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Yaxu Feng,* Qing Sun,* Pei Liu, Wei Fan, Bing Fan The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Fan; Bing Fan, Email weifan@whu.edu.cn; bingfan@whu.edu.cnBackground: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis.Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed.Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis.Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.Keywords: Au@AgNPs, resistance, photothermal therapy, antibacterial, silver ions, E. faecalis

Yinci Zhu,1,2 Zhong Zheng,1,2 Bihong Fan,1,2 Yun Sun,1,2 Junyu Zhai,1,2 Yanzhi Du1,2 1Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China; 2Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200135, People’s Republic of ChinaCorrespondence: Junyu Zhai; Yanzhi Du, Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200135, People’s Republic of China, Tel +86-21-20284525; +86-21-20284518, Email zhaijy2007@foxmail.com; duyz@sjtu.edu.cnPurpose: Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019.Patients and Methods: In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups.Results: Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes.Conclusion: E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.Keywords: estradiol decline, controlled ovarian hyperstimulation, oral contraceptive, in vitro fertilization, fertilization rate, live birth rate

Jia Zhao,1,* Wenbin Ding,1,* Benfang Fan,2 Chunxia Chen,1 Lihua Wang2 1Department of Interventional Radiology, Nantong First People’s Hospital, Nantong, 226001, People’s Republic of China; 2Nursing Department, Nantong First People’s Hospital, Nantong, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lihua Wang, Nursing Department, Nantong First People’s Hospital, No. 666 of Shengli Road, Chongchuan District, Nantong, 226001, People’s Republic of China, Tel +86 513 81111039, Email wanglihuawlh6@126.comObjective: We develop the Readiness for Hospital Discharge Scale (RHDS) for patients with bile duct carcinoma catheterized after percutaneous transhepatic cholangial drainage (PTCD) and test the reliability and validity of the scale, so as to provide a quantitative tool for evaluating the discharge readiness of patients catheterized after PTCD.Methods: The initial scale was developed following literature review, qualitative interviews, expert consultation, and other methods based on Meleis’ Theory of Transition. We selected a total of 286 patients with bile duct carcinoma catheterized after PTCD from four tertiary A-grade hospitals in Nantong City. We conducted a cross-sectional survey using the initial scale to test the validity and reliability of the scale.Results: RHDS for patients catheterized post-PTCD consisted of five dimensions, with a cumulative variance contribution rate of 74.6%. The Cronbach’s α coefficient of the scale was 0.856, and that of each dimension was between 0.740 and 0.891; the scale-content validity index (S-CVI) was 0.875.Conclusion: RHDS for patients with bile duct carcinoma catheterized after PTCD developed in this study, has good reliability and validity, and can be a useful tool for evaluating the discharge readiness of patients with bile duct carcinoma catheterized after PTCD.Keywords: bile duct carcinoma, discharge readiness, percutaneous transhepatic cholangial drainage, scale

Fengchun Mu,1,2,&ast; Bingjie Fan,1,&ast; Butuo Li,1 Wenru Qin,1 Haoqian Li,1,2 Chunni Wang,1 Bing Zou,1 Shijiang Wang,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Fax +86-531-67626141, Email wanglinlinatjn@163.comPurpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015– 2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups.Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥ 3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥ 3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p< 0.001) and imaging grade of 46% vs 10% (p< 0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades.Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.Keywords: EGFR-TKI, molecular targeted therapy, radiation pneumonitis, thoracic radiotherapy, lung adenocarcinoma

