenbin Zhou,1 Yayuan Zhang,1 Caineng Zhong,1 Jintao Hu,2 Hong Hu,1 Dongxian Zhou,1 MeiQun Cao3 1Department of Breast Surgery, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China; 2Department of Pathology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China; 3Shenzhen Institute of Geriatrics, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China Background: Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, has been implicated in autoimmune diseases. Dysregulation of  TRIM21 contributes to the progression of human malignancies, but its role and clinical significance in breast cancer remain unclear.Methods: The expression of TRIM21 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of TRIM21 in the progression of breast cancer was determined using in vitro and in vivo models. The upstream regulation of TRIM21 was investigated by luciferase reporter assay.Results: Here, we showed that TRIM21 expression in breast cancer tissues was decreased at both the mRNA and protein levels in comparison to that in nontumorous tissues. TRIM21 expression was closely associated with tumor size, estrogen receptor, human epidermal growth factor receptor 2, and clinical stage. Low TRIM21 expression was correlated with poor overall and disease-free survival in two independent cohorts containing 1,219 patients with breast cancer. A multivariate Cox regression model suggested TRIM21 as an independent factor for overall survival. In vitro data revealed that TRIM21 expression was suppressed by miR-494-3p directly targeting the 3′ untranslated region of TRIM21. Overexpression of TRIM21 impeded cell proliferation and tumor growth in breast cancer, whereas TRIM21 depletion enhanced these capacities.Conclusion: Collectively, our findings indicate that TRIM21 serves as a potential prognostic biomarker and functions as a tumor suppressor in breast cancer. Keywords: TRIM21, prognosis, cell proliferation, breast cancer

Wen-Peng Wang,1 Ning Li,1 Yuan-Yuan Zhang,1 Yu-Tao Gao,2 Yang-Chun Sun,1 Li Ge,1 Ling-Ying Wu1 1Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Gynecology, First Affiliated Hospital of Kunming Medical University, Kunming, China Background: The role that lymph node dissection (LND) plays in the management of ovarian carcinosarcoma (OCS) is unclear due to its rarity. This study investigated lymph node metastasis (LNM) prevalence in women with early OCS and effects of LND and LNM on survival. Methods: Data of women diagnosed with OCS, whose primary tumor was confined to ovaries (American Joint Committee on Cancer [AJCC] T1) or pelvic cavity (AJCC T2), between 1988 and 2010 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into lymphadenectomy (LND [+]) and no lymphadenectomy (LND [−]) groups. Results: A total of 363 women were included. The prevalence of LNM was 9.6% in AJCC T1 and 16.3% in AJCC T2. Multivariate analysis showed that LND and AJCC T categories were independent prognostic variables, irrespective of cancer-specific survival (CSS) or overall survival (OS). Subgroup analysis by AJCC T categories revealed that LND (+) group in AJCC T2 had a better survival outcome compared to LND (−) group (CSS, HR [95% CI] = 0.61 [0.43–0.87]; OS, HR [95% CI] = 0.59 [0.42–0.83]). There was no survival difference between groups in AJCC T1 (CSS, HR [95% CI] = 0.96 [0.56–1.65]; OS, HR [95% CI] = 0.88 [0.56–1.38]). Multivariate analysis was further carried out in LND (+) group and demonstrated that LNM and AJCC T2 had poor CSS and OS. Subgroup analysis by AJCC T categories showed that worse survival was observed in LNM (+) group compared to LNM (-) group in AJCC T2 (CSS, HR [95% CI] = 3.62 [1.50–8.73]; OS, HR [95% CI] = 3.71 [1.59–8.68]) but not in AJCC T1 (CSS, HR [95% CI] = 1.78 [0.50–6.37]; OS, HR [95% CI] = 1.97 [0.61–6.39]). Conclusion: Regional lymphadenectomy should be performed in patients with AJCC T2 OCS. LND and LNM were not significantly associated with prognosis in AJCC T1 while LNM had a trend toward worse survival. Keywords: ovarian mesodermal mixed tumor, ovarian müllerian mixed tumor, lymph node examined, lymphatic metastasis

