OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Objective: To investigate the emotional and behavioral problems among preschool children and the correlations with maternal parenting competence and family rearing environment, so as to provide a scientific basis and practical guidance for the physical and mental health development of preschool children. Methods: In June 2025, 660 preschool children aged 3-6 years old were selected from 10 kindergartens in Hefei, Anqing, and Tongling in Anhui Province by using a stratified cluster random sampling method. A questionnaire survey was conducted among all parents of preschool children using the Parent version of the Strengths and Difficulties Questionnaire, the Child Family Rearing Environment Scale, and the Chinese version of the Parenting Sense of Competence Scale. Pearson correlation analysis and multiple linear regression analysis were used to analyze the related factors of emotional and behavioral problems among preschool children. SPSS macro program Process 4.1 and Bootstrap method were used to test the mediating effect of family parenting environment between emotional and behavioral problems among preschool children and maternal parenting competence. Results: The detection rate of emotional and behavioral problems among preschool children was 20.15%. The total scores of family rearing environment and maternal parenting competence were negatively correlated with emotional and behavioral problems among preschool children ( r =-0.45,-0.79), and the total score of family rearing environment was positively correlated with the total score of maternal parenting competence ( r =0.43) (all P <0.01). Multiple linear regression showed that, after controlling whether being only child, parents educational level, registered residence location and other variables, family rearing environment, self efficacy and satisfaction were all negative predictors of emotional and behavioral problems among preschool children ( B =-0.07, -0.42, -0.42, all P <0.01). The mediation effect results showed that maternal parenting competence could positively predict the family rearing environment ( B =0.75), while maternal parenting competence and family rearing environment could both negatively predict emotional and behavioral problems among preschool children ( B =-0.49, -0.06 ) (all P <0.05). The Bootstrap sampling method test results showed that the effect value of the indirect effect of maternal parenting competence on emotional and behavioral problems through the family rearing environment was -0.04, and the effect proportion was 8.21 %. Conclusion Preschool children with a better family rearing environment and stronger maternal parenting competence are less likely to have emotional and behavioral problems, among which the family rearing environment has a mediating effect.

This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

BACKGROUND:The correlation between sacroiliac joint degeneration and lumbar degenerative disease has been analyzed in the literature in the past,but the clinical efficacy and imaging changes after interbody fusion with sacroiliac joint ankylosis in patients with lumbar degenerative disease have not been reported in the literature.OBJECTIVE:To investigate the effect of sacroiliac joint ankylosis on the clinical efficacy and lumbar sagittal regression after L5/S1 single-segment transforminal lumbar interbody fusion in patients with lumbar degenerative disease.METHODS:Thirty-seven patients who underwent L5/S1 segmental transforminal lumbar interbody fusion for lumbar degenerative disease with sacroiliac joint ankylosis between June 2020 and September 2023 in Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed as group A.Thirty-seven patients with lumbar degenerative disease without sacroiliac joint ankylosis who were matched for general information during the same period were selected as controls in group B.Clinical efficacy was assessed using the Oswestry disability index and visual analog scale for lumbar and lower limb pain.The lumbar sagittal parameters included lumbar anterior convexity angle,lumbar partial anterior convexity angle,and lower lumbar anterior convexity angle.Pfirrmann grading was used to assess the degree of preoperative disc degeneration,postoperative endplate damage and screw loosening,and to record the fusion of the operated segments at the final postoperative follow-up visit.RESULTS AND CONCLUSION:(1)There was no statistically significant difference in age,body mass index,bone mineral density,operation time,intraoperative bleeding,preoperative primary diagnosis and postoperative follow-up time between the two groups(P＞0.05).(2)The preoperative Pfirrmann grading of lumbar disc degeneration in group A patients(3.4±0.9)was significantly higher than that of group B(3.1±0.6),and the difference was statistically significant(t=2.059,P=0.044).(3)All patients showed significant improvement in postoperative lumbar sagittal parameters compared with preoperative ones(all P＜0.05).During the follow-up period,there was a loss of correction in patients in group A.There was no statistical difference in the lumbar anterior convexity angle,lower lumbar anterior convexity angle,and local anterior convexity angle at the last follow-up compared with the preoperative period(P＞0.05).The lumbar anterior convexity angle,lower lumbar anterior convexity angle,and local anterior convexity angle in group A were significantly lower than those of group B patients at both preoperative and final follow-up,and the differences were statistically significant(all P＜0.05).(4)There was no statistically significant difference in postoperative endplate injury between the two groups(x2=0.181,P=0.670),and screw loosening was significantly higher in group A than in group B,with a statistically significant difference(x2=4.163,P=0.041).(5)At the last follow-up,the incidence of grade 3 fusion and grade 4 fusion was significantly higher in group A than in group B.The difference in the distribution of fusion grades between the two groups was statistically significant(x2=7.848,P=0.031).(6)The Oswestry disability index and lower limb visual analog scale scores at the last follow-up of both groups were significantly improved compared with the preoperative period(P＜0.05).The visual analog scale scores for low back pain at 3 months after surgery and at the last follow-up of group A were significantly higher than those of group B(t=2.010,P=0.048;t=2.133,P=0.036).(7)It is concluded that regardless of whether it is accompanied by sacroiliac joint ankylosis or not,lumbar degenerative disease patients who undergo interbody fusion with foramen magnum can achieve good therapeutic effects,but lumbar degenerative disease patients with sacroiliac joint ankylosis who undergo interbody fusion with foramen magnum at the L5/S1 segments have a poorer improvement of low back pain than patients without sacroiliac joint ankylosis after the operation.Furthermore,patients with preoperative sacroiliac ankylosis who underwent L5/S1 segmental transforminal lumbar interbody fusion had a low fusion rate and were prone to loss of correction of the lumbar sagittal position.

