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Yi Lin,1 Kaushik Chattopadhyay,2 Xi Yang,3 Jia-Lin Li,4 Yan-Shu Chen,4 Ye Zhou,4 Li Li4 1Center for Health Economics, Faculty of Humanities and Social Sciences, University of Nottingham, Ningbo, Zhejiang Province, People’s Republic of China; 2Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; 3Department of Nutrition, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 4Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of ChinaCorrespondence: Li LiDepartment of Endocrinology and Metabolism, Ningbo First Hospital, 59, Liuting Street, Ningbo, 315010, Zhejiang Province, People’s Republic of ChinaTel +86 13757426626Email lilyningbo@163.comYi LinCenter for Health Economics, Faculty of Humanities and Social Sciences, University of Nottingham, 199, Taikang East Road, University Park, Ningbo, 315100, People’s Republic of ChinaTel +86-13916608572Email Lily.Lin@nottingham.edu.cnPurpose: Type 2 diabetes (T2D) is one of the major public health concerns in China. Studies on the association between dietary salt intake and the glycemic response of T2D are lacking in China. The aim was to investigate the association between the levels of dietary salt intake and the plasma glucose, insulin and hemoglobin A1c (HbA1c) levels in T2D patients.Methods: Patients with T2D, who accepted management and treatment by the National Standardized Metabolic Disease Management Center at Ningbo First Hospital from March 2018 to January 2020, were included in this study. Dietary salt intake was assessed through a standardized food frequency questionnaire. Anthropometry, blood pressure and biomarkers were measured by well-trained endocrinology nurses. Generalized linear models (GLMs) were used to examine the associations.Results: A total of 1145 eligible T2D patients with a mean age of 51.4 years were included in the study. Fasting plasma glucose (FPG), 2-hour postprandial plasma glucose and 2-hour postprandial insulin were significantly increased across dietary salt categories. The GLMs further showed that dietary salt intake > 8 g/day was positively associated with FPG and HbA1c.Conclusion: Higher daily salt intake was found to be associated with FPG and HbA1c in T2D patients. Lifestyle education and promotion of salt reduction should be provided to T2D patients.Keywords: dietary salt, type 2 diabetes, blood glucose, insulin, glycated hemoglobin A1c, China

Na Zhang,1,2 Jian-Feng Tu,1 Ying Lin,1 Jin-Ling Li,1 Xuan Zou,1 Yu Wang,1 Hewen Li,1 Xiao-Ya Wei,1 Li-Qiong Wang,1 Guang-Xia Shi,1 Shi-Yan Yan,1 Cun-Zhi Liu1 1International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Guang-Xia Shi; Shi-Yan Yan Email shiguangxia2008@126.com; yanshiyan0927@sina.comBackground: Whether the clinical effect of acupuncture in chronic pain is effective has always been a hot topic of research, which has a great relationship with the overall reporting descriptions of acupuncture, especially the sham acupuncture intervention. To confirm the effectiveness of acupuncture, more clinical studies are often required. Therefore, it is necessary to report high-quality and complete descriptions of acupuncture in clinical trials. This study aims to assess the overall reporting quality of acupuncture for chronic pain in randomized controlled trials (RCTs).Methods: Three databases from inception to March 2020 were searched, to assess the quality of acupuncture reports included the RCTs based on the pain-specific supplement to Consolidated Standards for Reporting Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. The quality of sham acupuncture descriptions was evaluated based on the Template for Intervention Description and Replication (TIDieR)-placebo checklist. Descriptive statistics and analysis of the results were carried out according to the percentage of each item.Results: A total of 74 RCTs were included which met the inclusion criteria. Based on the pain-specific CONSORT, the reporting rates of “Statistical methods”, “Participant flow”, and “Blinding” were “ 52.70%”, “ 70.27%”, and “ 77.03%”, respectively. The weakest reported items in STRICTA were related to the depth of insertion (Item 2c, 54.05%) and the setting and context of treatment (Item 4b, 0.00%). Based on the TIDieR-placebo checklist, the reporting rates of “Item 12”, “Item 11”, “Item 13”, “Item 3”, and “Item 4” were “ 8.11%”, “ 10.81%”, “ 29.73%”, “ 44.59% ”, and “ 47.30%”, respectively.Conclusion: At present, the overall report quality of acupuncture treatment for chronic pain in English journals is acceptable, but the report rate in some aspects is still low. In the future, researchers should report RCTs of acupuncture following cleaner checklists and guidelines.Keywords: randomized controlled trials, overall reporting quality, sham acupuncture, chronic pain

