Objective: To investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

IgA nephropathy is a common primary glomerular disease,and autophagy plays an important role in maintaining the homeostasis of the internal environment.Dysfunction of cellular autophagy can affect the occurrence and development of IgA nephropathy.This article focused on the molecular mechanism of TCM regulating autophagy in renal intrinsic cells,and found that TCM extracts and formulas mainly regulate autophagy through PI3K/Akt/mTOR,TLR4/NF-κB,MAPK,Nrf2/HO-1,NLRP3 and other signaling pathways.Furthermore,it could intervene in pathological damage such as renal fibrosis,inflammation,and oxidative stress,delaying the progression of IgA nephropathy,in order to provide reference for the clinical treatment and new drug development of IgA nephropathy.

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Diabetic kidney disease is one of the complications of diabetes,which can progress to end-stage renal disease.In recent years,it has been found that miRNAs have become a research hotspot,with miRNA-21 regulating transforming growth factor β1(TGF-β1)/Smads,phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),Wnt/β-catenin and other signaling pathways to promote the progress of diabetic kidney disease.Studies have showed that traditional Chinese medicine has a regulatory effect on the expression of miRNA-21 and can target miRNA-21 to regulate TGF-β1/Smads,phosphatase and tensin homolog/PI3K/AKT/mammalian target of rapamycin(mTOR),peroxisome proliferator activated receptors and other signal transduction pathways to trigger signal cascade reactions,which intervene in pathological processes such as fibrosis,inflammation,oxidative stress and autophagy.In this article,the role of miRNA-21 in diabetic kidney disease and the intervention of traditional Chinese medicine were summarized,in order to provide some reference for the treatment of diabetic kidney disease and the development of new drugs.

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Child ; DNA Copy Number Variations ; Female ; Genetic Testing ; Genetics, Medical ; Genome, Human/genetics* ; Genomics ; Humans ; Pregnancy ; United States

Objective:To observe the efficacy of dexamethasone intravitreal implant (DEX) combined with pars plana vitrectomy (PPV) in eyes with severe idiopathic epimacular membrane (IMEM).Methods:A prospective clinical case study. From December 2018 to May 2021, 24 patients with 25 eyes of severe IMEM diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, 7 males had 7 eyes, 17 females had 18 eyes. Age was 57 to 84 years old. The IMEM stage was 3 to 4 examined by spectral domain optical coherence tomography (SD-OCT). All eyes were performed best corrected visual acuity (BCVA) and central macular thickness (CMT) by SD-OCT. The patients were randomly divided into PPV group (11 eyes) and PPV+DEX group (14 eyes). Standard PPV by three-channel 25G was performed. Phacoemulsification, membrane stripping and intraocular lens implantation were combined during the operation. Patients received vitreous injection of 0.7 mg DEX in PPV+DEX group at the end of the operation. At 1 week, 1 month, 3 months and 6 months after operation, the same equipments and methods were used to perform relevant examinations. The changes of BCVA and CMT were compared between the two groups by t test. Results:Compared with before operation, at 1, 3 and 6 months after operation, the BCVA of the eyes in the PPV+DEX group was significantly improved ( t=3.974, 4.639, 4.453), CMT was significantly decreased ( t=2.955, 3.722, 4.364), the differences were statistically significant ( P<0.05); at 3 and 6 months after surgery, the BCVA of the eyes in the PPV group was significantly improved ( t=2.983, 4.436), CMT was significantly decreased ( t=2.983, 3.461), the differences were statistically significant ( P<0.05). Conclusion:In the treatment of severe IMEM, DEX can accelerate the early postoperative visual recovery and reduce CMT.