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Chao Zhuo,1 Yijiang Huang,2 Wenyuan Liu,3 Jin-Fu Xu,4 Wei Yun Zhu,5 Gregory G Stone,6 Jean Li Yan,7 Naglaa Mohamed8 1State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Respiratory Clinical Medical Center, Hainan Cancer Hospital, Hainan, People’s Republic of China; 3Respiratory Department, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Medical Department, Pfizer Investment Co. Ltd., Beijing, People’s Republic of China; 6Biopharmaceuticals Group, Pfizer Inc., Groton, CT, USA; 7Biopharmaceuticals Group, Pfizer Inc., Cambridge, MA, USA; 8Biopharmaceuticals Group, Pfizer Inc., New York, NY, USACorrespondence: Chao Zhuo, Email chaosheep@sina.comBackground: Ceftaroline fosamil has demonstrated superior clinical efficacy versus ceftriaxone for hospitalized adults with moderate-to-severe community-acquired pneumonia (CAP) in a Phase 3 trial in Asia and in a meta-analysis of three trials in Asia, North America, and Europe. Efficacy and safety outcomes for the subset of patients in China in the ASIA CAP trial were analyzed to determine if the same conclusions hold in the China subpopulation.Methods: Hospitalized adults with Pneumonia Outcomes Research Team risk class III–IV CAP were randomized (1:1) to receive either intravenous ceftaroline fosamil 600 mg every 12 h or ceftriaxone 2 g every 24 h for 5– 7 days. The primary efficacy variable was clinical response at test-of-cure (TOC) in the clinically evaluable (CE) population. Secondary endpoints included microbiological responses and safety.Results: Of 302 patients randomized in China, 205 were included in the CE population. Clinical cure rates at TOC were 80/105 (76.2%) for ceftaroline fosamil and 61/100 (61.0%) for ceftriaxone (difference 15.2%, 95% CI 2.5, 27.6), thereby meeting predefined non-inferiority and superiority criteria for the overall study. Subgroup analyses of the primary endpoint demonstrated consistency of favourable efficacy of ceftaroline fosamil across age groups, Pneumonia Outcomes Research Team risk classes and CURB-65 scores. Microbiological responses were presumed from clinical outcomes. Adverse events were consistent with the study treatments’ known safety profiles.Conclusion: The China subset results are consistent with the overall study population, despite the smaller sample size. Ceftaroline fosamil was both non-inferior and superior to ceftriaxone for empiric treatment of Chinese patients with moderate-to-severe CAP.Trial Registration: ClinicalTrials.gov identifier NCT01371838.Keywords: ceftriaxone, CURB-65, treatment outcomes, clinical trial

MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. The role of miR‐206 and E74‐like factor 3 (Elf3) has been identified in osteoarthritis (OA), while the effect of exosomal miR‐206 from bone marrow mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to explore the role of exosomal miR‐206 from BMSCs in OA with the involvement of Elf3. BMSCs and BMSC‐derived exosomes (BMSC‐exos) were obtained and identified. OA mouse models were constructed by anterior cruciate ligament transection and then treated with BMSC‐exos or BMSC‐exos containing miR‐206 mimic/inhibitor. The expression of miR‐206, Elf3, inflammatory factors, osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The pathological changes in mouse femur tissues were observed. The mouse osteoblasts were identified and treated with untransfected or transfected BMSC‐exos, and then, the expression of miR‐206, Elf3, OCN and BMP2 was determined. The alkaline phosphatase (ALP) activity, calcium deposition level, OCN secretion, proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. MiR‐206 was down‐regulated while Elf3 was up‐regulated in OA animal and cellular models. Exosomal miR‐206 ameliorated inflammation and increased expression of OCN and BMP2 in mouse femoral tissues. Moreover, exosomal miR‐206 promoted ALP activity, calcium deposition level, OCN secretion and proliferation and inhibited apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR‐206 up‐regulation‐induced effects on OA osteoblasts. BMSC‐derived exosomal miR‐206 promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. Our research may provide novel targets for OA treatment.