Bing Tan, Qi-Yuan Yang, Bin Fan, Qin Li, Xiao-Yan Zhang Department of Spine Surgery, The Third Hospital of MianYang, Sichuan Mental Health Center, Mianyang, Sichuan Province, 621000, People’s Republic of ChinaCorrespondence: Qi-Yuan Yang, Department of Spine Surgery, The Third Hospital of MianYang, Sichuan Mental Health Center, Mianyang, Sichuan Province, 621000, People’s Republic of China, Tel +8615882889797, Email qiyuan5988@163.comPurpose: This study aimed to explore the effectiveness and safety of digital subtractionangiography (DSA)-guided percutaneous kyphoplasty (PKP) in treating multi-segmental osteoporotic vertebral compression fracture (OVCF).Methods: We retrospectively reviewed 68 patients with multi-segmental OVCF who had unilateral PKP surgeries using DSA and C arm guiding at our hospital between October 2016 and June 2020 and were followed for at least two years. All patients were divided into two groups: DSA guidance (n = 31) and C‐arm guidance (n=37). In addition, we collected the clinical and radiological evaluation results during postoperative and last follow-up periods.Results: Our findings revealed that the DSA guidance group required lesser time for channel establishment and surgery than the C-arm guidance group at P < 0.05. The incidences of bone cement leakage, fluoroscopy times, and radiation dose of the DSA guidance group were significantly lesser than the C‐arm guidance group (P < 0.05). Compared to the C-arm guidance group, the deviation of puncture in the DSA guidance group was significantly lower, the puncture angle in the DSA guidance group was significantly larger, and better bone cement distribution was obtained (P < 0.05). Compared to preoperative data, the VAS score, median vertebral height, and Cobb angle were significantly improved one day after surgery and the final follow-up in both groups (P < 0.05). However, the VAS score, the median vertebral height, average length of stay, and Cobb angle were not significantly different between the two groups (P > 0.05).Conclusion: DSA-guided PKP in treating multi-segmental OVCF can shorten the operation time, improve puncture accuracy, reduce the times and dose of fluoroscopy, reduce the leakage of bone cement, and achieve better cement distribution.Keywords: digital subtraction angiography, percutaneous kyphoplasty, multi-segmental osteoporotic vertebral compression fracture

Wangjun Qin,1 Siyu Yuan,2 Li Zhao,1 Ying Liu,1 Liyuan Xu,3 Yi Zhang,3 Lihong Liu,1 Bifa Fan3 1Department of Pharmacy, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, Siping Central Hospital, Siping, Jilin Province, People’s Republic of China; 3Department of Pain Management, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Lihong Liu; Bifa Fan, China-Japan Friendship Hospital, 2 Yinghua Road, Heping District, Beijing, 100029, People’s Republic of China, Tel +860184205959, Fax +860184205559, Email hongllh@126.com; fyinsuo@yeah.netPurpose: Pharmacists are key members of the pain management interdisciplinary team in many developed countries. However, the implementation of clinical pharmacy services in pain management is impeded by the imbalance between the pain physicians and clinical pharmacists specializing in pain management in China. The purpose of this study was to elucidate the perceptions, expectations and current experience of Chinese pain physicians regarding clinical pharmacy services.Patients and Methods: An anonymous, self-administered questionnaire was designed according to previously published studies with minor modifications and distributed online to 1100 pain physicians selected randomly in hospitals across all 31 provinces of mainland China in 2021. Data were analyzed using descriptive and inferential statistics.Results: A total of 1071 valid questionnaires were included for analysis. The pain physicians were from all 31 provinces of mainland China and most of them were from tertiary hospitals holding an undergraduate degree. Among listed kinds of clinical pharmacy services, pain physicians were less comfortable with pharmacists treating minor illnesses (p < 0.001). Pain physicians’ experiences with clinical pharmacy services were far less than their expectations (p < 0.001), which is in line with the results that most of pain physicians (65.9%) interacted with pharmacists at a frequency of less than once a week. Significant differences in the experiences were found among ages (p < 0.01) and among years of work experience (p < 0.05) of pain physicians. Pain physicians’ expectations of pharmacists were positively correlated with their experiences with clinical pharmacy services (p < 0.001).Conclusion: Pain physicians in China had positive perceptions and high expectations, but relatively low experiences regarding clinical pharmacy services. Expanding clinical pharmacist pain management credentialing and increasing pain physicians’ exposure to clinical pharmacy services are favourable to support the interdisciplinary collaboration in pain management in China.Keywords: clinical pharmacy services, pain management, interdisciplinary collaboration, professional competence, primary health care

Bifa Fan,1 Shuiqing Li,2 Baishan Wu,3 Jinghua Zhang,4 Jing Zhou5 1Department of Pain, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pain, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Pain, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pain, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5KANTAR China, Beijing, People’s Republic of ChinaCorrespondence: Bifa Fan, Department of Pain, China-Japan Friendship Hospital, 2 Yinghua East Road, Chaoyang District, Beijing, People’s Republic of China, Tel +86 15010101616, Email fyinsuo@yeah.netBackground: While there is an extensive body of research regarding pain and its treatment in developed countries, little research on this topic has been performed in developing countries. This study aimed to investigate the diagnosis, treatment, and treatment satisfaction in individuals with pain in urban China using real-world data.Methods: All respondents from the 2013, 2015, and 2017 China National Health and Wellness Survey were included in the analysis and were classified into diagnosed and undiagnosed groups according to their self-reported physician diagnosis or experience in the past month. The following five categories of pain were analysed: headache, cancer-associated pain, musculoskeletal pain, neuropathic pain, and fibromyalgia. Rates for diagnosis, treatment, and satisfaction with medication were calculated overall and for each pain type.Results: A total of 3802 respondents reported experience of at least one type of pain in the past month. Among those, 61.2% were diagnosed with a pain-related condition, the majority of which (84.0%) were receiving treatment. For diagnosed respondents taking over-the-counter and/or prescription medication, 70.3% were satisfied with their treatment. Comparing between pain types, the diagnosis rates for cancer-associated pain (32.7%) and fibromyalgia (22.8%) were relatively low, whereas respondents with musculoskeletal pain has the highest diagnosis rate (61.1%). Respondents with cancer-associated pain had the lowest satisfaction (30.0%) with over-the-counter and prescription medication, while respondents with headache (76.2%) had the highest satisfaction rate with such medications.Conclusion: Our study highlights the importance of raising awareness for pain management as well as education and training for healthcare providers and patients.Keywords: pain management, diagnosis, treatment, treatment satisfaction, China

