Objective:To explore the clinical effect of precise intraepiphyseal wedge osteotomy for the treatment of congenital hypertrophic epiphysis of the distal phalanx of the thumbs in children.Methods:A retrospective analysis was conducted on the data of children with congenital hypertrophic epiphysis deformity of the distal phalanx of the thumb treated by precisely located intraepiphyseal wedge osteotomy in Dongguan Integrated Traditional Chinese and Western Medicine Hospital from January 2020 to January 2023. Preoperative X-ray films all showed asymmetric thickening of the secondary ossification centers, presenting as triangular, elliptical, unequal trapezoidal, and bipartite epiphyseal fusion shapes respectively. During the operation, precise localization was performed, and wedge osteotomy was conducted at 1.5 mm from the articular surface. The osteotomy angle and volume were adjusted according to the morphology of the hypertrophic epiphysis and the comprehensive condition of the distal and proximal phalanges, with axial over-correction of approximately 10° for fixation. Six months after surgery, the ulnar deviation angle of the distal phalanx with the interphalangeal joint of the thumb, the maximum passive flexion angle, and the thickness of the distal epiphyseal plate on X-ray were followed up. Statistical analysis was conducted using paired t-tests before and after surgery, and P<0.05 was considered statistically significant. Results:A total of 32 children with 34 thumbs were included, aged from 6 months to 8 years old, with an average age of 2.1 years old. There were 27 thumbs accompanied by radial polydactyly, the main and accessory thumbs were clear, and the epiphysis of the distal phalanx of the main thumb was thickened. The lateral deviation angle of the distal phalanx of the thumb before surgery was (35.6±13.2)° (15.0°-67.0°), the maximum passive flexion range was (62.8±7.7)° (38.0°-80.0°), and the maximum thickness of the distal phalanx epiphysis in the X-ray was (3.7±0.9) mm (2.3-5.9 mm). All surgeries of all children were successfully completed, the wounds healed well without redness, swelling or infection. Patients were discharged smoothly. The average follow-up time after surgery was 13 month (rang from 6-22 months), with an average deviation angle of (7.6±5.6)° (1.8°-13.4°) in the distal phalanx with the interphalangeal joint, compared with before surgery, the difference was statistically significant ( t=10.36, P=0.012). Five thumbs had residual ulnar deviation after surgery, with an average deviation of (16.6±2.3)° (12.0°-20.0°), two cases had corrected positive radial deviation (15°, 18°), while the other cases had no significant ulnar deviation in the distal phalanx of the thumb. The average maximum angle of passive flexion of the distal thumb after surgery was (62.9±7.5)° (35.0°-80.0°), compared with before surgery, the difference was not statistically significant ( t=0.16, P=0.359). The average maximum thickness of the distal epiphyses on postoperative X-rays was (1.9±0.5) mm (1.2-3.1 mm), compared with before surgery, the difference was statistically significant ( t=17.04, P=0.012). The epiphyses were flat and round, and the growth lines were normal. Conclusion:Using precise intraepiphyseal wedge osteotomy, combined with postoperative fixation with mild overcorrection for the treatment of congenital hypertrophic epiphysis at distal phalanx of the thumb in children, can achieve satisfactory correction of deviation, significantly shorten and improve the morphology of the epiphysis without affecting the growth plate, and cause minimal impact on joint flexion activity.