Rheumatoid arthritis (RA) is a chronic and inflammatory synovitis systemic disease. Due to the unknown pathogenesis, this study was to investigate the effect of microRNA (miR)-411 on apoptosis and joint function of synoviocytes in RA mice via RIPK1-mediated NF-κB signaling pathway. The collagen-induced arthritis model mice were induced via collagen type II and Freund’s adjuvant. The mice were injected with miR-411 mimics, si-RIPK1 or miR-411 mimics + oe-RIPK1 to figure out their roles in cell apoptosis and inflammation of synovial tissues. Synoviocytes were grouped as in animal experiments. Proliferation and apoptosis of synoviocytes were detected upon treatment with overexpressed miR-411 and silenced RIPK1. The expression of miR-411, RIPK1 and NF-κB in synovial tissues and synoviocytes of RA mice was detected by RT-qPCR and Western blot analysis. Poorly expressed miR-411, and highly expressed NF-κB and RIPK1 existed in synovial tissue and synoviocytes of RA. Additionally, it was found that si-RIPK1 decreased NF-κB expression, and miR-411 mimics decreased both RIPK1 and NF-κB. MiR-411 had a targeted relationship with RIPK1. si-RIPK1 or miR-411 mimics promoted cell apoptosis and strained inflammation in synovial tissues of mice with RA. Overexpressed miR-411 or silencing RIPK1 inhibited the proliferation and promoted apoptosis of synoviocytes of RA mice. Up-regulation of miR-411 or down-regulation of RIPK1 had a certain inhibitory effect on RA. This study suggests that up-regulated miR-411 or down-regulated RIPK1 promoted apoptosis and inhibited proliferation of synoviocytes of RA mice, which may be related to the inhibition of NF-κB activation.

IntroductionIn the present research, we formulated a modern chemotherapeutic drug by silver nanoparticles (AgNPs) containing Nigella sativa aqueous extract for the treatment of bone tumor.Material and methodsCharacterization of AgNPs was done by UV–Visible Spectroscopy (UV-Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant properties of AgNO3, N. sativa, and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-bone tumor effects of AgNO3, N. sativa, and AgNPs, MTT assay was used on the human bone Ewing’s sarcoma (CADO-ES1 and MHH-ES1), human bone osteosarcoma (HOS and MG-63), and human bone chondrosarcoma (SW-1353 and CH-3573) cell lines.ResultsDPPH test revealed similar antioxidant potentials for N. sativa, AgNPs, and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-bone tumor properties dose-dependently against CADO-ES1, MHH-ES1, HOS, MG-63, SW-1353, and CH-3573 cell lines without any cytotoxicity on the normal cell line. The best result of anti-bone tumor properties of AgNPs against the above cell lines was seen in the case of the MG-63 cell line.ConclusionsAccording to the above findings, the silver nanoparticles containing N. sativa aqueous extract can be administrated in humans for the treatment of several types of bone tumors.

Construction robotics are increasingly popular in the architectural fabrication community due to their accuracy and flexibility. Because of their high degree of motion freedom, these tools are able to assemble complex structures with irregular designs, which advances architectural aesthetics and structural performance. However, automated task and motion planning (TAMP) for a robot to assemble non-repetitive objects can be challenging due to (1) a nonrepetitive assembly pattern (2) the need for a continuous robotic motion throughout a sequence of movement (3) a congested construction scene and (4) occasional robot configuration constraints due to taught positions. Recent work has already begun to address these challenges for repetitive assembly processes, where the robot repeats a pattern of primitive behaviors (e.g. brick stacking or spatial extrusion). Yet, there are many assembly processes that can benefit from a non-repetitive pattern. For example, processes can change tools on an element-by-element level to accommodate a wider range of geometry. Our work is motivated by the necessity of robotic modeling and planning for a recently published timber assembly process which utilizes distributed robotic clamps to press together interlocking joints. In addition to pick-and-place operations, the robot needs to move numerous tools within the construction scene, similar to a tool-change operation. In order to facilitate an agile process for architectural design, construction process design, and TAMP, we introduce a flowchart-based specification language which allows various designers to describe their design and construction intent and knowledge. A compiler can then translate the assembly description, sequence, process flowchart, and robotic setup into a plan skeleton. Additionally, we present a linear and a non-linear solving algorithm that can solve the plan skeleton for a full sequence of robot motions. This algorithm can be customized to take into account designer intuition, which can speed up the planning process. We provide a comparison of the two algorithms using the timber assembly process as our case study. We validate our results by robotically executing and constructing a large-scale real-world timber structure. Finally, we demonstrate the flexibility of our flowchart by showing how custom assembly actions are modeled in our case study. We also demonstrate how other recently published robotic assembly processes can be formulated using our flowcharts to demonstrate generalizability., Proceedings SCF 2021 ACM Symposium on Computational Fabrication, October 28–29, 2021, ISBN:978-1-4503-9090-3

fib Symposium Proceedings, 55, ISSN:2617-4820, Proceedings of the International fib Symposium on the Conceptual Design of Structures, ISBN:978-2-940643-12-7