Wenru Qin,1,2,&ast; Bing Zou,2,&ast; Xinyu Fan,2,3 Bingjie Fan,2 Shijiang Wang,2 Linlin Wang2 1Department of Oncology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Email wanglinlinatjn@163.comAbstract: The most common pathologic type of thymic carcinoma (TC) is squamous cell carcinoma (SCC). Small cell carcinoma is relatively rare, accounting for approximately 2% to 5% of all thymic tumors. Histologic transformation of TC has not yet been reported. Available treatments for TC patients who progress after first-line therapy are limited, which contributes to their poor prognosis. We reported an extraordinary case of a 66-year-old man who was diagnosed with thymic small cell carcinoma that transformed into SCC after third-line treatment. Surprisingly, the patient had a progression-free survival (PFS) of 25 months and an overall survival (OS) of 10 years on anlotinib as fourth-line therapy. The tolerance was well. Thus, anlotinib may be a safe and promising treatment for TC patients, especially those who undergo histologic transformation.Keywords: thymic carcinoma, squamous cell carcinoma, small cell carcinoma, histologic transformation, anlotinib

Sun P, Huang W, Kang L, Jin M, Fan B, Jin H, Wang Q, Gao Z. Int J Nanomedicine. 2017;12:3221–3234 At the authors request, the Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. An investigation by the Publisher found overlap in images from Figure 5. Specifically, The image from Figure 5, 0 h, Blank, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 0h, Naked siRNA, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 24 h, Naked siRNA, has been duplicated with the same image for Figure 5, 24 h, H6R6-NP. The image from Figure 5, 48 h, Naked siRNA, has been duplicated with the image for Figure 5, 48 h, CS-NP. The authors cooperated with the investigation and provided data associated with the study. However, despite the authors’ assistance, they were unable to provide a satisfactory explanation for how the images came to be duplicated, and the validity of the published work could not be verified. The decision was made to retract the article and the authors agreed with this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yue Guo,1,2,&ast; Ying-Hui Zhou,1,&ast; Xian-Ping Wu,1 Chen-Yi Tang,1 Min Wang,3 Zhao-Hui Mo,4 John A Shepherd,5 Bennett K Ng,5 Bo Fan,5 Hou-De Zhou1 1National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Department of Endocrinology, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 4Department of Endocrinology, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of China; 5Department of Radiology & Biomedical Imaging, University of California at San Francisco, San Francisco, CA, 94143, USA&ast;These authors contributed equally to this workCorrespondence: Hou-De ZhouNational Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaTel +86-731-85292223Fax +86-731-85533525Email houdezhou@csu.edu.cnPurpose: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy.Patients and Methods: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1–L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation.Results: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4– 52.3% and in the femoral neck increased by 43.2– 79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued.Conclusion: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered.Keywords: bone mineral density, conventional treatment, hypophosphatemic osteomalacia

Yunxiao Liu, Hao Zhang, Mingyu Zheng, Chunlin Wang, Zhiqiao Hu, Yang Wang, Huan Xiong, BoYang Fan, Yuliuming Wang, Hanqing Hu, Qingchao Tang, Guiyu Wang Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Guiyu WangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaTel +86-451-86296599Email guiywang@163.comPurpose: Distant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients.Methods: Patients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan–Meier curves were generated and analyzed using Log rank tests.Results: A total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879– 0.922) and 0.899 (95% CI=0.865– 0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744– 0.782), 0.794 (95% CI=0.775– 0.813), and 0.822 (95% CI=0.803– 0.841) for the development cohort, and 0.785 (95% CI=0.754– 0.816), 0.748 (95% CI=0.717– 0.779) and 0.896 (95% CI=0.865– 0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639– 0.737) and 0.712 (95% CI=0.681– 0.743).Conclusion: The population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.Keywords: T1N0 colon cancer, distant metastasis, nomogram, SEER