Na Zhang,1,2 Li-Qiong Wang,1 Jin-Ling Li,1 Xin-Tong Su,1 Fang-Ting Yu,1 Guang-Xia Shi,1 Jing-Wen Yang,1 Cun-Zhi Liu1 1International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Cun-Zhi LiuSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing 100029, People’s Republic of ChinaEmail lcz_tg@126.comObjective: Acupuncture therapy is an effective non-drug therapy for sciatica, but it has not yet formed an effective treatment strategy and recommendations. Our objective was to establish an expert consensus on acupuncture treatment of sciatica for clinical guidance based on the improved Delphi survey.Methods: A group of 80 clinical specialists was invited to participate in two rounds of semi-open clinical issue investigation. At the same time, the PubMed, Embase, and Cochrane Library databases were searched for systematic reviews on acupuncture treatment of sciatica, and the quality of evidence was evaluated. Then the three-round Delphi survey was undertaken with 30 experts based on the clinical issue investigation and systematic reviews.Results: In round 1 of the Delphi survey, the experts evaluated 17 items identified from the results of the clinical investigation and literature review. The criterion for achieving consensus was a threshold of 80% agreement. After the three-round Delphi survey, 16 items (94.12%) achieved consensus, including 5 domains: the principle of acupuncture treatment for sciatica; the “dose” of acupuncture; the clinical effects of acupuncture; the adverse effects, and others.Conclusion: This Delphi survey achieved an expert consensus on key items in the management of sciatica for acupuncture, which provides the current opinions in China. We trust that these treatment recommendations may facilitate their implementation in the future.Keywords: acupuncture, sciatica, expert consensus, Delphi survey

Pu-Yuan Xing,1,* Shou-Zheng Wang,1,* Ju-Fang Shi,2 Le Wang,2 Zhou-Guang Hui,3 Jian-Song Ren,2 Shang-Mei Liu,4 You-Lin Qiao,5 Min Dai,2 Jun-Ling Li1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Ling Li; Ju-Fang Shi Email lijunling@cicams.ac.cn; shijf@cicams.ac.cnBackground: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients.Patients and Methods: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors.Results: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets.Conclusion: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.Keywords: non-small cell lung cancer, chemotherapy, neo-adjuvant chemotherapy, adjuvant chemotherapy, epidemiology

Jin-Ling Li,1,2 Chao-Qun Yan,1 Xu Wang,3 Shuai Zhang,4 Na Zhang,5 Shang-Qing Hu,1 Li-Qiong Wang,1 Cun-Zhi Liu1 1School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of Acupuncture and Moxibustion, Wangjing Hospital, Beijing, People’s Republic of China; 5School of Acupuncture and Moxibustion, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Cun-Zhi LiuSchool of Acupuncture and Moxibustion, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing 100029, People’s Republic of ChinaTel +86 15901261692Email lcz_tg@126.comObjective: Chronic shoulder pain (CSP) is a common health problem associated with shoulder dysfunction and persistent pain for many different reasons. However, the studies of pain-related functional brain regions in CSP have been poorly investigated. The main purpose of our study was to observe whether there are abnormal functional changes in brain regions in patients with CSP by using functional magnetic resonance imaging (fMRI).Patients and Methods: We compared the differences of brain regions between 37 patients with CSP and 24 healthy controls (HC) using regional homogeneity (ReHo) method. The patients with chronic shoulder pain and healthy controls were matched for age and gender. Brain regions which had abnormal ReHo values were defined as seed region of interests. The approach of seed-based functional connectivity (FC) was further performed to analyze the connectivity between the seeds and whole brain regions. The relationship between abnormal regions and current clinical pain was also evaluated.Results: Compared to healthy controls, the patients with CSP showed increased ReHo values in the left middle temporal gyrus and decreased ReHo values in right orbitofrontal cortex (OFC). The seed-based analyses demonstrated decreased connectivity between the right OFC and right rectus, superior frontal gyrus in patients with chronic shoulder pain. However, a correlation between ReHo values and clinical characteristics in CSP patients was not found.Conclusion: The observed results indicate that there are abnormal ReHo values in brain regions of patients with CSP, especially in the OFC and middle temporal gyrus. Our findings demonstrate that the experience of CSP patients may be mainly associated with cognitive-affective pain processing, rather than nociception.Keywords: functional magnetic resonance imaging, chronic shoulder pain, cognition, emotion