Additive robotic construction of building-scale discrete bar structures, such as trusses and space frames, is increasingly attractive due to the potential improvements in efficiency, safety, and design possibilities. However, programming complex robots, such as manipulators with seven degrees of freedom, to successfully complete construction tasks can be tedious, challenging, or impossible for a human to do manually. Namely, the structure must be constructed in a sequence that preserves structural properties, such as stiffness, at each step. At the same time, this sequence must allow for the robot to precisely manipulate elements within the in-progress structure while respecting geometric constraints that, for example, ensure the robot does not collide with what it has built. In this work, we present an automated and newly generalized planning approach for jointly finding a construction sequence and robot motion plan for additive construction that satisfies these requirements. Our approach can be applied in a variety of additive construction processes, and we demonstrate it specifically on spatial extrusion and discrete bar assembly in this paper. We demonstrate the effectiveness of our approach on several simulated and real-world extrusion and assembly tasks, including a human-scale physical prototype, for which our algorithm is deployed for the first time to plan the assembly of a complicated double tangent bar system design.

ObjectiveTo assess the diagnostic value of W score which was supposed to identify laryngopharyngeal reflux disease (LPRD) patients from the normal population by Dx-pH monitoring, comparing with Ryan score.MethodsOne hundred and eight patients with suspected LPRD and complete follow-up results after more than 8 weeks of anti-reflux therapy were enrolled from the Department of Otolaryngology-Head and Neck Surgery, Gastroenterology and Respiratory Medicine of seven hospitals. Their Dx-pH monitoring data before treatment were reanalyzed to obtain the W score besides Ryan score and then the diagnostic sensitivity and specificity were compared according to the result of anti-reflux therapy.ResultsEighty-seven (80.6%) cases were anti-reflux therapy effective, and 21 patients (19.4%) were ineffective. Twenty-seven patients (25.0%) had a positive Ryan score. The W score was positive in 79 (73.1%) patients. There were 52 patients who had a negative Ryan score, but a positive W score. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of the Ryan score were 28.7%, 90.5%, 92.6% and 23.5%, respectively (kappa = 0.092, p = 0.068), whereas those of the W score for LPRD were 83.9%, 71.4%, 92.4% and 51.7%, respectively (kappa = 0.484, p ConclusionsW score is much more sensitive for the diagnosis of LPRD. Prospective studies with larger patient populations are necessary to validate and improve the new diagnostic criteria.Trial RegistrationChinese Clinical Trial Registry: ChiCTR1800014931.

Background The purpose of this meta-analysis is to examine changes in radiological variables and clinical outcomes between open and closed wedge high tibial osteotomy (OWHTO and CWHTO, respectively), which have ongoing controversial issues in numerous quantitative clinical studies. Methods PubMed, Embase, and the Cochrane Library were systematically searched for suitable controlled trials between Jan 1, 1999, and Feb 2, 2018. The inclusion criteria included studies written in English, studies with a level of evidence of I–IV, and studies presenting comparisons between OWHTO and CWHTO. The main clinical and radiographic results were extracted and pooled using Stata 12.0. Results After searching for and screening trials, 28 trials involving 2840 knees were eligible for the meta-analysis. After OWHTO or CWHTO, clinical scores, including the American Knee Society Score, Hospital for Special Surgery Knee Score, Lysholm score, and Visual Analog Scale pain score, improved (p < 0.05), but the range of motion was unchanged (p > 0.05). The anatomical femorotibial angle (SMD 0.04, 95% CI − 0.66 to 0.74) and hip-knee-ankle angle (SMD 0.11, 95% CI − 0.11 to 0.33) data suggested that the OWHTO and CWHTO groups were similar in function of correction. Posterior tibial slope increased (SMD − 0.71, 95% CI − 1.04 to − 0.37) after OWHTO but decreased (SMD 0.72, 95% CI 0.35 to 1.08) after CWHTO. OWHTO decreased patellar height (p < 0.05), while patellar height did not change significantly after CWHTO (p > 0.05). Conclusion This meta-analysis indicates that compared with CWHTO, OWHTO increases the posterior slope, decreases the patellar height, and provides a similar accuracy of correction; however, CWHTO leads to a decreased posterior slope and an unchanged patellar height. Therefore, programs should be personalized and customized for the specific situation of each patient.

