1.Mediating effect of sleep duration between depression symptoms and myopia in middle school students.
Wei DU ; Xu-Xiang YANG ; Ru-Shuang ZENG ; Chun-Yao ZHAO ; Zhi-Peng XIANG ; Yuan-Chun LI ; Jie-Song WANG ; Xiao-Hong SU ; Xiao LU ; Yu LI ; Jing WEN ; Dang HAN ; Qun DU ; Jia HE
Chinese Journal of Contemporary Pediatrics 2025;27(3):359-365
OBJECTIVES:
To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students.
METHODS:
This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia.
RESULTS:
The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081).
CONCLUSIONS
Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans
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Myopia/etiology*
;
Male
;
Female
;
Depression/physiopathology*
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Cross-Sectional Studies
;
Sleep
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Adolescent
;
Students
;
Child
;
Time Factors
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Sleep Duration
2.Bacteroi des fragilis-derived succinic acid promotes the degradation of uric acid by inhibiting hepatic AMPD2: Insight into how plant-based berberine ameliorates hyperuricemia.
Libin PAN ; Ru FENG ; Jiachun HU ; Hang YU ; Qian TONG ; Xinyu YANG ; Jianye SONG ; Hui XU ; Mengliang YE ; Zhengwei ZHANG ; Jie FU ; Haojian ZHANG ; Jinyue LU ; Zhao ZHAI ; Jingyue WANG ; Yi ZHAO ; Hengtong ZUO ; Xiang HUI ; Jiandong JIANG ; Yan WANG
Acta Pharmaceutica Sinica B 2025;15(10):5244-5260
In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.
3.mRNA delivery and safety evaluation of arginine-rich amphipathic cationic lipopeptides in vivo and in vitro
Yi-chun WANG ; Yi-yao PU ; Qun-jie BI ; Xiang-rong SONG ; Rong-rong JIN ; Yu NIE
Acta Pharmaceutica Sinica 2024;59(4):1079-1086
mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by
4.Data Mining of Medication Rules of Chinese Herbal Prescriptions for Oral Use in the Treatment of Venomous Snake Bites
Song-Jie ZHANG ; Dian-Hong LI ; Wei-Cai CAI ; Qing-Xiang WU ; Jian-Liang LIN ; Man-Guang LIANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):251-256
Objective Data mining method was used to analyze the Chinese herbal prescriptions for oral use in treating venomous snake bites collected from the major domestic literature databases and the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions),so as to explore their potential prescription and medication rules,and to provide references for the treatment of venomous snake bites in the primary hospitals.Methods The Chinese herbal prescriptions for oral use in treating venomous snake bites were retrieved from the CNKI,VIP and Wanfang databases,and the ancient formulas for treating venomous snake bites were screened in the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions).Excel software was used to extract the relevant information of the formulas,and R language was used to analyze the medication frequency,properties,flavors and meridian tropism of the herbs as well as their association rules and clustering analysis.Results A total of 187 prescriptions for oral use in treating venomous snake bite were obtained,involving 284 Chinese herbal medicines.The top 15 Chinese herbal medicines in decreasing sequence of medication frequency were Lobeliae Chinensis Herba,Rhei Radix et Rhizoma,Angelicae Dahuricae Radix,Glycyrrhizae Radix et Rhizoma,Paridis Rhizoma,Rehmanniae Radix,Coptidis Rhizoma,Scutellariae Radix,Lonicerae Japonicae Flos,Paeoniae Radix Rubra,Moutan Cortex,Hedyotis Diffusae Herba,Imperatae Rhizoma,Plantaginis Herba,and Scutellariae Barbatae Herba.The flavor of herbs in the prescription for the treatment of venomous snakebite was usually bitter,pungent and sweet,and their property was relatively cold.Most of the herbs had the meridian tropism of the liver meridian and lung meridian.The core prescription mainly composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,and Paridis Rhizoma was obtained after association rule analysis and cluster analysis.Conclusion The herbs for the treatment of venomous snake bites often have the actions of clearing heat and removing toxins,and the prescription is usually composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,Paridis Rhizoma together with the compatibility of medicines for clearing heat and cooling blood,extinguishing wind and arresting convulsion,clearing heat and promoting urination.
5.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
6.Epidemiological characteristics of sexually transmitted diseases in Dehong Prefecture, Yunnan Province from 2010 to 2022
Yurong GONG ; Fan ZHANG ; Yuecheng YANG ; Renhai TANG ; Runhua YE ; Jibao WANG ; Lifen XIANG ; Jie GAO ; Na HE ; Yingying DING ; Song DUAN
Shanghai Journal of Preventive Medicine 2023;35(10):987-992
ObjectiveTo understand the epidemiological characteristics and trends of sexually transmitted diseases (STDs) in Dehong Prefecture, Yunnan Province from 2010 to 2022, so as to provide a basis for the prevention and control of STDs in Dehong Prefecture. MethodsThe 2010‒2022 epidemic cards of STD cases in Dehong Prefecture were downloaded from the China Disease Control and Prevention Information System, and descriptive analysis of the incidence rate and demographic characteristics by disease type was conducted. The syphilis screening data of various populations in Dehong Prefecture between 2014 and 2022 were obtained from the National STD Control and Management Information System, and the syphilis positivity rates of key populations were calculated. ResultsA total of 18 225 STD cases were reported in Dehong Prefecture from 2010 to 2022, and the reported incidence rate increased from 17.1/105 in 2010 to 172.0/105 in 2022, showing an increasing trend (χ2trend=42.9, P<0.001). The number of reported cases of gonorrhea, syphilis, condyloma acuminatum, genital chlamydia infection, and genital herpes were 7 801 (42.8%), 4 563 (25.0%), 3 462 (18.8%), 1 660 (9.1%), and 775 (4.3%), respectively. The majority of the reported STD cases were males (12 336 cases, 67.7%), young adults aged 15 to <45 years (15 839 cases, 87.2%), and farmers (9 230 cases, 50.7%). The elderly group aged 65 years and over accounted for 10.5% of syphilis cases. Among different types of key populations, the highest syphilis positivity rate was found among men who have sex with men (10.1%), followed by STD clinic attendees (8.1%), and the syphilis positivity rates among clandestine prostitutes, voluntary counseling and testing population, drug addicts, and drug rehabilitation center/re-education through labor center population were 2.2%, 1.6%, 1.4%, and 1.3%, respectively. ConclusionFrom 2010 to 2022, the STD epidemic in Dehong Prefecture showed a rapidly increasing trend, with a higher incidence of gonorrhea and syphilis, and a higher syphilis positivity rate among men who have sex with men, drug addicts, clandestine prostitutes, and STD clinic patients. In the future, publicity, education and behavioral interventions for these groups should be strengthened to reduce the prevalence and transmission of STDs.