Xiao-Dong Zhang,1,2 Guang-Xue Liu,3 Xiao-Yue Wang,2 Xiao-Jie Huang,4 Jing-Li Li,1 Rui-Li Li,2 Hong-Jun Li2 1Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, People’s Republic of China; 2Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of China; 3Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Rui-Li Li; Hong-Jun LiDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmen Wai, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 010 83997337Fax +86 010 63051182Email 1985lrli@sina.com; lihongjun00113@sina.comObjective: This study assessed the possible effect of syphilis co-infection in the brain function in young HIV patients by using voxel-wise degree centrality (DC) analysis.Methods: Forty-four syphilis-co-infected HIV patients (HIV+/syphilis+), 45 HIV patients without syphilis history (HIV+/syphilis-) and 43 matched healthy controls (HC) underwent resting-state fMRI examinations. Laboratory tests and a battery of neuropsychological tests were performed before each MRI examination. One-way ANOVA was used to compare the differences of DC among the three groups. The correlations between MRI metrics and laboratory/neuropsychological tests in each patient’s group were performed by Pearson correlation analysis.Results: Compared with HIV+/syphilis-, worse performance in complex motor skills was found in HIV+/syphilis+. Compared with HC, HIV+/syphilis+ and HIV+/syphilis- groups showed attenuated DC in the right orbital frontal cortex and increased DC in the left parietal/temporal cortex. Besides, we also found increased DC in the left inferior frontal cortex and bilateral posterior cingulated cortex/precuneus in HIV+/syphilis+ compared with HC. Moreover, compared with HIV+/syphilis-, HIV+/syphilis+ displayed decreased DC in the left middle occipital cortex. Additionally, in HIV+/syphilis+ group, the mean z value of DC was correlated to the CD4+ cell counts and the learning and delayed recall score.Conclusion: Syphilis co-infection might be related to more brain functional reorganization in young HIV patients which could be reflected by DC value.Keywords: syphilis, HIV, functional connectivity, fMRI, brain

Chen Y, Huang L, Wang S, et al. Cancer Manag Res. 2019;11:2415-2424 At the authors request, the Editor and Publisher of Cancer Management and Research wish to retract the published article. The authors have informed the journal that they have concerns regarding the reliability of the published Western blot results and cannot locate or provide any original Western blot data relating to their study. The authors can no longer verify the findings as reported and the Editor has agreed with the request to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Hui Zhang,1 Wen-Ting Tong,2 Chang-Rong Zhang,1 Jun-Long Li,1 Hao Meng,3 Hai-Gan Yang,3 Min Chen31The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi, People’s Republic of China; 3Department of Andrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Min ChenDepartment of Andrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Ji-chang Road, Guangzhou 51000, Guangdong, People’s Republic of ChinaTel +86 203 659 1359Fax +86 203 659 1127Email wiiiiiki@gmail.comObjective: To investigate the effect of gross saponins of Tribulus terrestris (GSTT) on erectile function in rats resulting from type 2 diabetes mellitus (T2DMED).Methods: The T2DMED model was constructed by high-fat and high-sugar feeding and streptozotocin injection. After 4 weeks of GSTT intervention. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured in each group. The level of nitric oxide (NO) in the cavernous tissue was detected using the nitrate reductase method. The production of reactive oxygen species (ROS) was detected using DHE fluorescent probe detection. Cyclic adenosinemonophosphate (cGMP) level was detected by enzyme-linked immunosorbent assay, and endothelial nitricoxide synthase (eNOS) was detected using immunohistochemistry. Masson staining was used to detect the cavernosal smooth muscle/collagen ratio. Apoptosis in endothelial cells was measured using TUNEL. Western blotting method to detect the protein expression level of eNOS, TIMP-1, cleaved caspase 3, and cleaved caspase 9.Results: After treatment, the ICP and ICP/MAP values of the GSTT were significantly higher than those of the T2DMED group (P0.05), and the mixed group had higher levels than these two groups (P

