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Hongqi Meng,1 Ying Zhao,1 Hang Cai,2 Di You,3 Ying Wang,4 Siyu Wu,1 Yixin Wang,5 Wenlai Guo,1 Wenrui Qu1,6 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 3Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130031, People’s Republic of China; 4Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, 157011, People’s Republic of China; 5Department of Plastic Surgery, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 6Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Wenlai Guo, Email guowl19@jlu.edu.cnPurpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats.Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition.Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance.Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing. Keywords: MRSA, infection, diabetic wounds, hydrogels, CS-AuNPs, antimicrobial

Huili Tang, Xueqing Wu, Jiamei Feng, Qingqian Gao, Shijun Shao, Wenchao Qu, Lu Xie, Jiaye Sun Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Xueqing Wu, Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 185 Pu ‘an Road, Huangpu District, Shanghai, People’s Republic of China, Tel + 86-13817792022, Fax + 86-200021, Email snow_zi@hotmail.comPurpose: To determine the risk factors, clinical characteristics, and prognosis of adolescent non-puerperal mastitis patients.Patients and methods: A retrospective analysis was conducted on 10 cases of NPM in adolescents who underwent surgical treatment at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from August 2021 to August 2023. We analyze the patient’s general information, clinical characteristics, related medical history, laboratory indicators, breast magnetic resonance imaging examination, postoperative pathology, prognosis, etc.Results: The clinical manifestations of NPM in adolescents mainly included redness, swelling and pain in the breasts, congenital nipple retraction, and extensive lesion range. Inflammatory markers and prolactin were elevated. Magnetic resonance imaging showed circular enhancement with abscess formation as the main type. All patients underwent surgical treatment with a fast recovery time after surgery. No recurrence was observed during follow-up and the postoperative breast appearance was satisfactory. Multivariate Logistic regression analysis indicated that congenital nipple retraction, elevated prolactin levels and trauma were independent risk factors for adolescents non-puerperal mastitis.Conclusion: Adolescent non-puerperal mastitis is a rare and unique type. Summarizing its main risk factors, clinical characteristics, and prognosis provides a basis for further research.Keywords: adolescents, non-puerperal mastitis, risk factors, clinical characteristics, prognosis

Wenjie Qu,1,2,* Xinyu Wang,1,* Yufei Liu,3 Jinfeng Mao,2 Mengchi Liu,4 Yaqin Zhong,1,2 Bella Gao,5 Miaomiao Zhao,1 Yuexia Gao1,2 1Department of Health Management, School of Public Health, Nantong University, Nantong, People’s Republic of China; 2Institute for Health Development, Nantong University, Nantong, People’s Republic of China; 3Faculty of Health Sciences, University of Macau, Macau, People’s Republic of China; 4National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 5Ulink College of Suzhou Industrial Park, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Miaomiao Zhao; Yuexia Gao, Department of Health Management, School of Public Health, Nantong University, 9 Seyuan Road, Jiangsu, 226019, People’s Republic of China, Tel +86150 0450 1812 ; +86139 6296 8819, Email zhaomiaomiao@ntu.edu.cn; yxgao@ntu.edu.cnBackground: Self-medication with antibiotics (SMA) among children is a common practice in low-income and middle-income countries, which has accelerated antibacterial abuse.Objective: This study aimed to estimate the prevalence and associated factors of SMA among children in China, including parents’ knowledge, attitudes, and practices towards antibiotic use.Methods: A cross-sectional study based on a structured questionnaire survey of parents was conducted in Nantong between July and September 2020. A total of 1699 respondents participated. Information on participants’ demographic and family characteristics, knowledge, attitudes, and practices towards antibiotics use was collected. Hierarchical binary logistic regression was used to examine the predictors of SMA among children.Results: Among 1699 participants, 23.31% practiced SMA to their children in the past year. Cough (59.6%) was the most common symptom leading to self-medication and penicillins (85.4%) were the most commonly used drugs. Hierarchical regression indicated that parents with higher level of antibiotic knowledge scores (OR=1.163, 95% CI: 1.067– 1.268) and buying antibiotics without a prescription from pharmacy (OR=1.475, 95% CI: 1.097– 1.983) were more likely to practice SMA to their children both in urban and in rural areas. Storing antibiotics at home resulted in an increased likelihood of self-medication in urban areas but not in rural areas. In addition, there was also a higher probability of non-prescribed antibiotics in children without chronic diseases (OR=1.959, 95% CI:1.072– 3.578).Conclusion: The prevalence of SMA in children is high in China. Higher knowledge scores and practices of buying and storing non-prescribed antibiotics behaviors increased parents’ antibiotic self-medication in their children. Practical and effective education intervention for children’s rational use of antibiotics is urgently strengthened.Keywords: antibiotic, self-medication, children, China, antibiotic knowledge, attitude

