2022年中国眼科药物临床试验进展

目的:了解2022年我国眼科药物临床试验的进展,探讨其与2014~2021年的变化,为新药研发、临床试验的实施提供最新数据参考,为相关决策提供依据。方法:采用横断面研究,检索国家药品监督管理局“药物临床试验登记与信息公示平台”数据库,纳入公示日期为2022-01-01/12-31且适应证为眼病的眼科药物临床试验。描述眼科药物试验整体情况、适应证及试验分期及占比情况、实施效率、主要研究者的地域分布情况。结果:2022年我国眼科药物临床试验共公示55项,占所有临床试验的1.66%,呈稳步增长趋势,以化学药物占比最高为58.18%。开展试验最多的前三个适应证为年龄相关性黄斑变性、近视、干眼。开展基因治疗药物临床试验2项。7个药物品种开展≥2项临床试验,其中以硫酸阿托品、重组抗血管内皮生长因子(VEGF)人源化单克隆抗体开展数量最多,分别为7、5项。试验分期以Ⅰ期、Ⅲ期为主,分别占比36.36%、27.27%。2022年Ⅰ期试验启动耗时为2.72(0.77,3.47)mo,较2014~2021年的启动耗时3.87(3.00,6.30)mo显著缩短(Z=-2.630,P=0.009),BE、Ⅱ、Ⅲ、Ⅳ期与2014~2021年相比均无差异(P>0.05)。结论:2022年我国眼科药物临床试验开展的数量、实施效率均稳步增长。适应证以眼底病、近视和干眼为主。多数新药处于早期研发或临近上市状态。基因治疗药物崭露头角。

Endoscopic Ruler for varix size measurement:A multicenter pilot study

BACKGROUND We invented Endoscopic Ruler,a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension.AIM To assess the feasibility and safety of Endoscopic Ruler,and evaluate the agreement on identifying large oesophageal varices(OV)between Endoscopic Ruler and the endoscopists,as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler.METHODS We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals,all of whom got esophagogastroduodenoscopy(EGD)with Endoscopic Ruler.The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler.The secondary outcomes included adverse events,operation time,the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists,together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler.RESULTS From November 2020 to April 2022,a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event.The median operation time of Endoscopic Ruler was 3.00 min[interquartile range(IQR):3.00 min].The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52,demonstrating a moderate agreement.The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77,demonstrating a substantial agreement.CONCLUSION The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension.Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.

Distribution of IOP and its relationship with refractive error and other factors:the Anyang University Students Eye Study

AIM:To investigate the distribution of intraocular pressure(IOP)and its relationship with refractive error and other factors in university students from Anyang,China.METHODS:A university-based study was conducted.Subjects were invited to complete ophthalmic examinations,including visual acuity,noncontact tonometr y(NCT),cycloplegic autorefraction,and ocular biometry.Univariable and multivariable analyses were used to evaluate the associations between IOP and other factors.Only data from right eyes were used in analysis.RESULTS:A total of 7720 subjects aged 16 to 26 years old were included,and 2834(36.4%)of the participants were male.The mean IOP of the right eye for all subjects was 15.52±3.20 mm Hg(95%CI:15.45,15.59).Using multivariate linear regression analysis,IOP was found to correlate significantly with younger age(P<0.001;standardized regression coefficientβ,-0.061;regression coefficientβ,-0.139;95%CI:-0.18,-0.09),higher myopic refractive error(P=0.044;standardizedβ,-0.060;regression coefficientβ,-0.770;95%CI:-0.15,-0.002),higher central corneal thickness(P<0.001;standardizedβ,0.450;regression coefficientβ,0.044;95%CI:0.04,0.05),and shorter axial length(AL;P<0.001;standardizedβ,-0.061;regression coefficientβ,-0.163;95%CI:-0.25,-0.07).CONCLUSION:This study described the normal distribution of IOP.In Chinese university students aged 16-26 y,higherIOP is associated with younger age,higher myopic refractive error,higher thickness of the central cornea,and shorter AL.

Forecast of cosmological constraints with superluminous supernovae from the Chinese Space Station Telescope

Superluminous supernovae(SLSNe)are a class of intense celestial events that can be standardized for measuring cosmological parameters,bridging the gap between type Ia supernovae and the cosmic microwave background.In this work,we discuss the cosmological applications of SLSNe from the Chinese Space Station Telescope(CSST).Our estimation suggests that SLSNe rate is biased tracing the cosmic star formation rate,exhibiting a factor of(1+z)^(1.2).We futher predict that CSST is poised to observe~360 SLSNe in the 10 square degrees ultra-deep field survey within a span of 2.5 years.A stringent constraint on cosmological parameters can be derived from their peak-color relationship.CSST is anticipated to uncover a substantial number of SLSNe,contributing to a deeper understanding of their central engines and shedding light on the nature of dark energy at high redshifts.

