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Can Chang,1 Huan Wang,1 Lianjun Zhang,1 Junling Hao,1 Xiaoning Wang,1 Yaoyao Wang,2 Fei Qi,2 Jingwei Lou,2 Jiangman Zhao,2 Junying Dong1 1Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Heze Branch, Heze, Shandong, 274000, People’s Republic of China; 2Shanghai Zhangjiang Institute of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd, Shanghai, 201204, People’s Republic of ChinaCorrespondence: Junying Dong, Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Heze Branch, Caozhou Road 2888, Heze, Shandong, 274000, People’s Republic of China, Tel +86- 13723908695, Email dongjunying2023@163.com Jiangman Zhao, Shanghai Zhangjiang Institute of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd, Zhangheng Road 180, Shanghai, 201204, People’s Republic of China, Tel +86- 18817517482, Email zhaojiangman86@163.comPurpose: Severe pneumonia causes the highest mortality rate in immunocompromised patients. This study aimed to investigate the pathogen diagnostic efficacy of metagenomic next-generation sequencing (mNGS) using sputum sample in patients with pneumonia according to patients’ disease severity and immune conditions.Patients and Methods: A total of 180 patients suffering from pneumonia were recruited, and sputum samples were collected in duplicate for pathogen detection by both conventional microbiological tests (CMT) and mNGS. Then, the performance of pathogen identification was examined between two methods, according to disease severity and patients’ immune status.Results: In comparison to CMT, mNGS had higher positivity rates in all patients with pneumonia (85.0% vs 62.2%, P=9.445e-07). The most commonly detected microorganism in sputum of pneumonia patients was Acinetobacter baumannii (42/180, 23.3%) in bacterum level, Candida albicans in fungus level (44/180, 24.4%), and Human herpesvirus 1 (39/180, 27.5%) in virus level. However, for mNGS results, Candida albicans in 34.9% of positive patients, and Human herpesvirus 1 in 7.7% of positive cases were confirmed as pathogens causing pneumonia. Acinetobacter baumannii detected by mNGS in 75% of positive patients was diagnosed as pathogen of pneumonia. The microorganism profile of sputum mNGS differed according to disease severity and immune status of patients. Pneumocystis jirovecii was more likely to infect immunocompromised patients (P=0.002). Pseudomonas aeruginosa (14.8% vs 0.0%, P=0.008) and Human herpesvirus 1 (26.1% vs 5.3%, P=0.004) had higher infection rate in patients with severe pneumonia compared with non-severe cases. mNGS had overwhelming advantages over CMT in detecting a lot of microorganisms including Streptococcus pneumoniae, Enterococcus faecium, Pneumocystis jirovecii, and majority of viruses.Conclusion: mNGS is a complementary tool of CMT for detecting suspected pathogens for patients with lower respiratory infections. The interpretation of opportunistic pathogens identified by mNGS is challenging, and needs comprehensive consideration of sequencing data and clinical factors.Keywords: lower respiratory infections, severe pneumonia, immunocompromised patient, conventional microbiological test, metagenomic-next generation sequencing

Robert Hernandez Jr,1,2 Jennie Lou,1,3 Basem Al-Omari,1,3 Lujain Aloum,1,4 Saly Kanj,1 Sawsan Ismaiel,1 John Rock5 1Department of Academic Affairs, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; 2Department of Medicine, Kirk Kerkorian School of Medicine, University of Nevada Las Vegas, Las Vegas, NV, USA; 3Department of Epidemiology and Population Health, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; 4Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; 5Dean’s Office, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab EmiratesCorrespondence: Robert Hernandez Jr, Department of Medicine, Kirk Kerkorian School of Medicine, University of Nevada Las Vegas, 2040 W. Charleston Blvd., 4th Floor, Las Vegas, NV, 89102, USA, Tel +1 702-895-2662, Email robert.hernandez@unlv.eduAbstract: Learning community programs have been widely implemented in higher education institutions, including many accredited medical schools in North America. Learning communities have been shown to create a sense of belonging, enhance teaching and learning, and promote an inclusive educational environment that reinforces collaboration, professionalism, and wellbeing. Based on their demonstrated success, a learning community program was included in the development of Khalifa University College of Medicine and Health Sciences (KU CMHS), the first medical school in the capital city of Abu Dhabi and the first to offer a postbaccalaureate, Doctor of Medicine (MD) degree in the United Arab Emirates (UAE). Named the Falcon Learning Communities (FLCs), the program adopted the core values of the Learning Communities Institute and integrated them into curricular, co-curricular, and extra-curricular programming. This paper presents an overview on the development of the FLC program, its implication for both students and faculty, preliminary feedback from teachers and learners, and considerations for future work.Keywords: undergraduate medical education, teaching, learning, strategies

