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:To investigate the characteristics of early motor development in small for gestational age (SGA) infants at high risk of brain injury.Methods:This study retrospectively enrolled a total of 81 SGA infants and appropriate for gestational age (AGA) infants who were at high risk of brain injury and attended outpatient follow-up visits in Xi'an Children's Hospital from February to October 2022. Seventeen SGA infants (SGA group) and 24 AGA infants (AGA group) were assessed for motor development using the Test of Infant Motor Performance (TIMP) at 2-5 weeks of corrected age (CA) and 20 SGA infants (SGA group) and 20 AGA infants (AGA group) were assessed at 14-17 weeks of CA. Independent samples t-test, rank-sum test, and Chi-square test were used to compare the demographic characteristics, high-risk factors of brain injury, and TIMP scores between the two groups. Results:At 2-5 weeks and 14-17 weeks of CA, the birth weights of SGA group were both less than those of AGA group [(1 817.1±440.3) vs. (2 630.0±560.9) g, t=－4.98; (1 752.0±434.4) vs. (2 226.3±699.8) g, t=－2.58; both P<0.05], but there were no significant differences in gestational age at birth or high-risk factors of brain injury between the two groups (all P>0.05). (1) At 2-5 weeks of CA: SGA group had lower total TIMP score [(71.6±13.7) vs. (80.5±11.5) scores, t=－2.26, P=0.029], elicited item score [61.0 scores (41.0-85.0 scores) vs. 69.1 scores (49.0-96.0 scores), Z=－2.15, P=0.037], sitting position score [8.8 scores (3.0-19.0 scores) vs. 11.2 scores (5.0-22.0 scores), Z=－2.07, P=0.038], and prone position score [(9.8±3.1) vs. (12.3±3.1) scores, t=－2.19, P=0.034] when compared with AGA group. (2) At 14-17 weeks of CA: The standing position score of the SGA group was lower than that of the AGA group [6.5 scores (4.0-11.0 scores) vs. 7.7 scores (2.0-11.0 scores), Z=－2.05, P=0.040], but no statistical difference was observed in the total TIMP score or the scores of sitting, supine, prone, turning, and lateral positions between the two groups (all P>0.05). Conclusion:Early motor performance of SGA infants is inferior to AGA infants before five months of age, which is embodied in the poor head control at 2-5 weeks of CA that further affects the stability of standing posture in them at 14-17 weeks of CA.

Objective: To investigate the impact of tumor necrosis factor ligand superfamily member 13(TNFSF13) derived from M2 macrophages on temozolomide(TMZ) resistanceviaregulating interferon regulatory factor 8(IRF8) in glioblastoma(GBM) cells. Methods: Immunohistochemistry(IHC) was used to detect the expression of TNFSF13 in normal brain tissues and GBM tissues. ELISA was used to measure the expression of TNFSF13 in the conditioned media(CM) of M0-type macrophages and M2-type macrophages. M0-CM and M2-CM were used to culture U251 sensitive(U251/S) and resistant(U251/R) cells. The TMZ treatment group was also treated with 800 μmol/L TMZ. The U251/R cells were divided into the following groups: con group, M2vector-CM group, M2vector-CM+TMZ group, M2TNFSF13-CM group, M2TNFSF13-CM+TMZ group, si-IRF8 group, and si-IRF8+M2TNFSF13-CM group. CCK-8 assay was used to detect cell viability and calculate the IC50value. Transwell assay was used to detect cell invasion. Flow cytometry was used to detect apoptosis. Western blot was used to detect the expression of IRF8. Nude mouse xenograft models were constructed and the nude mice were divided into the following groups: U251+M2si-NCgroup, U251+M2si-TNFSF13group, U251+M2si-NC+TMZ group, U251+M2si-TNFSF13+TMZ group. The tumor volume and mass of each group were measured, and IHC was used to detect the expression of TNFSF13 and CD206 in tumor tissues of each group. Results: Compared with adjacent tissues and M0-CM, the expression of TNFSF13 was up-regulated in cancer tissues and M2-CM. Compared with the M0-CM group, the IC50value of TMZ and the number of cell invasions in U251/S and U251/R cells in the M2-CM group significantly increased(allP<0.05). Overexpression of TNFSF13 in M2 macrophages could promote the IC50value of TMZ in U251/R cells, promote cell invasion, and inhibit cell apoptosis(allP<0.05). Overexpression of TNFSF13 promoted the expression of IRF8, and knocking down IRF8 could attenuate the TMZ resistance of U251/R mediated by overexpression of TNFSF13.In vivostudies showed that knocking down TNFSF13 alone or combined with TMZ treatment significantly inhibited tumor growth and reduced the expression of TNFSF13 and CD206. Conclusion TNFSF13 derived from M2 macrophages promotes TMZ resistance in GBM cells by activating IRF8.

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.

Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury(CCI).Methods Fifty-six SD rats were divided randomly into eight groups:normal group,sham group,model 1 group,model 2 group,tuina 1 group,tuina 2 group,tuina 1+transient receptor potential vanilloid-1(TRPV1)antagonist group,and tuina 2+transient receptor potential ankyrin 1(TRPA1)antagonist group.The model,tuina,and tuina+antagonist groups were established with minor CCI models.The tuina and tuina+antagonist groups received the three-method three-point intervention(point method,dial method,kneading method,Yinmen point,Chengshan point,Yanglingquan point)7 days after modeling.The model and sham groups were subjected to grasping restraint,and the normal group received no intervention.After the respective interventions,each group was tested for changes in mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)to detect different types of pain.The nitric oxide(NO)content of the dorsal root ganglion(DRG)was determined by the nitrate reductase method,and changes in protein and gene expression levels of components of the TRPV1/TRPA1-NO-cGMP-protein kinase G(PKG)signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay,Western blot,and qPCR.Results Compared with the model group,MWT and TWL were prolonged in the tuina 1 and tuina 2 groups.Expression levels of TRPV1,TRPA1,NO,soluble guanylate cyclase-β,cGMP,and PKG1 in the DRG were significantly decreased in the tuina 1,tuina 2,tuina 1+TRPV1 antagonist,and tuina 2+TRPA1 antagonist groups.Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention.Tuina can exert immediate and continuous analgesic effects via the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

Objective:To investigate the effect of gracilis flap in repair of radiation-induced vesicovaginal fistula.Methods:The data of 18 patients with radiation-induced vesicovaginal fistula treated in the Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2021 to August 2022 were retrospectively reviewed. Their age was (57.3±10.4) years. All patients underwent radical surgery for cervical cancer, and received (24.6±2.8)(range from 20 to 30)times of radiotherapy after surger. The median time between the end of radiotherapy and the onset of vesicovaginal fistula was 14.0(7.8, 18.2)months. The median duration of fistula urine was 12.0(9.8, 18.0)months. All patients were required to use median 19.5(15.8, 27.5) pads per day before surgery. The life quality score(QOL)of 18 cases was median 5.0(5.0, 6.0) points. Three cases had performed laparoscopic vesicovaginal fistula repair, two cases had underwent transvaginal vesicovaginal fistula repair, one case had underwent transvaginal and laparoscopic vesicovaginal fistula repair successively, and the remaining 12 cases were new vesicovaginal fistulas. Two cases were combined with rectovaginal fistulas. All patients underwent the repair of vesicovaginal fistula with gracilis flap interposition in prone and folded knife position, by transvaginal route, the vesicovaginal fistula was mobilized and the two layers were closed, and the vascular pedicle gracilis flap of left inner leg was romoved under the skin tunnel to repair the vesicovaginal fistula. Meanwhile, two cases combined rectovaginal fistulas were repaired and closed the rectovaginal fistulas. The urinary catheters were removed at 3 weeks after the operation and urination was recorded.Results:All patients underwent smooth surgery in (96.6±13.2) minutes. The median follow-up was 13.0(9.8, 20.2)(range from 6 to 24)months. The median number of urine pads used per day in 18 patients was 2.0(1.0, 11.8), and significantly reduced ( P<0.01).QOL score was median 1.0(0, 4.2) point and significantly reduced ( P<0.01).Successful outcome was achieved in 12 patients with no leakage of urine in the vagina. Two cases developed urinary incontinence and required conservative treatment, but the curative effect was poor. Two cases still had vaginal urine leakage performed vesicovaginal fistula repair again. One case was successfully repaired without significant urine leakage.The other case still had significant urine leakage and the QOL score was 3 points. She refused further treatment for self-satisfied. Two cases still had vesicovaginal fistula and rectovaginal fistula after the surgery, and refused further surgery. Conclusions:Repair with gracilis flap interposition is a surgical method with few complications and reliable surgical effect for patients with radiation-induced vesicovaginal fistula.

Objective To summarize the occurrence of complications in renal graft biopsy,and to analyze the indications for puncture and types of pathological diagnosis.Methods The data of 703 samples of ultrasound-guided renal graft biopsy from 644 kidney transplant recipients from January 1,2017,to December 31,2022 was retrospectively analyzed.The puncture qualification rate,complications,indicative biopsy indications and pathological diagnosis types were analyzed.The application of surveillance biopsy and pathological diagnosis were also analyzed.Results The qualification rate of renal tissue puncture biopsy was 99.9％,and the complications of puncture bleeding included one sample of perinephric hematoma and one sample of hematuria.Increased serum creatinine(76.8％)and proteinuria(13.8％)were the main indications for puncture,and 48 samples(6.8％)were surveillance biopsy for the assessment of therapeutic effects.A total of 399 samples of pathological diagnosis of rejection,including 293 samples of cellular rejection reaction,60 samples of antibody rejection reaction,and 46 samples of mixed rejection reaction.One hundred and ninety-five samples of recurrence or new-onset kidney disease,mainly including 144 samples of IgA nephropathy and 42 samples of focal segmental glomerulosclerosis.Fifty-seven samples of infection related kidney disease,including 56 samples of BK virus-associated nephropathy(BKVAN).Thirty-one samples of calcineurin inhibitor(CN1)nephrotoxicity injury,including 15 samples of acute CNI nephrotoxicity injury and 16 samples of chronic CNI nephrotoxicity injury.Forty-five samples for other diagnoses.Conclusions The success rate and safety of renal graft biopsy are high,and at present,cellular rejection reaction is still the main pathological diagnosis of indicative biopsy for renal graft.