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 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.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:To explore and compare the reference ranges of four coagulation tests in normal pregnant women during early and late pregnancy and the influence of age.Methods:Values of four coagulation tests from 4 974 pregnant women, who gave single birth at Peking University First Hospital, Obstetrics and Gynecology Hospital of Fudan University, West China Second University Hospital, Peking University Third Hospital and Shengjing Hospital of China Medical University from February 2017 to July 2020, were measured and analyzed in this study, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT). The four normal reference ranges of coagulation during early and late pregnancy phases were expressed as P2.5- P97.5. The difference of two pregnancy phases was compared by non-parametric test of two related samples. And the difference between pregnant women of advanced and non-advanced age in the same pregnancy phase was compared by independent sample non-parametric test. Chi-square test was used to compare the incidence of pregnancy complications in different coagulation reference ranges. Results:The reference ranges of PT of normal pregnant women′s early and late pregnancy were 10.0-13.9 s and 9.6-12.3 s, the reference ranges of APTT were 22.6-35.3 s and 22.4-30.9 s, the reference ranges of Fib were 2.4-5.0 g/L and 3.0-5.7 g/L, the reference ranges of TT were 12.0-19.0 s and 11.5-18.4 s. Compared with early pregnancy, PT, APTT and TT shortened significantly, while the Fib significantly increased in late pregnancy (all P<0.001). PT, APTT and TT of advanced and non-advanced age pregnant women were significantly different (all P<0.01). Compared with the ranges of non-pregnant population, more pregnant women were included in the normal pregnant reference ranges of PT in early pregnancy and APTT in the early and late pregnancy, while the incidence of pregnancy complications had no significant differences (all P>0.05). The incidence of fetal distress was higher and the incidence of preterm birth was lower in the reference range of PT in late pregnancy. The incidence of gestational diabetes mellitus was higher in the early and late gestational Fib reference ranges, and the incidence of hypertensive disorders in pregnancy was higher in the late gestational Fib reference range (all P<0.05). Conclusions:The coagulation function of pregnant women increases significantly with the growth of pregnancy, and there is a significant difference between advanced significantly and non-advanced age pregnant women. The recommended ranges of normal pregnant women′s early and late pregnancy PT are 10.0-13.9 s and 9.6-12.3 s, the recommended ranges of APTT are 22.6-35.3 s and 22.4-30.9 s, the recommended ranges of TT are 12.0-19.0 s and 11.5-18.4 s. The appropriate ranges of normal pregnant women′s early and late pregnancy Fib still need further exploration.

Objective To investigate the effect of improving the human immunodeficiency virus (HIV)posi-tive detection rate by single sample nucleic acid amplification test (SS-NAT) in Shenzhen ,and to explore the effect of SS-NAT on reducing the risk of HIV infection in transfusion .Methods 269 228 blood samples were performed parallel detection by SS-NAT (Procleix Tigris ) and two kinds of enzyme-linked immuno sorbent assay(ELISA)reagents ,and then the samples with nonreactive by ELISA and reactive by SS-NAT were tested by HIV identification assay .The blood donors with reactive HIV identification assay were made tracing tests . All the samples with reactive by ELISA or HIV identification assay were sent to the Shenzhen Center for Dis-ease Control and Prevention (CDC) for Western Blot (WB) diagnostic tests .Results The samples with reac-tive by the third generation ELISA reagents ,the fourth generation ELISA reagents ,both ELISA reagents and SS-NAT were 188 ,340 ,422 and 103 ,which reactive rate was 0 .698‰(188/269 228) ,1 .263‰(340/269 228) , 1 .567‰(422/269 228) and 0 .383‰(103/269 228) ,respectively .We found four samples with nonreactive by ELISA but reactive by SS-NAT .The four donors were found HIV reactive by both ELISA and SS-NAT after tracing .All the samples with reactive by ELISA or HIV identification assay were sent to CDC for confirmatory tests and 103 of them were positive .The positive detection rate of transfusion-transmissible HIV infection af-ter ELISA detection was 1∶67 307(4/269 228) .Conclusion The application of SS-NAT in blood screening can improve the HIV positive detection rate ,shorten window period of HIV detection and reduce residual risk of transfusion-transmissible HIV infection ,and then blood safety can be effectively improved .

