OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

AIM:This study aimed to identify the key active components and signaling pathways in the tradi-tional Chinese medicine Fructus Aurantii that contribute to the prevention and treatment of cardiac hypertrophy,along with experimental validation.METHODS:H9C2 cardiomyocytes were pretreated with nobiletin(NOB)for 1 h and then ex-posed to 100 nmol/L angiotensin Ⅱ(Ang Ⅱ)for 24 h.RT-qPCR was used to quantify the mRNA expression of hypertrophy-related genes,including atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and myosin heavy chain 7(MYH7).Immunofluorescence staining was employed to assess the surface area of cardiomyocytes.Additionally,a kit was utilized to measure levels of pyroptosis-related factors such as lactate dehydrogenase(LDH),interleukin-1β(IL-1β),IL-18 and caspase-1,while Western blot was performed to evaluate the expression of gasdermin D and caspase-1.RESULTS:Network pharmacology analyses indicated that NOB is the key active component in Fructus Aurantii that regu-lates cardiac hypertrophy,potentially through the pyroptosis pathway.Further molecular biology experiments confirmed that NOB inhibits Ang Ⅱ-induced cardiac hypertrophy and pyroptosis.Furthermore,the involvement of the pyroptosis pathway was highlighted in the protective effects of NOB against cardiac hypertrophy.CONCLUSION:The active compo-nent NOB in the traditional Chinese medicine Fructus Aurantii alleviates cardiac hypertrophy by inhibiting pyroptosis.

AIM:This study aimed to identify the key active components and signaling pathways in the tradi-tional Chinese medicine Fructus Aurantii that contribute to the prevention and treatment of cardiac hypertrophy,along with experimental validation.METHODS:H9C2 cardiomyocytes were pretreated with nobiletin(NOB)for 1 h and then ex-posed to 100 nmol/L angiotensin Ⅱ(Ang Ⅱ)for 24 h.RT-qPCR was used to quantify the mRNA expression of hypertrophy-related genes,including atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and myosin heavy chain 7(MYH7).Immunofluorescence staining was employed to assess the surface area of cardiomyocytes.Additionally,a kit was utilized to measure levels of pyroptosis-related factors such as lactate dehydrogenase(LDH),interleukin-1β(IL-1β),IL-18 and caspase-1,while Western blot was performed to evaluate the expression of gasdermin D and caspase-1.RESULTS:Network pharmacology analyses indicated that NOB is the key active component in Fructus Aurantii that regu-lates cardiac hypertrophy,potentially through the pyroptosis pathway.Further molecular biology experiments confirmed that NOB inhibits Ang Ⅱ-induced cardiac hypertrophy and pyroptosis.Furthermore,the involvement of the pyroptosis pathway was highlighted in the protective effects of NOB against cardiac hypertrophy.CONCLUSION:The active compo-nent NOB in the traditional Chinese medicine Fructus Aurantii alleviates cardiac hypertrophy by inhibiting pyroptosis.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

The inflammatory effect of dietary is strongly related to the development of cancer,therefore,the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary,inflammation and tumors.In this paper,we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies.The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies,with the strongest association with colorectal cancer,followed by esophageal and gastric cancers,and then pancreatic cancer,and the least evidence of studies with liver cancer.Among these studies,the level of evidence for esophageal cancer is lower than colorectal cancer,the study of gastric cancer has gender differences and problems in adjusting for confounders,and the study of pancreatic cancer has heterogeneous results.In view of the current research progress and deficiencies,prospective studies or population-based cohort studies,as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future.This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O