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

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor originating from the intrahepatic bile duct epithelium. Current clinical consensus emphasizes that early detection,timely diagnosis,and R0 resection (when feasible) are critical strategies for improving outcomes. Advances in surgical techniques and multidisciplinary approaches have facilitated precision medicine-guided systemic therapies,including adjuvant and neoadjuvant regimens. These interventions significantly delay postoperative recurrence and improve 5-year survival rates. Systemic treatments have also modestly enhanced prognoses for advanced ICC patients. Artificial intelligence-driven radiomics and deep learning technologies show substantial efficacy in ICC diagnosis,prognostic assessment,and lymph node metastasis prediction,advancing precision medicine applications. Despite these therapeutic advances,survival outcomes-particularly for advanced-stage ICC-remain suboptimal. Future efforts should prioritize molecular signature-guided therapies,novel combination regimens,and artificial intelligence-assisted comprehensive management to establish a molecularly driven precision treatment framework.

OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

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.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor originating from the intrahepatic bile duct epithelium. Current clinical consensus emphasizes that early detection,timely diagnosis,and R0 resection (when feasible) are critical strategies for improving outcomes. Advances in surgical techniques and multidisciplinary approaches have facilitated precision medicine-guided systemic therapies,including adjuvant and neoadjuvant regimens. These interventions significantly delay postoperative recurrence and improve 5-year survival rates. Systemic treatments have also modestly enhanced prognoses for advanced ICC patients. Artificial intelligence-driven radiomics and deep learning technologies show substantial efficacy in ICC diagnosis,prognostic assessment,and lymph node metastasis prediction,advancing precision medicine applications. Despite these therapeutic advances,survival outcomes-particularly for advanced-stage ICC-remain suboptimal. Future efforts should prioritize molecular signature-guided therapies,novel combination regimens,and artificial intelligence-assisted comprehensive management to establish a molecularly driven precision treatment framework.

Lumbar spinal stenosis (LSS) is a common disabling condition in the elderly, and its clinical assessment relies not only on imaging and neurofunctional indicators but also on traditional Chinese medicine (TCM) syndrome differentiation. To evaluate the concordance between existing LSS animal models and clinical characteristics of TCM and Western medicine, clarify their advantages and limitations, and explore their translational potential, Chinese and English databases, including CNKI, Wanfang Data, PubMed, and Web of Science, are searched using combinations of the terms "lumbar spinal stenosis," "model," "guideline," "consensus," and "norm" from inception to the end of June 2025. After screening, a total of 21 publications are included, of which 15 report animal experimental studies, and 6 are guidelines, consensus statements, or normative documents. Based on these, the existing modeling methods are summarized, diagnostic indicators are extracted from clinical guidelines and expert consensus, and clinical concordance is evaluated using an assessment system proposed in the relevant literature. The results show that the existing animal models are categorized into three concordance levels: high (laminectomy/spinous process removal with filling; laminectomy/spinous process + ligament/muscle removal with filling; autologous bone backfilling), moderate (nylon tape dural binding method, adjustable screws, fixation combined with removal of ligament/muscle), and low (balloon compression method, adjustable balloon compression method, bipedal standing, ligament/muscle resection, steel wire cerclage method). Overall, current animal models of LSS generally perform well in terms of structural construction but show clear limitations in replicating clinical diagnostic logic and TCM syndromes. Future research should enhance syndrome phenotype collection and enrich TCM-based evaluation systems based on existing models. Additionally, multifactorial integrated modeling strategies should be introduced to extend the depth of syndrome-level simulation. This study aims to analyze LSS animal models that can faithfully recapitulate disease pathogenesis, conform to clinical realities of both Western medicine and TCM clinical practice, and have broad application potential, so as to narrow the translational gap between experimental findings and clinical practice.

Objective: To assess the current status of bacterial detection capabilities in various blood collection and supply and related laboratories across China, and to identify key factors affecting the consistency of test results. Methods: A pooled analysis was conducted on data from 21 external quality assessment (EQA) rounds for blood bacterial detection carried out by the China International Transfusion Infection Prevention and Control (CITIC) project from 2019 to 2025. The study covered three types of laboratories-blood centers, central blood stations, and commercial laboratories—across 23 provincial-level administrative regions in China. Statistics were compiled on the number of participating laboratories, and the concordance rates were calculated for different institution types, different automated blood culture systems, different bacterial concentrations, and different strains. Non-standard reporting issues were also reviewed, and statistical methods were applied for analysis. Results: Over the seven-year period, the number of participating laboratories increased from 161 to 236, with an average annual growth rate of 6.58%, and the annual concordance rates ranged from 82.61% to 94.92%. The overall laboratory concordance rates for the three types of participating laboratories were all>89.0% (P>0.05), while commercial laboratories showed a significant year-by-year increase (70.97%-100%, P<0.05). The concordance rates of automated blood culture systems from eight manufacturers showed no significant differences (97.98%-100%, P>0.05), indicating stable performance across all devices. The overall sample concordance rate was 98.88%, with negative samples showing a lower rate than positive samples (97.97% vs 99.14%); positive sample rates increased with higher concentrations; and low-concentration Gram-negative bacterial samples had a lower concordance rate than Gram-positive ones (93.15% vs 100%). A total of 50 instances of non-standard result reporting were identified, with incorrect time units accounting for the highest proportion (52.0%). Conclusion The participation scale and overall testing proficiency of blood collection and supply and related laboratories nationwide have improved year by year, and all types of automated blood culture devices can meet the requirements for blood bacterial screening. Detection of negative and low-concentration positive samples remains a weak link in current bacterial EQA, and the standardization of laboratory data reporting requires further strengthening. Continuous: external quality assessment, targeted training, and standardized reporting procedures can effectively enhance the homogenization level of blood bacterial testing across the country and ensure the safety of clinical transfusion.

Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.