Background Limited data exist on VTE risk and prophylaxis in Chinese inpatients. The Identification of Chinese Hospitalized Patients' Risk Profile for Venous Thromboembolism-2 (DissolVE-2), a nationwide, multicenter, cross-sectional study, was therefore designed to investigate prevalence of VTE risks and evaluate VTE prophylaxis implementation compliant with the latest prophylaxis guidelines (American College of Chest Physicians [CHEST], 9th edition). Methods Adults admitted (≥ 72 h) to 60 urban, tertiary Chinese hospitals due to acute medical conditions or surgery from March to September 2016 were assessed for VTE risk. Risk assessments were made by using the Padua Prediction Scoring or Caprini Risk Assessment model, risk factors, and prophylaxis based on the CHEST guidelines, 9th edition. Results A total of 13,609 patients (6,986 surgical and 6,623 medical) were analyzed. VTE risk in surgical inpatients was categorized as low (13.9%; 95% CI, 13.1-14.7), moderate (32.7%; 95% CI, 31.6-33.8), and high (53.4%; 95% CI, 52.2-54.6); risk in medical patients was categorized as low (63.4%; 95% CI, 62.2-64.6) and high (36.6%; 95% CI, 35.4-37.8). Major risk factors in surgical and medical patients were major open surgery (52.6%) and acute infection (42.2%), respectively. Overall rate of any prophylaxis and appropriate prophylactic method was 14.3% (19.0% vs 9.3%) and 10.3% (11.8% vs 6.0%) in surgical and medical patients. Conclusions A large proportion of hospitalized patients reported VTE risk and low rate of CHEST-recommended prophylaxis. The data highlight the insufficient management of VTE risk and show the great potential for improving physicians' awareness and current practices across China. Trial Registry Chinese Clinical Trial Registry; No.: ChiCTR-OOC-16010187; URL: http://www.chictr.org.cn/showproj.aspx?proj=17077.

To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP).This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS).A total of 343 patients were randomized (sitafloxacin 100 mg qd,Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Background Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammatory changes. This work aims to investigate the protective role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) against the apoptosis of chondrocytes. Methods Chondrocyte cell lines, CHON-001, and ATDC5 were treated with different doses of interleukin-1β (IL-1β) to mimic the inflammatory response during OA pathogenesis. Quantitative real-time polymerase chain reaction was performed to measure MEG3, miR-9-5p, and Krüppel-like factor 4 (KLF4) mRNA expression levels. MEG3 and KLF4 overexpression plasmids, MEG3 shRNA, miR-9-5p mimics, and miR-9-5p inhibitors were transfected into the cells. Cell counting kit-8, wound healing assay, and flow cytometry were conducted to determine cell viability, migration, and apoptotic rate. Dual-luciferase reporter assay was adopted to verify the targeting relationships among MEG3, miR-9-5p, and KLF4. Western blot was used to detect KLF4 protein expression. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors. Results MEG3 expression in chondrocytes was down-regulated by the stimulation of IL-1β, and MEG3 negatively regulated miR-9-5p expression but positively regulated KLF4 expression. MEG3 overexpression strengthened the viability and migration of CHON-001 and ATDC5 cells but restrained the apoptosis and inflammatory response, while MEG3 knockdown had opposite effects. miR-9-5p inhibition or KLF4 overexpression could counteract the effects of MEG3 knockdown on chondrocytes. Besides that, MEG3 was proved to be a molecular sponge for miR-9-5p, and KLF4 was verified as the target of miR-9-5p. Conclusion MEG3 can promote chondrocyte proliferation and migration and inhibit apoptosis and inflammation by sponging miR-9-5p to induce KLF4 expression, which provides a promising therapy target for OA treatment.

