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 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.

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:To investigate the value of fetal heart quantification (fetal HQ) in assessing ventricular function of fetuses with small-for-gestational-age (SGA) and fetal growth restriction (FGR).Methods:A total of 152 singleton pregnancies with estimated fetal weight (EFW) or abdominal circumference less than the 10th percentile in the Third Affiliated Hospital of Zhengzhou University were prospectively selected from August 2022 to September 2023, where fetal EFW or abdominal circumference were in the 3rd to 9th percentile with normal Doppler findings were classified as the SGA group ( n=79), and the rest as the FGR group ( n=73). In the same period, 161 cases of normal single fetuses were matched as the control group.Based on the gestational week in which FGR occurred, the FGR group were categorized into the early-onset group (<32 weeks, n=46) and the late-onset group (≥32 weeks, n=27), and fetuses in the FGR group with absent end-diastolic velocity of the umbilical artery were defined as severe FGR ( n=11), and the rest as mild FGR ( n=62). Fetal ventricular fractional area change (FAC), global longitudinal strain (GLS), longitudinal fractional shortening (LFS) and 24-segment fractional shortening (FS) were obtained by fetal HQ. The cardiac systolic function between groups were compared, the correlations between each parameter and gestational week were analyzed, the inter-observer and intra-observer repeatability tests were performed. Results:Compared with the control group, ventricular FAC, LFS, and GLS were lower in the SGA and the FGR group, right ventricular FS of segments 9-24 were reduced in the SGA group, and left ventricular FS of segments 10-19, 21-24 and right ventricular FS of segments 18-24 were reduced in the FGR group, the differences were statistically significant (all P<0.05). Left ventricular GLS, LFS and right ventricular FAC, GLS, LFS, FS of segments 1-14 were lower in the severe FGR group than in the mild FGR group, the differences were statistically significant (all P<0.05). The values of left ventricular GLS and LFS were higher in the early-onset FGR group than in the late-onset FGR group, the differences were statistically significant (all P<0.05). The ROC showed that the ventricular systolic function parameters predicted adverse perinatal outcomes with an AUC>0.6 (all P<0.05). Left ventricular GLS and right ventricular partial-segments FS were no correlations with gestational week in the FGR group (-0.3< rs<0.3, all P<0.05). There was no correlation between the parameters and gestational week in the SGA group (all P>0.05). The inter-observer and intra-observer intraclass correlation coefficients (ICC) were >0.75, with good reproducibility. Conclusions:Fetal HQ can quantitatively assess the changes of ventricular function in SGA and FGR fetuses, and the ventricular overall, longitudinal and localized contractile function in SGA and FGR fetuses are reduced, and abnormal ventricular systolic function is associated with adverse perinatal outcomes.

Objective:To assess the effect of mild intraventricular hemorrhage（IVH）on the early motor development of infants at high risk of brain injury,and to guide the intervention according to its characteristics.Methods:A retrospective cohort study was conducted to select neonates discharged from the Neonatal Unit of Xi 'an Children 's Hospital from February 1，2022 to March 31，2023，with one or more high-risk factors of brain injury.The patients were assigned to low-grade IVH group and no IVH group according to ultrasound diagnosis.The research subjects exclucled other brain injury diseases besides mild IVH.Motor development was assessed using test of infant motor performance(TIMP)，reflecting performance in head control，auditory and visual responses，defensive movements，trunk movements，limb movements，and more.Both groups completed TIMP assessment between discharge and 16 weeks of the corrected age(CA).The differences of TIMP scores between two groups were compared . Results:A total of 329 neonates at high risk for brain injury were recruited，including 98 cases with grade Ⅰ-Ⅱ IVH（low-grade IVH group）diagnosed through brain ultrasonography and 231 controls(no IVH group).The Z scores of TIMP in the low-grade IVH group were lower than that in no IVH group（-0.25 ±0.87 vs.0.03 ±0.71， P=0.015）.The risk factors of brain injury were matched for further comparison.At CA2-5 weeks，the scores in low-grade IVH group of TIMP total scores（74.10 ±12.28 vs.84.24 ±7.71），observation items（10.57 ±1.47 vs.11.24 ±1.29），elicitation（63.17 ±12.13 vs.73.00 ±7.36），sitting（9.14 ±2.90 vs.11.65 ±3.26），supine（22.07 ±4.73 vs.24.79 ±3.55），prone position（10.35 ±3.74 vs.12.82 ±3.15）and lateral position（4.00 ±2.85 vs.5.48 ±2.13）were significantly lower than those in no IVH group（ P<0.05）.At CA6-9 weeks，the scores in low-grade IVH group of sitting position（10.44 ±4.01 vs.12.96 ±3.02），supine position（24.04 ±4.60 vs.26.83 ±3.53），lateral position（4.83 ±2.53 vs.6.25 ±2.6）were significantly lower than those in no IVH group（ P<0.05）.At CA12-15 weeks，the low-grade IVH group showed significant differences in TIMP total score（104.00 ±12.98 vs.114.10 ±13.16），elicitation（92.00 ±12.64 vs.102.00 ±13.10），sitting（17.00 ±3.50 vs.19.13 ±3.55）and lateral position（7.35 ±2.14 vs.9.00 ±2.37）compared with those from no IVH group（ P<0.05）. Conclusion:Mild intraventricular hemorrhage affected the early motor development of high-risk infants with brain injury，mainly manifested as a lag in the ability of head control at CA2-5 weeks，and the trend continued until CA12-15 weeks.Early monitoring of motor ability and intervention of head control ability should be carried out in high-risk children with mild intraventricular hemorrhage.

The structure and biological function of CXCL12/CXCR4 are the basis of physiological and pathological function.Combination of HIV-1 envelope protein and CXCR4 will promote the entry of virus into host cells.CXCL12 can reduce the number of CXCR4 through rapid endocytosis and inhibit the replication and transmission of HIV.The interaction of CXCL12/CXCR4 axis with in-flammation and autophagy plays an important role in HIV infection.Previous research has found that gene expression profiles of differ-ent TCM syndromes of acquired immunedeficiency syndrome(AIDS)are different.CXCR4 has different expression in AIDS,lung and spleen qi deficiency syndrome,Qi Yin deficiency syndrome and dampness heat syndrome,which is related to chemokine signaling pathway;the differential gene CXCR4 in peripheral blood of AIDS patients with lung and spleen qi deficiency syndrome is related to au-tophagy process.According to the intervention of Yiaikang Capsule,CXCR4 expression is increased,indicating that Yiaikang Capsule can regulate the expression of autophagy related genes.Research on the role of CXCL12/CXCR4 in TCM syndromes of AIDS is condu-cive to better play the therapeutic advantages of TCM and provide a new direction for gene targeted therapy.

Objective:To systematically evaluate the qualitative research on experience of fear of falling in the elderly, so as to provide theoretical basis for nursing practice.Methods:Qualitative researches on the fear of falling among the elderly were systematically searched in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc. The search period was from database establishment to November 5, 2023. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center, and the results were integrated using the Meta-synthesis.Results:A total of 13 articles were included, 44 themes were extracted, categorized into 12 categories, and refined into four integrated results, namely perception of fear of falling, influencing factors of fear of falling, coping strategies in attitude and behavior, and multidimensional needs for rehabilitation nursing.Conclusions:Medical and nursing staff should pay attention to and understand the fear of falling among the elderly, evaluate their fear of falling from multiple dimensions and dynamically, provide personalized guidance based on coping behaviors, create support systems to alleviate their fear of falling and meet their multidimensional needs, so as to improve their quality of life.