1.Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial
Yan ZHAO ; Jianzhong ZHANG ; Bin YANG ; Jingyi LI ; Yangfeng DING ; Liming WU ; Litao ZHANG ; Jinyan WANG ; Xiaohong ZHU ; Furen ZHANG ; Xiaohua TAO ; Yumei LI ; Chunlei ZHANG ; Linfeng LI ; Jianyun LU ; Qingchun DIAO ; Qianjin LU ; Xiaoyong MAN ; Fuqiu LI ; Xiujuan XIA ; Hao CHENG ; Yingmin JIA ; Guoqing ZHAO ; Jinchun YAN ; Bo CHEN
Chinese Medical Journal 2024;137(2):200-208
Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.
2.Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability
Yan LI ; Litao QIN ; Ke YANG ; Xin CHEN ; Hongjie ZHU ; Luya MI ; Yaoping WANG ; Xinrui MA ; Shixiu LIAO
Chinese Journal of Medical Genetics 2024;41(5):533-539
Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.
3.Ocular biometric parameters among primary and secondary school students of Naxi,Bai and Han ethnicity in Yunnan Province
Qiang ZHANG ; Litao CHANG ; Peiqian LI ; Jie XIAO ; Dafeng HUANG ; Xueni XIE ; Jin-Jiao ZHANG ; Zixue MA ; Qianqian LI ; Xiao LUO ; Maosen CHEN ; Ying HUANG
Recent Advances in Ophthalmology 2024;44(5):365-369
Objective To assess ocular biometric parameters among primary and secondary school students from Naxi,Bai and Han ethnic groups in Yunnan Province.Methods The school-based study was conducted in October 2020.A total of 724 second-,third-and seventh-graders were selected from Dali and Lijiang,where Bai and Naxi ethnic groups inhabit,using a stratified cluster sampling method to receive questionnaire surveys and eye examinations.Non-cycloplegic spherical equivalent(SE),axial length(AL),anterior chamber depth(ACD),corneal radius of curvature(CR),central corneal thickness(CCT),white-to-white(WTW)distance,and the AL/CR ratio were measured.Covariance analysis was used to examine the differences in SE and ocular biometric parameters in terms of ethnicity,sex and grade,while Pearson correlation was used to test the associations among the said indicators.Results There were no significant differences in daily outdoor time,screen time and sleep time among the three ethnic groups regardless of grades(all P>0.05).The mean CCT of Naxi students was lower than that of Han and Bai students[grade 2 and grade 3:(542.48±39.76)μm vs.(553.81±31.83)μm and(559.27±32.79)μm;grade7:(538.86±34.91)μm vs.(547.41±33.55)μm and(548.26± 32.98)μm,all P<0.05],while no significant differences were found in the other ocular biometric parameters among the three ethnic groups(all P>0.05).Among the seventh-graders,the SE,AL and AL/CR ratio of Naxi students were signifi-cantly different from those of Han and Bai students(all P<0.05).The AL,CR,ACD,CCT,WTW distance,and mean SE were lower in girls than in boys(all P<0.05).Compared with grade 2 and grade 3,students of grade 7 had longer AL,deeper ACD and thinner CCT(all P<0.05),while no significant differences were found in CR and WTW distance(all P>0.05).Correlation analysis showed that the AL/CR ratio was highly correlated with SE(r=-0.78,P<0.05).Conclu-sion Multiethnic primary and secondary school students may face similar environmental risks.Yet,disparities in ocular biometric parameters caused by ethnicity,sex and age should be noted.