Peiyu Xing,1,&ast; Bo Meng,2,&ast; Xiaojia Hu,1 Wei Qu,2 Shaowei Wang2 1Department of Ophthalmology, China Medical University the Fourth People’s Hospital of Shenyang, Shenyang, People’s Republic of China; 2Department of Ophthalmology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaowei Wang, Department of Ophthalmology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email h04014@hrbmu.edu.cnObjective: To assess the functional and anatomical effects of transitioning to conbercept intravitreal injection (IVC) treatment in patients with diabetic macular edema (DME) who had inadequate responses to prior anti-vascular endothelial growth factor (anti-VEGF) injections.Methods: We retrospectively included eyes with persistent DME after at least 3 injections of intravitreal ranibizumab (IVR). The analysis included the assessment of best corrected visual acuity (BCVA) and central macular thickness (CMT) during 6 months after the switch.Results: A total of 30 patients (30 eyes) were included. CMT dropped sharply from 437.8± 40.67μm at baseline to 363.59± 45.09,312.52 ± 39.15, 278.51 ± 37.92, and 292.59 ± 38.09 after 1, 2, 3 and 6 months of IVC, respectively (p < 0.001). BCVA in log MAR units was significantly improved from 0.73± 0.15 at baseline to 0.50± 0.09,0.46± 0.72, 0.40± 0.06 and 0.48± 0.04 after 1, 2, 3 and 6 months, respectively (p < 0.001).Conclusion: Switching to Conbercept effectively improved visual and anatomical structure in DME patients who had not responded satisfactorily to previous anti-VEGF injections.Keywords: diabetic macular edema, anti-vascular endothelial growth factor, central macular thickness, best corrected visual acuity, DME, CMT, anti-VEGF, BCVA

Weikun Qu,1,2,&ast; Yalu Yao,1,&ast; Yaqian Liu,1,&ast; HyonSu Jo,1,3 Qianran Zhang,1,&ast; Haidong Zhao1,&ast; 1Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 2OPO Office, The Second Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 3Department of General Surgery, the Hospital of Pyongyang Medical University, Pyongyang, 999093, Democratic People’s Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Haidong Zhao; Qianran Zhang, Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, 467, Zhongshan Road, Shahekou District, Dalian, Liaoning, 116023, People’s Republic of China, Tel +86 13354288881 ; +86 13278089966, Email z.hddl@hotmail.com; 382026591@qq.comPurpose: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA.Patients and Methods: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays.Results: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models.Conclusion: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.Keywords: carboxylesterase 2, breast cancer, fluorescent probe, bioinformatics, molecular markers

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. We, the Editor and Publisher of Cancer Management and Therapy are retracting the published article. Since publication, concerns have been raised about the duplication of images in this article with those from other unrelated articles. Specifically, The image from Figure 2D, A498, si-NC, has been duplicated with the image from Figure 4C, C-33A, agomir-NC from Wu F, Sui Y, Wang Y, Xu T, Fan L, Zhu H. Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4. Onco Targets Ther. 2020;13:685–699. https://doi.org/10.2147/OTT.S232542 (RETRACTED). The image from Figure 5C, 786-O, si-NC, has been duplicated with the image from Figure 2D, H460, si-NC from Dai J, Wang B, Zhao Y, et al. RETRACTED ARTICLE: Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression. Cancer Manag Res. 2020;12:12697–12708. https://doi.org/10.2147/CMAR.S277113 (RETRACTED). The image from Figure 5C, 786-O, si-CASC19+miR-532 inhibitor, and Figure 6E, 786-O, si-CASC19+pcDNA3.1-ETS1 has been duplicated with the image from Figure 6D, A549, agomiR-NC, and Figure 6E, A549, agomiR-NC, respectively, from Kang X, Kong F, Wu S, et al. microRNA-612 suppresses the malignant development of non-small-cell lung cancer by directly targeting bromodomain-containing protein 4. Onco Targets Ther. 2019;12:4167–4179. https://doi.org/10.2147/OTT.S204004 (RETRACTED). The image from Figure 5D, 786-O, si-CASC19+NC inhibitor, has been duplicated with the image from Figure 6F, Hep3B, 2, from Yun Z, Meng F, Jiang P, Yue M, Li S. microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA. Cancer Manag Res. 2019;11:5821–5834.https://doi.org/10.2147/CMAR.S198615 (RETRACTED).The image from Figure 5D, A498, si-NC, has been duplicated with the image from Figure 5D, CAOV-3, miR-control from Li C, Yu S, Wu S, Ni Y, Pan Z. MicroRNA-936 targets FGF2 to inhibit epithelial ovarian cancer aggressiveness by deactivating the PI3K/Akt pathway. Onco Targets Ther. 2019;12:5311–5322. https://doi.org/10.2147/OTT.S213231 (RETRACTED) and Figure 5d, TPC-1, si-LINC00520+antagomir-577, from Sun Y, Shi T, Ma Y, Qin H, Li K. RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression. Cell Cycle. 2020;19(7):787–800. DOI: https://doi.org/10.1080/15384101.2020.1731062 (RETRACTED). The image from Figure 6D, 786-O, si-CASC19+pcDNA3.1-ETS1, has been duplicated with the image from Figure 4D, Migration, HOS, agomir-760, from Yin R, Liu J, Zhao D, Wang F. Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression. Onco Targets Ther. 2020;13:2261–2274. https://doi.org/10.2147/OTT.S240022 (RETRACTED). The image from Figure 6E, A498, si-NC, has been duplicated with the image from Figure 2D, Eca109, si-NC, from Gao J, Zhang Z, Su H, Zong L, Li Y. Long Noncoding RNA FGD5-AS1 Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression. Cancer Manag Res. 2020;12:2265–2278. https://doi.org/10.2147/CMAR.S236576 (RETRACTED). When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient original data from their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Zijun Huang,1,2 Zixuan Wang,1,2 Weiguo Qu1,2 1Department of Psychology, School of Education Science, Hunan Normal University, Changsha, People’s Republic of China; 2Department of Psychology, Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, People’s Republic of ChinaCorrespondence: Weiguo QuDepartment of Psychology, School of Education Science, Hunan Normal University, 36 Lushan Road, Changsha, 410081, Hunan, People’s Republic of ChinaTel +86 13308419159Email qwgqyt@163.comPurpose: Donation behavior plays a crucial role in promoting the development of social and public welfare undertakings. Previous studies have partially explored the influencing factors of donation behavior, but effective methods for boosting individuals’ donation behavior remain unclear. Based on the resource dependence theory, our present study further explored the promoting effect of self-affirmation on the relationship among cost, self-control, and individuals’ donation behavior, and provided empirical basis for boosting individuals’ donation behavior.Methods: In preliminary experiment, Carlson’s real donation paradigm was conducted to examine the effect of cost on individuals’ donation behavior. In experiment 1, we examined the effects of cost, self-control ability, and self-affirmation on individuals’ donation behavior. Individuals with high or low self-control ability were assigned to complete the experimental induction of self-affirmation or non-affirmation. Subsequently, all participants completed the donation task under three cost conditions same as preliminary experiment. In experiment 2, we examined the effects of cost, self-control resource, and self-affirmation on individuals’ donation behavior. Participants were assigned to complete the different Stroop task to induce the state of self-control resource exhaustion or non-exhaustion. Then, they completed the priming of self-affirmation or non-affirmation same as experiment 1. Finally, all participants completed the donation task under three cost conditions same as preliminary experiment.Results: The results of preliminary experiment indicated that participants engaged in more donation behavior under low- and medium-cost conditions compared with high-cost condition. The results of experiment 1 demonstrated that self-affirmation exerted a promoting effect on the donation behavior for individuals with low self-control ability under low-, medium-, and high-cost conditions. The results of experiment 2 demonstrated that self-affirmation promoted the donation behavior of individuals with self-control resource exhaustion under low-, medium-, and high-cost conditions.Conclusion: Self-affirmation could promote the donation behavior of individuals with low self-control ability and those with self-control resource exhaustion, whether donation’s cost was high or low. Self-affirmation plays a crucial role for boosting individuals’ donation behavior.Keywords: cost, self-control, self-affirmation, donation behavior