BACKGROUND:The correlation between sacroiliac joint degeneration and lumbar degenerative disease has been analyzed in the literature in the past,but the clinical efficacy and imaging changes after interbody fusion with sacroiliac joint ankylosis in patients with lumbar degenerative disease have not been reported in the literature.OBJECTIVE:To investigate the effect of sacroiliac joint ankylosis on the clinical efficacy and lumbar sagittal regression after L5/S1 single-segment transforminal lumbar interbody fusion in patients with lumbar degenerative disease.METHODS:Thirty-seven patients who underwent L5/S1 segmental transforminal lumbar interbody fusion for lumbar degenerative disease with sacroiliac joint ankylosis between June 2020 and September 2023 in Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed as group A.Thirty-seven patients with lumbar degenerative disease without sacroiliac joint ankylosis who were matched for general information during the same period were selected as controls in group B.Clinical efficacy was assessed using the Oswestry disability index and visual analog scale for lumbar and lower limb pain.The lumbar sagittal parameters included lumbar anterior convexity angle,lumbar partial anterior convexity angle,and lower lumbar anterior convexity angle.Pfirrmann grading was used to assess the degree of preoperative disc degeneration,postoperative endplate damage and screw loosening,and to record the fusion of the operated segments at the final postoperative follow-up visit.RESULTS AND CONCLUSION:(1)There was no statistically significant difference in age,body mass index,bone mineral density,operation time,intraoperative bleeding,preoperative primary diagnosis and postoperative follow-up time between the two groups(P＞0.05).(2)The preoperative Pfirrmann grading of lumbar disc degeneration in group A patients(3.4±0.9)was significantly higher than that of group B(3.1±0.6),and the difference was statistically significant(t=2.059,P=0.044).(3)All patients showed significant improvement in postoperative lumbar sagittal parameters compared with preoperative ones(all P＜0.05).During the follow-up period,there was a loss of correction in patients in group A.There was no statistical difference in the lumbar anterior convexity angle,lower lumbar anterior convexity angle,and local anterior convexity angle at the last follow-up compared with the preoperative period(P＞0.05).The lumbar anterior convexity angle,lower lumbar anterior convexity angle,and local anterior convexity angle in group A were significantly lower than those of group B patients at both preoperative and final follow-up,and the differences were statistically significant(all P＜0.05).(4)There was no statistically significant difference in postoperative endplate injury between the two groups(x2=0.181,P=0.670),and screw loosening was significantly higher in group A than in group B,with a statistically significant difference(x2=4.163,P=0.041).(5)At the last follow-up,the incidence of grade 3 fusion and grade 4 fusion was significantly higher in group A than in group B.The difference in the distribution of fusion grades between the two groups was statistically significant(x2=7.848,P=0.031).(6)The Oswestry disability index and lower limb visual analog scale scores at the last follow-up of both groups were significantly improved compared with the preoperative period(P＜0.05).The visual analog scale scores for low back pain at 3 months after surgery and at the last follow-up of group A were significantly higher than those of group B(t=2.010,P=0.048;t=2.133,P=0.036).(7)It is concluded that regardless of whether it is accompanied by sacroiliac joint ankylosis or not,lumbar degenerative disease patients who undergo interbody fusion with foramen magnum can achieve good therapeutic effects,but lumbar degenerative disease patients with sacroiliac joint ankylosis who undergo interbody fusion with foramen magnum at the L5/S1 segments have a poorer improvement of low back pain than patients without sacroiliac joint ankylosis after the operation.Furthermore,patients with preoperative sacroiliac ankylosis who underwent L5/S1 segmental transforminal lumbar interbody fusion had a low fusion rate and were prone to loss of correction of the lumbar sagittal position.

