Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

BACKGROUND:Postoperative delirium is one of the serious complications after total knee arthroplasty,usually occurring 1-5 days after surgery,with confusion and cognitive impairment as the main manifestations,which is not conducive to the recovery of joint function in elderly patients.At present,the risk factors affecting delirium after total knee arthroplasty in the elderly are not clear,and there is a lack of clinical prediction studies to directly present them for promotion and application. OBJECTIVE:To explore the risk factors of delirium after total knee arthroplasty in elderly patients and establish a prediction model of nomogram. METHODS:Medical record data of 116 elderly patients receiving total knee arthroplasty treated in Ganzhou Hospital of Traditional Chinese Medicine,Jiangxi University of Chinese Medicine from January 2019 to December 2021 were retrospectively analyzed,of which 29 elderly patients with delirium after total knee arthroplasty were selected as the observation group,and the remaining 87 elderly patients without delirium after total knee arthroplasty were selected as the control group.Preoperative general clinical data,laboratory examination results,and surgical data were compared between the two groups.Multivariate Logistic regression analysis was used to analyze risk factors for delirium after total knee arthroplasty in elderly patients.The receiver operating characteristic curve was used to analyze the independent risk factors and obtain the best cut-off value.The nomogram model was constructed by R software. RESULTS AND CONCLUSION:(1)There were significant differences in age,cerebrovascular accident history,preoperative hospital stay,preoperative albumin,hemoglobin,American Society of Anesthesiologists classification,operation time,anesthesia time,and intraoperative blood transfusion volume between the two groups(P<0.05).(2)Multivariate Logistic regression analysis showed that old age,long hospital stay before surgery,high American Society of Anesthesiologists classification grade,and long operation time were risk factors for postoperative delirium in elderly knee arthroplasty patients,while high albumin and high hemoglobin were protective factors for postoperative delirium in elderly knee arthroplasty patients.(3)The areas under the curve of age,preoperative hospital stay,albumin,hemoglobin,American Society of Anesthesiologists classification grade,and operation time were 0.784,0.706,0.853,0.762,0.617,and 0.542,respectively.The optimal cut-off values were 75 years,7 days,40 g/L,125 g/L,3 and 200 minutes,respectively.(4)After internal data for verification,the consistency index was 0.974.The actual curve of the model was in good agreement with the ideal curve.(5)These results indicate that this nomogram model based on old age,long hospital stay,high American Society of Anesthesiologists classification grade,low albumin,low hemoglobin,and long operation time has far-reaching clinical significance for early identification,early warning and diagnosis of delirium risk in elderly patients after total knee arthroplasty.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.