Li-Hong Pan,1,* Ming Qian,1,* Weihua Qu,2 Qin Tang,2 Yuzhong Yan3 1Department of Psychiatry, Shanghai Pudong Nanhui Mental Health Center, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Prison General Hospital, Shanghai, People’s Republic of China; 3Department of Research, Shanghai University of Medicine and Health Science Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuzhong Yan Email jykwsw@126.comBackground: Serum levels of C-reactive protein (CRP) were measured in patients with deficit schizophrenia (DS) to confirm the association between CRP level and cognitive performance and to determine whether CRP was a new biological indicator with the potential clinical applications in DS patients.Methods: Three independent samples [41 DS and 50 non-deficit schizophrenia (NDS) and 30 sex- and age-matched healthy controls (HCs)] were recruited in our study. Serum CRP levels were measured by immunofluorescence. The Positive and Negative Syndrome Scale (PANSS) and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also assessed. And the relationships between serum CRP levels and both PANSS and RBANS scores were finally analyzed.Results: The results of serum CRP level were showed significantly different among the three groups and increased from the HCs to NDS patients to DS patients. There were also significant differences in the cognitive subdomain analyses among the three groups. Serum CRP levels were found positively correlated with total and negative PANSS scores, and showed negatively correlated with overall cognitive test scores in the DS samples.Conclusion: Serum C-reactive protein levels and their association with cognitive performance were different between deficit schizophrenia and non-deficit schizophrenia samples, and higher serum CRP level was associated with worse cognitive performance in the DS patients. The results indicated that CRP could be a potential biomarker, and DS could be a distinct subset of schizophrenia.Keywords: schizophrenia, deficit schizophrenia, C-reactive protein, inflammation, cognitive impairment

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. The Editor and Publisher of Cancer Management and Research wish to issue an Expression of Concern for the published article. Following publication, concerns were raised were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not respond to our queries or provide the requested files to confirm the authenticity of the data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern.