Yao Chen,1,2 Liping Huang,3 Suihai Wang,4 Ji-Liang Li,4,5 Ming Li,1 Yingsong Wu,4 Tiancai Liu41School of Medical Laboratory and Biotechnology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2State Key Laboratory of Organ Failure, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Obstetrics and Gynecology Centre, Nanfang Hospital, Guangzhou 510515, People’s Republic of China; 4School of Biotechnology, Southern Medical University, Guangzhou 510515, People’s Republic of China; 5Faculty of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Plymouth, PL6 8BU, UKObjective: To understand the role of WFDC2 in metastasis of ovarian cancer.Methods: By knockdown or overexpression of WFDC2, we demonstrated the role of WFDC2 in epithelial–mesenchymal transition (EMT).Results: We demonstrated that stable knockdown of WFDC2 suppressed EMT along with the upregulation of E-cadherin and the downregulation of Vimentin. In addition, WFDC2 knockdown decreases matrix metalloproteinase-2 (MMP-2) expression in in vitro cell model and in in vivo nude mice xenografts. The correlation of WFDC2 and MMP-2 expression in the clinical sample confirmed that WFDC2 was tightly correlated with the development of tumor. More importantly, the EMT phenotype and cell invasion induced by WFDC2 overexpressing can be reversed by the siMMP-2 and P13K/AKT signaling inhibitor.Conclusion: WFDC2 contributed to ovarian cancer metastasis and EMT as a positive regulator by activating AKT signaling pathway and inducing MMP-2 expression.Keywords: WFCD2, ovarian cancer, metastasis, cell migration and invasion, epithelial-mesenchymal transition

Xun Tang,1 Hui-Ying Wang,1 Min Wang,2 Xiao-Hua Ren,3 Fu-Rong Jiang,1 Jian-Ling Li1,3 1Clinical Psychology Department of Xiangya Hospital, Xiangya Medical School, Central South University, Changsha, China; 2Department of HIV, The First Hospital of Changsha, Changsha, China; 3Traning Department of Xiangya Hospital, Central South University, Changsha, China Introduction: People living with HIV/AIDS (PLWHA) have a higher rate of suicide compared to the general population. Psychosocial factors closely correlate with suicidal ideation and it is essential to explain the relationships between related factors among PLWHA.Objectives: To establish a structural equation model and examine direct and indirect effects of social support, coping strategy, depression symptoms and suicidal ideation among PLWHA.Patients and methods: A total of 504 PLWHA completed a set of questionnaires in the HIV clinic of Changsha Infectious Disease Hospital between December 2015 and January 2016.Results: Among the 504 respondents, a total of 27.2% (n=137) had experienced suicidal ideation in their lifetime. The goodness of fit for the two structural equations model was highly satisfactory. Depression symptoms had a significant direct impact on suicidal ideation (β1=0.401, β2=0.422), while problem-focused coping (β=-0.067), emotion-focused coping (β=-0.081) and social support (β=-0.137) had a significant indirect effect with suicidal ideation via depression symptoms. Factors of total effects were ranked from large to small as follows: depression, social support, emotion-focused coping and problem-focused coping.Conclusion: Findings provide more understanding of direct and indirect associations between variables, suggesting that depression screening services, and the strengthening of social support and psychological care services among PLWHA can potentially prevent suicide. Keywords: SEM, PLWHA, depression, problem-focused coping, emotion-focused coping

