[Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases].

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

[A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review].

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

[Dynamic variation trend and prognostic value of bronchial wall thickness in severely burned patients combined with inhalation injury].

Objective: To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients. Methods: Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test. Results: (1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively. Conclusions: The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.

[Impact on platelet recovery of recombinant human thrombopoietin in severe aplastic anemia patients with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate and analyze the impact on PLT recovery of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of Hematology Division of General Hospital of Jinan Military Command was conducted in the 85 SAA cases who treated with allo-HSCT from January 2010 to March 2017. According to the administration of medicines for platelets, 85 patients were divided into rhTPO group (n=29), rhIL-11 group (n=27) and blank group (n=29), respectively. The median time of PLT ≥20×109/L, PLT ≥50×109/L, and PLT ≥100×109/L, the numbers of megakaryocytes in marrow smear (25±5) days after transplantation and the quantities of platelet transfusion were analyzed retrospectively. The adverse events of rhTPO and rhIL-11 groups were observed. Results: There were no significant differences in the recovery of granulocytes and PLT ≥20×109/L among the three groups (P>0.05). The time of PLT ≥50×109/L in rhTPO group was shorter than that in blank group [16.5 (11-39) d vs 22 (14-66) d, P<0.05], as well as the time of PLT ≥100×109/L [rhTPO: 23 (12-51) d; rhIL-11: 28 (12-80) d; blank group: 35 (18-86) d, P<0.05]. Platelet transfusions were also less in rhTPO group than in rhIL-11 and blank groups [20 (10-30) U, 30 (10-50) U, 35 (10-70) U, P<0.05]. The counts of megakaryocyte in rhTPO group, rhIL-11 group and blank group were 31.5 (0-200), 12 (0-142) and 11(0-187) (P<0.05), respectively. The difference between rhTPO group and rhIL-11 group was statistically significant (P<0.05), but no difference between rhIL-11 group and blank group (P>0.05). Multivariate analysis showed that rhTPO was an independent factor for platelet recovery [HR=4.01 (95%CI 1.81-9.97), P=0.010]. The rhTPO group had no obvious adverse events. Conclusion: rhTPO can promote platelet recovery of SAA patients after allo-HSCT, reduce platelet transfusion with safety.

Intestinal lactic acid bacteria from Muscovy duck as potential probiotics that alter adhesion factor gene expression.

The purpose of this study was to assess the suitability of lactic acid bacteria (LABs) isolated from Muscovy duck as a potential probiotic. Isolates were identified by targeted polymerase chain reaction and assessed in vitro for probiotic characteristics such as autoaggregation; surface-charge; hydrophobicity; tolerance to acidic pH, bile salts and protease; and expression of genes involved in Caco-2 cell adhesion. The LAB isolates exhibited strong resistance to high bile concentration and acidic pH, produced lactic acid, and bacteriostatic (P < 0.05) were identified as bacilli compared with LAB isolates of cocci. Additionally, the LAB isolates showed high sensitivity to penicillin and tetracycline antibiotics, while they were resistant to ofloxacin, Macrodantin, and cotrimoxazole. The level of F-actin mRNA increased in the groups treated with CM3, Salmonella enterica, and CM3 + S. enterica (P < 0.0001, P < 0.05 and P < 0.05 ). The level of cell adhesion molecule (CAM) and E-cadherin (E-cad) mRNA expression was significantly lower in the treatment group (P < 0.05 for both) than in the control. The F-actin, CAM, and E-cad mRNA levels were significantly lower in the S. enterica and CM3 + S. enterica groups (P < 0.01) than in the CM3 group. Among these, RNA levels were higher in the CM3 + S. enterica than S. enterica group. These results indicate that the natural duck gut microflora is an excellent source for probiotic bacteria and can facilitate the establishment of criteria to select probiotic strains for the prevention of diarrhea.

Dysregulated module approach identifies disrupted genes and pathways associated with acute myelocytic leukemia.

OBJECTIVE: To identify disrupted genes and pathways involved in acute myelocytic leukemia (AML) by systematically tracking the dysregulated modules across normal and AML conditions. MATERIALS AND METHODS: In this study, we firstly integrated the protein interaction data and expression profiles to infer and reweight the normal and AML networks using Pearson correlation coefficient (PCC). Next, clustering-based on maximal cliques (CMC) approach and a maximum weight bipartite matching method were implemented to infer the condition-specific modules and capture the disturbed modules, respectively, from two conditional networks. Then, the gene compositions and functional enrichment analysis were performed to identify the dysregulated genes and pathways. Finally, reverse transcription polymerase chain reaction (RT-PCR) was implemented to study the expression level of several key genes in AML patients. RESULTS: In two conditional-specific networks, universal changes of gene correlations were revealed, making the differential correlation density among disrupted module pairs. In this work, a total of 84 altered modules were identified by comparing modules in normal and AML networks. Functional enrichment analysis showed that genes in altered modules mainly involved in cell cycle, nucleic acids and cancer signaling process, and differentially expressed genes (DEGs) and changed gene correlations were mainly participated in natural killer cell-mediated cytotoxicity and acute myeloid leukemia pathway. The key genes, such as MYC, EGFR, MAPK1 and CCNA1, were all significantly differentially expressed in AML patients. CONCLUSIONS: This module approach effectively identifies dysregulated pathways and genes associated with AML. The considerable differences of gene correlations yield to these dysfunctional modules, and the coordinated disruption of these very modules contributes to leukemogenesis.