Shuhua Ran,1,* Zhiwei Zuo,2,* Chang Li,3 Xuntao Yin,4 Wei Qu,5 Qianying Tang,5 Yao Wang,1 Yanshu Shi,1 Haitao Li1 1Department of Radiology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 3Department of Radiology, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 4Department of Medical Imaging, Guizhou Provincial People’s Hospital, Guizhou, People’s Republic of China; 5Department of Psychology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haitao Li Email liihait@163.comPurpose: Impairments in intra- and inter-hemispheric information transfer circuits have been reported in patients with major depressive disorder (MDD). However, the specific anomalous connection (intra- and/or inter-hemispheric) and hemisphere (left and/or right) in which this connection plays a more dominant role in the pathogenic mechanism underlying MDD are still poorly understood.Patients and Methods: Structural magnetic resonance imaging and resting-state functional magnetic resonance imaging were performed in 33 patients with MDD and 33 healthy controls. The intra- and inter-hemispheric functional connectivity (FC) strength in the default mode network areas and volume of the callosal subregions were computed using independent samples t-tests. The partial correlations between the volumes and FCs were also computed.Results: The patients with MDD had smaller volumes in the genu of the corpus callosum than the controls. The intrahemispheric FCs of the bilateral posterior cingulate gyrus, left precuneus, left medial superior frontal gyrus, left medial orbitofrontal gyrus, left angular gyrus and left middle temporal gyrus, and interhemispheric FCs of the bilateral posterior cingulate gyrus in the patients with MDD were lower than those in the controls. Moreover, the intrahemispheric FCs of the precuneus and interhemispheric FCs of middle frontal gyrus, orbital middle frontal gyrus, and anterior cingulate gyrus in the patients with MDD showed right-lateralized asymmetry, which were opposite from the asymmetry patterns observed in the controls. The functional asymmetry of the anterior cingulate gyrus was correlated with the volume of the genu of the corpus callosum and disease duration.Conclusion: These findings provide robust evidence that intra- and inter-hemispheric disconnections are involved in MDD, and that functional disruptions in the left hemisphere may be more relevant to the pathophysiology of MDD. Furthermore, imbalanced interhemispheric exchanges may contribute to the anatomical deficits in the corpus callosum in patients with MDD.Keywords: major depressive disorder, asymmetry, functional connectivity, corpus callosum

Jun Jiao,1 Xinlin Jiao,1 Qingqing Liu,1 Wenjie Qu,1 Daoxin Ma,2 Youzhong Zhang,1 Baoxia Cui1 1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Hematology Oncology Center, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of ChinaCorrespondence: Baoxia Cui Tel +8618560081862Email cuibaoxia@sdu.edu.cnPurpose: Accumulating evidence indicates that circular RNAs (circRNAs) are closely involved in canceration and cancer progression. However, the role of circRNAs in cervical cancer (CC) is largely unknown. Here, we characterized the role of circRNA_101308 in CC.Materials and Methods: The expression of circRNA_101308 in CC tissues was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, circRNA_101308 was overexpressed in CC cells to detect its function by proliferation and apoptosis assays, Transwell assays and animal experiments. The potential mechanism of circRNA_101308 in CC was explored by RNA pull-down, Gene Ontology (GO) and pathway analyses.Results: CircRNA_101308 was significantly downregulated in CC tissues. The level of circRNA_101308 was much lower in CC patients with lymph node metastasis or deep myometrial invasion compared to those patients without lymph node metastasis and superficial myometrial invasion. CircRNA_101308 overexpression inhibited CC cell proliferation, invasion and migration. MiR-26a-5p, miR-196a-5p, miR-196b-5p, miR-335-3p, and miR-1307-3p were found to be sponged by circRNA_101308 in CC cells. Further, GO and pathway analyses predicted the potential functional processes and pathways of circRNA_101308 in CC.Conclusion: CircRNA_101308 is downregulated and acts as a tumor suppressor in CC. CircRNA_101308 can participate in many different processes by sponging different miRNAs in CC cells. This exploration of circRNA_101308 provides new directions for research on cancer development and the clinical treatment of CC.Keywords: circular RNA, cervical cancer, circRNA_101308, microRNA

Zhenming Gao,1,* Jidong Sui,1,* Rong Fan,2 Weikun Qu,1 Xuepeng Dong,1 Deguang Sun1 1Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People’s Republic of China; 2Department of International Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenming Gao; Rong FanDepartment of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University Department of International Medicine, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, Liaoning 116027, People’s Republic of ChinaEmail gaozhenmingdl@163.com; fanrongdl@126.comAim: Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved.Materials and Methods: Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence.Key Findings: Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385.Conclusion: Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.Keywords: emodin, acute pancreatitis, lung injury, Nrf2, NLRP3 inflammasome