Objective To discuss the regulatory mechanism of nucleotide-binding oligomerzation domain 2(NOD2)/receptor interacting protein 2(RIP2)signaling pathway on inflammatory activation of macrophages in intestinal mucosa and provide experimental evidence for intestinal mucosal inflammation caused by bacterial products.Methods Using the THP-1 monocyte cell line,macrophages were stimulated with muramyl dipeptide(MDP)at varying concentrations and durations.mRNA and protein expression levels of NOD2 and RIP2 were detected.The secretion levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in the cell culture supernatant were measured.The most effective siRNA targeting RIP2 and optimal transfection concentration were screened,and the impact of RIP2 gene silencing on MDP-induced inflammatory activation of macrophages was observed.Results After silencing the RIP2 gene,MDP induced a significant decrease in TNF-α and IL-1βsecretion in macrophages,but the changes in cell phenotype were not significantly affected.Conclusion This study revealed the important role of NOD2/RIP2 signaling pathway in inflammatory activation of macrophages,and it is possible to effectively inhibit inflammatory activation of macrophages by interfering with this signaling pathway.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Objective:To analyze the relationship between cuprotosis-realted gene DLD expression in pan-cancer and progno-sis,tumor microenvironment and tumor immune infiltration by bioinformatics methods combined with multiple databases.Methods:TCGA,GTEx,TISDB,GEO,UCSC,TARGET,TIMER2.0,GEPIA2,SangerBox,PrognoScan and related R software packages were used to analyze the difference of DLD expression between human cancer and adjacent normal tissues,inestigate relationship between prognosis,explore expression of DLD in different immune subtypes and molecular subtypes of human cancer,analyze correlation between DLD expression and tumor immune infiltration and tumor microenvironment,detecet relationship between DLD expression and 60 immune checkpoint genes.Results:There were differences in expression of DLD in different tumor tissues;low DLD expression in 6 tumors and high DLD expression in 3 tumors were significantly associated with better prognosis;15 tumor immune subtypes,11 molecular subtypes of tumors were significantly correlated with DLD expression;DLD expression was significantly correlated with immune infiltration in 37 cancer types;DLD expression was significantly associated with immune infiltration in 23 tumor stroma scores,26 tumor immune scores and 25 tumor ESTIMATE scores;60 immune checkpoint genes in 39 tumors were significantly associated with DLD expression.Conclusion:Expression of DLD in pan-cancer is related to tumor prognosis and immune invasion,DLD may be a potential predictor of prognosis in tumors,and may be an immunomodulator of tumors.

Objective To discuss the regulatory mechanism of nucleotide-binding oligomerzation domain 2(NOD2)/receptor interacting protein 2(RIP2)signaling pathway on inflammatory activation of macrophages in intestinal mucosa and provide experimental evidence for intestinal mucosal inflammation caused by bacterial products.Methods Using the THP-1 monocyte cell line,macrophages were stimulated with muramyl dipeptide(MDP)at varying concentrations and durations.mRNA and protein expression levels of NOD2 and RIP2 were detected.The secretion levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in the cell culture supernatant were measured.The most effective siRNA targeting RIP2 and optimal transfection concentration were screened,and the impact of RIP2 gene silencing on MDP-induced inflammatory activation of macrophages was observed.Results After silencing the RIP2 gene,MDP induced a significant decrease in TNF-α and IL-1βsecretion in macrophages,but the changes in cell phenotype were not significantly affected.Conclusion This study revealed the important role of NOD2/RIP2 signaling pathway in inflammatory activation of macrophages,and it is possible to effectively inhibit inflammatory activation of macrophages by interfering with this signaling pathway.