Prevalence and risk factors of stroke in China:a national serial cross-sectional study from 2003 to 2018

Stroke imposes a substantial burden worldwide.With the rapid economic and lifestyle transition in China,trends of the prevalence of stroke across different geographic regions in China remain largely unknown.Capitalizing on the data in the National Health Services Surveys(NHSS),we assessed the prevalence and risk factors of stroke in China from 2003 to 2018.In this study,data from 2003,2008,2013,and 2018 NHSS were collected.Stroke cases were based on participants’self-report of a previous diagnosis by clinicians.We estimated the trends of stroke prevalence for the overall population and subgroups by age,sex,and socioeconomic factors,then compared across different geographic regions.We applied multivariable logistic regression to assess associations between stroke and risk factors.The number of participants aged 15 years or older were 154,077,146,231,230,067,and 212,318 in 2003,2008,2013,and 2018,respectively,among whom,1435,1996,3781,and 6069 were stroke patients.The age and sex standardized prevalence per 100,000 individuals was 879 in 2003,1100 in 2008,1098 in 2013,and 1613 in 2018.Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018,while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018.Across geographic regions,the central region consistently had the highest prevalence,but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018(Ptrend<0.001),surpassing the eastern region in 2013.Advanced age,male sex,rural area,central region,hypertension,diabetes,depression,low education and income level,retirement or unemployment,excessive physical activity,and unimproved sanitation facilities were significantly associated with stroke.In conclusion,the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions.It is important to develop targeted prevention programs in underdeveloped regions.Besides traditional risk factors,more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

Phosphatase and Tensin Homologue Genetic Polymorphisms and their Interactions with Viral Mutations on the Risk of Hepatocellular Carcinoma

Background： Chronic hepatitis B virus （HBV） infection is the major cause of hepatocellular carcinoma （HCC）. Some HBV mutants and dysregulation of phosphatase and tensin homolog （PTEN） may promote the development of HCC synergistically. We aimed to test the effects of PTEN genetic polymorphisms and their interactions with important HBV mutations on the development of HCC in HBV-infected subjects. Methods： Quantitative po[ymerase chain reaction was applied to genotype PTEN polymorphisms （rs1234220, rs2299939, rsl234213） in 1012 healthy controls, 302 natural clearance subjects, and 2011 chronic H BV-infected subjects including 1021 HCC patients. HBV mutations were determined by sequencing. The associations of PTEN polymorphisms and their interactions with HBV mutations with HCC risk were assessed using multivariate logistic regression analysis. Results： Rs1234220 C allele was significantly associated with HCC risk compared to healthy controls （adjusted odds ratio [AOR] = 1.35, 95% confidence interval [CI] = 1,07-1.69） and HCC-free HBV-infected subjects （AOR = 1.27, 95% CI = 1.01-1 .57）. rsl234220 C allele was significantly associated with increased frequencies of HCC-risk A 1652G, C 1673T, and C 1730G mutations in genotype B H BV-in fected subjects. Rs2299939 GT genotype was inversely associated with HCC risk in HBV-infected patients （AOR 0.75, 95% CI 0.62-0.92）. The interaction of rs2299939 variant genotypes （GT＋TT） with A3054T mutation significantly increased HCC risk （AOR = 2.41, 95% CI = 1.08-5.35）; whereas its interaction with C3116T mutation significantly reduced HCC risk （AOR = 0.34, 95% CI 0.18-0.66）. These significant effects were only evident in males alter stratification. Conclusions： PTEN polymorphisms and their interactions with HBV mutations may contribute to hepatocarcinogenesis in males. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

FISSION 1A and FISSION 1 B Proteins Mediate the Fission of Peroxisomes and Mitochondria in Arabidopsis

Peroxisomes and mitochondria are metabolically diverse organelles that act in concert in a number of pathways in eukaryotes, including photorespiration and lipid mobilization in plants. The division machineries of these two types of organelles also share several components such as dynamin-related proteins （DRPs） and their organelle anchor, the FISSION1 （FIS1） protein. In Arabidopsis, members of the DRP3 and FIS1 small protein families, namely DRP3A, DRP3B, FISIA, and FISIB, are each dual-targeted to peroxisomes and mitochondria and are required for the division of both organelles; DRP3A and DRP3B are partially redundant in function. To further determine the contribution of FISIA and FISIB to the division of peroxisomes and mitochondria, we analyzed plants overexpressing FISIA or FISIB and mutants in which the functions of both proteins were disrupted. Domains in FISIA and FISIB required for peroxisomal targeting were also dissected. Our results demonstrate that FISIA and FISIB play rate-limiting and partially overlapping roles in promoting the fission of peroxisomes and mitochondria. Furthermore, although the C-terminus of FIS1 is both necessary and sufficient for targeting to peroxisomes, the role of the short C-terminal segment adjacent to the transmembrane domain may differ among diverse species in peroxisomal targeting.