Yu Luo, Feng Liu, Chunhui Yan, Wei Qu, Liang Zhu, Zheng Guo, Fan Zhou, Wei Zhang Department of Urology, The 161st Hospital of the People’s Liberation Army, Wuhan, Hubei 430010, People’s Republic of ChinaCorrespondence: Feng LiuDepartment of Urology, The 161st Hospital of the People’s Liberation Army, No. 68, Huangpu Road, Wuhan, Hubei 430010, People’s Republic of ChinaEmail liufwh@163.comPurpose: The long non-coding RNA cancer susceptibility 19 (CASC19) is recognized as an important regulator in gastric cancer, colorectal cancer, and non-small cell lung cancer. Nevertheless, to the best of our knowledge, the expression status and detailed roles of CASC19 in clear cell renal cell carcinoma (ccRCC) have not been elucidated. Hence, we aimed to determine CASC19 expression in ccRCC and investigate its roles in ccRCC oncogenicity. The molecular mechanisms underlying CASC19 functions in ccRCC were also determined.Methods: CASC19 expression was measured by using reverse transcription-quantitative polymerase chain reaction. The effects of CASC19 on ccRCC cell proliferation, colony formation, migration, and invasiveness in vitro, as well as on tumor growth in vivo, were examined by the MTT assay, colony formation assay, cell migration and invasiveness assays, and tumor xenograft in nude nice, respectively.Results: CASC19 was overexpressed in ccRCC tissues and cell lines. High expression of CASC19 was closely associated with unfavorable clinicopathological parameters and predicted negative clinical outcomes in patients with ccRCC. Knockdown of CASC19 decreased ccRCC cell proliferation, colony formation, migration, and invasiveness, as well as attenuated tumor growth in vivo. Mechanistically, CASC19 functioned as a competing endogenous RNA and upregulated the expression of ETS proto-oncogene 1 (ETS1) through sponging microRNA-532 (miR-532). Furthermore, rescue assays revealed that inhibiting miR-532 or restoring ETS1 expression partially abolished the impacts of CASC19 knockdown on ccRCC cells.Conclusion: The CASC19/miR-532/ETS1 regulatory pathway is crucial for the malignant manifestations of ccRCC, which makes it an attractive target for potential treatments of ccRCC.Keywords: cancer, MTT assay, cell migration, invasiveness, xenograft, knockdown

Yiping Liu,* Fang Xu,* Hong Hu, Jingjing Wen, Jing Su, Qiaolin Zhou, Wen QuDepartment of Hematology, Mianyang Central Hospital, Mianyang 621000, Sichuan, People’s Republic of China*These authors contributed equally to this workBackground: Acute promyelocytic leukemia (APL) is commonly characterized by the fusion of retinoic acid receptor alpha (RARA) with promyelocytic leukemia (PML). Most APL patients acquire long-term survival after treatment with all-trans retinoic acid (ATRA) or arsenic agents-based chemotherapy.Case presentation: A rare case of APL was reported after IRF2BP2-RARA was detected in the relapsed process using next-generation RNA-sequencing analysis. In addition, the mutation of NRAS was also detected. ATRA and arsenic trioxide combined with daunorubicin were used during induction treatment. The patient acquired complete remission but relapsed in 12 months. The patient was resistant to all other chemotherapies and refused any further therapy. The literature review indicated that allogeneic hematopoietic stem cell transplantation might be a therapeutic method to treat APL with IRF2BP2-RARA fusion.Conclusion: Atypical APL should be considered even if the patients present with normal chromosomal karyotype and no classic PML-RARA fusions, but classical clinical features and bone marrow cell morphology. We reported a case of APL with IRF2BP2-RARA fusion was shown to harbor the NRAS mutation at relapse.Keywords: acute promyelocytic leukemia, IRF2BP2-RARA, variant translocation, gene fusion, NRAS, mutation

Kiok Kim,1,* Kyung-Min Shin,2,* Christy L Hunt,3 Zhen Wang,4 Brent A Bauer,5 Ojin Kwon,2 Jun-Hwan Lee,2,6 Bok-Nam Seo,7 So-Young Jung,2 Yousuk Youn,1 Sang Ho Lee,1 Jung Chul Choi,1 Jae Eun Jung,8 Jaehong Kim,1 Wenchun Qu,3,9 Tae-Hun Kim,10 Jason S Eldrige9 1Department of Spine Center, Mokhuri Neck & Back Hospital, Seoul, South Korea; 2Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 3Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 4Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 5Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; 6Korean Medicine Life Science, Campus of Korea Institute of Oriental Medicine, University of Science & Technology (UST), Daejeon, South Korea; 7Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea; 8Hongik Neurosurgery Hospital, Seongnam, South Korea; 9Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 10Korean Medicine Clinical Trial Center, Korean Medicine Hospital, Kyung Hee University, Seoul, South Korea *These authors contributed equally to this work Background: Lumbar spinal stenosis (LSS) is a chronic condition that causes low back pain and neurogenic claudication, often resulting in significant limitation of daily activities. In this open-label randomized controlled pilot study, we assessed the safety and feasibility of 4-week novel integrative inpatient treatments for LSS. Methods: Thirty-six symptomatic LSS patients were randomly and equally allocated to one of the three groups: Mokhuri Chuna treatment 1 (MT1) group, Mokhuri Chuna treatment 2 (MT2) group, or conventional management treatment (CMT) group. MT1 patients were treated with herbal medication, Mokhuri Chuna, and acupuncture, and received daily physician consultation; MT2 patients were treated with Mokhuri Chuna and acupuncture without any herbal medication, and received daily physician consultation; and CMT patients received conventional pain management therapy that included epidural steroid injection, oral NSAID, and muscle relaxant medication, along with daily physiotherapy. The primary outcome of this pilot study was safety as measured by the type and incidence of adverse events (AEs). The secondary outcome measures included VAS score for low back pain and leg pain, Oswestry Disability Index, Oxford Claudication Score (OCS), walking capacity on a 50 m flat track and treadmill, and EuroQol-5D score. Magnetic resonance imaging was also performed up to 6 months after treatment cessation. Results: Thirty-four treated patients were included in the analysis, based on the modified intention-to-treat principle. No serious AEs were observed or reported. Compared to the CMT group, the MT1 and MT2 groups did show significant improvement at 3 and 6 months in various domains, including pain (VAS score for leg and back pain) and function (OCS and treadmill walking). Conclusion: These novel multimodal integrative treatments for LSS are both clinically safe and logistically feasible. Larger, adequately powered randomized controlled trials will be necessary to assess comparative efficacy and thoroughly analyze the cost-effectiveness of each treatment approach. Clinical trial registration number (CRIS): KCT0001218. Keywords: lumbar spinal stenosis, complementary and alternative medicine, acupuncture, Chuna, epidural steroid injection, low back pain