Wangjun Qin, 1 Yifan Li, 2 Botao Liu, 2 Ying Liu, 1 Yi Zhang, 2 Xianglin Zhang, 1 Pengmei Li, 1 Bifa Fan 2 1Department of Pharmacy, China–Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pain Management, China–Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Pengmei Li; Bifa Fan 2 Yinghua Dongjie, Hepingli, Beijing 100029, People’s Republic of ChinaTel/Fax +86 10 8420 5330; +86 10 84205959Email article2019@163.com; fyinsuo@yeah.netPurpose: Intrathecal morphine infusion therapy via a percutaneous port (IMITPP) has been used widely for its relatively low initial cost. However, there is scarce knowledge about IMITPP. In this study, we sought to evaluate efficacy, complications, and the interval required to achieve the cost equivalence of IMITPP in patients with refractory cancer pain in China.Patients and Methods: A retrospective chart review was conducted on cancer patients who had received IMITPP at our hospital between April 2017 and April 2019. Data from the numeric pain rating scale and Karnofsky performance scores, and complications and costs related to IMITPP were collected from medical records. Daily analgesic costs before and after IMITPP were calculated based on the doses of opioids on admission and at discharge, respectively. The doses of systemic opioids before IMITPP were stratified into very high doses [VHD, oral morphine equivalent dose (OMED) > 599 mg/day], high doses (HD, 300 mg/day ≤ OMED ≤ 599 mg/day), and regular doses (RD, OMED < 300 mg/day).Results: Intrathecal morphine infusion therapy via a percutaneous port provided significant pain relief, but impaired activities of daily living in patients with refractory cancer pain. The commonly reported complications included nausea/vomiting and urinary retention, most of which were managed with symptomatic therapies. The median interval required to achieve cost equivalence was 11.44 months. The median intervals of VHD group and HD group were significantly shorter than that of RD group.Conclusion: Intrathecal morphine infusion therapy via a percutaneous port provided effective cancer pain management without causing serious complications. Patients with higher doses of systemic opioids would economically benefit from IMITPP in a shorter time.Keywords: intrathecal, morphine, port catheter, cost-benefit analysis, cancer pain

Jinghua Sun,1,2,* Xiaoyan Li,2,* Anqi Chen,2,* Wenwen Cai,2 Xiaoyang Peng,1 Liping Li,3 Bo Fan,3 Lingjie Wang,2 Huanhu Zhang,4 Ruiping Zhang2 1Center for Translational Medicine Research, Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 2Imaging Department, The Affiliated Da Yi Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China; 3Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 4The Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruiping ZhangThe Affiliated Da Yi Hospital of Shanxi Medical University, No. 99, Longcheng Street, Taiyuan, Shanxi 030000, People’s Republic of ChinaEmail zrp_7142@sxmu.edu.cnHuanhu ZhangThe Affiliated Tumor Hospital of Shanxi Medical University, No. 3 ZhiGongXinCun, Taiyuan, Shanxi 030000, People’s Republic of ChinaEmail Zhhh31@163.comBackground: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death and early stage diagnosis can greatly increase the survival rate of patient. However, the accurate detection of HCC remains an urgent challenge in medical diagnosis. The combination of magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) are conducive for accurate locating of cancerous tissue. Therefore, it is necessary to explore a more facile and biosafe dual-modal contrast agent for orthotopic HCC detection.Methods: In this study, a promising contrast agent had been identified based on gadolinium chelated melanin nanoparticles and evaluated its usage as a dual-modal T1 MRI and PAI contrast agent for orthotopic HCC detection.Results: The gadolinium-based melanin nanoparticles presented ultrasmall size, high chelation stability and negligible cytotoxicity estimated by CCK-8 assay. Moreover, the nanoparticle exhibited higher r1 relaxivity (45.762 mM−1 s−1) than clinically approved Gadodiamide (4.975 mM−1 s−1) at 1.5 T MR scanning. A linear regression analysis confirmed that the nanoparticles were ideal candidates for PAI in vitro. After the nanoparticles were injected into vein in mice with orthotopic HCC, a dramatic increase in signal of the liver was observed at 0.5 hr by MRI and PAI, while the tumor exerted remarkable signal enhancement at 7 hrs, showing excellent detection sensitivity. In addition, the nanoparticles exhibited excellent biocompatibility and they can be excreted through both hepatobiliary and renal pathways after diagnosis.Conclusion: These results indicate that the ultrasmall gadolinium chelated melanin nanoparticles is a promising candidate as a dual-modal MRI/PAI contrast agent for the detection of orthotopic HCC.Keywords: melanin nanoparticles, gadolinium, magnetic resonance imaging, photoacoustic imaging, orthotopic hepatocellular carcinoma

