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Considering the energy consumption of the crushed zone caused by blasting, the energy dissipation characteristics were investigated through theoretical calculation and a plug-in for calculation of energy reduction was made. As a result, an improved CDEM method suitable for studying blast-induced crack propagation was proposed. The improved CDEM method was then used to numerically simulate the blast-induced crack propagation under three different in-situ stress conditions: uniaxial in-situ stress, biaxial equal in-situ stresses and biaxial unequal in-situ stresses. It was found that the in-situ stress conditions had significant effects on the distribution of the blast-induced cracks, the evolution of blast-induced stresses and the propagation of the blast-induced cracks. At the uniaxial in-situ stress condition, the vertical in-situ stress reduced the tip stresses of the horizontal crack and inhibited the propagation of the horizontal crack. At the biaxial equal in-situ stress condition, the peak radial stresses and circumferential stresses of the gauging points decreased gradually with the increase of in-situ stresses. In particular, the circumferential stresses of the gauging points gradually changed from tension to compression with an increasing in-situ stress. At the biaxial unequal in-situ stress condition, there were different inhibitions on crack propagation in the horizontal direction and the vertical one. [ABSTRACT FROM AUTHOR]

Background and Objective: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). Methods: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters—maximum observed serum concentration (Cmax), area under the serum concentration–time curve from zero to the last quantifiable concentration at time t (AUC0–t), and area under the serum concentration–time curve from time zero to infinity (AUC0–∞)—of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80–125% bioequivalence standard. Safety and immunogenicity were also evaluated. Results: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0–t, and AUC0–∞ between the two groups were 107.53% (102.25–113.07%), 108.31% (103.57–113.26%), and 108.34% (103.57–113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). Conclusion: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults. [ABSTRACT FROM AUTHOR]

This paper contributes to the literature by investigating the effects of farmland property rights on public security using the China Labor-force Dynamics Survey data. The results indicate that farmland property rights positively impact public security. This study uses the instrumental variable to solve the endogenous problem. Based on the results, farmland property rights have a positive and significant effect on public security due to the reduction of land acquisition conflicts and social poverty. Hence, this research suggests that the protection of farmland property rights plays a crucial role in ensuring the harmonious development of rural society. [ABSTRACT FROM AUTHOR]

According to the traditional blasting theory and practice, the slotted cartridge blasting can form straight cracks extending along the slot direction and achieve directional fracture. In this paper, an experimental study has been carried out to determine the influence of incident stress waves and reflected stress waves. Under the influence of stress waves, the propagation path of the main crack in slotted cartridge blasting is not straight, and the directional fracture effect is inadequate. Under the experimental conditions in this paper, the propagation of main cracks mainly experienced three stages: directional propagation stage, counterclockwise deflecting propagation stage, and clockwise deflecting propagation stage. The difference between incident stress waves and reflected stress waves results in the difference in the deflecting direction, transforming the main crack into a wing shape. In rock roadway drilling and blasting engineering, the propagation path of main cracks produced by peripheral boreholes using the slotted cartridge blasting is also affected by the incident and reflected stress waves. These stress waves are inevitably generated from free faces and adjacent boreholes; however, these are rarely considered in the design of blasting parameters. Therefore, the design and optimization of blasting parameters considering the interaction of stress waves and main cracks in the slotted cartridge blasting need to be further developed. [ABSTRACT FROM AUTHOR]

This research aimed to determine the effects of near work on macular choroidal blood flow and thickness in young adults. A total of 109 participants (19–28 years old) were recruited from Capital Medical University in China. The participants spent 40 min reading a book text at a distance of 33 cm. Swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) was performed to measure the changes in choriocapillaris perfusion area (CCPA) and choroidal thickness (ChT) after 40 min of near work. The SS-OCT/OCTA data covered an area of 6 mm × 6 mm, which centered on the fovea. The baseline ChT and CCPA before near work were negatively correlated with AL, while positively correlated with the magnitude of spherical equivalent (p <.001). Total CCPA decreased significantly by 6 mm × 6 mm macular area after near work compared to that before near work (24.26 ± 1.96 vs. 24.63 ± 1.61 mm2, p<.001). The macular ChT was lower after 40 min of reading than that before 40 min of reading, but no significant difference was observed (302.25 ± 77.69 vs. 304.92 ± 79.73 μm, p =.078). The extent of choroidal thinning was significantly positively correlated with the magnitude of CCPA reduction (p <.001). The decline in CCPA after near work was significantly positively correlated with axial length (AL; p <.001). This study demonstrated that near work significantly decreased CCPA. The extent of CCPA reduction after near work was associated with higher severity of myopia and choroidal thinning. The baseline CCPA and ChT decreased gradually with AL. [ABSTRACT FROM AUTHOR]