Jiayan Lou, Lingjia Wei, He Wang Department of Gynecology and Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: He Wang, Department of Gynecology and Oncology, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 13481138393, Email wanghe10430@126.comIntroduction: Ovarian cancer (OV) is a common malignancy affecting women globally; recognizing useful biomarkers has been one of the key priorities. Since SCNN1A was reported to be relevant to tumor progression in a variety of cancers, but rarely in ovarian cancer, we explored the roles of SCNN1A in OV.Methods: RNA sequencing data from TCGA and GEO were utilized to analyze the expression of SCNN1A and related differentially expressed genes (DEGs) in ovarian cancer. We performed GO, GSEA and immune cell infiltration analysis on SCNN1A-associated DEGs. Correlation of SCNN1A methylation levels and its mRNA expression was analyzed by cBioPortal and UCSC Xena databases. To assess the prognostic impact of SCNN1A, Kaplan–Meier plot analysis and Cox regression analysis were performed; ROC curves and nomogram were also plotted.Results: Compared to normal tissues, SCNN1A was highly expressed in ovarian cancer. The methylation level of SCNN1A negatively correlated with the SCNN1A expression. Moreover, high expression of SCNN1A was correlated with poor prognosis in OV patients and associated with immune infiltrates.Conclusion: High SCNN1A expression could be a promising biomarker for poor outcomes in OV and correlated with tumor immune cells infiltration. The findings might help illuminate the function of SCNN1A in tumorigenesis and lay a foundation for further research.Keywords: ovarian cancer, SCNN1A, biological function, prognostic biomarker, immune infiltrates

Wenbin Wei,1 Youxin Chen,2 Bojie Hu,3 Mingwei Zhao,4 Mei Han,5 Hong Dai,6 Harvey S Uy,7 Michelle Y Chen,8 Kate Wang,8 Jenny Jiao,8 Jean Lou,8 Xiao-Yan Li8 1Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China; 4Peking University People’s Hospital, Beijing, People’s Republic of China; 5Tianjin Eye Hospital, Tianjin, People’s Republic of China; 6Beijing Hospital, Beijing, People’s Republic of China; 7Peregrine Eye and Laser Institute, Makati City, Philippines; 8Allergan, an AbbVie company, Irvine, CA, USACorrespondence: Wenbin WeiBeijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of ChinaEmail tr_weiwenbin@163.comPurpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) compared with laser photocoagulation in patients with diabetic macular edema (DME).Patients and Methods: This Phase 3, multicenter, randomized, efficacy evaluator–masked, parallel-group, 12-month clinical study enrolled adults in China and the Philippines with reduced visual acuity secondary to fovea-involved DME in the study eye. Participants were randomized 1:1 to study eye treatment with laser photocoagulation every 3 months as needed (n = 139) or DEX every 5 months (n = 145). The main efficacy measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and leakage area. The primary endpoint was the average change in BCVA from baseline over 12 months (area-under-the-curve method). Preplanned subgroup analyses evaluated outcomes in Chinese patients.Results: Mean average change in BCVA from baseline during the study (letters) was 4.3 with DEX (n = 145) versus 1.4 with laser (n = 127) overall (P = 0.001) and 4.6 with DEX (n = 129) versus 0.6 with laser (n = 113) in Chinese patients (P < 0.001). At Month 12, mean change in CRT from baseline was − 209.5 μm with DEX versus − 120.3 μm with laser (P < 0.001) and mean change in total leakage area from baseline was − 8.367 mm2 with DEX versus − 0.637 mm2 with laser (P < 0.001). The most common treatment-emergent adverse events in the DEX group were increased intraocular pressure and cataract.Conclusion: DEX administered every 5 months provided significantly greater improvement in BCVA, CRT, and total leakage area compared with laser treatment. DEX demonstrated an acceptable safety profile, consistent with an intraocular corticosteroid, and similar to that reported in completed global registration studies.Keywords: central retinal thickness, corticosteroid, dexamethasone, diabetic retinopathy, drug delivery device, laser photocoagulation, randomized controlled trial, macular edema, visual acuity