Background: Behavioral change is the key to alter individuals' lifestyle from sedentary to active. The aim was to assess the feasibility of delivering a Lifestyle-integrated Functional Exercise programme and evaluate the delivery of the intervention by use of digital technology (eLiFE) to prevent functional decline in 61–70 year-old adults.Methods: This multicentre, feasibility randomized controlled trial was run in three countries (Norway, Germany, and the Netherlands). Out of 7,500 potential participants, 926 seniors (12%) were screened and 180 participants randomized to eLiFE (n = 61), aLiFE (n = 59), and control group (n = 60). eLiFE participants used an application on smartphones and smartwatches while aLiFE participants used traditional paper-based versions of the same lifestyle-integrated exercise intervention. Participants were followed for 12 months, with assessments at baseline, after a 6 month active trainer-supported intervention, and after a further 6 months of unsupervised continuation of the programme.Results: At 6 months, 87% of participants completed post-test, and 77% completed the final assessment at 12 months. Participants were willing to be part of the programme, with compliance and reported adherence relatively high. Despite small errors during start-up in the technological component, intervention delivery by use of technology appeared acceptable. No serious adverse events were related to the interventions. All groups improved regarding clinical outcomes over time, and complexity metrics show potential as outcome measure in young seniors.Conclusion: This feasibility RCT provides evidence that an ICT-based lifestyle-integrated exercise intervention, focusing on behavioral change, is feasible and safe for young seniors.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03065088. Registered on 14 February 2017.

XianHu Zhou,1,2* GuiDong Shi,1,2* BaoYou Fan,1,2 Xin Cheng,1,2 XiaoLei Zhang,1,2 Xu Wang,1,2 Shen Liu,1,2 Yan Hao,1,2 ZhiJian Wei,1,2 LianYong Wang,3 ShiQing Feng1,2 1International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedic Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, People’s Republic of China; 3Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, People’s Republic of China *These authors contributed equally to this work Background: Spinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI. Purpose: In this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI. Patients and methods: Polycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation. Results: The iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds were ~0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model. Conclusion: This study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future. Keywords: induced pluripotent stem cells, polycaprolactone, spinal cord injury

Xi Yang,1,2,* Bo Fan,3,* Wei Gao,4,5,* Liping Li,2 Tingting Li,3 Jinghua Sun,2 Xiaoyang Peng,2 Xiaoyan Li,2 Zhenjun Wang,2 Binquan Wang,4,5 Ruiping Zhang,2 Jun Xie1 1Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 5Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Background: Effective endosomal escape is still a critical bottleneck for intracellular delivery of small interfering RNAs (siRNAs) to maximize their therapeutic efficacy. To overcome this obstacle, we have developed a photothermally triggered system by using the near-infrared (NIR) irradiation to achieve “on-demand” endosomal escape and subsequent siRNA release into cytoplasm. Materials and methods: Herein, the poly-l-lysine (PLL) was successfully conjugated with melanin to obtain melanin-poly-l-lysine (M-PLL) polymer as a siRNA vehicle. The melanin was an efficient photothermal sensitizer, and the positive pendant amino groups of PLL could condense siRNAs to form stable complexes by electrostatic interactions. Results and discussion: Inspired by its excellent photothermal conversion efficiency, the melanin was first involved in the siRNA delivery system. Confocal laser scanning microscopic observation revealed that after cellular uptake the photothermally induced endosomal escape could facilitate siRNAs to overcome endosomal barrier and be delivered into cytoplasm, which resulted in significant silence in the luciferase expression over the NIR- and melanin-free controls. Moreover, the anti-survivin siRNA-loaded M-PLL nanoparticles displayed great inhibitory effect on 4T1 tumor growth in vitro and in vivo. Conclusion: These findings suggest that the M-PLL-mediated siRNA delivery is a promising candidate for therapeutic siRNA delivery and shows improved effect for cancer therapy via enhanced endosomal escape. Keywords: melanin, poly-l-lysine, photothermal effect, endosomal escape, siRNA delivery