SAL001, a recombinant form of parathyroid hormone, is a biosimilar drug to teriparatide and is planned to be used in osteoporosis treatment. A single‐dose, randomized, open‐label, 2‐way crossover trial was conducted in healthy subjects to compare the pharmacokinetics (PK) and safety between SAL001 and the reference drug. Sixty‐four subjects were enrolled in the study, and 61 subjects completed the study. In each period, 20 μg of the test or reference formulation was administered subcutaneously. SAL001 was administered by autoinjector pen, whereas the reference drug was administered by a self‐matched injection pen. Serial blood samples were obtained for the analyses of PK and serum calcium concentration. Geometric mean ratios with 90%CIs for the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) were estimated. The safety of these 2 formulations was also evaluated. Overall, the 90%CIs for the geometric mean ratios of Cmax, AUC from time 0 to the last quantifiable time point, and AUC from time 0 extrapolated to infinity of the test or reference product were within 80.0%–125.0% of biosimilarity criteria. Other PK parameters, serum calcium concentration, and safety profiles had no significant differences between the 2 formulations. SAL001 demonstrated PK similarity to the reference drug, and the serum calcium concentration and safety profiles of SAL001 were also considered comparable to the reference drug. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to evaluate myopia progression and axial elongation after stopping 0.01% atropine eye drops through a 2‐year cross‐over study. Methods: This study was a randomized, double‐masked, placebo‐controlled, cross‐over trial in mainland China. 220 children aged 6–12 years with spherical equivalent range of −1.00 D to −6.00 D in both eyes were enrolled in Phase 1 for 1 year. Children who had completed the first year's follow‐up continued in the second phase. In Phase 2, the placebo group was crossed over to the 0.01% atropine group (referred to as the 'placebo‐atropine group'), and the 0.01% atropine group was crossed over to the placebo group (referred to as the 'atropine‐placebo group'). All children underwent the examination of cycloplegic refraction and axial length at a 6‐month interval. Only data from right eyes were included in analysis. Results: One hundred thirty‐three subjects completed 2 years of follow‐up. In the first year, the mean myopia progression in atropine‐placebo group was 0.21 ± 0.08 D slower than that in placebo‐atropine group. After cross‐over treatment, the mean myopia progression in atropine‐placebo group was 0.22 ± 0.07D faster than that in placebo‐atropine group in the second year. Over 2 years, the mean myopia progression was −1.26 ± 0.66D and −1.25 ± 0.70D in the atropine‐placebo and placebo‐atropine groups (p = 0.954). Conclusions: The difference in myopia progression between atropine‐placebo group and placebo‐atropine group in Phase 1 was similar to Phase 2 during the cross‐over treatment. Through our cross‐over trial, the results suggest that there is no rebound effect after using 0.01% atropine eye drops to prevent progression of myopia. [ABSTRACT FROM AUTHOR]