Kaixiang Zhou,1 Chao Li,1 Dongmei Chen,2 Yuanhu Pan,1 Yanfei Tao,2 Wei Qu,2 Zhenli Liu,2 Xiaofang Wang,3 Shuyu Xie1 1MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei, China; 3Animal Husbandry and Veterinary Institute of Hebei Province, Baoding, Hebei, China Abstract: Staphylococcus aureus (S. aureus) is an important zoonotic bacteria and hazardous for the health of human beings and livestock globally. The characteristics like biofilm forming, facultative intracellular survival, and growing resistance of S. aureus pose a great challenge to its use in therapy. Nanoparticles are considered as a promising way to overcome the infections’ therapeutic problems caused by S. aureus. In this paper, the present progress and challenges of nanoparticles in the treatment of S. aureus infection are focused on stepwise. First, the survival and infection mechanism of S. aureus are analyzed. Second, the treatment challenges posed by S. aureus are provided, which is followed by the third step including the advantages of nanoparticles in improving the penetration and accumulation ability of their payload antibiotics into cell, inhibiting S. aureus biofilm formation, and enhancing the antibacterial activity against resistant isolates. Finally, the challenges and future perspective of nanoparticles for S. aureus infection therapy are introduced. This review will help the readers to realize that the nanosystems can effectively fight against the S. aureus infection by inhibiting biofilm formation, enhancing intracellular delivery, and improving activity against methicillin-resistant S. aureus and small colony variant phenotypes as well as aim to help researchers looking for more efficient nanosystems to combat the S. aureus infections. Keywords: Staphylococcus aureus, infection mechanism, resistance, antibiotics, nanoparticles

Wei Qu,1 Bo Meng,1 Yangyang Yu,2 Shaowei Wang1 1Department of Ophthalmology, The 2nd Affiliated Hospital of Harbin Medical University, 2Department of Ophthalmology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, People’s Republic of China Abstract: In this study, topotecan-loaded mesoporous silica nanoparticles were prepared and surface conjugated with folic acid (FTMN) to enhance the therapeutic efficacy of topotecan for the treatment of retinoblastoma (RB) cancers. The particles were nano-sized and exhibited a sustained release of drug in the physiological conditions. The folic acid-conjugated nanoformulations exhibited a remarkable uptake in RB cells compared to that of non-targeted nanoparticles. These results clearly indicate that receptor-mediated endocytosis is the mechanism of cellular internalization. The greater cellular uptake of FTMN resulted in significantly higher cytotoxic effect in Y79 cancer cells compared to that of other formulations. The results were well corroborated with the live/dead assay and nuclear fragmentation assay. FTMN consistently induced apoptosis of cancer cells with an efficiency of ~58%. Our results clearly showed that nanoparticulate encapsulation of TPT exhibited superior anticancer efficacy in Y79 cancer cells compared to that of free drug or non-targeted nanoparticles. As expected, FTMN exhibited a remarkable reduction in the overall tumor volume compared to any other group with less presence of tumor cells in histology staining. Overall, folic acid-conjugated nanoparticulate system could provide an effective platform for RB treatment. Keywords: retinoblastoma, topotecan, mesoporous silica nanoparticles, apoptosis, anticancer effect