7.Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway.
Miao YANG ; Wen-Jing YU ; Chun-Xiang HE ; Yi-Jie JIN ; Ze LI ; Ping LI ; Si-Si DENG ; Ya-Qiao YI ; Shao-Wu CHENG ; Zhen-Yan SONG
China Journal of Chinese Materia Medica 2023;48(2):534-541
This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats
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Animals
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Mitophagy
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Alzheimer Disease/genetics*
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Powders
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Protein Kinases/metabolism*
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Ubiquitin-Protein Ligases/metabolism*
8.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
9.Safety of delayed vaccination with the national immunization program vaccines in children aged 0-6 years from 2019 to 2021 in Xuhui District, Shanghai City in China.
Qiang Song WU ; Shu Qian MAO ; Yan XU ; Rui Jie GONG ; Qi ZHOU ; Min LIU ; Jing Yi LIU ; Dan Hong ZHU ; Xiang GUO
Chinese Journal of Preventive Medicine 2023;57(7):983-991
Objective: To understand the incidence of delayed vaccination with the national immunization program vaccines among children aged 0-6 years in Xuhui District, Shanghai, and to evaluate the safety of delayed vaccination. Methods: A stratified random sampling was used to obtain six vaccination clinics in Xuhui District, Shanghai. The vaccination records of children 0-6 years from these six vaccination clinics were collected from the Shanghai Immunization Program Information Management System. Adverse events following immunization (AEFI) data were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology was used to analyze the data. Children were divided into the timely vaccination group and delayed vaccination group according whether they were delayed in vaccination (received one month or more after the recommended age among children aged ≤1 year; received three months or more after the recommended age among children aged >1 year). The safety of four vaccination methods-individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination-were further compared. Differences between groups were compared using chi-square test. Results: From 2019 to 2021, six vaccination clinics in Xuhui District administered 124 031 doses of the national immunization program vaccines among children aged 0-6 years, and delayed vaccinations accounted for 25.99% (32 234/124 031) of these doses. In 2020, the delayed vaccination rate during the first-level COVID-19 public health emergency response period in Shanghai was significantly higher than that in the same period in 2019 (34.70% vs. 24.19%, χ2=136.23, P<0.05). The delayed vaccination rate during the COVID-19 vaccination campaign in 2021 was significantly higher than that in the same period in 2019 (25.27% vs. 22.55%, χ2=82.80, P<0.05). From 2019 to 2021, a total of 475 cases of AEFI were reported in six vaccination clinics, with a reported incidence of 382.97 per 100 000 doses, including 421 cases of common adverse reaction (88.63%, 339.43 per 100 000 doses), 51 cases of rare adverse reaction (10.74%, 41.12 per 100 000 doses) and 3 cases of coincidences (0.63%, 2.42 per 100 000 doses). The reported incidence of AEFI among delayed vaccinations was significantly lower than that among timely vaccinations (291.62 per 100 000 doses vs. 415.05 per 100 000 doses). The incidence of AEFI for the four delayed vaccination methods (individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination) was lower than that for timely vaccination. There were significant differences between the groups except for the routine vaccination group (χ2=9.82, P<0.05; χ2=5.46, P<0.05; χ2=2.97, P>0.05; χ2=11.89, P<0.05). Conclusions: In Xuhui District of Shanghai, 25.99% of doses of the national immunization program vaccines administered to children 0-6 years were delayed. Delayed vaccination does not increase the risk of AEFI compared with timely vaccination.
10.Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses.
Dan Dan TAN ; Yi Dan LIU ; Yan Bin FAN ; Cui Jie WEI ; Dan Yang SONG ; Hai Po YANG ; Hong PAN ; Wei Li CUI ; Shan Shan MAO ; Xiang Ping XU ; Xiao Li YU ; Bo CUI ; Hui XIONG
Chinese Journal of Pediatrics 2023;61(4):345-350
Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.
Humans
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Abnormalities, Multiple
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Retrospective Studies
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Intellectual Disability/genetics*
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Bone Diseases, Developmental/complications*
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Tooth Abnormalities/complications*
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Facies
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Muscular Dystrophy, Duchenne/complications*
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Muscular Atrophy, Spinal/complications*
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Carrier Proteins
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Nuclear Proteins

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