Background: Surgeons face challenges in selecting cost-effective and biologically active agents for rotator cuff healing, given the numerous commercial products available, such as polydeoxyribonucleotide (PDRN) and atelocollagen (ATC). However, the precise efficacy of PDRN and ATC in rotator cuff healing remains debatable, and there is currently a lack of studies directly comparing the effects of the 2 agents on repaired cuff tendons. Therefore, the purpose of this study was to compare the efficacy of PDRN and ATC on bone-to-tendon interface (BTI) healing using a chronic rotator cuff tear (RCT) model in rabbits. Methods: Forty-eight rabbits were randomly divided into 3 groups. To create chronic RCT models, transected tendons were left untreated for 6 weeks, and then were repaired in a transosseous manner with PDRN and ATC injection into the repair site according to group allocation (group A: saline, group B: PDRN, group C: ATC; n = 16 per group). Genetic and immunofluorescence analyses were performed at 4 weeks after surgery. Furthermore, genetic, histologic, and biomechanical analyses were performed at 12 weeks after surgery. Results: At 4 weeks after surgery, ATC-injected shoulders showed the highest mRNA expression levels of collagen type I alpha 1 and aggrecan compared to the other 2 groups (p < 0.001 and p = 0.002, respectively). Meanwhile, there was more preliminary fibrocartilaginous matrix formation in the ATC-injected group. At 12 weeks after surgery, ATC-injected shoulders demonstrated better collagen fiber continuity and orientation, denser collagen fibers, a more mature bone-to-tendon junction, and greater fibrocartilage layer formation compared to the other 2 groups (all p < 0.001). Furthermore, ATC-injected shoulders also demonstrated a significantly higher load-to-failure value (40.4 ± 4.5 N/kg) than the remaining groups (group A, 26.7 ± 3.0 N/kg; group B, 32.8 ± 4.2 N/kg; p < 0.001). Conclusions ATC demonstrated superior efficacy in promoting BTI healing following surgical repair in a chronic RCT model of rabbits.

OBJECTIVE: To investigate the effect of miR-483-5p on hepatocellular carcinoma (HCC) cells proliferation and stemness, as well as the attenuating effect of Pien Tze Huang (PZH). METHODS: Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells (HCSCs) were identified by a miRNA microarray assay. miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness. HepG2 cells and HCSCs were treated with PZH (0, 0.25, 0.50 and 0.75 mg/mL) to explore the effects of PZH on the proliferation and stemness, both in non-induced state and the state induced by miR-483-5p mimics. RESULTS: miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells (P<0.05). PZH not only significantly inhibited proliferation in HepG2 cells, but also significantly suppressed the cell proliferation and self-renewal of HCSCs (P<0.05). The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH. CONCLUSIONS miR-483-5p promotes proliferation and enhances stemness of HepG2 cells, which were attenuated by PZH, demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
Humans ; MicroRNAs/metabolism* ; Cell Proliferation/drug effects* ; Liver Neoplasms/drug therapy* ; Carcinoma, Hepatocellular/drug therapy* ; Hep G2 Cells ; Neoplastic Stem Cells/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gene Expression Regulation, Neoplastic/drug effects*

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.