Objective To evaluated the HCV genotyping results which obtained by genotype diagnostic kit in Shenzhen area. Methods 158 samples which ELISA test of anti-HCV were positive were collected from voluntary blood donors from 2014 to 2015,and were tested by PCR fluorescence probe method for viral load.The samples which viral load were greater than 1.0 ×103 IU/mL were then tested by HCV RNA genotype diagnostic kit.To analysis the proportion of different genotypes and the correla-tion between genotypes with vrial load.Results 54 HCV RNA reactive sample were quantity by PCR fluorescence probe method from 158 anti-HCV positive samples.The genotyping data for 45 cases which vrial load greater than 1.0×103 IU/mL were obtained by HCV RNA genotype diagnostic kit.The frequencies HCV genotype 1b,2,3 and 6 were 57.78%(26/45),6.67%(3/45),8.89%(4/45)and 26.67%(12/45),respectively.One-way ANOVA analysis showed that significant difference in viral loads was found be-tween different HCV genotype 1b and 2(F =2.861,P <0.05),and there was a significant difference in viral loads and anti-HCV S/CO by sex(P <0.05).Fisher′s exact test showed the significance difference between age and genotypes(P <0.05 ).Conclusion HCV 1b and 6 were the most predominant genotypes due to the higher viral load than the other subtypes among volunteer blood do-nors in Shenzhen,while the proportion of HCV 2,3 declined.

Objective To investigate the clinical characteristics of twice-weekly hemodialysis patients.Methods Data were collected from Shanghai Renal Registry.A total of 1288 patients undergoing regular hemodialysis (HD) with dialysis adequacy index and other biochemical parameters in Shanghai in January 2007 were enrolled into the cohort study with 2 years follow-up.Clinical characteristics and outcome of twice-weekly HD patients were analyzed as compared with thrice-weekly HD patients.Results Compared with patients on thrice-weekly HD,the twice-weekly HD patients were significantly younger and had significantly shorter HD vintage,smaller body surface area,longer HD session time,higher single-pool Kt/V (spKt/V) and serum albumin but lower weekly Kt/V (P＜0.05).There was no statistical difference in ultrafiltration volume between two groups.Kaplan-Meier survival analysis indicated that both groups had similar two-year survival.Multivariate Cox regression analysis showed that age,body mass index,serum albumin and weekly Kt/V were predictors of patient mortality.Conclusion It is acceptable for some hemodialys patients with twice-weekly HD,and close monitor of dialysis adequacy and volume status is necessary for this therapy model.

Objective To evaluate the efficacy and safety of motherwort (herbs leonuri/leonurus heterophyllus sweet) injection for preventing postpartum hemorrhage after caesarian section. Methods The prospective study was designed as a randomized and single blind multi-center research matched with positive agent as controls from Apt 2007 to Aug 2007. 440 women underwent caesarian section (CS) indicated by obstetric factors were enrolled from 15 teaching hospitals in China and assigned into three groups: group of motherwort: 147 cases were administered by motherwort 40 rag uterine injection during CS and 20 mg intramuscular injection per 12 hours 3 times after CS; group of motherwort + oxytocin : 144 cases were administered by motherwort 40 mg and oxytocin 10 U uterine injection during CS and motherwort 20 mg intramuscular injection per 12 hours 3 times after CS and group of oxytocin: 149 cases were administered by oxytocin 10 U uterine injection and oxytocin 10 U + 5% glucose 500 nd intravenously injection during operation and oxytocin 10 U intramuscular injection per 12 hours 3 times after CS. The following clinical parameter were collected and analyzed: (1) The amount of blood loss during operation, at 2, 6, 12, 24, 48 hours after operation. (2) The total amount of blood loss in 24 hours after CS and the incidence of postpartum hemorrhage. (3) The change of level of hemoglobin (Hb) and counting of red blood cell ( RBC ) from prepartum to postpartum. (4) Adverse reaction. Results (1) The mean amount of blood loss during operation were (368±258) ml in group of motherwort, (255±114) mi in group of motherwort + oxytocinand (269±141 ) ml in group of oxytocin, which exhibited significant difference among three groups ( P<0.01 ). Meanwhile, no statistical different amount of blood loss among three groups were observed at 2,6,12, 24, 48 hours after CS. (2)The amount of blood loss of postpartum at 24 hours were (480±276)ml ingroup of motherwort, (361±179) ml in group of motherwort + oxytocin, (381±179) nd in group of oxytocin, which showed significant difference among 3 groups(P <0.01 ). (3) The incidence of postpartum hemorrhage were 32.0% (47/147) in group of motherwort, 11.1% (16/144) in group of motherwort + oxytocin, and 18.8% in (28/149) in group of oxytocin. When comparing the lowest rate of postpartum blood loss in group of motherwort + oxytocin and the highest rate in group of motherwort, it displayed statistical difference (P<0.01). (4) The decreased level of RBC and Hb were shown that RBC(0.3±0.5)×10<'12<‘/L and Hb(9±13)g/L in group of motherwort, RBC (0.2±0.4)×10<'12/L and Hb ( 6±10) g/Lin group of motherwort + oxytocin and RBC (0.2±0.4)×10<'12/L and Hb(7±30) g/L in group of oxytocinrespectively. However, the comparison of different value of RBC and lib in group of oxytocin and motherwort +oxytocin showed significant difference (P<0.05 ). (5) Two cases with allery reaction was observed.Conclusion It is safe and efficacious that combined use of motherwort injection and oxytocin was to preventpostpartum hemorrhage during or after caesarian section.