4.Dapansutrile(OLT1177)alleviates acute radiation-induced lung injury
Weihao CI ; Yating LI ; Litao XU ; Chen CHEN ; Xiaoming YANG ; Guangming REN
Military Medical Sciences 2024;48(5):334-339
Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile(OLT1177)-against acute radiation lung injury.Methods Mice were divided into the control group,OLT1177 injection group,irradiation group,and irradiation+OLT1177 injection group.A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury.After 6 h of radiation,OLT1177(100mg/kg,once daily)was administered intraperitoneally.After 14 consecutive days of administration,lung tissues were collected and weighed while the lung coefficient was calculated.Hematoxylin-eosin(HE)staining and F4/80 immuno-histochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues.Real-time quantitative PCR(qPCR)was used to detect the transcription levels of NLRP3,IL-1β,and other mRNAs in lung tissues.Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA).The activation of Caspase-1 and IL-18 was detected by Western blotting.Results Radiation caused acute inflammation in the lung tissues of mice,manifested as edema in the lung tissues and destruction of the alveolar structure,increased macrophage infiltration,and elevated expressions of inflammatory genes NLRP3,IL-1β,TNF-α,and IL-6 in the lung tissues and higher serum levels of TNF-α,IL-6.Treatment with OLT1177 significantly improved the above symptoms induced by radiation.OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation.Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice,which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.
5.Discriminante analysis of risk factors Nomograms of myopia in children and adolescents in Yunnan Province
Chinese Journal of School Health 2023;44(9):1387-1391
Objective:
To explore the related factors of myopia among children and adolescents in Yunnan Province, and to predict and evaluate the influencing factors, so as to provide a scientific theoretical basis for the prevention and control of myopia.
Methods:
From March 9 to 14, 2023, 848 students from 6 primary and secondary schools in Dali and Lijiang of Yunnan Province were selected by multi stage stratified random cluster sampling method for visual acuity detection and questionnaire survey on myopia related factors. Multivariate Logistic regression analysis was used to establish a Nomogram prediction model for the selected influencing factors.
Results:
The overall myopia rate of the respondents was 68.3%, the myopia rate of boys (63.4%) was lower than that of girls (72.9%), and the myopia rate of primary school students (46.7%) was lower than that of junior high school students (81.1%), and the difference was statistically significant( χ 2=8.71, 108.07, P <0.05). Daily eye exercises, activities outside the teaching building during recess, having daily sleep time of 7-9 and >9 h, having both parents without myopia were negatively correlated with the occurrence of myopia in children and adolescents in Yunnan Province ( OR=0.64, 0.63, 0.56, 0.28, 0.48, P < 0.05 ). The reading and writing time after school ≥3 h per day and parents unrestricted time to play video games were positively correlated with myopia ( OR=1.94, 1.78, P <0.05). Based on the influencing factors, a Nomogram prediction model was established to quantitatively evaluate the risk of myopia. The results showed that greater risk for myopia was associated with sleep duration, parental history of myopia, and the time spent reading and writing after school every day.
Conclusion
Both genetic factors and environmental factors are related to myopia in children and adolescents. The prediction model of nomogram is beneficial for screening high risk factors of myopia and taking corresponding prevention and treatment measures.
6.Practice and Thinking of Promoting Spiritual Culture Cultivation by Inheriting the Red Gene in Public Hospital
Qi JIN ; Litao JIA ; Yuheng CHEN ; Yan ZHOU ; Ping ZHANG
Chinese Medical Ethics 2023;36(2):211-215
The red gene is the crystallization of the ideas and wisdom of the Chinese Communist Party’s century-long struggle, and plays an irreplaceable and decisive role in cultivating socialist hospital culture and medical professionals in the new era. The Chinese Academy of Medical Science (CAMS) Cancer Hospital has a distinctive red gene trait. For more than 60 years since its establishment, through the protection of the red gene inheritance carrier, the enrichment of the content and expression form of the red gene inheritance, and the exploration and demonstration of the role model in the red gene inheritance, it has always integrated the red gene inheritance into the whole process of hospital construction, development and spiritual culture cultivation, and has achieved remarkable results, accumulated rich practical experience, and provided a useful reference for the spiritual and cultural construction of public hospitals.
7.Recent advance in corneal confocal microscopy for neurological diseases
Jihong LIU ; Yingxiao JI ; Rui ZHAI ; Min CHEN ; Zhipeng CAI ; Litao LI
Chinese Journal of Neuromedicine 2023;22(1):97-100
Corneal confocal microscopy (CCM) is a non-invasive, simple and rapid visual corneal imaging technique, which can directly conduct real-time collection and quantitative analysis of corneal nerve fibers. Studies have shown that CCM can be used in the diagnosis and prognosis evaluation of degenerative diseases, demyelinating diseases, degenerative diseases and other types of diseases of the central nervous system. In this paper, the recent advance in CCM in neurological diseases is summarized to provide new ideas for their diagnosis and prognosis evaluation.