Yanpeng Zhang,1,2 Zhuocheng Li,2 Xiaolong He,1 Fanglin Ding,2 Weiqing Wu,2 Yong Luo,2 Bing Fan,2 Hong Cao1 1Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China; 2Laboratory Department of the First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, China Purpose: Acinetobacter baumannii is an important pathogen in the nosocomial infections worldwide. Combining with carbapenemases, efflux pumps and outer membrane proteins (OMPs) have been thought to affect the development of carbapenem resistance in A. baumannii. This study aimed to investigate the contributions of different efflux pumps and OMPs in developing carbapenem resistance in a clinical isolate of A. baumannii and reveal the possible mechanism of overproduction of main efflux pumps. Patients and methods: In this study, an imipenem-susceptible clinical isolate was identified as A. baumannii and named SZE. Several common carbapenemases were detected by polymerase chain reaction (PCR). Imipenem-selected mutants were selected from SZE by serial subcultivations on Mueller–Hinton agar, and the minimum inhibitory concentration (MIC) was detected. Gene expressions of four families of efflux pumps, five OMPs, and blaOXA-51 were determined by reverse transcription quantitative PCR, and comparisons were made between SZE strain and the imipenem-selected mutants. The adeRS system in SZE and its mutant was sequenced and aligned. Results: Under consecutive imipenem-selected stress, the MIC to imipenem increased gradually from 0.125 μg/mL to 8 μg/mL. The effect of resistance inducement was almost neutralized when treated with an efflux pump inhibitor. The expression of efflux pumps, adeB, adeG, and adeJ, was increased by 6.9-, 4.0-, and 2.1-fold in mutants, respectively, compared to SZE. A single mutation (G to A) at position 58 was detected in the regulatory adeRS system and possibly upregulated the adeB expression, and then affected the carbapenem resistance in A. baumannii strains. Conclusion: In conclusion, under consecutive imipenem-selected stress in vitro, A. baumannii strain evolved the ability to reduce susceptibility to a variety of antimicrobials by overproduction of efflux pumps. Especially, the resistance-nodulation-cell division super family and a nucleotide mutant in adeRS regulating system caused the overexpression of adeABC. Keywords: Acinetobacter baumannii, efflux pump, multidrug resistance, imipenem, outer membrane protein

Ping Sun,1 Wei Huang,1 Lin Kang,1 Mingji Jin,1 Bo Fan,1 Hongyan Jin,2 Qi-Ming Wang,1 Zhonggao Gao1 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Yanbian University Hospital, Jilin, People’s Republic of China Abstract: An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: cellular-mediated internalization and endosomal escape. Poly(histidine-arginine)6(H6R6) peptide was introduced into chitosan (CS) to create a new CS derivative for siRNA delivery, 6-polyarginine (R6) as cell-penetrating peptides facilitated nanoparticle cellular internalization has been proved in our previous research, and 6-polyhistidine (H6) mediated the nanoparticle endosome escape resulted in the siRNA rapid releasing into tumor cytoplasm. H6R6-modified CS nanoparticles showed higher transfection efficiency and better endosomal escape capacity compared to ungroomed CS nanoparticle in vitro. Noticeably, H6R6-modified CS nanoparticles effectively inhibited tumor cell growth and metastases in vivo and significantly improved survival ratio. Therefore, we concluded that H6R6-modified CS copolymer can act as an ideal carrier for siRNA delivery and as a promising candidate in breast cancer therapy. Keywords: poly(histidine-arginine)6-peptide-modified chitosan nanoparticle, cell-penetrating peptides, endosome/lysosome escape, gene delivery, breast carcinoma

Ping Sun,1,2 Wei Huang,1,2 Mingji Jin,1,2 Qiming Wang,1,2 Bo Fan,1,2 Lin Kang,1,2 Zhonggao Gao1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis. Keywords: PEGylated chitosan, non-viral vector, siRNA delivery, breast anti-tumor therapy