Purpose As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. Methods In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). Results Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. Conclusions Mobile asthma management can improve adherence and asthma control compared to traditional management. Trial Registration ClinicalTrials.gov Identifier: NCT02917174

Medical thoracoscopy is a commonly used endoscopic technique for the diagnosis and treatment of respiratory diseases. As an invasive technique, it is mainly used for pleural effusions and pleural diseases that cannot be diagnosed by non-invasive methods. It is also of great application in the diagnosis and treatment of certain other diseases. Any technical operation requires special skills. There must be a learning process for mastering these skills. Although internal thoracoscopic surgery is simple, especially for respiratory specialists who have undergone training for thoracentesis or closed drainage, there are discrepancies in thoracoscopic diagnosis and treatment in hospitals in China; furthermore, the surgical methods are not uniform, and some even lead to serious complications. Therefore, the thoracoscopic diagnostic and treatment technology in China needs to be standardized. The Respiratory Professional Committee of the Integrated Medical Branch of the Chinese Medical Doctor Association invited relevant Chinese experts to formulate this standard after several rounds of discussion.

Background Omalizumab has > 15 years of real-world evidence of effectiveness in Caucasian patients. In August 2017, it was approved as an add-on therapy for the management of moderate-to-severe asthma in China. Objective To compare the efficacy and safety of omalizumab in Chinese and Caucasian patients. Methods This analysis included clinical trial data from a Chinese study (NCT01202903) and four studies with predominantly Caucasian patients (008, 009, EXTRA and INNOVATE). The following outcomes were analyzed: change from baseline in morning peak expiratory flow (mPEF), percentage predicted forced expiratory volume in one second (FEV1), patient-reported outcomes (PROs), asthma exacerbation and safety. Further, a population pharmacokinetic/pharmacodynamic (PK/PD) was also assessed. Results In the Chinese study, omalizumab significantly improved the mPEF from baseline vs placebo at Weeks > 4-8 through > 16-20; however, the change in mPEF did not reach statistical significance at Week 24. A similar trend towards improvement in mPEF was observed in the studies with Caucasians (INNOVATE, 008 and 009). In all studies, omalizumab showed greater improvement in %predicted FEV1, AQLQ score, and GETE score vs placebo. In addition, asthma symptom scores and seasonal exacerbations were lower, especially during winter, in the Chinese study, and was comparable to studies in Caucasians. PK/PD analyses showed that steady-state PK of omalizumab; free or total immunoglobulin E levels were similar in all studies. Conclusions The clinical efficacy and safety of omalizumab was comparable among Chinese and Caucasian patients with moderate-to-severe asthma supporting therapeutic effectiveness, irrespective of race, ethnicity and geographical factors.

There is increasing demand for automated systems that can fabricate 3D structures. Robotic spatial extrusion has become an attractive alternative to traditional layer-based 3D printing due to a manipulator's flexibility to print large, directionally-dependent structures. However, existing extrusion planning algorithms require a substantial amount of human input, do not scale to large instances, and lack theoretical guarantees. In this work, we present a rigorous formalization of robotic spatial extrusion planning and provide several efficient and probabilistically complete planning algorithms. The key planning challenge is, throughout the printing process, satisfying both stiffness constraints that limit the deformation of the structure and geometric constraints that ensure the robot does not collide with the structure. We show that, although these constraints often conflict with each other, a greedy backward state-space search guided by a stiffness-aware heuristic is able to successfully balance both constraints. We empirically compare our methods on a benchmark of over 40 simulated extrusion problems. Finally, we apply our approach to 3 real-world extrusion problems.

Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.

Background Omalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. Methods A post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma (NCT01202903). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. Results This analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of

Purpose Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. Methods A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. Results There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). Conclusions Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

We conducted the first real-world study of treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in Chinese patients with severe allergic asthma.The primary objective was the steroid-sparing effect of omalizumab after 12 and 16 weeks of treatment. Characteristics of the patient population, treatment patterns, response rate, and other measures of therapeutic effectiveness were also reported.This nationwide, retrospective, real-world study was conducted in patients with severe allergic asthma who were treated with omalizumab in China. Data, including demographics, Asthma Control Test (ACT) and laboratory and lung function test results, and omalizumab use information, were extracted from patient records collected as part of a previously conducted real-world survey (Asthma Group of the Respiratory Disease Society of the Chinese Medical Association).In total, 139 patient records were included; 131 and 118 patients remained on treatment at the ≥12- and ≥16-week time points, respectively. The mean ± standard deviation age and median asthma duration (interquartile range) were 47.4 ± 14.3 and 7 (4, 15) years, respectively; 75.6% of patients had a history of allergic disease. Reductions (versus baseline) in inhaled corticosteroid/long-acting β2 agonists or oral corticosteroids were reported in 61.1% and 63.6% of patients at ≥12 and ≥ 16 weeks, respectively. There were significant improvements in ACT scores (6.08, P .001) and nitric oxide fraction in exhaled air (-13.0, P = .01) from baseline. Multivariate analysis revealed that age and allergic medical history were predictors of omalizumab treatment response. No serious adverse events were reported.Real-world omalizumab treatment was efficacious and well-tolerated in Chinese patients with severe allergic asthma.