Christopher M Aiudi,1 W Michael Hooten,2 Rebecca A Sanders,2 James C Watson,2 Susan M Moeschler,2 Halena M Gazelka,2 Bryan C Hoelzer,2 Jason S Eldrige,2 Wenchun Qu,3 Tim J Lamer2 1Mayo Clinic School of Medicine, 2Division of Pain Medicine, Department of Anesthesia and Perioperative Medicine, Mayo Clinic, 3Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA Objective: Intra-articular injections of the C1–2 joint are an effective therapeutic option for pain generated from degenerative and inflammatory conditions affecting the joint. Limited information exists about the adverse events (AEs) associated with these injections. The primary aim of this study is to describe the frequency and type of AEs associated with C1–2 joint injections. The secondary aim is to identify clinical factors associated with the occurrence of AEs of C1–2 joint injections. Design/methods: A retrospective chart review was conducted on all C1–2 joint injections performed at the Mayo Pain Medicine Clinic in Rochester, MN, from January 1, 2005 through July 31, 2015. AE data were extracted from procedural and post-procedural clinical notes. Analysis was conducted to determine correlations between any AE and demographic and clinical characteristics. Using univariate and multivariate logistic regression analyses, associations were determined. Results: From January 1, 2005 to July 31, 2015, 135 C1–2 injections were performed on 72 patients. Overall, at least 1 AE was reported in 18.5% of the injections. The most common AEs were post-procedural increase in pain and procedural vascular contrast uptake. There was a significant association between AE occurrence and greater pre-procedural maximum pain score. Conclusions: AEs from C1–2 joint injections occurred commonly, but there were no persistent or serious AEs associated with these injections. The data also demonstrate that patients with higher pre-procedural maximum pain scores are more likely to experience an AE. Keywords: C1–2 joint, facet, injection, adverse event

Drew Trainor,1 Susan Moeschler,2 Matthew Pingree,1,2 Brian Hoelzer,2 Zhen Wang,2 William Mauck,2 Wenchun Qu1,2 1Department of Physical Medicine and Rehabilitation, 2Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USABackground: Chronic postherniorrhaphy groin pain (CPGP) is a debilitating condition, which is often refractory to conservative medical management. To our knowledge, there have been no studies directly comparing landmarked-based and ultrasound-guided approaches in this population.Objective: To compare the effectiveness of landmark-based and ultrasound-guided ilioinguinal/iliohypogastric nerve blocks in the treatment of CPGP.Study design: This is a retrospective chart review of patients who presented to our tertiary care pain medicine clinic with a diagnosis of CPGP. Inclusion criteria were the following: age >18 years, diagnosis of groin pain, and prior history of herniorrhaphy. Exclusion criteria included those who were seen for initial consultation but were lost to follow-up. Primary outcomes were 50% or greater reduction in pain on visual analog scale (VAS). Secondary outcomes were 30% or greater reduction in VAS pain score, changes in VAS pain scores, and reported complications.Results: A total of 36 patients were included in the study. Of them, 20 patients underwent the landmark-based and 16 underwent the ultrasound-guided techniques. There was no significant difference in baseline demographics. The average VAS score preinjection was 7.08 in the landmark-based and 7.0 in the ultrasound-guided groups (P=0.65). A total of 14 patients (70%) in the landmark-based and eleven patients (79%) in the ultrasound-guided groups experienced at least a 50% reduction in VAS scores. There was no statistically significant difference between the two groups (P=1.0), and no complications were noted. We also did not find a significant difference in terms of number of patients with 30% or greater reduction (P=0.71) and changes in VAS pain scores (P=0.64). No complications were reported in either group.Conclusion: In our study, there was no statistically significant difference between the landmark-based and ultrasound-guided groups in terms of a reduction in VAS pain scores, and no complications were noted in either group.Keywords: abdominal wall, intramuscular injections, ultrasound, anatomic landmarks

Sofia Rubinstein,1 Chengwei Wang,1 Wenchun Qu2 1Department of Medicine, Nassau University Medical Center, East Meadow, NY, USA; 2Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA Objective: Previous studies on occupational risk for chronic kidney disease (CKD) have analyzed a limited range of occupations and focused on nephrotoxins. The primary purpose of this study was to examine the relative risk for the occurrence of CKD between different occupations in the US adult population. Materials and methods: This was a population-based survey study of 91,340 participants in the US, who completed the National Health Interview Survey, 2004 through 2008. The outcome variable, CKD, was defined as having weakening/failing kidneys in the past 12 months, as diagnosed by a physician. The predictor variable, occupation, was obtained using the census occupational codes, regrouped according to North American Industrial Classification System. Results: After controlling for age, gender, hypertension, and education, and with the category Life, Physical, and Social Science Occupations as a reference group, the likelihood of developing CKD was 4.3 times higher in respondents working in Building, Grounds Cleaning and Maintenance Occupations, 4.4 times higher in Healthcare Practitioners and Technical Occupations, 4.7 times higher in Transportation and Material Moving Occupations and in Computer and Mathematical Occupations, 4.8 times higher in Production Occupations, 5.3 times higher in Food Preparation and Serving Related Occupations, and 6.1 times higher in Healthcare Support Occupations and in Legal Occupations. Conclusion: This study identified occupation groups in US adult population with increased risk for CKD. Alleviation of workplace stress is suggested as a goal for behavioral intervention in high-risk occupations. Keywords: CKD, risk factors, occupations