Jeffrey L Goldberg,1 Amy G Lau,2 Bo Fan,2 Lisa Ford,3 Howard E Greenberg3 1Byers Eye Institute, Stanford University, Palo Alto, CA, 2Janssen Research & Development, LLC, Horsham, PA, 3Janssen Research & Development, LLC, Titusville, NJ, USA Abstract: Occasional reports of uveitis following topiramate use necessitated an investigation of relevant cases from safety databases and published biomedical literature. Data mining of the Food and Drug Administration Adverse Event Reporting System and cumulative review of cases from the global safety database (sponsor database) and published literature were conducted to assess association between topiramate use and uveitis. The Food and Drug Administration Adverse Event Reporting System search identified disproportional reporting of uveitis (n=23) and related terms (choroidal detachment, n=25; iridocyclitis, n=17). The postmarketing reporting frequency of uveitis and related events from the global safety database and based on an estimated topiramate exposure of 11,185,740 person-years from launch to April 2015 was 0.38 per 100,000 person-years and assigned as very rare. A total of 14 potential uveitis cases were identified from the cumulative review. Seven of these 14 cases were complicated by inadequate documentation, appearance of uveitic signs following drug withdrawal, or concurrent use of other sulfonamides. In acute angle-closure glaucoma and uveal effusions cases, insufficient evidence for underlying inflammation suggested that uveitis was not a component. Only seven of 14 cases were well documented, potentially topiramate-associated uveitis cases. Uveitis may occur in the setting of topiramate use only in very rare instances. Current evidence did not reveal a dose- or duration-dependent relationship between uveitis and topiramate use. Keywords: topiramate, uveitis, acute angle-closure glaucoma, drug safety, Food and Drug Administration Adverse Event Reporting System, postmarketing

Zhou X, Shi G, Fan B, et al. Int J Nanomedicine. 2018;13:6265–6277. Following a review of our data post-publication, we found the incorrect original image was supplied for Figure 4C. The correct image is shown in this corrigendum. This correction of the image has no impact to the findings of the study. The authors apologize for this error.Read the original article

Wei Fan,1,* Daming Wu,1,* Franklin R Tay,2 Tengjiao Ma,1 Yujie Wu,1 Bing Fan1 1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 2Department of Endodontics, Georgia Regents University, Augusta, Georgia, USA *These authors contributed equally to this work Abstract: Mesoporous calcium-silicate nanoparticles (MCSNs) are advanced biomaterials for controlled drug delivery and mineralization induction. Nanosilver-incorporated MCSNs (Ag-MCSNs) were prepared in the present study using both the adsorption and template methods. Both versions of Ag-MCSNs showed characteristic morphology of mesoporous materials and exhibited sustained release of ions over time. In antibacterial testing against planktonic Enterococcus faecalis, Ag-MCSNs showed significantly better antibacterial effects when compared with MCSNs (P

The generation of electrical voltage through the flow of an electrolyte over a charged surface may be used for energy transduction. Here, we show that enhanced electrical potential differences (i.e., streaming potential) may be obtained through the flow of salt water on liquid-filled surfaces that are infiltrated with a lower dielectric constant liquid, such as oil, to harness electrolyte slip and associated surface charge. A record-high figure of merit, in terms of the voltage generated per unit applied pressure, of 0.043 mV Pa-1 is obtained through the use of the liquid-filled surfaces. In comparison with air-filled surfaces, the figure of merit associated with the liquid-filled surface increases by a factor of 1.4. These results lay the basis for innovative surface charge engineering methodology for the study of electrokinetic phenomena at the microscale, with possible application in new electrical power sources.

The introduction of inorganic components into a polymer matrix to form polymer composites is an emerging and promising approach to dielectric materials for capacitive energy storage. Ferroelectric polymers are particularly attractive as matrices for dielectric polymer composites owing to their highest dielectric constant (≥10) among the known polymers. Here, the important aspects and recent advances in the development of the ferroelectric-polymer-based dielectric polymer composites for high-energy-density capacitor applications are summarized. The preparation methods of ferroelectric-polymer composites with 0D, 1D, and 2D nanostructured fillers, surface-modified nanofillers, and hierarchically structured fillers, and their comprehensive impacts on the dielectric properties, breakdown strength, and energy density of the resulting composites are described. The most recent progress on the incorporation of multiple nanofillers with complementary functionalities into ferroelectric polymers and the design of layer-structured ferroelectric-polymer composites is also highlighted. A discussion of the scientific and technological issues that remain to be addressed and an outlook for the future of ferroelectric polymer-based dielectric composites are also presented.

A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis.IntroductionThe purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults.MethodsWe recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60-88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes.ResultsThere was a -3.0° (95% CI -5.2, -0.8) between-group difference in change in Cobb angle, p = 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (p = 0.03) and SRS-30 self-esteem (p  0.05.ConclusionsSpine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis.Trial registration number and name of trial registerClinicalTrials.gov; identifier NCT01751685.

