OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

OBJECTIVES: To investigate the clinical sub-phenotype (SP) of pediatric acute kidney injury (AKI) and their association with clinical outcomes. METHODS: General status and initial values of laboratory markers within 24 hours after admission to the pediatric intensive care unit (PICU) were recorded for children with AKI in the derivation cohort (n=650) and the validation cohort (n=177). In the derivation cohort, a least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify death-related indicators, and a two-step cluster analysis was employed to obtain the clinical SP of AKI. A logistic regression analysis was used to develop a parsimonious classifier model with simplified metrics, and the area under the curve (AUC) was used to assess the value of this model. This model was then applied to the validation cohort and the combined derivation and validation cohort. The association between SPs and clinical outcomes was analyzed with all children with AKI as subjects. RESULTS: In the derivation cohort, two clinical SPs of AKI (SP1 and SP2) were identified by the two-step cluster analysis using the 20 variables screened by LASSO regression, namely SP_d1 group (n=536) and SP_d2 group (n=114). The simplified classifier model containing eight variables (P<0.05) had an AUC of 0.965 in identifying the two clinical SPs of AKI (P<0.001). The validation cohort was clustered into SP_v1 group (n=156) and SP_v2 group (n=21), and the combined derivation and validation cohort was clustered into SP1 group (n=694) and SP2 group (n=133). After adjustment for confounding factors, compared with the SP1 group, the SP2 group had significantly higher incidence rates of multiple organ dysfunction syndrome and death during the PICU stay (P<0.001), and SP2 was significantly associated with the risk of death within 28 days after admission to the PICU (P<0.001). CONCLUSIONS This study establishes a parsimonious classifier model and identifies two clinical SPs of AKI with different clinical features and outcomes.The SP2 group has more severe disease and worse clinical prognosis.
Humans ; Acute Kidney Injury/diagnosis* ; Prognosis ; Male ; Female ; Child ; Child, Preschool ; Phenotype ; Infant ; Logistic Models ; Adolescent

OBJECTIVES: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations. METHODS: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations. RESULTS: The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified. CONCLUSIONS Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
Humans ; Male ; Proteinuria/genetics* ; Kidney Failure, Chronic/etiology* ; Child ; Mutation ; Female ; Child, Preschool ; Retrospective Studies ; Phosphoinositide Phospholipase C

In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74％,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71％and 64％,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations.Methods A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted,along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations.Results The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease.Renal biopsy showed focal segmental glomerulosclerosis.Two years and five months after kidney transplantation,the patient had persistent negative proteinuria and normal renal function.Whole-exome sequencing identified two pathogenic heterozygous variants:c.961C>T and c.3255_3256delinsT,with c.3255_3256delinsT being a novel mutation.Family screening revealed no renal involvement in the parents,but among five siblings,one brother died at age of 4 years from end-stage renal disease.A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney,with proteinuria resolving after one year of follow-up.A 3-year-old brother died after kidney transplantation due to severe pneumonia.The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations.The main clinical phenotype was nephrotic syndrome(87%,39/45),and renal pathology predominantly showed focal segmental glomerulosclerosis(57%,16/28).No mutation hotspots were identified.Conclusions Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease,with favorable outcomes following kidney transplantation.Family screening is crucial for early diagnosis,and medullary sponge kidney may be a novel phenotype associated with these gene mutations.Citaion:[Chinese Journal of Contemporary Pediatrics,2025,27(5):580-587]

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

A 3-month-old female infant was admitted for incessant crying for 3 days.Examination revealed a rapidly growing massive retroperitoneal mass that was difficult to resect.Needle biopsy confirmed infantile fibrosarcoma.Initial chemotherapy with the VAC regimen(vincristine,actinomycin D,and cyclophosphamide)was administered,but the response was poor.The common fusion in infantile fibrosarcoma is ETV6-NTRK3,and next-generation sequencing detected an RBPMS-NTRK3 gene fusion in this patient.To our knowledge,this is the first reported case of infantile fibrosarcoma with RBPMS-NTRK3 fusion in China.Treatment with larotrectinib resulted in marked tumor shrinkage.

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.