Cartilage repair using tissue engineering is the most advanced clinical application in regenerative medicine, yet available solutions remain unsuccessful in reconstructing native cartilage in its proprietary form and function. Previous investigations have suggested that the combination of specific bioactive elements combined with a natural polymer could generate carrier matrices that enhance activities of seeded stem cells and possibly induce the desired matrix formation. The present study sought to clarify this by assessing whether a chitosan-hyaluronic-acid-based biomimetic matrix in conjunction with adipose-derived stem cells could support articular hyaline cartilage formation in relation to a standard chitosan-based construct. By assessing cellular development, matrix formation, and key gene/protein expressions during in vitro cultivation utilizing quantitative gene and immunofluorescent assays, results showed that chitosan with hyaluronic acid provides a suitable environment that supports stem cell differentiation towards cartilage matrix producing chondrocytes. However, on the molecular gene expression level, it has become apparent that, without combinations of morphogens, in the chondrogenic medium, hyaluronic acid with chitosan has a very limited capacity to stimulate and maintain stem cells in an articular chondrogenic state, suggesting that cocktails of various growth factors are one of the key features to regenerate articular cartilage, clinically.

We present the first algorithm for designing volumetric Michell Trusses. Our method uses a parametrization-based approach to generate trusses made of structural elements aligned with the primary direction of an object's stress field. Such trusses exhibit high strength-to-weight ratio while also being parametrically editable which can be easily integrated with parametric editing tools such as Autodesk Fusion. We show a number of examples that demonstrate that the output of our algorithm produces truss structures that are aligned with an object's underlying stress tensor field, are structurally sound and that their global parametrization facilitates the creation of unique structures in a number of domains.

The histogram of metabolic effect of eight RTK inhibitors on CCLE. The high number of affected metabolic components indicates strong metabolic effect of corresponding RTK inhibitor in the model MCPM. (DOC 758 kb)

Summary of the impact of eight RTK inhibitors on breast cancer cell lines from CCLE. (DOC 18 kb)

Background Receptor tyrosine kinase (RTK) inhibitors are frequently used to treat cancers and the results have been mixed, some of these small molecule drugs are highly successful while others show a more modest response. A high number of studies have been conducted to investigate the signaling mechanisms and corresponding therapeutic influence of RTK inhibitors in order to explore the therapeutic potential of RTK inhibitors. However, most of these studies neglected the potential metabolic impact of RTK inhibitors, which could be highly associated with drug efficacy and adverse effects during treatment. Methods In order to fill these knowledge gaps and improve the therapeutic utilization of RTK inhibitors a large-scale computational simulation/analysis over multiple types of cancers with the treatment responses of RTK inhibitors was performed. The pharmacological data of all eight RTK inhibitor and gene expression profiles of 479 cell lines from The Cancer Cell Line Encyclopedia were used. Results The potential metabolic impact of RTK inhibitors on different types of cancers were analyzed resulting in cancer-specific (breast, liver, pancreas, central nervous system) metabolic signatures. Many of these are in line with results from different independent studies, thereby providing indirect verification of the obtained results. Conclusions Our study demonstrates the potential of using a computational approach on signature-based-analysis over multiple cancer types. The results reveal the strength of multiple-cancer analysis over conventional signature-based analysis on a single cancer type. Electronic supplementary material The online version of this article (10.1186/s12885-019-5804-0) contains supplementary material, which is available to authorized users.