In modern society, multi-agent consensus is applied in many applications such as distributed machine learning, wireless sensor networks and so on. However, some agents might behave abnormally subject to external attack or internal faults, and thus fault-tolerant consensus problem is studied recently, among which Q-consensus is one of the state-of-the-art and effective methods to identify all the faulty agents and achieve consensus for normal agents in general networks. To fight against Q-consensus algorithm, this paper proposes a novel strategy, called split attack, which is simple but capable of breaking consensus convergence. By aggregating all the states of neighboring nodes with an extra perturbation, the normal nodes are split into sub-groups and converge to two separate values, so that consensus is broken. Two scenarios, including the introduction of additional faulty nodes and compromise of the original nodes, are considered. More specifically, in the former case, two additional faulty nodes are adopted, each of which is responsible to mislead parts of the normal nodes. While in the latter one, two original normal nodes are compromised to mislead the whole system. Moreover, the compromised nodes selection is fundamentally a classification problem, and thus optimized through CNN. Finally, the numerical simulations are provided to verify the proposed schemes and indicate that the proposed method outperforms other attack methods. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to determine whether the application of 0.01% atropine eye drops could impact the disparity in refraction and axial length (AL) between the right and left eyes in Chinese children. Methods: The study was designed as a double-blind, placebo-controlled randomized trial. A total of 220 children aged 6–12 years were recruited from the Beijing Tongren Hospital in Beijing, China. Participants were randomized in a 1:1 ratio and were prescribed 0.01% atropine or placebo eye drops to be administered once a night to both eyes for the duration of 1 year. The cycloplegic refraction and AL were recorded including baseline, 6 months, and again at the 12 months. Results: After 1-year follow-up period, 76 (69%) and 83 (75%) subjects of the initial 220 participants were identified as the 0.01% atropine and placebo groups, respectively. The inter-ocular difference in spherical equivalent refraction (SER) and AL demonstrated stable values in the 0.01% atropine treatment group (SER: p = 0.590; AL: p = 0.322) analyzed after 1 year, but found a significant increase (SER: p < 0.001; AL: p = 0.001) in the placebo group. Furthermore, over 1 year, eyes with greater myopia in the atropine group exhibited slower myopia progression (0.45 ± 0.44 D) than the lesser myopic eye (0.56 ± 0.44 D) (p = 0.003). Conclusion: This study demonstrated that 0.01% atropine could maintain the inter-ocular SER and AL difference. And 0.01% atropine appeared to be more effective in delaying the progression of myopia in eyes with more myopia than in the less myopic eyes. [ABSTRACT FROM AUTHOR]

Purpose: To assess neural changes in perceptual effects induced by myopic defocus and hyperopic defocus stimuli in ametropic and emmetropic subjects using functional magnetic resonance imaging (fMRI). Methods: This study included 41 subjects with a mean age of 26.0 ± 2.9 years. The mean spherical equivalence refraction was −0.54 ± 0.51D in the emmetropic group and −3.57 ± 2.27D in the ametropic group. The subjects were instructed to view through full refractive correction, with values of +2.00D to induce myopic defocus state and −2.00D to induce hyperopic defocus state. This was carried over in three random sessions. Arterial spin labeling (ASL) perfusion was measured using fMRI to obtain quantified regional cerebral blood flow (rCBF). Behavioral tests including distant visual acuity (VA) and contrast sensitivity (CS), were measured every 5 min for 30 min. Results: Myopic defocus induced significantly greater rCBF increase in four cerebral regions compared with full correction: right precentral gyrus, right superior temporal gyrus, left inferior parietal lobule, and left middle temporal gyrus (P < 0.001). The differences were less significant in low myopes than emmetropes. In the hyperopic defocus session, the increased responses of rCBF were only observed in the right and left precentral gyrus. Myopic defocused VA and CS improved significantly within 5 min and reached a plateau shortly after. Conclusion: This study revealed that myopic defocus stimuli can significantly increase blood perfusion in visual attention-related cerebral regions, which suggests a potential direction for future investigation on the relationship between retinal defocus and its neural consequences. [ABSTRACT FROM AUTHOR]

