Chiglitazar, a novel PPARα/γ/δ pan-agonist, showed favorable effects on glycemic control and lipid modulation with well tolerated safety profile in phase 2 trials. This trial aimed to compare the efficacy and safety of chiglitazar with DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled with diet and exercise (ClinicalTrials.gov NCT02173457). Patients were randomly assigned to receive chiglitazar 32 mg or 48 mg, or sitagliptin 100 mg once daily. The primary endpoint was change in HbA1c from baseline at week 24, with a non-inferiority of each chiglitazar dose versus sitagliptin. Analysis was done in all randomized patients who received at least one dose of study drug (n=739). Chiglitazar showed comparable HbA1c lowering effect compared with sitagliptin at 24 weeks (LS mean difference -0.04% [95% CI -0.22 to 0.15] and -0.08% [95% CI -0.27 to 0.10] for 32 mg and 48 mg, respectively), along with different trends in secondary endpoints. Overall adverse events were comparable across study groups. The incidences of weight gain and edema were generally low but relatively higher in chiglitazar 48 mg. In conclusion, chiglitazar showed non-inferior effect compared with sitagliptin on HbA1c reduction with well tolerated safety profile. Disclosure W. Jia: None. J. Ma: None. H. Miao: None. C. Wang: None. X. Wang: None. Q. Li: None. W. Lu: None. J. Yang: None. L. Zhang: None. J. Yang: None. G. Wang: None. X. Zhang: None. M. Zhang: None. L. Sun: None. X. Yu: None. J. Du: None. B. Shi: None. C. Xiao: None. D. Zhu: None. H. Liu: None. L. Zhong: None. C. Xu: None. Q. Xu: None. G. Liang: None. Y. Zhang: None. G. Li: None. M. Gu: None. J. Liu: None. Z. Ning: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. Funding Ministry of Science and Technology of the People´s Republic of China (2013ZX09401301)
A single-shot experimental method is proposed to study non-repetitive evolutions of high order solitons. In our experiments, high order solitons are prepared in the building up process of a soliton fiber laser, and the order of high order soliton is controlled via changing the parameters of the laser. The evolution of high order soliton is recorded by the single-shot spectral measurements-time stretch dispersive Fourier transform. A 4th order soliton evolution under perturbations of gain saturation and saturable loss is studied, showing how a leading pulse wins the competition against the tailing one. Our work provides a controllable technique to study the high order solitons evolutions, which can be applied in the research of ultrafast laser amplifications and supercontinuum generations.
The incidence of neovascular eye disease is increasing year by year, seriously threatening human vision health and becoming an urgent public health problem. Tongmai fuming decoction as an experienced prescription can treat ischemic eye disease.To investigate the therapeutic effect of Tongmai fuming decoction combined with anti-VEGF therapy on neovascular ophthalmopathy.52 patients (62 eyes) with neovascular ophthalmopathy who met the inclusion criteria from January 2018 to July 2020 were randomly divided into the control and observation groups. The control group was given an intravitreal injection of antivascular endothelial growth factor (VEGF) drugs once a day combined with on-demand treatment. The observation group was treated with traditional Chinese medicine Tongmai fuming decoction in addition to the treatment of anti-VEGF drugs. The best-corrected visual acuity (BCVA) was examined before and after treatment, and optical coherence tomography angiography (OCTA) was used to examine the mean retinal thickness and neovascularization in the macular area. Patients were followed for one year and the number of anti-VEGF injections was recorded.After treatment, the average thickness of BCVA and macular retina in the two groups significantly improved. The BCVA of the control group was 0.59 ± 0.39 3 months after treatment, and that of the experimental group was 0.42 ± 0.25 3 months after treatment. The average thickness of the macular retina in the control group was 304.8 ± 79.7 3 months after treatment, and that in the experimental group was 267.7 ± 64.6 3 months after treatment; The average number of injections of anti-VEGF therapy in the control group was 2.32 ± 1.15 times, and that in the experimental group was 1.74 ± 0.76 times. There was a significant difference between the two groups.Tongmai fuming decoction and anti-VEGF therapy have a synergistic effect in the treatment of neovascular ophthalmopathy, which can reduce the treatment times of anti-VEGF drugs.
The concept of dissipative solitons has provided new insight into the complex pulse dynamics in mode-locked lasers and stimulated novel laser cavity designs. However, most of these studies are restricted to qualitative regimes, because it is difficult to quantify dissipative effects in a mode-locked laser. Meanwhile, the quantification of dissipative effects is a general problem that can be also encountered in other dissipative systems. In this paper, we demonstrate a method for quantifying dissipative effects in a mode-locked laser based on analyzing the soliton dynamics traced by time-stretch dispersive Fourier transform. As a result, we are able to quantitatively reproduce the evolution of the pulse that seeds mode-locking through simulations and gain a deeper understanding of the whole process. The obtained physical picture of mode-locking allows us to propose a simple method to quantify the energy threshold for mode-locking buildup and the stability of mode-locked states. A parameter is introduced to evaluate mode-locking conditions, which can serve as a criterion for designing mode-locked lasers. This work opens up new possibilities in the diagnosis and improvement of mode-locked lasers and studies of soliton physics.