Design, methodology, and preliminary results of the follow-up of a population-based cohort study in rural area of northern China:Handan Eye Study

Background:Handan Eye Study (HES),a large population-based cohort study in rural area of northern China,was one of the few studies focusing on the major eye diseases of rural Chinese population.The aim of this study was to introduce the design,methodology and to assess the data quality of the follow-up phase of HES.Methods:All participants were recruited in Yongnian county of Handan city between 2012 and 2013.Main outcomes were measured by visual quality scales and ocular examinations.We performed the Chi-square test to make comparison of categorical data among groups,One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups,a post-hoc test was done to make further pairwise comparison.Inter-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different operators.Logistic regression was used to explore the influence factors of death,odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence factor.Results:The follow-up rate was 85.3%.Subjects were classified into three groups:the follow-up group (n =5394),the loss to follow-up group (n =929),and the dead group (n =507),comparison of their baseline information was done.Compared with the other two groups,age of the dead group (66.52 ± 10.31 years) was the oldest (Z =651.293,P < 0.001),male proportion was the highest (59.0 %)(x2 =42.351,P < 0.001),only 65.9 % of the dead finished middle school education (Z =205.354,P < 0.001).The marriage percentage,body mass index (BMI),best-corrected visual acuity (BCVA),and intra-ocular pressure of the dead group was the lowest either.Spherical equivalent error (SER) of the dead group was the highest.Besides,history of smoking,hypertension,diabetes,and heart disease were more common in the dead group.Multivariate analysis showed that age (OR =1.901,95% CI:1.074-1.108),gender (OR =0.317,95% CI:0.224-0.448),and BCVA (OR =0.282,95% CI:0.158-0.503) were associated with death.While between the follow-up group and the loss to follow-up group,there was only difference on age,gender,BMI,systolic blood pressure and SER.The Cronbach coefficients of all scales used in the follow-up were ≥0.63 and the cumulative variances were ≥0.61,indicating good reliability and validity.The ICCs and Kappa coefficients between different operators were ≥0.69.Conclusions:HES has a high follow-up rate and a low risk of loss to follow-up bias.Age,gender,and BCVA are influence factors of death.Specifically,male subjects are at a higher risk of death than female,age is a risk factor of death while BCVA is a protective factor for death.

A spherical parameterization approach based on symmetry analysis of triangular meshes

We present an efficient spherical parameterization approach aimed at simultaneously reducing area and angle dis-tortions. We generate the final spherical mapping by independently establishing two hemisphere parameterizations. The essence of the approach is to reduce spherical parameterization to a planar problem using symmetry analysis of 3D meshes. Experiments and comparisons were undertaken with various non-trivial 3D models, which revealed that our approach is efficient and robust. In particular, our method produces almost isometric parameterizations for the objects close to the sphere.

Geodesic Structure of a Non-linear Magnetic Charged Black Hole Surrounded by Quintessence

This paper aims to investigate the geodesic motion in the spacetime of a non-linear magnetic charged black hole surrounded by quintessence. By varying the Lagrangian corresponding to the metric, the orbital motion equation has been obtained. The effects of the magnetic charge Q, positive normalization factor C, angular momentum b, and energy E on time-like and null geodesic motion are discussed from three aspects: orbital stability, orbital types, and circular orbits. By comparing the effects of the above parameters C, b on the effective potential, it is found that quintessence has an impact on the types and stability of orbits. In addition, for time-like orbital motion, when 3.443113 ≤ b ≤ 6.392 578(for fixed C = 0.0002, M = 1, Q = 0.7), there are bound orbits, and within this range, the stable circular orbits exist,and the radii of the innermost and outermost stable circular orbit are r = 5.912 654 and r = 56.745 933, respectively. For null orbital motion, the orbital types have only unstable circular orbit which occur at r = 2.951 072(E2= E22= 0.4),absorb orbits and escape orbits, but no stable circular orbits, and bound orbits.