Autogenous tissue grafting remains the gold standard in the treatment of critical sized bone and certain cartilage defects, while the translation of tissue engineered osteogenesis or chondrogenesis from the lab bench into clinical practice, utilizing natural or synthetic biomimetic devices, remains challenging. One of the crucial underestimated reasons for non-translatability could be the imprecision and inconsistency of generated gene expression profiles, utilizing improperly optimized and standardized quantitative gene assays. Utilizing GeNorm for downstream qRT-PCR applications, the stability of reference genes in relation to optimal cDNA amounts was assessed on human bone marrow-derived mesenchymal and adipose-derived stem cells neat and made to differentiate into chondrocytes including normal human derived chondrocytes and muscle tissue from rats. Results showed that reference genes can vary substantially across separately and/or combined cell lines and/or tissue types including treatment parameters. The recommendations to all bone and cartilage tissue engineers utilizing qRT-PCR is not to assume that reference gene stability and quantity remain conserved across cell lines or tissue types but to always determine, for each new experiment, the stability and normalization quantity of reference genes anew.

Background Omalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. Methods A post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma ( NCT01202903 ). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. Results This analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of Conclusions In Chinese patients with moderate-to-severe allergic asthma, baseline IgE and allergen profile (number/PAR history) are potential predictors of treatment response to omalizumab. Trial registration NCT01202903 ( www.clinicaltrials.gov ).

The FULFIL study evaluated once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100 µg/62.5 µg/25 µg versus twice-daily budesonide/formoterol (BUD/FOR) 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. FULFIL demonstrated clinically meaningful and statistically significant improvements at Week 24 in trough forced expiratory volume in 1 second (FEV

Background: Unilateral and bilateral percutaneous balloon kyphoplasty (PKP) are 2 main approaches for the treatment of patients with osteoporotic vertebral compression fractures (OVCFs). Numerous published systematic reviews and meta-analyses evaluating the effectiveness of 2 approaches remain inconclusive. In order to propose a significant principle to make decisions for comparing clinical safety and efficacy of unilateral versus bilateral PKP for treating OVCFs patients based on the currently best available evidence, a systematic review of overlapping meta-analysis was conducted. Methods: Three electronic databases, Pubmed/Medline, Embase2 and the Cochrance Library, were searched systematically to retrieve and identify all eligible systematic reviews and meta-analyses comparing unilateral and bilateral PKP for the treatment of patients with OVCFs. Only systematic reviews or meta-analyses with an exclusively pooled analysis of randomized controlled trials (RCTs) met the minimum eligibility criteria in this investigation. The Oxford Levels of Evidence, Jadad algorithm and Assessment of Multiple Systematic Reviews (AMSTAR) instrument were adopted for evaluation of the methodological quality for each included literature to select currently best available evidence. Results: Screening determined that out of 2159, 9 meta-analyses with level II or III of evidence met the inclusion criteria in the systematic review of overlapping meta-analyses. The multiple systematic reviews scores ranged from 8 to 9 with a mean of 8.55 (median 8.5). According to the search process and selection strategies of the Jadad algorithm, a meta-analysis by Feng et al with the best available evidence (12 RCTs and an AMSTAR score of 9) demonstrated that unilateral and bilateral PKP are both nice choices for the treatment of patients with OVCFs, and no significant differences were revealed in clinical scores, radiological outcomes, and quality of life with long-term follow-up. However, compared with bilateral PKP, unilateral PKP produced a shorter surgery time, smaller dosage of cement, lower risk of cement leakage, and relieved a higher degree of intractable pain at short-term follow-up after surgery. Conclusion: Unilateral percutaneous balloon kyphoplasty is more advantageous and superior to bilateral percutaneous kyphoplasty, and should be considered an effective option for the treatment of patients with osteoporotic vertebral compression fractures.

While robotic spatial extrusion has demonstrated a new and efficient means to fabricate 3D truss structures in architectural scale, a major challenge remains in automatically planning extrusion sequence and robotic motion for trusses with unconstrained topologies. This paper presents the first attempt in the field to rigorously formulate the extrusion sequence and motion planning (SAMP) problem, using a CSP encoding. Furthermore, this research proposes a new hierarchical planning framework to solve the extrusion SAMP problems that usually have a long planning horizon and 3D configuration complexity. By decoupling sequence and motion planning, the planning framework is able to efficiently solve the extrusion sequence, end-effector poses, joint configurations, and transition trajectories for spatial trusses with nonstandard topologies. This paper also presents the first detailed computation data to reveal the runtime bottleneck on solving SAMP problems, which provides insight and comparing baseline for future algorithmic development. Together with the algorithmic results, this paper also presents an open-source and modularized software implementation called Choreo that is machine-agnostic. To demonstrate the power of this algorithmic framework, three case studies, including real fabrication and simulation results, are presented., Comment: 24 pages, 16 figures

