OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies.Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group,and cyclophosphamide+fungal infection low,medium,and high dose groups,with 12 animals in each group.General clinical observations were performed daily,and the serum levels of immunoglobulin(Ig)G and IgM and galactomannan(GM)were detected by ELISA on the 3rd and 7th days of modeling.Simultaneously,the ratio of CD4+and CD8+cells,content of white blood cells(WBCs)and neutrophils(Neu)in peripheral blood,the Aspergillus niger load in alveolar lavage,and morphological changes to rat lung tissue were observed.Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling,and rats in the cyclophosphamide+fungal infection group also had shortness of breath and audible wet rhonchi in the lungs.Compared with the normal control group,rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+,WBC,Neu,IgG,and IgM in the blood,and their proportion of CD8+cells was significantly higher(P＜0.05,P＜0.01).Compared with the cyclophosphamide control group,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly reduced blood levels of IgG,IgM,and CD4+cells(P＜0.05,P＜0.01);while the cyclophosphamide+fungal infection low-,medium-,and high-dose groups had significantly reduced blood levels of WBC and Neu(P＜0.05,P＜0.01).Additionally,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly increased blood CD8+cells(P＜0.05,P＜0.01),Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide+fungal infection low-,medium-,and high-dose groups compared with the cyclophosphamide control group(P＜0.05,P＜0.01).The lung tissues of the cyclophosphamide+fungal infection low-,medium-,and high-dose groups showed mycelial distribution and destruction of alveolar epithelium,increase of bronchial epithelial cup cells in the alveoli,and infiltration of inflammatory cells,and the degree of lesions was positively correlated with the modeling dose.Conclusions In this study,we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease.The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time,confirming that cellular immunity plays an important role in the pathogenesis of the disease.At the same time,Ig can also affect the development of invasive pulmonary aspergillosis,and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective:To establish an animal model of pneumonia for research on clinical prevention and treatment of bacterial pneumonia by infecting immunocompromised rats with drug-resistant Acinetobacter baumannii ( Ab) strains. Methods:Drug-resistant Ab strains were selected. Forty-eight SD rats were randomly divided into four groups: normal group, cyclophosphamide control group (intraperitoneal injection of 45 mg/kg cyclophosphamide), bacterial infection group (intratracheal instillation of 1.5×10 8 CFU Ab suspension), and bacterial infection+ immunosuppression group (intraperitoneal injection of 45 mg/kg cyclophosphamide+ intratracheal instillation of 1.5×10 8 CFU Ab suspension). Flow cytometry analysis was used to detect the proportion of CD4 + , CD8 + and NK cells in rat peripheral blood before as well as 3 d and 7 d after infection. A lung function meter was used to detect peak inspiratory flow (PIF), peak expiratory flow (PEF), tidal volume (Vt ) and forced expiratory volume in the second second/forced vital capacity (FEV 200/FVC) at 3 d and 7 d after modeling. ELISA was used to detect the levels of IL-6, TNF-α and IL-10 in the alveolar lavage fluid. HE staining was used to observe the morphology of rat lung tissues in each group. Bacterial loads in rat lung tissues were counted by bacterial culturing. Results:A decrease in voluntary activity was observed in rats in the cyclophosphamide control group, bacterial infection group and bacterial infection+ immunosuppression group after modeling. Lung rales could be heard in the bacterial infection group and bacterial infection+ immunosuppression group. Compared with the normal group, the cyclophosphamide control group showed decreased proportion of CD4 + and CD11b + NK cells and increased CD8 + cells in peripheral blood; the bacterial infection group showed decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in the alveolar lavage fluid, and higher bacterial load in lung tissues with mild widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). Compared with the cyclophosphamide control group and the bacterial infection group, the bacterial infection+ immunosuppression group showed a lower proportion of CD4 + cells and a higher proportion of CD8 + cells in rat peripheral blood, decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in alveolar lavage fluid, higher bacterial load in lung tissues, and aggravated widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). The proportion of CD11b + NK cells in peripheral blood of rats in the bacterial infection+ immunosuppression group was significantly lower than that in the bacterial infection group ( P<0.05, P<0.01). Conclusions:A bacterial pneumonia model was successfully constructed by infecting rats with Ab alone or in combination with cyclophosphamide immunosuppression. In the model constructed with Ab and cyclophosphamide immunosuppression, the rats had more severe pneumonia, which might be related to the reduced cellular immune function and the aggravated bacterial infection in rat lung tissues by cyclophosphamide.

OBJECTIVE: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. METHODS: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group ( RESULTS: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% CONCLUSIONS More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.
Autoantibodies ; Child ; Humans ; Myelin-Oligodendrocyte Glycoprotein ; Optic Neuritis ; Recurrence ; Retrospective Studies

