OBJECTIVE: To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene. METHODS: A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords "TSEN2 gene" "PCH2B" and "Pontocerebellar Hypoplasia 2B" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892). RESULTS: The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis. CONCLUSION The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.
Child ; Female ; Humans ; Cerebellar Diseases/genetics* ; Exome Sequencing ; Heterozygote ; Mutation

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Objective To investigate the relationship between serum stem cell factor receptor(c-kit)and myocardial fibrosis,cardiac function and prognosis in patients with dilated cardiomyopathy(DCM)complicat-ed with heart failure.Methods A total of 77 patients with DCM complicated with heart failure who were trea-ted in 3201 Hospital from May 2020 to June 2022 were enrolled in the study as study group,and 70 DCM pa-tients without heart failure were enrolled as the control group.The levels of serum c-kit mRNA and three my-ocardial fibrosis markers[α-smooth muscle actin(α-SMA),collagen type Ⅰ and collagen type Ⅲ]were detec-ted in the two groups.Cardiac function parameters were obtained by echocardiography.The relationship be-tween serum c-kit mRNA level and myocardial fibrosis and cardiac function was analyzed.According to the oc-currence of major adverse cardiovascular events(MACE),the patients were divided into poor prognosis group and good prognosis group.Multivariate Logistic regression analysis was used to analyze the factors affecting the prognosis of DCM patients complicated with heart failure.Receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum c-kit mRNA level in predicting the prognosis of DCM patients.Results The serum c-kit mRNA level in the study group was lower than that in the control group(P＜0.05).The levels of three myocardial fibrosis indicators in the study group were higher than those in the con-trol group(P＜0.05).The left ventricular ejection fraction(LVEF)in the study group was lower than that in the control group(P＜0.05),and the left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV)in the study group were higher than those in the control group(P＜0.05).Pearson correlation analysis showed that serum c-kit mRNA level was positively correlated with LVEF(r=0.677,P＜0.05),while negatively correlated with α-SMA,collagen type Ⅰ,collagen type Ⅲ,LVEDV and LVESV(r=-0.725,-0.748,-0.744,-0.745,-0.662,P＜0.05).Multivariate Logistic regression analysis showed that serum c-kit mRNA level is an independent factor for the prognosis of DCM patients with heart failure.ROC curve analysis showed that serum c-kit mRNA level had a sensitivity of 82.80％,a specificity of 81.80％,and an area under the curve of 0.829(95％CI:0.745-0.912,P＜0.001)for evaluating the progno-sis of DCM patients complicated with heart failure.Conclusion The serum c-kit mRNA level is significantly decreased in patients with DCM complicated with heart failure,and the serum c-kit mRNA level is correlated with myocardial fibrosis and cardiac function.The detection of serum c-kit mRNA level has a high efficacy in evaluating the prognosis of patients with DCM complicated with heart failure.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective:To evaluate the clinical performance of direct antimicrobial susceptibility test in blood culture-positive broth, and to provide a basis for optimizing the antibiotic use strategy in clinical bloodstream infection.Methods:A retrospective analysis was conducted on 780 blood culture-positive samples collected in Peking University People′s Hospital from May 2017 to December 2021. The direct antimicrobial susceptibility test was performed by disk diffusion method on blood culture-positive broth. The antimicrobial susceptibility breakpoints were in accordance with Clinical and Laboratory Standards Institute (CLSI) M100 S32 edition document.Results:In this study, a total of 331 strains of Gram-negative bacteria (139 strains of Escherichia coli, 79 strains of Klebsiella pneumoniae, 35 strains of Pseudomonas aeruginosa, 21 strains of Acinetobacter baumannii) and 396 strains of Gram-positive cocci (25 strains of Staphylococcus aureus, 316 strains of coagulase-negative staphylococci, 47 strains of Enterococcussp.) were collected, after excluding 53 cases with two or more isolates. Compared with the routine antimicrobial susceptibility test (AST), the rates of category agreement (CA), major error (ME), and very major error (VME) of Gram-negative bacteria were 86.0% (1368/1 591), 8.7% (139/1 591), and 0.5% (8/1 591), respectively. On the other hand, the CA%, ME%, and VME% of Gram-positive cocci were 89.2% (960/1 076), 7.5% (81/1 076), and 1% (11/1 076), respectively. Regarding the individual antimicrobial agents, the CA% of Escherichia coli was 16/17 for imipenem, 90.1% (109/121) for meropenem, and 70.8% (85/120) for cefepime. For Klebsiella pneumoniae, the CA% of was 10/13 for imipenem, 80.9% (55/68) for meropenem, and 80.3% (53/66) for cefepime. The CA% of meropenem in Pseudomonas aeruginosa and Acinetobacter baumannii were 96.0% (24/25) and 16/16. The CA% of linezolid and cefoxitin in Staphylococcus aureus were 100% (25/25) and 100% (24/24), respectively. The CA% of linezolid, cefoxitin and gentamicin in coagulase-negative staphylococci were 98.9% (269/272), 94.5% (277/293) and 71.6% (194/271) respectively. Finally, for Enterococcus sp., the CA% of vancomycin and ampicillin were 91.5% (43/47) and 94.7% (36/38), respectively. Conclusion:Compared with the conventional AST, the blood culture-positive broth direct AST exhibited high category agreement and low error rates for both Gram-negative bacteria and Gram-positive cocci, which can serve a rapid alternative for AST in cases of clinical bloodstream infection.

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.