Qingshan Huang,1,2 Chenglong Chen,1,2 Jingbing Lou,1,2 Yi Huang,1,2 Tingting Ren,1,2 Wei Guo1,2 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Musculoskeletal Tumor, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaTel/Fax +86-10-88324471Email bonettumor@163.comBackground: Due to the obvious heterogeneity of osteosarcoma, many patients are not sensitive to neoadjuvant chemotherapy. In this study, the clinical characteristics and auxiliary examinations of patients with osteosarcoma were used to predict the effect of preoperative chemotherapy, so as to guide the clinical adjustment of the treatment plan to improve the prognosis of patients.Methods: In this study, 90 patients with pathologically confirmed osteosarcoma were included, and they were randomly divided into training cohort (n=45) and validation cohort (n=45). A prediction model of preoperative chemotherapy efficacy for osteosarcoma was established by multivariate logistic regression analysis, and a nomogram was used as the visualization of the model. The ROC curve and C-index were used to evaluate the accuracy of the nomogram. Decision curve analysis (DCA) was used to evaluate the net benefit of the nomogram in predicting the efficacy of neoadjuvant chemotherapy under different threshold probabilities.Results: In the study, the age, gender, location, tumor volume, metastasis at the first visit, MSTS staging, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were used in the multivariate logistic regression analysis and the construction of the nomogram. The AUC and C-index of the training cohort were 0.793 (95% CI: 0.632, 0.954) and 0.881 (95% CI: 0.776, 0.986), respectively. The AUC and C-index in the validation cohort were 0.791 (95% CI: 0.644, 0.938) and 0.813 (95% CI: 0.679, 0.947), respectively, which were close to the training cohort. DCA showed that the model had good clinical application value.Conclusion: Based on the clinical characteristics of patients and auxiliary examinations, the nomogram can be good used to predict the efficacy of preoperative chemotherapy for osteosarcoma.Keywords: osteosarcoma, nomogram, chemotherapy, ROC, necrosis rate

Hongliang Zhang,1,2 Kang Yang,3 Tingting Ren,1,2 Yi Huang,1,2 Xin Liang,1,2 Yiyang Yu,1,2 Wei Wang,1,2 Jianfang Niu,1,2 Jingbing Lou,1,2 Xiaodong Tang,1,2 Wei Guo1,2 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People’s Republic of China; 3Department of Orthopedics, Yangzhou University Affiliated Hospital, Yangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Tang; Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing 100044, People’s Republic of ChinaTel +86 10 8832 4471Fax +86.10.8837.8544Email tang15877@163.com; guobonetumor@163.comPurpose: Our research aimed to illuminate the role of miR-100-5p in chordoma and potential mechanism.Materials and Methods: We used microRNA array analysis to explore differentially expressed miRNAs in chordoma tissue and then verified by qRT-PCR. Cell proliferation and transwell assay were used to evaluate the function of miR-100-5p. Cell apoptosis was analyzed by flow cytometry, and using biological software, we predicted that the insulin-like growth factor 1 receptor (IGF1R) could be the target gene of miR-100-5p, which was then validated by dual luciferase assays and Western blot.Results: miR-100-5p was downregulated in chordoma tissues. Overexpression of miR-100-5p could suppress the growth of chordoma both in vitro and in vivo, and miR-100-5p could inhibit the migration and invasion of chordoma cells partially by suppressing epithelial–mesenchymal transition (EMT). Furthermore, IGF1R was validated as the target gene of miR-100-5p and expressed in most chordoma tissues.Conclusion: In conclusion, our results showed that miR-100-5p was lowly expressed in chordoma and inhibited tumor malignant progression by targeting IGF1R.Keywords: chordoma, miRNA, miR-100-5p, IGF1R