Xian-Wu Luo,1 Xue-Qing Du,2 Jie-Li Li,2 Xiao-Ping Liu,3,4 Xiang-Yu Meng3,4 1Department of Health Management, School of Health Sciences, Wuhan University, 2Department of Hematology, Zhongnan Hospital of Wuhan University, 3Department of Evidence-Based Medicine and Clinical Epidemiology, Second Clinical School, Wuhan University, 4Center for Evidence-based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China Background: The refractory/relapsed multiple myeloma (RRMM) remains a big clinical challenge, due to its biological and clinical complexity. Leading hematologists have performed many randomized controlled trials (RCTs) worldwide, and their findings were summarized in a recently published network meta-analysis (NMA) but with certain limitations. Materials and methods: We performed an updated NMA of RCTs related to RRMM treatment, focusing on efficacy measures including the nonresponse rate (NRR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS). The PubMed database was searched. We extended the literature search strategy of a previous NMA to June 30, 2017 and included additional primary RCTs. The surface under the cumulative ranking curve (SUCRA) was calculated to rank the regimens. A weighted-average method was used to rank the regimens by summarizing SUCRAs across different outcome measures. Results: Finally, a total of 24 RCTs were included in this updated NMA. According to the result, the combination of daratumumab, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of NRR, TTP, and PFS (NRR: odds ratio [OR] =0.046, 95% credible interval [CrI] =[0.024, 0.085]; TTP: hazard ratio [HR] =0.14, 95% CrI =[0.092, 0.2]; PFS: HR =0.12, 95% CrI =[0.077, 0.18], compared with dexamethasone singlet). The combination of ixazomib, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of OS (HR =0.30, 95% CrI =[0.17, 0.54], compared with dexamethasone). The combination of daratumumab, lenalidomide, and dexamethasone ranked first in terms of overall efficacy (weighted average of SUCRAs =0.920). Conclusion: The combination of daratumumab, lenalidomide, and dexamethasone may currently be the most effective regimen in the population of RRMM patients. Triplet regimens containing daratumumab, ixazomib, carfilzomib, or elotumumab plus lenalidomide and dexamethasone can be recommended as first-line therapies for RRMM patients. Keywords: multiple myeloma, refractory/relapsed, treatment regimens, efficacy, network meta-analysis

Jiulong Li,1 Bing Tian,1 Tao Li,1 Shang Dai,1 Yulan Weng,1 Jianjiang Lu,2 Xiaolin Xu,2 Ye Jin,1 Renjiang Pang,1 Yuejin Hua1 1Key Laboratory for Nuclear-Agricultural Sciences of Chinese Ministry of Agriculture and Zhejiang Province, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang, People’s Republic of China Background: Biosynthesis of noble metallic nanoparticles (NPs) has attracted significant interest due to their environmental friendly and biocompatible properties.Methods: In this study, we investigated syntheses of Au, Ag and Au–Ag bimetallic NPs using protein extracts of Deinococcus radiodurans, which demonstrated powerful metal-reducing ability. The obtained NPs were characterized and analyzed by various spectroscopy techniques.Results: The D. radiodurans protein extract-mediated silver nanoparticles (Drp-AgNPs) were preferably monodispersed and stably distributed compared to D. radiodurans protein extract-mediated gold nanoparticles (Drp-AuNPs). Drp-AgNPs and Drp-AuNPs exhibited spherical morphology with average sizes of 37.13±5.97 nm and 51.72±7.38 nm and zeta potential values of -18.31±1.39 mV and -15.17±1.24 mV at pH 7, respectively. The release efficiencies of Drp-AuNPs and Drp-AgNPs measured at 24 h were 3.99% and 18.20%, respectively. During the synthesis process, Au(III) was reduced to Au(I) and further to Au(0) and Ag(I) was reduced to Ag(0) by interactions with the hydroxyl, amine, carboxyl, phospho or sulfhydryl groups of proteins and subsequently stabilized by these groups. Some characteristics of Drp-AuNPs were different from those of Drp-AgNPs, which could be attributed to the interaction of the NPs with different binding groups of proteins. The Drp-AgNPs could be further formed into Au–Ag bimetallic NPs via galvanic replacement reaction. Drp-AuNPs and Au–Ag bimetallic NPs showed low cytotoxicity against MCF-10A cells due to the lower level of intracellular reactive oxygen species (ROS) generation than that of Drp-AgNPs.Conclusions: These results are crucial to understand the biosynthetic mechanism and properties of noble metallic NPs using the protein extracts of bacteria. The biocompatible Au or Au–Ag bimetallic NPs are applicable in biosensing, bioimaging and biomedicine. Keywords: extreme bacterium, green synthesis, noble metallic nanoparticles, reactive oxygen species