Polyhedral cuprous oxide nanoparticles (Cu2O NPs) with rough surfaces were prepared by a one-pot sonochemical precipitation method. The products were characterized by SEM, XRD, EDS, XPS, and UV–Vis DRS, respectively. The adsorption behavior of Congo red (CR) from aqueous solution onto the as-prepared Cu2O NPs was systematically investigated. The equilibrium and kinetic studies suggested that the adsorption process followed Freundlich isotherm and pseudo-second order model, respectively. The as-prepared Cu2O NPs exhibited remarkable adsorption properties toward CR. The maximum adsorption capacity at 20 °C was 3904 mg g−1, which was the highest reported value so far in adsorption removal of CR. Together with the evaluation of the thermodynamic parameters such as Gibbs free energy, enthalpy and entropy change, our results show that the adsorption of CR onto Cu2O is a spontaneous, endothermic and chemisorption process. A putative interaction model between CR and Cu2O NPs was proposed. Moreover, the Cu2O adsorbent could be photocatalytically regenerated and reused without significant loss of its adsorption capability.

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

Background: Funnel technique is a method used for the insertion of screw into thoracic pedicle.Aim: To evaluate the biomechanical characteristics of thoracic pedicle screw placement using the Funnel technique, trying to provide biomechanical basis for clinical application of this technology.Methods: 14 functional spinal units (T6 to T10) were selected from thoracic spine specimens of 14 fresh adult cadavers, and randomly divided into two groups, including Funnel technique group (n=7) and Magerl technique group (n=7). The displacement-stiffness and pull-out strength in all kinds of position were tested and compared.Results: Two fixed groups were significantly higher than that of the intact state (P0.05). The mean pull-out strength in Funnel technique group (789.09±27.33) was lower than that in Magerl technique group (P

BACKGROUND Glycopyrronium is a once-daily (od) long-acting muscarinic antagonist for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The GLOW7 study evaluated the efficacy and safety of od glycopyrronium 50 μg in predominantly Chinese patients with moderate-to-severe COPD. METHODS In this 26-week, multi-center, double-blind, placebo-controlled, parallel-group study, men and women ≥40 years with moderate-to-severe COPD were randomized to glycopyrronium 50 μg od or placebo (2:1). The primary objective was to confirm the significant improvement of trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment with glycopyrronium compared with placebo. Secondary objectives included the effect of glycopyrronium on health status (St George's Respiratory Questionnaire), breathlessness (Transition Dyspnea Index), other lung function parameters, rescue medication use, and COPD exacerbations. Safety and tolerability were also evaluated. RESULTS Of the 460 patients randomized, 459 were included in the full analysis set (glycopyrronium, n=306; placebo, n=154; mean age 64.7 years; mean post-bronchodilator FEV1: 50.8% predicted); 425 (92.4%) completed the study. At Week 12, glycopyrronium signifcantly improved trough FEV1 with a least square means treatment difference of 141 mL (95% confidence interval 111 mL, 171 mL; P

Objective This clinical study was designed to evaluate the efficacy and safety of this therapy in the treatment of respiratory and urinary infections caused by ceftriaxone-resistant bacteria in comparison with the effect of cefoperazone/sulbactam on cefoperazone-resistant bacteria. Methods A total of 285 patients aged from 18 to 65 years old, with a respiratory or urinary tract bacterial infection, were enrolled into this multicentre, open-label, controlled clinical study, and bacteria that were either ceftriaxone-resistant or cefoperazone-resistant were isolated from the patients, whose condition had not improved after three days of treatment with ceftriaxone or cefoperazone. To be selected for the study, bacterial cultures obtained from the patients had to be positive before enrolment, and all of the isolates were required to be β-lactamase-positive. Of these patients, 253 completed the trial, and 263 were enrolled into the intention-to-treat (ITT) analysis. All of the 285 patients were included in the safety analysis. Results The cure and effective rates were 39.55% and 85.07% in the ceftriaxone/sulbactam group and 36.43% and 79.84% in the cefoperazone/sulbactam group; the bacterial eradication rates were 83.58% and 83.72%; and the adverse-event rates were 7.48% and 7.80%, respectively. There were no significant differences between the two groups (p > 0.05). Conclusion Ceftriaxone/sulbactam is as effective and well-tolerated as cefoperazone/sulbactam for the treatment of intermediate and severe bacterial infections caused by resistant strains.