Jinrong Qiu, 1,* Fuping Zhou, 1,* Xinchun Li, 2,* Sufang Zhang, 2 Zhuo Chen, 2 Zenghui Xu, 2 Gaoxiong Lu, 2 Zhi Zhu, 3 Na Ding, 2 Jinxing Lou, 4 Zhenlong Ye, 2 Qijun Qian 1, 2, 4 1Department of Biotherapy, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 2Shanghai Baize Medical Laboratory, Shanghai, People’s Republic of China; 3Department of Pathology, Changhai Hospital, The Second Military Medical University of Chinese PLA, Shanghai, People’s Republic of China; 4Shanghai Mengchao Cancer Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qijun Qian; Zhenlong YeShanghai Baize Medical Laboratory, Yuanguo Road, Shanghai 201805, People’s Republic of ChinaEmail qian@shcell.org; yezl@shcell.orgObjective: The evaluation of lymphocyte subsets is widely regarded as an important factor for monitoring tumor progression and response to therapy. This study was designed to establish a comprehensive and detailed assessment of peripheral lymphocyte subsets with a multi-parametric flow cytometry assay for response prediction and prognosis evaluation of cancer patients.Methods: Peripheral blood samples collected from 40 cancer patients and 23 age- and sex-matched healthy volunteers were tested for 29 lymphocyte subsets by flow cytometry. The univariate analysis was applied to establish the reference interval of healthy samples, and the ratio and proportion of 29 lymphocyte subsets between patient samples and healthy controls were compared to evaluate their clinical significance by Mann–Whitney U-test model.Results: The reference ranges of 29 lymphocyte subsets were established with a normal distribution and no significant differences were observed between genders. Compared with healthy control group, lower proportion and ratio of specific parameters, such as Naïve Th cells (p< 0.01), Naïve Tc cells (p< 0.01), CM (central memory) Tc cells (p< 0.01), Naïve T cells/Memory T cells (p< 0.001), Naïve T cells/EM (effector memory) T cells (p< 0.001) and Naive Th cells/Memory Th cells (p< 0.001), and higher proportion and ratio of EM Th cells (p< 0.001), EM Tc cells (p< 0.01), effector Tc cells (p< 0.05), EM Th cells/CM Th cells (p< 0.01) and EM Tc cells/CM Tc cells (p< 0.01), as well as Breg (p< 0.001), B cells (p< 0.05) and CD16-NK cells (p< 0.001) were found in cancer cohorts.Conclusion: This study suggests that the changes in certain lymphocyte subsets might be helpful to evaluate the immunity of cancer patients, and holds great potential for clinical application.Keywords: solid tumor, lymphocyte subsets, clinic significance, reference intervals, flow cytometry

Hanyu Cao,1,* Lin Li,1,* Bowen Yang,2 Gupo Luo,2 Jiangyan Lou,1 Mingrong Xi1,*1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu City, Sichuan Province, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital, Sichuan University, Chengdu City, Sichuan Province, People’s Republic of China*These authors contributed equally to this workObjectives: We conducted this study to explore the clinical characteristics, prognosis, and prevalence of unexpected uterine sarcoma (UUS) after hysterectomy and myomectomy for presumed leiomyoma.Study design: The records of women who underwent hysterectomy or myomectomy through laparoscopy or laparotomy for preoperatively presumed uterine leiomyomas from January 2009 to December 2016 were reviewed and data were retrospectively analyzed.Results: Eleven patients had morcellation of uterine sarcoma. Eighty-eight patients were diagnosed with uterine sarcomas (total prevalence: 0.33%) including 29 leiomyosarcomas (LMS), 48 endometrial stromal sarcomas (ESS), and 11 adenosarcomas. ESS patients with advanced stage were significantly associated with worse overall survival (p