Huaqiao Tang,1,2,* Nana Long,1,2,* Lin Lin,1,2 Yao Liu,1 Jianlong Li,1,2 Fenghui Sun,1,2 Lijuan Guo,1,2 Fen Zhang,3 Min Dai1,2 1School of Laboratory Medicine, 2Laboratory of Veterinary Drug Residue Prevention and Control Technology of Animal-derived Food, 3School of Humanities and Information Management, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. Materials and methods: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated. Results: The administration of an attack dose of MRSA caused serious symptoms of infection and resulted in a 40% mortality rate in the mice. MRSA induced strong inflammation and oxidative stress in the mice, predominantly caused by significant increases in interleukin (IL)-1β, IL-4, IL-6, macrophage inflammatory protein, glutathione S-transferase (GST), and malondialdehyde, and decreases in oxygen radical absorbance capacity and glutathione levels in the liver. The expression of IL-2, tumor necrosis factor-α, and GST was briefly suppressed, but increased on days 3 and 7. The increased inflammation and oxidative stress further induced a significant decrease in the mRNA levels and activities of CYP450 1A2, 2D22, 2E1, and 3A1 in MRSA-infected mice within the first day of infection. Conclusion: These results show that MRSA infection leads to inflammation and oxidative stress, and reduces the expression levels and activities of drug metabolism enzymes, which decreased drug metabolism in patients infected with MRSA. Therefore, to avoid a drug overdose, the plasma concentration of patients with MRSA infection should be continuously monitored. Keywords: MRSA, infection, cytokines, oxidative stress, CYP450

Xiangquan Kong,* Xueqing Zhang,* Yunxia Huang, Lirui Tang, Qingqin Peng, Jinluan Li Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work. Background: Colorectal signet ring cell (SRC) carcinoma occurs rarely with a poor prognosis. The present study assessed the prognostic factors and predictive value of SRC ratio in colorectal mucinous adenocarcinoma (MAC) with SRCs (MAC-SRC).Patients and methods: A total of 95 consecutive colorectal MAC-SRC patients, confirmed pathologically from February 1987 to December 2015, were analyzed retrospectively in our institute. Clinical characteristics, pathological grade, TNM staging, and SRC ratio were assessed to identify the prognostic factors related to progression-free survival (PFS) and overall survival (OS). SPSS 22.0 was used for statistical analyses.Results: The median follow-up time was 29.7 months (range 0.8–165). Meanwhile, 5-year PFS and OS rates were 25.6% (95% confidence interval [CI] 16.192–35.008%) and 40.5% (95% CI 29.524–51.476%), respectively. Among the 81 patients who underwent surgery, 78 (96.3%) were diagnosed as stage T3 or T4; 74 (91.4%) showed lymph node involvement, and 27 (29.3%) presented distant metastasis. Metastases of the peritoneal cavity and ovaries were observed commonly in colorectal MAC-SRC. In the multivariate Cox regression model, SRC ratio ≥35%, absence of preoperative radiotherapy, and distant metastasis were independent predictors of PFS. Furthermore, SRC ratio ≥35%, absence of preoperative chemotherapy (pre-CT), and distant metastasis were independent risk factors for poor prognosis.Conclusion: A long-term follow-up of colorectal MAC-SRC reveals that it is a rare subtype of colorectal MAC with a dismal prognosis. Furthermore, SRC ratio, pre-CT, and M stage seem to affect OS independently. Keywords: colorectal mucinous adenocarcinoma, signet ring cell, progression-free survival, overall survival, prognostic factors