Objective:To evaluate the optimized efficacy of erector spinae plane block (ESPB) with high volume of ropivacaine combined with general anesthesia for patients undergoing thoracoscopic pulmonary surgery.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg/m 2, scheduled for elective thoracoscopic pulmonary surgery, were divided into 2 groups ( n=30 each) using a random number table method: ESPB with high volume (40 ml) of 0.4% ropivacaine combined with general anesthesia group (E40 group) and ESPB with conventional volume (20 ml) of 0.4% ropivacaine combined with general anesthesia group (E20 group). Ultrasound-guided ESPB was performed on the operated side before general anesthesia induction in both groups.In E40 group, 0.4% ropivacaine 40 ml was injected.In E20 group, 0.4% ropivacaine 20 ml was injected.Total intravenous anesthesia was applied in both groups.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after the end of operation.The PCIA pump was set up with a 2 ml bolus dose (0.04 μg/kg), a 10 min lockout interval and background infusion at a rate of 0.05 μg·kg -1·h -1.The analgesia lasted for 48 h after operation, and the numeric rating scale (NRS) score was maintained ≤ 3.When NRS score ≥ 4, morphine 5 mg was intravenously injected for rescue analgesia.The onset time of block, intraoperative consumption of propofol and remifentanil, time to first pressing the analgesia pump, the first requirement for morphine and the ratio of patients using morphine within 48 h after surgery were recorded.The cumulative consumption of requirement for opioids (effective pressing dose of analgesic pump+ consumption of requirement for morphine) within 12, 24, 36 and 48 h after surgery and satisfaction with analgesia were recorded.The extubation time, length of ICU stay, the first postoperative off-bed time, the chest tube removal time and duration of stay in hospital were recorded.The incidence of intraoperative adverse events (hypertension and hypotension) and postoperative adverse events (dizziness, nausea and vomiting) were recorded. Results:Compared with E20 group, the onset time of block was significantly shortened, the cumulative consumption of requirement for opioids within 24, 36 and 48 h after surgery was decreased, the ratio of paitents using morphine within 48 h after surgery was decreased, time to first pressing the analgesia pump and the first requirement for morphine were prolonged, satisfaction with analgesia score was increased, and the first postoperative off-bed time and the chest tube removal time were shortened in group E40 ( P<0.05). There was no significant difference in the incidence of adverse events between the 2 groups ( P>0.05). Conclusion:Compared with ESPB with the conventional volume of ropivacaine combined with general anesthesia, ESPB with the high volume of ropivacaine combined with general anesthesia can reduce the postoperative consumption of opioids, and prolong the duration of effective analgesia, which are helpful for postoperative rapid recovery without increasing the development of adverse events in patients undergoing thoracoscopic pulmonary surgery.

Objective: To evaluate the oncologic and functional outcomes of laryngeal squamous cell carcinomas treated by supracricoid laryngectomy. Methods: The clinical data of 134 patients with laryngeal cancer who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) between July 2005 and April 2014 at Shandong Provincial ENT Hospital were retrospectively reviewed. Ninety-one patients including 31 cases of stage Ⅰ, 36 of stage Ⅱ, 18 of stage Ⅲ and 6 of stage Ⅳ underwent CHEP and 43 patients underwent CHP. Two patients received CHEP due to recurrence after open surgery and laser surgery. Three patients received CHP due to the recurrence of disease after open surgery and postradiotherapy persistence of disease. The Kaplan-Meier method was used to calculate the 3-year and 5-year survival rates. The Chi-square test was used to compare the survival rates between different surgical procedures. Results: All 91 patients who underwent CHEP had successful removals of PEG tubes, and 88 (96.7%) of them had tracheostomy tube decannulation. Among 43 patients with CHP, 42(97.6%) cases removal of PEG tubes(97.6%), including and 40(93.0%) cases with tracheostomy tube decannulation. There was one patient with local recurrence in all cases. In CHEP group, 3-year local control rate was 98.2%; 3-year and 5-year overall survival rate were 94.5% and 93.9%, respectively. In CHP group, 3-year local control rate was 97.6%; 3-year and 5-year overall survival rates were 86.0% and 83.3%, respectively. Pharyngeal fistula appeared in 2 cases of CHEP group and 4 cases of CHP group, and all of them were cured by conservative treatment. Conclusion Supracricoid laryngectomy shows excellent oncologic and functional results for treatment of laryngeal cancer while maintaining laryngeal functions, especially in terms of local control rate and tracheostomy tube decannulation.

Objective To investigate the cognition on patient safety culture of resident doctors re-ceiving standardized training in two affiliated hospitals, analyze the effectiveness of publicity and education in patient safety culture and put forward suggestions for improvements. Methods A total of 913 resident doctors receiving standardized training in the two affiliated hospitals during 2014 to 2016 were enrolled. Their cognition on patient safety culture were investigated using questionnaire surveys from May to October in 2016, and the main factors influencing the cognition on patient safety culture in standardized training were put forward through expert interviews. All statistical analyses were performed with SPSS 17.0 software with Chi-square test. Results The response rate of the questionnaire was 87.62％ (800/913). Three factors were involved in the patient safety system, including the hospital security objectives, security feedbackchannels, and adverse event warning mechanism. The cognitiive level of A hospital (68.96％, 62.52％, 62.81％) was higher than that of B hospital (52.99％, 46.16％, 47.01％), and the difference was statistically significant (P<0.05). The publicity of pre-service training, education in the department, and encouragement from teachers (82.13％, 84.48％, 78.33％) was better in A hospital than in B hospital (68.38％, 71.8％, 62.39％) (P<0.05). The reporting rate of adverse events in A hospital was higher than that in B hospital (P <0.05). Conclusion It is necessary for hospitals to further intensify the publicity and education on patient safety culture. We can improve students' cognition on patient safety culture to reduce medical errors by cre-ating a favorable atmosphere, establishing standardized admission education and training system, improving teachers' teaching ability, and strengthening the training for clinical skills.