Jiajiang Xie,1,2,* Zhongxiong Fan,2,* Yang Li,2,* Yinying Zhang,2 Fei Yu,3 Guanghao Su,4 Liya Xie,5 Zhenqing Hou2 1Xiamen Xianyue Hospital, Xiamen, China; 2Research Center of Biomedical Engineering of Xiamen, Key Laboratory of Biomedical Engineering of Fujian Province, Fujian Provincial Key Laboratory for Soft Functional Materials Research, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, China; 3College of Medicals, Xiamen University, Xiamen, China; 4Children’s Hospital of Soochow University, Suzhou, China; 5The First Affiliated Hospital of Xiamen University, Xiamen, China *These authors contributed equally to this work Aim: We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. Methods: A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff’s base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). Results: The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. Conclusion: The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy. Keywords: pH-sensitive prodrug, self-assembly, targeting, combination therapy, nanoparticles

Paula Zaman,1 Julia Wang,1 Adam Blau,1 Weiping Wang,2 Tina Li,1 Daniel S Kohane,2 Joseph Loscalzo,1 Ying-Yi Zhang1 1Department of Medicine, Brigham and Women’s Hospital, 2Department of Anesthesiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Incorporation of proteins into dextran sulfate (DS)-chitosan (CS) nanoparticles (DSCS NPs) is commonly performed using entrapment procedures, in which protein molecules are mixed with DS and CS until particle formation occurs. As DS is an analog of heparin, the authors examined whether proteins could be directly incorporated into preformed DSCS NPs through a heparin binding domain-mediated interaction. The authors formulated negatively-charged DSCS NPs, and quantified the amount of charged DS in the outer shell of the particles. The authors then mixed the DSCS NPs with heparin-binding proteins (SDF-1α, VEGF, FGF-2, BMP-2, or lysozyme) to achieve incorporation. Data show that for DSCS NPs containing 100 nmol charged glucose sulfate units in DS, up to ~1.5 nmol of monomeric or ~0.75 nmol of dimeric heparin-binding proteins were incorporated without significantly altering the size or zeta potential of the particles. Incorporation efficiencies of these proteins were 95%–100%. In contrast, serum albumin or serum globulin showed minimal incorporation (8% and 4%, respectively) in 50% physiological saline, despite their large adsorption in water (80% and 92%, respectively). The NP-incorporated SDF-1α and VEGF exhibited full activity and sustained thermal stability. An in vivo aerosolization study showed that NP-incorporated SDF-1α persisted in rat lungs for 72 h (~34% remaining), while free SDF-1α was no longer detectable after 16 h. As many growth factors and cytokines contain heparin-binding sites/domains, incorporation into preformed DSCS NPs could facilitate in vivo applications of these proteins. Keywords: polyelectrolyte complex, polysaccharide, glycan, glycosaminoglycan

Yuan-Yuan Zhang,1,2* Yu-Chen Fan,3* Min Wang,1,2 Dong Wang,1,2 Xiao-Hong Li1,21Department of Neurology, Jinan Central Hospital affiliated to Shandong University, Jinan, People’s Republic of China; 2School of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Hepatology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China*Yuan-Yuan Zhang and Yu-Chen Fan contributed equally to this workBackground and aim: Amyloid-beta (Aβ) peptide is reported to initiate flexible inflammation in the hippocampus of the human brain in Alzheimer’s disease (AD). The present study aimed to investigate the possible effects of atorvastatin on the production of inflammation cytokines in the hippocampus and the potential impacts on behavioral ability, in an AD model.Methods: We firstly established AD rat models using intracerebroventricular injection of Aβ1-42. A Morris water maze was also performed to determine the spatial learning and memory ability in the AD models. Intracellular staining of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha was determined using immunohistochemical staining at 6 hours and day 7 after the injection of Aβ.Results: The escape latency of the atorvastatin-treated AD group (5 mg/kg/d) was significantly shorter than that of AD group on day 3 (41 ± 1.05 seconds versus 47 ± 1.05 seconds, P < 0.01) and day 4 (34 ± 1.25 seconds versus 43 ± 1.01 seconds, P < 0.01) after the beginning of the training. Furthermore, the atorvastatin-treated AD group displayed a significant higher mean number of annulus crossings than did the AD group (2.9 ± 0.5 versus 2.4 ± 0.9, P < 0.05). Fewer injured nerve cells and proliferated glial cells were also demonstrated in the atorvastatin-treated AD group than in the AD group. Of great importance, we demonstrated that IL-1β, IL-6, and tumor necrosis factor alpha were significantly decreased in the atorvastatin-treated AD group than that in the AD group.Conclusion: Atorvastatin might attenuate the damage of nerve cells and improve learning and memory ability by inhibiting inflammatory response in the progression of AD.Keywords: amyloid-beta, inflammation, interleukin-1β, interleukin-6, tumor necrosis factor

We calculate the radiative parton energy loss in the deeply inelastic scattering (DIS) off a large nucleus within a generalized high-twist approach. The final gluon radiation spectrum is a convolution of the hard partonic part and the transverse momentum dependent (TMD) quark-gluon correlation function, without the twist expansion in the transverse momentum of the initial gluons used in original high twist approach. The TMD quark-gluon correlation function can be factorized approximately as the product of initial quark distribution and TMD gluon distribution which can be used to define the generalized or TMD jet transport coefficient. The radiation spectrum will recover the Gylassy-Levai-Vitev (GLV) result in the first order of the opacity expansion, under the static scattering center and soft gluon radiation approximation. We also investigate numerically the difference as a result of the soft gluon radiation approximation, under the static scattering center approximation.

We revisit radiative parton energy loss in deeply inelastic scattering (DIS) off a large nucleus within the perturbative QCD approach. We calculate the gluon radiation spectra induced by double parton scattering in DIS without collinear expansion in the transverse momentum of initial gluons as in the original high-twist approach. The final radiative gluon spectrum can be expressed in terms of the convolution of hard partonic parts and unintegrated or transverse momentum dependent (TMD) quark-gluon correlations. The TMD quark-gluon correlation can be factorized approximately as a product of initial quark distribution and TMD gluon distribution which can be used to define the generalized or TMD jet transport coefficient. Under the static scattering center and soft radiative gluon approximation, we recover the result by Gylassy-Levai-Vitev in the first order of the opacity expansion. The difference as a result of the soft radiative gluon approximation is investigated numerically under the static scattering center approximation.

Two lysophospholipase activities (designated I and II) were identified in the macrophage-like cell line P388D1. Lysophospholipase I was purified (8,500-fold) to homogeneity by DEAE-Sephacel, Sephadex G-75, Blue-Sepharose, and chromatofocusing chromatography. Lysophospholipase II was separated from the lysophospholipase I in the Blue-Sepharose step. The apparent molecular mass of lysophospholipase I and II are 27,000 and 28,000 daltons, respectively, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Their pI values were 4.4 and 6.1 respectively, as determined by isoelectric focusing. Lysophospholipase I exhibited a broad pH optimum between 7.5-9.0. The double-reciprocal plot of the substrate dependence curve of the purified lysophospholipase I showed a break around the critical micelle concentration of the substrate (1-palmitoyl-sn-glycerol-3-phosphorylcholine). The apparent Km, determined from substrate concentrations above 10 microM was 22 microM, and the apparent Vmax was 1.3 mumol min-1mg-1. The purified enzyme did not have phospholipase A1, phospholipase A2, acyltransferase, or lysophospholipase-transacylase activity. No activity was detected toward triacylglycerol, diacylglycerol, p-nitrophenol acetate, p-nitrophenol palmitate, or cholesterol ester. The enzyme did, however, hydrolyze monoacylglycerol although at a rate 20-fold less than lysophospholipid, 0.06 mumol min-1mg-1. The lysophospholipase I was inhibited by fatty acids but not by glycerol-3-phosphorylcholine, glycerol-3-phosphorylethanolamine, or glyc-fjerol-3-phosphorylserine. A synthetic manoalide analogue 3(cis,cis,-7,10)hexadecadienyl-4-hydroxy-2-butenolide inhibited the enzyme with half-inhibition (IC50) at about 160 microM. Triton X-100 decreased the enzymatic activity, although this apparent inhibition can be explained by a "surface dilution" effect. The pure lysophospholipase I was stable for at least 5 months at -20 degrees C in the presence of glycerol and beta-mercaptoethanol. Lysophospholipid also demonstrated a protective effect during the later stage of purification.