Importance This is the first comprehensive comparison between ab interno approach and ab externo approach for microcatheter‐assisted trabeculotomy in primary congenital glaucoma with clear cornea. Background: Ab externo microcatheter‐assisted trabeculotomy is considered to be the gold standard for primary congenital glaucoma. The novel ab interno approach would intuitively be similar to ab externo approach for microcatheter‐assisted trabeculotomy in eyes with clear cornea; however, there is no evidence yet. Design Non‐contemporary comparison of retrospective case series. Participants: Fifty‐eight and fifty‐seven consecutive primary congenital glaucoma eyes with clear corneas underwent ab interno and ab externo microcatheter‐assisted trabeculotomy, respectively. Methods: Retrospective comparison of clinical outcomes. Main Outcome Measures: Surgical success was defined as a postoperative intraocular pressure of ≤21 mmHg with at least a 30% reduction from preoperative IOP with or without the use of anti‐glaucoma medication (qualified and complete success, respectively). Results: The qualified success rate (87.9% vs 82.2%, P =.40) and complete success rates (81.0% vs 73.3%, P =.32) were comparable between groups. Complications were minimal and comparable. Less than 360° trabeculotomy (P =.009) and a higher number of previous surgeries (P =.03) were both associated with worse surgical outcomes. Conclusions and Relevance: Ab interno approach provide good and comparable outcomes as ab externo approach for microcatheter‐assisted trabeculotomy in primary congenital glaucoma eyes with clear cornea. It should be considered as the initial choice in these patients with the benefit of sparing conjunctiva. Successful trabeculotomy with either technique during the first attempt is critical to overall success and underscores the need for proficiency before independent practice. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) rs4612666 and rs10754558 in the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) gene and the susceptibility to rheumatoid arthritis (RA) in a Han Chinese population. mRNA expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were determined in peripheral blood mononuclear cells (PBMCs) and neutrophils using reverse-transcription quantitative PCR. The results demonstrated that the C allele at rs4612666 locus and the G allele at rs10754558 locus were associated with significantly increased risk of RA. A statistical significance was also revealed in the dominant model (CC+CT vs. TT: OR=1.549; 95% CI=1.120-2.144; and GG + GC vs. CC: OR=2.000; 95% CI=1.529-2.616; P<0.05). Additionally, the mRNA expression of NLRP3, ASC and caspase-1 in PBMCs and neutrophils derived from patients with RA were significantly upregulated compared with the controls. Furthermore, the mRNA levels of NLRP3, ASC and caspase-1 in PBMCs and neutrophils from patients with active RA were notably increased compared with patients in remission. NLRP3 expression was positively correlated with the levels of C-reaction protein, erythrocyte sedimentation rate and disease activity score of 28 joint counts. Overall, the current study indicated that the NLRP3 rs4612666 and rs10754558 loci were associated with susceptibility to RA. In addition, the results of the present study demonstrated that the high expression of NLRP3 could serve a critical role in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

A series of novel ligustrazine derivatives 8a–r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 × 106; for 8r, IC50 BuChE/IC50 AChE = 1.32 × 107). Of note, 8q and 8r also presented potent inhibitory activities against Aβ aggregation, with IC50 values of 17.36 µM and 49.14 µM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 μM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest. [ABSTRACT FROM AUTHOR]

• 24 novel 5-methylpyrazolo[1,5- a ]pyrimidine derivatives were synthesized as antitumor agents. • Most of compounds exhibited remarkable selective inhibition toward c-Met. • Most of compounds showed good to excellent antiproliferative activities on four cell lines. • Compound 10b had a potent selective cytotoxic effect on MDA-MB-231 cells. • Compound 10f showed a potent cytotoxic effect on A549 cells. A series of novel 5-methylpyrazolo[1,5- a ]pyrimidine derivatives (10a–10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC 50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC 50 values of 26.67 ± 2.56 μM and 26.83 ± 2.41 μM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC 50 values of 20.20 ± 2.04 μM and 21.65 ± 1.58 μM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure–activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R 2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R 2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents. [ABSTRACT FROM AUTHOR]

Background: SAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects., Methods: In this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.5, 1.5, 3.0, 5.0, 7.5, 10.0, 15.0, or 20.0 mg) of SAR107375E ( N  = 44) or placebo ( N  = 16). Plasma and urine concentrations of SAR107375E were measured and used to calculate pharmacokinetic parameters. Coagulation functions were measured and compared with baseline values. Treatment-emergent adverse events were recorded to evaluate safety., Results: In plasma, from the 0.5 to 20.0 mg dose group, t 1/2 is 1.51-4.00 h, C max is 59.05-1360 ug/L, and AUC 0-t is 25.01-528.45 h*ug/L. And it shows dose proportionality in the 5.0-20.0 mg range. Activated partial thromboplastin time and Ecarin clotting time correlated linearly with drug plasma concentration. No serious adverse events were reported during the study., Conclusion: SAR107375E exhibits good safety and tolerability, predictable pharmacokinetics and pharmacodynamics., Clinical Trial Registration: www.chinadrugtrials.org.cn, identifier is CTR20211082.

