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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.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a major complication of long-term or excessive clinical use of glucocorticoids. Allicin is a classical ingredient extracted from garlic and has many functions such as anti-apoptosis and antibacterial effects. The purpose of this study was to investigate the effect and the mechanism of allicin on apoptosis of osteoblasts induced by dexamethasone (Dex) and SANFH in rats. In vitro, we performed CCK-8, western blotting, TUNEL and other experiments, and the results of these experiments showed that allicin could inhibit the Dex-induced abnormal expression of C-caspase3, C-caspase9, Bax, cytochrome C and Bcl-2 by activating the PI3K/AKT pathway. In vivo, the results of micro-CT, hematoxylin-eosin staining and immunohistochemical analysis suggested that allicin could effectively inhibit the progress of SANFH in rats. In summary, our experiments indicate that allicin is a potential drug for the treatment of SANFH.

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

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.

Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population.From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS).Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires.Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

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.

To investigate the association of DNA repair gene XPB, XPD and XPG gene polymorphisms and haplotypes with genetic susceptibility to lung cancer.A case-control study was conducted, the case group was 100 lung cancer patients in Hainan Province, while the control group was 100 cases of respiratory diseases in Hainan Province. The polymorphism of XPB gene rs4150441 and rs4150434 loci, the polymorphism of the rs171140 and rs11878544 loci of the XPD gene, the XPG gene rs4771436, and the polymorphism of the rs2094258 and rs17655 loci were detected by mass spectrometry. Halopview software was used to investigate the association between XP gene polymorphism and haplotype and genetic susceptibility to lung cancer.The experimental result showed that the rs4150434 locus of XPB gene, the rs4771436 locus of XPG gene and the rs2094258 locus of XPG gene were associated with the genetic susceptibility of lung cancer(P0. 05). Among the rs4150434 loci of XPB gene, the susceptibility of individuals carrying heterozygous GA to lung cancer was 2. 071 times than wild type GG(OR = 2. 071, 95% CI = 1. 055-4. 067). The susceptibility of individuals with mutant AA to lung cancer was 2. 535 times than wild type GG(OR =2. 535, 95%CI = 1. 063-6. 044). In the rs4771436 locus of XPG gene, the susceptibility of individuals carrying mutant GG to lung cancer was 2. 494 times than wild type TT(OR = 2. 494, 95% CI = 1. 038-5. 992). In the rs2094258 locus of XPG gene, the susceptibility of individuals carrying mutant AA to lung cancer was 3. 020 times than wild type GG(OR = 3. 020, 95%CI = 1. 015-8. 980). As haplotype result show, compared with GG haplotypes of rs4150441-rs4150434 loci in XPB gene, the risk of lung cancer in GA haplotype was 3. 643 times than GG haplotype(OR = 3. 643, 95% CI = 1. 113-11. 921). Compared with GTC haplotypes of rs2094258-rs4771436-rs17655 loci in XPG gene, the risk of lung cancer in ATC haplotype was 3. 800 times than GTC haplotype(OR = 3. 800, 95%CI = 1. 073-13. 459).XPB rs4150434, XPG rs4771436, XPG rs2094258 locus polymorphism and haplotype are associated with the genetic susceptibility to lung cancer.

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.

Background It is important to evaluate clinical efficacy and safety of posterior internal fixation using pedicle screw system. Objectives To investigate clinical characteristics of patients diagnosed with fracture-dislocation of the thoracic spine with or without minimal spinal cord. Methods Twenty-eight patients with fracture-dislocation of thoracic spine with or without minimal spinal cord injury were retrospectively analyzed. All patients received posterior reduction and internal fixation using pedicle screw system. Results The mean follow-up duration was 11.4 months. Among 28 patients, 24 cases were complicated with bilateral pedicle or laminal fracture. Preoperatively, the percentage of vertebral displacement was (32.1 ± 20.6)%, significantly declined to (7.5 ± 6.0)% (t= 4.575, P= 0.001) and maintained at (7.9 ± 6.3)% at the final follow-up. Preoperative local kyphosis angle was measured as (16.2 ± 11.3)∘, restored to (15.4 ± 5.9)∘ postoperatively and (15.8 ± 5.4)∘ during the final follow-up. No statistical significance was observed at three time points (all P> 0.05). The remaining 25 patients were evaluated with normal and complete neurological function. No severe complications were observed intra- and postoperatively. Conclusions Posterior internal fixation using pedicle screw is an efficacious and safe therapy which achieves proper reduction and preserves spinal cord function.

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.

Frame shapes, which are made of struts, have been widely used in many fields, such as art, sculpture, architecture, and geometric modeling, etc. An interest in robotic fabrication of frame shapes via spatial thermoplastic extrusion has been increasingly growing in recent years. In this paper, we present a novel algorithm to generate a feasible fabrication sequence for general frame shapes. To solve this non-trivial combinatorial problem, we develop a divide-and-conquer strategy that first decomposes the input frame shape into stable layers via a constrained sparse optimization model. Then we search a feasible sequence for each layer via a local optimization method together with a backtracking strategy. The generated sequence guarantees that the already-printed part is in a stable equilibrium state at all stages of fabrication, and that the 3D printing extrusion head does not collide with the printed part during the fabrication. Our algorithm has been validated by a built prototype robotic fabrication system made by a 6-axis KUKA robotic arm with a customized extrusion head. Experimental results demonstrate the feasibility and applicability of our algorithm.

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.