Background: Uveal Melanoma (UM) is the most prevalent primary intraocular malignancy in adults. This study assessed the importance of chromatin regulators (CRs) in UM and developed a model to predict UM prognosis. Methods: Gene expression data and clinical information for UM were obtained from public databases. Samples were typed according to the gene expression of CRs associated with UM prognosis. The prognostic key genes were further screened by the protein interaction network, and the risk model was to predict UM prognosis using the least absolute shrinkage and selection operator (LASSO) regression analysis and performed a test of the risk mode. In addition, we performed gene set variation analysis, tumor microenvironment, and tumor immune analysis between subtypes and risk groups to explore the mechanisms influencing the development of UM. Results: We constructed a signature model consisting of three CRs (RUVBL1, SIRT3, and SMARCD3), which was shown to be accurate, and valid for predicting prognostic outcomes in UM. Higher immune cell infiltration in poor prognostic subtypes and risk groups. The Tumor immune analysis and Tumor Immune Dysfunction and Exclusion (TIDE) score provided a basis for clinical immunotherapy in UM. Conclusion: The risk model has prognostic value for UM survival and provides new insights into the treatment of UM.
Gain dispersion impedes the generation of ultrashort dissipative solitons, especially in mode-locked lasers, by limiting the transform-limited pulse width and causing instability near zero dispersion. We have found a hyper-surface in the parameter space of a mode-locked laser for the best suppression of the gain dispersion effects. This is achieved by analyzing the proximity of a dissipative soliton to the stationary solution of the complex cubic-quintic Ginzburg–Landau equation in the absence of gain dispersion with the method of moments. Theoretical and experimental investigations show that the combinations of system parameters in a specific region near the hyper-surface allow for a dissipative soliton width that is very close to the minimum value, as well as a large stable mode-locking region at anomalous group delay dispersion. These findings provide new insights into ultrashort dissipative soliton generation and help to optimize mode-locked lasers with dispersion, nonlinearity, loss, and gain all taken into account simultaneously.
By studying the nonlinear absorption of ultrafast laser pulses in fused silica, we examine, both with experiments and numerical simulations, the different polarization dependence of multiphoton ionization and avalanche ionization. Results show multiphoton ionization and avalanche ionization play different roles in femtosecond and picosecond laser micromachining, and the contribution via avalanche ionization increases with pulse duration. Meanwhile, the spatial distribution of the free carriers generated by circularly polarized pulses is more concentrated than those generated by linear polarization for picosecond laser pulses. These properties make the circular polarized ultrafast laser a possible way to improve the ultrafast laser micromachining efficiency and spatial quality, and can help to reduce some problematic nonlinear effects in ultrafast laser micromachining of low energy band materials.
In this paper, we demonstrate a simple and cost-effective fiber chirped pulse amplification (CPA) laser system, where a nonlinear amplifier is employed to generate broadband seeding pulses. The nonlinear amplifier can generate stable pulses with 50 nm spectral bandwidth and linear chirp. With such a seeding configuration being adapted into a fiber CPA laser system, the output bandwidth can be expanded from 7 nm to 20 nm, with only minor changes to a standard industrial fiber CPA system. The increased bandwidth allows for pulse durations of less than 100 fs, which is significantly shorter than the original configuration's 250 fs. When combined with a Fourier pulse shaper, such a fiber laser system is expected to produce pulses with energy exceeding 100 µJ and duration shorter than 100 fs.
Asthma and cognitive dysfunction represent significant public health challenges. Our study aimed to investigate the relationship between asthma and cognitive dysfunction in adults aged ≥ 60 years, and explore the role of systemic immune inflammation index (SII) in asthma - cognitive dysfunction link. The retrospective cross-sectional study included 2,579 participants aged ≥ 60 years from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) cycles. Asthma diagnosis was confirmed using the MCQ010 questionnaire, cognitive function assessed through the Digit Symbol Substitution Test (DSST). SII was calculated using the formula: (platelet count × neutrophil count)/lymphocyte count. Controlling for demographic variables including sex, age, race and/ethnicity, poverty-to-income ratio (PIR) and education level, a negative association was found between asthma and DSST scores (β = -1.75, 95% CI: -3.38, -0.120, P = 0.037). This association persisted even after further adjustments for body mass index (BMI) and diabetes (β = -1.72, 95% CI: -3.38, -0.057, P = 0.043). Moreover, subgroup analysis showed no significant association of sex, age, race/ethnicity, BMI or diabetes with the relationship between asthma and cognitive function. Mediation analysis indicated SII was a mediator of asthma-induced cognitive impairment, a notable Average Causal Mediated Effect (ACME) (P = 0.004) between SII and cognitive dysfunction. Our investigation indicated that elderly asthma (aged ≥ 60 years) was predisposed to cognitive dysfunction, independent of sex, age, race/ethnicity, BMI and diabetes. Furthermore, mediation analysis suggested that asthma might contribute to cognitive dysfunction through the involvement of SII.
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