8.Diagnosis and treatment of a patient with intestinal obstruction caused by malignant tumor in rectosgmoid region
Jingyi WANG ; Jinglong CHEN ; Litao ZHANG ; Xiaolong LI
Chinese Journal of Digestive Surgery 2023;22(S1):98-100
Intestinal obstruction is a common disease in surgical acute abdomen. Due to the diverse causes of intestinal obstruction and rapid disease progression, there are difficulties in diagnosis and treatment. Actively searching for the cause is beneficial for assisting in formulating treatment plans for patients. Treatment plan for intestinal obstruction can be divided into conservative treatment and surgical treatment. Conservative treatment mainly includes targeted treatment such as retained gastrointestinal decompression, enema, and fluid replacement, while surgical treatment mainly includes open exploration and laparoscopic exploration. After the cause of disease is determined, patients who are temporarily exempt from surgical treatment can be given conservative treatment. During the process of conservative treatment, the need for surgical treatment is determined based on the patient′s symptoms and signs. Premature surgery may lead to additional surgical trauma for patients who could have been relieved of obstruction through conservative treatment, and if not treated promptly, it may lead to intestinal necrosis and perforation, leading to septic shock and, patient death in severe cases. Whether laparoscopic exploration can be performed during surgical treatment and whether treatment can be performed under laparoscopy after laparoscopic exploration is another choice. The authors report the diagnosis and treatment of a patient with intestinal obstruction caused by malignant tumor in rectosigmoid region, aiming to provide reference for the treatment of related diseases.
9.Thoughts on fund compensation of adverse events following immunization in China
Ting SU ; Zhilei ZHONG ; Dan YOU ; Litao RUAN ; Shengran YANG ; Qian LI ; Qiuyu CHEN ; Zexu YU ; Cheng LI
Shanghai Journal of Preventive Medicine 2022;34(4):382-387
After the promulgation and implementation of the Vaccine Administration Law of the People’s Republic of China, the compensation of suspected adverse reactions in China is to be reformed and innovated. There have been attempts at compensation through government finance and insurance, but there has been no precedent for a fund of vaccine-related compensation in China, which means that this could be a new method of solving disputes of compensation for vaccine-related incidences and enhancing public confidence in vaccination. It is suggested that under the current system, we can select a province as a pilot to explore the fund compensation mechanism. The fund comes from special financial allocation, special taxation of vaccine enterprises, fund investment income, charitable donation and other channels. Through a special fund management organization, the independent identification and compensation process can be realized, so as to shorten the current compensation procedure, improve the amount of compensation, ultimately protect the interests of all parties, and promote the steady development of vaccination.
10.Corneal confocal microscopy and its application in ischemic cerebrovascular disease
Jihong LIU ; Yingxiao JI ; Min CHEN ; Rui ZHAI ; Zhipeng CAI ; Litao LI
International Journal of Cerebrovascular Diseases 2022;30(8):605-610
Corneal confocal microscopy (CCM) is an in vivo corneal imaging technique, which can directly quantify corneal nerve fibers in real time. It has the characteristics of non-invasive, objective and high sensitivity. CCM can not only be used for the diagnosis and treatment evaluation of corneal diseases, but also plays an important role in the diagnosis and prognosis evaluation of some peripheral and central nervous system diseases, such as diabetes peripheral neuropathy and Parkinson's disease. In addition, the changes of corneal nerve fibers can indirectly reflect the severity of ischemic cerebrovascular disease, and it is expected to become a noninvasive bioimaging marker of ischemic cerebrovascular disease. This article reviews CCM and its application in ischemic cerebrovascular disease, in order to provide better means for early diagnosis and prognosis evaluation of ischemic cerebrovascular disease.


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