Aims: To investigate the prevalence and predictors of pseudomyopia in Chinese children and its association with myopia progression., Methods: A prospective, school-based, cohort study of 6- and 13-year-old children was conducted in Anyang, China. Pre-cycloplegic and post-cycloplegic autorefraction were performed at baseline and 1 year later. Pseudomyopia was defined as spherical equivalent refractive (SER) error in the better-seeing eye ≤-0.50 D before cycloplegia and >-0.50 D after cycloplegia. Among pseudomyopic children, pseudomyopic power was defined as non-cycloplegic SER subtracted from cycloplegic SER. Market survey was collected in all optometry stores in Anyang city to investigate how cycloplegia is used for refracting children., Results: A total of 2612 children aged 6 years and 1984 children aged 13 years were included. Of the two cohorts, median cycloplegic SER (IQR) was 1.00 D (0.50, 1.38) and -1.13 D (-2.63, 0.13) respectively, myopia prevalence was 5.2% and 61.0%, pseudomyopia prevalence was 24.1% and 18.9%, and median pseudomyopic power was 1.13 D (0.63, 1.63) and 0.38 D (0.13, 0.88). In both cohorts, greater baseline hyperopia was the strongest predictor of pseudomyopia (p<0.001), whereas time spent on near work was not associated with pseudomyopic power (p>0.05). After 1 year, 15.6% (98/629) of 6-year-olds and 10.7% (40/374) of 13-year-olds with pseudomyopia developed myopia. Compared with myopes, pseudomyopic children with the same pre-cycloplegic SER had slower myopic progression (p<0.001). Among all 127 optometry stores in Anyang, only 4 (3.15%) used cycloplegia for refracting children., Conclusion: Pseudomyopia is more prevalent in younger, more hyperopic children. Pseudomyopia is not an independent risk factor for myopic progression in this setting., Competing Interests: Competing interests: The authors declare that they have no competing interest. Professor NC works as Director of Research at Orbis, a non-governmental organisation working in eye health., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the prevalence and associations of visual impairment and spectacle use in university students in central China., Design: Cross-sectional study., Methods: This study included students aged 16-26 years in China. Study subjects from 2 universities underwent distance visual acuity (VA) assessment in both eyes with a logarithm of the minimum angle of resolution chart and their refractions were measured by cycloplegic autorefraction. Blindness was defined as presenting VA less than three-sixtieth in the better eye (World Health Organization definition), and visual impairment was defined as presenting VA less than six-twelfths., Results: Overall, 9710 undergraduates were enumerated, 7704 (79.3%) subjects were included in this study. The prevalence of uncorrected VA less than six-twelfths and less than three-sixtieth in the better eye were 69.9% and 0.9%, respectively. Only 77.0% (4148/5388) of subjects with uncorrected VA in the better eye of less than six-twelfths wore glasses. For presenting VA, the prevalence of mild (VA <6/12 to 6/18), moderate (VA <6/18 to 6/60), and severe (VA <6/60 to 3/60) visual impairment was 6.3%, 11.2%, and 0.7%, respectively. Overall, 71.7% (4300/6001) of students with myopia (spherical equivalent ≤-0.5 diopters) wore spectacles. In multiple logistic regression analysis, visual impairment was associated with female sex (P < .001) and lower year level of education (P = .006) when presenting with VA., Conclusions: This study has documented a relatively high prevalence of visual impairment and relatively low spectacle coverage in Chinese university students. Given the potential impact of visual impairment, target education and accessible refraction services are highly important to solve the problem., (Copyright © 2019 Elsevier Inc. All rights reserved.)