Wei Qu,1,2 Yong Li,2,* Lars Hovgaard,3 Song Li,1 Wenbin Dai,1 Jiancheng Wang,1 Xuan Zhang,1 Qiang Zhang1,*1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China; 2Department of Nutrition and Food Hygiene, Peking University Health Science Center, Beijing 100191, PR China; 3Oral Formulation Development, Novo Nordisk A/S, Maalov, Denmark*Both authors contributed equally to this workBackground: Glucagon-like peptide-1 (GLP-1) (7–36) is a peptide incretin hormone released from the endocrine L-cells of the intestinal mucosa with unique antidiabetic potential. Due to low absorption efficiency and instability in the gastrointestinal tract, the introduction of orally active GLP-1 is a large challenge. Here we developed a novel silica-based pH-sensitive nanomatrix of GLP-1 (SPN-GLP-1) in order to provide a strategy for oral peptide delivery.Methods: SPN-GLP-1 composed of silica nanoparticles and pH-sensitive Eudragit® was prepared and characterized by dynamic light scattering, scanning electron microscope, transmission electron microscope, high-performance liquid chromatography, surface analysis, drug release, and so on. Its permeability across the Caco-2 cell monolayer and intestinal mucosa, proteolytic stability against the intestinal enzymes, pharmacokinetics, hypoglycemic effect in the intraperitoneal glucose tolerance test (IPGTT), and primary toxicity were then evaluated.Results: It was indicated that the nanomatrix system obtained had a unique nanoscale structure and pH-sensitivity in drug release. It displayed a five-fold intestinal mucosa permeability and significantly higher proteolytic stability compared to native GLP-1 (P < 0.001). A longer half-life was observed after oral administration of SPN-GLP-1, and its relative bioavailability was 35.67% in comparison to intraperitoneal GLP-1. Oral delivery of SPN-GLP-1 significantly reduced the blood glucose level and its hypoglycemic effect over intraperitoneal GLP-1 reached 77%. There was no evident toxicity of SPN-GLP-1 found from both animal status and histochemical analysis of gastrointestinal tissues.Conclusion: The silica-based pH-sensitive nanomatrix designed and prepared here might be considered as a potential oral delivery system not only for GLP-1, but also for other peptide or macromolecular drugs.Keywords: nanomatrix, oral peptide delivery, silicon nanoparticles, pH-sensitive, GLP-1

Investigation of the breakup and transfer effect of weakly bound nuclei on the fusion process has been an interesting research topic in the past several years. However, owing to the low intensities of the presently available radioactive ion beam (RIB), it is difficult to clearly explore the reaction mechanisms of nuclear systems with unstable nuclei. In comparison with RIB, the beam intensities of stable weakly bound nuclei such as 6,7Li and 9Be, which have significant breakup probability, are orders of magnitude higher. Precise fusion measurements have already been performed with those stable weakly bound nuclei, and the effect of breakup of those nuclei on the fusion process has been extensively studied. Those nuclei indicated large production cross sections for particles other than the α + x breakup. The particles are originated from non-capture breakup (NCBU), incomplete fusion (ICF) and transfer processes. However, the conclusion of reaction dynamics was not clear and has the contradiction. In our previous experiments we have performed 6Li+96Zr and 154Sm at HI-13 Tandem accelerator of China Institute of Atomic Energy (CIAE) by using HPGe array. It is shown that there is a small complete fusion (CF) suppression on medium-mass target nucleus 96Zr different from about 35% suppression on heavier target nucleus 154Sm at near-barrier energies. It seems that the CF suppression factor depends on the charge of target nuclei. We also observed one neutron transfer process. However, the experimental data are scarce for medium-mass target nuclei. In order to have a proper understanding of the influence of breakup and transfer of weakly bound projectiles on the fusion process, we performed the 6Li+89Y experiment with incident energies of 22 MeV and 34 MeV on Galileo array in cooperation with Si-ball EUCLIDES at Legnaro National Laboratory (LNL) in Italy. Using particle-particle and particle-γ coincidences, the different reaction mechanisms can be clearly explored.

Using atmospheric forcing data generated from a general circulation climate model, sixteen land surface schemes participating in the Project for the Intercomparison of Land-surface Parametrization Schemes (PILPS) were run off-line to equilibrium using forcing data from a GCM representative of a tropical forest and a mid-latitude grassland grid point. The values for each land surface parameter (roughness length, minimum stomatal resistance, soil depth etc.) were provided. Results were quality controlled and analyzed, focusing on the scatter simulated amongst the models. There were large differences in how the models' partitioned available energy between sensible and latent heat. Annually averaged, simulations for the tropical forest ranged by 79 W m-2 for the sensible heat flux and 80 W m-2 for the latent heat flux. For the grassland, simulations ranged by 34 W m-2 for the sensible heat flux and 27 W m-2 for the latent heat flux. Similarly large differences were found for simulated runoff and soil moisture and at the monthly time scale. The models' simulation of annually averaged effective radiative temperature varied with a range, between all the models, of 1.4 K for tropical forest and 2.2 K for the grassland. The simulation of latent and sensible heat fluxes by a standard 'bucket' models was anomalous although this could be corrected by an additional resistance term. These results imply that the current land surface models do not agree on the land surface climate when the atmospheric forcing and surface parameters are prescribed. The nature of the experimental design, it being offline and with artificial forcing, generally precludes judgements concerning the relative quality of any specific model. Although these results were produced de-coupled from a host model, they do cast doubt on the reliability of land surface schemes. It is therefore a priority to resolve the disparity in the simulations, understand the reasons behind the scatter and to determine whether this lack of agreement in decoupled tests is reproduced in coupled experiments.