Objective:To explore the clinical effect of precise intraepiphyseal wedge osteotomy for the treatment of congenital hypertrophic epiphysis of the distal phalanx of the thumbs in children.Methods:A retrospective analysis was conducted on the data of children with congenital hypertrophic epiphysis deformity of the distal phalanx of the thumb treated by precisely located intraepiphyseal wedge osteotomy in Dongguan Integrated Traditional Chinese and Western Medicine Hospital from January 2020 to January 2023. Preoperative X-ray films all showed asymmetric thickening of the secondary ossification centers, presenting as triangular, elliptical, unequal trapezoidal, and bipartite epiphyseal fusion shapes respectively. During the operation, precise localization was performed, and wedge osteotomy was conducted at 1.5 mm from the articular surface. The osteotomy angle and volume were adjusted according to the morphology of the hypertrophic epiphysis and the comprehensive condition of the distal and proximal phalanges, with axial over-correction of approximately 10° for fixation. Six months after surgery, the ulnar deviation angle of the distal phalanx with the interphalangeal joint of the thumb, the maximum passive flexion angle, and the thickness of the distal epiphyseal plate on X-ray were followed up. Statistical analysis was conducted using paired t-tests before and after surgery, and P<0.05 was considered statistically significant. Results:A total of 32 children with 34 thumbs were included, aged from 6 months to 8 years old, with an average age of 2.1 years old. There were 27 thumbs accompanied by radial polydactyly, the main and accessory thumbs were clear, and the epiphysis of the distal phalanx of the main thumb was thickened. The lateral deviation angle of the distal phalanx of the thumb before surgery was (35.6±13.2)° (15.0°-67.0°), the maximum passive flexion range was (62.8±7.7)° (38.0°-80.0°), and the maximum thickness of the distal phalanx epiphysis in the X-ray was (3.7±0.9) mm (2.3-5.9 mm). All surgeries of all children were successfully completed, the wounds healed well without redness, swelling or infection. Patients were discharged smoothly. The average follow-up time after surgery was 13 month (rang from 6-22 months), with an average deviation angle of (7.6±5.6)° (1.8°-13.4°) in the distal phalanx with the interphalangeal joint, compared with before surgery, the difference was statistically significant ( t=10.36, P=0.012). Five thumbs had residual ulnar deviation after surgery, with an average deviation of (16.6±2.3)° (12.0°-20.0°), two cases had corrected positive radial deviation (15°, 18°), while the other cases had no significant ulnar deviation in the distal phalanx of the thumb. The average maximum angle of passive flexion of the distal thumb after surgery was (62.9±7.5)° (35.0°-80.0°), compared with before surgery, the difference was not statistically significant ( t=0.16, P=0.359). The average maximum thickness of the distal epiphyses on postoperative X-rays was (1.9±0.5) mm (1.2-3.1 mm), compared with before surgery, the difference was statistically significant ( t=17.04, P=0.012). The epiphyses were flat and round, and the growth lines were normal. Conclusion:Using precise intraepiphyseal wedge osteotomy, combined with postoperative fixation with mild overcorrection for the treatment of congenital hypertrophic epiphysis at distal phalanx of the thumb in children, can achieve satisfactory correction of deviation, significantly shorten and improve the morphology of the epiphysis without affecting the growth plate, and cause minimal impact on joint flexion activity.

Objective:To analyze the relationship between cuprotosis-realted gene DLD expression in pan-cancer and progno-sis,tumor microenvironment and tumor immune infiltration by bioinformatics methods combined with multiple databases.Methods:TCGA,GTEx,TISDB,GEO,UCSC,TARGET,TIMER2.0,GEPIA2,SangerBox,PrognoScan and related R software packages were used to analyze the difference of DLD expression between human cancer and adjacent normal tissues,inestigate relationship between prognosis,explore expression of DLD in different immune subtypes and molecular subtypes of human cancer,analyze correlation between DLD expression and tumor immune infiltration and tumor microenvironment,detecet relationship between DLD expression and 60 immune checkpoint genes.Results:There were differences in expression of DLD in different tumor tissues;low DLD expression in 6 tumors and high DLD expression in 3 tumors were significantly associated with better prognosis;15 tumor immune subtypes,11 molecular subtypes of tumors were significantly correlated with DLD expression;DLD expression was significantly correlated with immune infiltration in 37 cancer types;DLD expression was significantly associated with immune infiltration in 23 tumor stroma scores,26 tumor immune scores and 25 tumor ESTIMATE scores;60 immune checkpoint genes in 39 tumors were significantly associated with DLD expression.Conclusion:Expression of DLD in pan-cancer is related to tumor prognosis and immune invasion,DLD may be a potential predictor of prognosis in tumors,and may be an immunomodulator of tumors.