Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.

Organ transplantation has brought new hope for patients with end-stage organ failure. However, post-transplant infections, immune rejection, and medication-related complications remain key challenges. The high incidence of post-transplant infections significantly affects long-term patient survival. In recent years, laboratory testing for pathogens related to organ transplantation has made significant progress, providing important support for clinical practice. Future advancements in laboratory testing needs to optimize techniques, integrate multidimensional clinical indicators, and improve the accuracy and practicality of pre-, intra-, and post-transplant monitoring. With the combination of basic research and clinical practice, transplant medicine is expected to achieve greater breakthroughs in improving patient prognosis and survival rates.

Objective:This study aimed to analyze the infection status of viral viruria within one year after kidney transplantation, its impact on renal allograft function, and associated risk factors.Methods:A retrospective case-control study was conducted, involving 370 patients who underwent allogeneic kidney transplantation at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from January 1, 2020 to December 31, 2021. Urinary viral loads of BK virus (BKV), JC virus (JCV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were detected using PCR fluorescent probe assays. Patients were categorized into infection and non-infection groups. Glomerular filtration rate (GFR) and tacrolimus trough concentration was measured during infections, and clinical data were collected. Univariate analysis was performed to identify risk factors for viral viruria.Results:The 1-year patient survival rate and graft survival rate were both 98.6%. The incidence rates of viral viruria were as follows: JCV (42.7%), BKV (29.7%), CMV (11.6%), and EBV (2.9%), with statistically significant differences among viruses ( P<0.001). Single viral infection accounted for 48% of cases, while co-infections were predominantly BKV+JCV (9%). JCV infection rates remained consistently high throughout the year (22.4%-28.9%), whereas BKV infections peaked at 3 months postoperatively (20.5%). Co-infection with low-load JCV (>2 000 copies/ml) and CMV (>6 000 copies/ml) led to a significant decline in GFR at 6 months post-transplantation [median difference: 16.7 ml/(min×1.73 m2), P=0.019]. Univariate analysis revealed that elevated tacrolimus trough concentration was independent risk factor for BKV (4.90 vs. 4.30 ng/ml, Z=4.29, P<0.001) and JCV infections (5.30 vs. 4.80 ng/ml, Z=4.25, P<0.001). Conclusion:High incidences of JCV and BKV infections were observed post-kidney transplantation. Co-infection with low-load JCV and CMV accelerates renal function impairment, highlighting the critical role of tacrolimus concentration management in reducing viral infection risks.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective To investigate the characteristics and clinical significance of serum immunoglob-ulins in patients with Cronkhite-Canada syndrome(CCS).Methods This retrospective study included CCS patients admitted to Peking Union Medical College Hospital from December 2009 to September 2024 who under-went serum immunoglobulin testing.Clinical manifestations and ancillary examination results were analyzed ret-rospectively.Results Fifty-two patients were included(male:36[69.2%],female:16[30.8%]),with median onset age of 60(54-64)years and median diagnostic delay of 5(3-12)months.Common manifesta-tions included diarrhea(86.5%),abdominal pain(40.4%),hematochezia(19.2%),weight loss(86.5%),nail malnutrition(100.0%),pigmentation(88.5%),hair loss(84.6%),and hypogeusia(69.2%).Serum IgG reduction occurred in 21 patients(50.0%),while total IgE elevation was observed in 20(71.4%).Elevated serum IgG4 levels were noted in 11 patients(23.4%),with no significant clinical differences between IgG4-elevated and normal groups.IgG4 levels showed no statistical difference between active(n=43)and remission(n=27)groups.The hair loss rate was significantly higher in the total IgE-ele-vated group than that in the normal total IgE group(P=0.0383).Conclusions CCS patients exhibit periph-eral blood immunoglobulin disorders,with elevated IgE levels correlating with hair loss.This suggests an im-mune-mediated mechanism may underlie hair loss in CCS.

Radiomics can provide a large number of features derived from medical images, which can be correlated with certain biological characteristics and clinical endpoints. Delta radiomics enables the analysis of feature changes across different acquisition time points, typically before and after treatment. Compared with traditional radiomics, delta radiomics allows the evaluation of changes in radiomic features at different time points to better guide clinical diagnosis and treatment, thereby facilitating the development of personalized treatment plans for patients. Delta radiomics offers certain advantages in the differential diagnosis, prognosis prediction, treatment response assessment, and side effect evaluation of oncological diseases. This article reviews the applications of delta radiomics in the diagnosis and treatment of head and neck tumors, lung cancer, gastrointestinal tumors, pancreatic cancer, prostate cancer, breast cancer, and soft tissue tumors.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation