OBJECTIVE: To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS). METHODS: A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). RESULTS: The infant was born prematurely at 35⁺³ weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. CONCLUSION This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.
Humans ; Serine Peptidase Inhibitor Kazal-Type 5/genetics* ; Netherton Syndrome/genetics* ; Female ; Infant, Newborn ; Infant, Premature ; Mutation ; Exome Sequencing ; Male

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:To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).Methods:A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children′s Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). Results:The infant was born prematurely at 35 + 3 weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c. 1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. Conclusion:This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c. 1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.

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 summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.

Objective:To summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.

Objective:To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).Methods:A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children′s Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). Results:The infant was born prematurely at 35 + 3 weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c. 1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. Conclusion:This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c. 1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.

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 To elucidate the influence of two procedures aortic root remodeling using a straight tubular artificial vessel while preserving the aortic valve and the Florida sleeve procedure on the biomechanics of the aortic root.Methods Five finite element models of the aortic root were reconstructed using computed tomography angiography images,including two cases of aortic root remodeling(A1 and A2),two cases of the Florida sleeve procedure(B1 and B2),and one control group without aortic root pathology(C).Numerical simulations were performed to obtain the blood flow and pressure distribution result to assess the differences in the hemodynamics of the aortic root.Results There were no significant differences in the peak systolic velocity between the two procedures and the control.However,the flow velocity after aortic root remodeling was smoother,similar to the model of the control group,with a more stable average aortic pressure and wall shear stress.In the Florida sleeve procedure,high-speed blood flow affected the vessel wall,leading to various degrees of wall shear stress and pressure concentrations along the aortic wall.Conclusions After aortic root replacement with valve preservation,blood flow patterns in the reconstructed aortic root depended on postoperative changes in sinus geometry.Both surgical procedures showed favorable blood flow patterns;however,the flow pattern after aortic root remodeling was more stable than that after the Florida sleeve procedure.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.