Yanjun Guo,1 Shuhui Wang,1 Bin Jiang,1 Jianle Li,1 Lei Liu,2 Jiawei Wang,2 Weiqin Zhao,1 Jianping Jia1 1Department of Neurology, Beijing Friendship Hospital, Capital Medical University. Beijing, China; 2Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Background: Approximately 200 cases of mild encephalitis with reversible splenial (MERS) and deep cerebral white matter lesions have been reported since MERS was first defined in 2004. MERS occurs more frequently in children; in adults, only ~60 cases have been reported. Until now, only four cases of MERS in adults have been associated with Epstein–Barr virus (EBV). Case presentation: We report three adult cases of MERS associated with EBV infection in China. For all three patients, cranial magnetic resonance imaging (MRI) indicated solitary reversible splenial and/or perilateral ventricle white matter lesions with reduced diffusion. In the present report, all patients were adults presenting with high fever, headache, apathy, and confusion, as well as significant signs of meningeal inflammation. These symptoms peaked 10–14 days after disease onset, with serious hyponatremia (112–129 mmol/L), an elevated cerebrospinal fluid white blood cell count (80–380/mm3), and significantly increased protein levels (1,010–1,650 mg/dL). Cranial MRI indicated abnormal signal intensity in the splenium of corpus callosum and symmetrically reversible lesions scattered in the thalamus and deep cerebral white matter. The clinical symptoms tended to improve after ~10–14 days of antiviral treatment. However, these patients recovered more slowly than patients with viral meningitis. Conclusion: MERS associated with EBV infection in adults occurs less frequently but with more severe symptoms than in children. EBV infection should be considered for patients with MERS symptoms. MERS has a good prognosis. Keywords: mild encephalitis with reversible splenial lesions, Epstein-Barr virus, apathy, hyponatremia, corpus fluid

Lingdong Shao,* Qingqin Peng,* Kaixin Du,* Junyan He, Yaping Dong, Xiaoyi Lin, Jinluan Li, Junxin Wu Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The tumor cell (TC) PD-L1 expression has been reported by several studies in various types of cancer, and it reduces the cytotoxicity of T-cells toward cancer and evades the anticancer immune response. Herein, our study focuses on the impact of PD-L1 expression in prognosis and the correlation with clinical prognostic factors for local advanced rectal cancer with neoadjuvant radiotherapy (RT). A total of 68 rectal cancer patients treated with neoadjuvant RT were retrospectively enrolled in the present study. PD-L1 expression was investigated using immunohistochemistry. A regression model was used to identify prognostic factors associated with the disease-free survival, the local recurrence-free survival (LRFS), and the overall survival rates. The median follow-up was 32.5 months. Seven patients presented TC PD-L1 positive (TC PD-L1+), while the others were TC PD-L1 negative (TC PD-L1–). TC PD-L1+ patients showed frequent tumor recurrence than TC PD-L1– patients. Several patients with TC PD-L1– underwent long-course RT. TC PD-L1 expression was similar to interstitial cell (IC) PD-L1 expression, and the relationship between IC PD-L1 and pathological T stage was observed. TC PD-L1+ was related to poor LRFS. The multivariate analysis showed TC PD-L1+ as an independent negative prognostic factor for LRFS. In conclusion, TC PD-L1 expression putatively predicts the LRFS for patients with rectal cancer following neoadjuvant RT. The patients with TC PD-L1+ are susceptible to high local recurrent rate, thereby proposing a novel immunotherapeutic strategy for PD-L1 inhibition-mediated control. Keywords: PD-L1, rectal cancer, neoadjuvant radiotherapy, prognosis

JingLun Li,1 JiaoJiao Deng,2 JinXian Yuan,1 Jie Fu,1 XiaoLing Li,2 AiPing Tong,2 YueLong Wang,2 YangMei Chen,1 Gang Guo2 1Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China Abstract: Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(L-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future. Keywords: spinal cord injury, zonisamide, nanomicelles

Li Zhang,1,2 Tengteng Wang,1,2 Qiang Li,1,2 Jing Huang,3 Hao Xu,1,2 Jinlong Li,1,2 Yongjun Wang,1,2 Qianqian Liang1,21Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, 3Biochemistry and Molecular Biology, School of Life Science, East China Normal University, Shanghai, People’s Republic of China Abstract: Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is –35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. Keywords: triptolide, toxicity, poly-γ-glutamic acid, drug carrier system