UNLABELLED: This study examined trends in osteoporosis and low bone mass in older US adults between 2005 and 2014 using bone mineral density (BMD) data from the National Health and Nutrition Examination Survey (NHANES). Osteoporosis and low bone mass appear to have increased at the femur neck but not at the lumbar spine during this period. INTRODUCTION: Recent preliminary data from Medicare suggest that the decline in hip fracture incidence among older US adults may have plateaued in 2013-2014, but comparable data on BMD trends for this time period are currently lacking. This study examined trends in the prevalence of osteoporosis and low bone mass since 2005 using BMD data from NHANES. The present study also updated prevalence estimates to 2013-2014 and included estimates for non-Hispanic Asians. METHODS: Femur neck and lumbar spine BMD by DXA were available for 7954 adults aged 50 years and older from four NHANES survey cycles between 2005-2006 and 2013-2014. RESULTS: Significant trends (quadratic or linear) were observed for the femur neck (mean T-score and osteoporosis in both sexes; low bone mass in women) but not for the lumbar spine. The trend in femur neck status was somewhat U-shaped, with prevalences being most consistently significantly higher (by 1.1-6.6 percentage points) in 2013-2014 than 2007-2008. Adjusting for changes in body mass index, smoking, milk intake, and physicians diagnosis of osteoporosis between surveys did not change femur neck trends. In 2013-2014, the percent of older adults with osteoporosis was 6% at the femur neck, 8% at the lumbar spine, and 11% at either site. CONCLUSIONS: There was some evidence of a decline in femur neck BMD between 2005-2006 and 2013-2014, but not in lumbar spine BMD. Changes in the risk factors that could be examined did not explain the femur neck BMD trends.

Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts. Furthermore, we found that while overexpression of Jag1 alone does not lead to liver tumour development, overexpression of Jag1 synergizes with activated AKT signalling to promote liver carcinogenesis in AKT/Jag1 mice. Histologically, tumours consisted exclusively of ICC, with hepatocellular tumours not occurring in AKT/Jag1 mice. Furthermore, tumours from AKT/Jag1 mice exhibited extensive desmoplastic reaction, an important feature of human ICC. At the molecular level, we found that both AKT/mTOR and Notch cascades are activated in AKT/Jag1 ICC tissues, and that the Notch signalling is necessary for ICC development in AKT/Jag1 mice. In human ICC cell lines, silencing of Jag1 via specific small interfering RNA reduces proliferation and increases apoptosis. Finally, combined inhibition of AKT and Notch pathways is highly detrimental for the in vitro growth of ICC cell lines. In summary, our study demonstrates that Jag1 is an important upstream inducer of the Notch signalling in human and mouse ICC. Targeting Jag1 might represent a novel therapeutic strategy for the treatment of this deadly disease.

Background/objectivesObesity is a significant worldwide epidemic that necessitates accessible tools for robust body composition analysis. We investigated whether widely available 3D body surface scanners can provide clinically relevant direct anthropometrics (circumferences, areas and volumes) and body composition estimates (regional fat/lean masses).Subjects/methodsThirty-nine healthy adults stratified by age, sex and body mass index (BMI) underwent whole-body 3D scans, dual energy X-ray absorptiometry (DXA), air displacement plethysmography and tape measurements. Linear regressions were performed to assess agreement between 3D measurements and criterion methods. Linear models were derived to predict DXA body composition from 3D scan measurements. Thirty-seven external fitness center users underwent 3D scans and bioelectrical impedance analysis for model validation.Results3D body scan measurements correlated strongly to criterion methods: waist circumference R2=0.95, hip circumference R2=0.92, surface area R2=0.97 and volume R2=0.99. However, systematic differences were observed for each measure due to discrepancies in landmark positioning. Predictive body composition equations showed strong agreement for whole body (fat mass R2=0.95, root mean square error (RMSE)=2.4 kg; fat-free mass R2=0.96, RMSE=2.2 kg) and arms, legs and trunk (R2=0.79-0.94, RMSE=0.5-1.7 kg). Visceral fat prediction showed moderate agreement (R2=0.75, RMSE=0.11 kg).Conclusions3D surface scanners offer precise and stable automated measurements of body shape and composition. Software updates may be needed to resolve measurement biases resulting from landmark positioning discrepancies. Further studies are justified to elucidate relationships between body shape, composition and metabolic health across sex, age, BMI and ethnicity groups, as well as in those with metabolic disorders.

Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.Methods: Data were pooled from six studies includi

Background:Body shape is a known risk factor for diabetes and mortality, but the methods estimating body shape, BMI and waist circumference are crude. We determined whether a novel body shape measure, trunk to leg volume ratio, was independently associated

Clinical scores of mammographic breast density are highly subjective. Automated technologies for mammography exist to quantify breast density objectively, but the technique that most accurately measures the quantity of breast fibroglandular tissue is not k