Weihui Zheng,1,2 Yibiao Zhang,3 Liang Guo,2 Shengye Wang,4 Meiyu Fang,5 Weimin Mao,1 Jianlin Lou21Center of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215000, People’s Republic of China; 2Department of Head and Neck Surgery, Zhejiang Cancer Hospital & Creative Laboratory of Head and Neck Oncology in Zhejiang Province, Hangzhou 310022, People’s Republic of China; 3Department of Clinical Laboratory, Jinhua Guangfu Hospital, Jinhua 321000, People’s Republic of China; 4Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, People’s Republic of China; 5Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, People’s Republic of ChinaObjective: This study aimed to investigate the feasibility of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and clinical value of CTCs in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC).Methods: 31 patients with LAHNSCC, 12 healthy volunteers, and 6 patients with benign tumor serving as controls were enrolled in this study. CTCs were enriched with the CytoSorter®, a microfluidic based immune capture system. CTC detection was performed before and after induction chemotherapy, as well as after surgery and/or radiotherapy. Correlations between CTC enumerations at different time points and survival outcome and recurrence risk were evaluated. The correlation between CTCs and clinicopathological characteristics was appraised. Follow-up of patients continued until March 2019.Results: While CTCs were not found in the controls, they were detected in 24 of 31 LAHNSCC patients. CTCs could be used to distinguish diseased people from the healthy (P60 years old vs

Adnan Tufail,1 Sue Lightman,1 Ahmed Kamal,2 Uwe Pleyer,3 Nuria María Gajate Paniagua,4 Corrine Dot,5,6 Xiao-Yan Li,7 Jenny Jiao,7 Jean Lou,7 Yehia Hashad7 For the CONSTANCE Study Group 1Moorfields Eye Hospital, London, UK; 2Aintree University Hospital, Liverpool, UK; 3University Eye Hospital, Uveitis Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin, and Berlin Institute of Health, Berlin, Germany; 4University Hospital of Burgos, Burgos, Spain; 5Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France; 6French Military Health Service Academy, Val de Grâce, Paris, France; 7Allergan Plc, Irvine, CA, USA Purpose: To evaluate the long-term safety of dexamethasone intravitreal implant (DEX) in patients treated for macular edema associated with retinal vein occlusion (RVO) or noninfectious posterior segment uveitis (NIPSU) in clinical practice.Patients and methods: Multicenter (102 sites in France, Germany, Spain, UK), prospective, observational, post-authorization safety study in adult patients treated with DEX. Data collected up to 2 years after enrollment included serious adverse events (SAEs) and adverse events of special interest (AESIs; adverse drug reactions that are considered important risks associated with DEX and listed in the European Union Ozurdex Risk Management Plan).Results: Overall, 803 patients (652 RVO, 151 NIPSU) received on-study DEX treatment, and 73.1% completed 24 months of follow-up; 72.6% were DEX-naïve. Median number of on-study injections per treated eye was 2 (range, 1–7); median reinjection interval was 27.1 weeks. Nonocular SAEs affected 9.5% of patients; none were considered DEX-related. Ocular SAEs (most common: cataract progression) occurred in 3.2% of treated eyes. SAEs were similar in eyes stratified by previous DEX use and number of on-study DEX injections (≤2 or >2), in both RVO and NIPSU. The most common AESIs were cataract formation and progression (20.0% and 19.2% of treated phakic eyes, n=551), increased intraocular pressure (19.0% of treated eyes), and vitreous hemorrhage (3.3% of treated eyes). Cataract progression was more frequent in baseline phakic eyes that were previously treated with DEX or received >2 on-study DEX injections.Conclusion: The long-term safety profile of DEX was acceptable. No new safety concerns were identified. Keywords: corticosteroid, dexamethasone, drug delivery device, retinal vein occlusion, safety profile, uveitis

Jin Lou,1,2 Junjie Huang,1 Zitong Wang,3 Bingbing Wen,1 Chuanqing Tu,4 Wangxiang Huang,5 Zhimin Zhai,2 Xin Du1 1Department of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China; 2Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; 3School of Medicine, University of Sydney, Sydney, NSW, Australia; 4Department of Hematology, People’s Hospital of Baoan District, Shenzhen 518101, China; 5Department of Hematology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China Background: Treatment-free remission (TFR) is becoming an essential goal for chronic myeloid leukemia (CML) patients in clinical practice. Few studies have emphasized patient attitudes or preferences about discontinuing tyrosine kinase inhibitors treatment. This study aimed to evaluate the characteristics of Chinese CML patients and their views and perspectives on TFR. Methods: A total of 329 CML patients participated in this multicenter, questionnaire-based, standardized, semi-structured, interview-guided, open-ended, cross-sectional study. Information about demographics, diagnosis information, treatment history, quality of life (QoL), and TFR preference was collected. Results: The adherence rate was 50% (N=163) and sex dependent (males, OR=2.24, 95% CI=1.40–3.58). Physical activity, symptom burden, mood impact, and daily impact were found to be better among adherent patients. Thirty-four percent of the patients were willing to attempt TFR positively. The reasons for preferring TFR were due to side effects (56%) followed by high cost (52%), inconvenience (42%), and pregnancy need (41%). Multivariate analysis indicated that patients who were younger (OR=0.96, 95% CI=0.94–0.99) with shorter disease duration (OR=0.90, 95% CI=0.82–0.98) and higher disease symptom burden (OR=1.08, 95% CI=0.98–1.21) were more likely positive about TFR. Conclusion: Patients who were younger with shorter disease duration and higher disease symptom burden were more likely to try TFR. They expressed several perceived noncost factors of TFR. Our data may help promote the management of CML and designing of clinical trials for TFR in some developed regions of China. Keywords: CML, TKI, TFR, preference, perception

Jie Lou,1 Wenjing Hu,2 Rui Tian,3 Hua Zhang,1 Yuntao Jia,4 Jingqing Zhang,1 Liangke Zhang11Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Xijiao Hospital, Chongqing, People’s Republic of China; 3The Experimental Teaching Centre, Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Pharmacy, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaAbstract: This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic® F127 and Pluronic® F68 concentrations on the sol–gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application.Keywords: diabetic retinopathy, sustained release, ocular drug delivery, desolvation method

Case summary An 18-month-old female domestic shorthair cat was referred for investigation of a 6 month period of regurgitation. Contrast radiography indicated an intramural oesophageal structure. Ultrasound-guided fine-needle aspiration of the area retrieved viscous fluid containing high numbers of squamous epithelial cells. Computed tomography disclosed a thin-walled contrast-enhancing structure containing non-enhancing homogenous contents. Exploratory thoracotomy confirmed an intramural cystic oesophageal structure, which was resected. Histopathological analysis of the resected tissue demonstrated an intramural oesophageal duplication cyst. A 12 month follow-up period has seen complete resolution of the cat’s clinical signs. Relevance and novel information This is the first report of successful oesophageal duplication cyst removal in a cat. Oesophageal duplication cysts should be included on the differential list for dysphagia and regurgitation in cats. Complete surgical removal in this cat carried a good long-term outcome.

The western honey bee (Apis mellifera) is the most frequent floral visitor of crops worldwide, but quantitative knowledge of its role as a pollinator outside of managed habitats is largely lacking. Here we use a global data set of 80 published plant-pollinator interaction networks as well as pollinator effectiveness measures from 34 plant species to assess the importance of A. mellifera in natural habitats. Apis mellifera is the most frequent floral visitor in natural habitats worldwide, averaging 13% of floral visits across all networks (range 0 – 85%), with 5% of plant species recorded as being exclusively visited by A. mellifera. For 33% of the networks and 49% of plant species, however, A. mellifera visitation was never observed, illustrating that many flowering plant taxa and assemblages remain dependent on non-A. mellifera visitors for pollination. Apis mellifera visitation was higher in warmer, less variable climates and on mainland rather than island sites, but did not differ between its native and introduced ranges. With respect to single-visit pollination effectiveness, A. mellifera did not differ from the average non-A. mellifera floral visitor, though it was generally less effective than the most effective non-A. mellifera visitor. Our results argue for a deeper understanding of how A. mellifera, and potential future changes in its range and abundance, shape the ecology, evolution, and conservation of plants, pollinators, and their interactions in natural habitats.

© 2015 by the authors; licensee MDPI, Basel, Switzerland.Existing antibodies (Abs) used to treat botulism cannot enter the cytosol of neurons and bind to botulinum neurotoxin (BoNT) at its site of action, and thus cannot reverse paralysis. However, Abs tar

© 2015 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public