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.

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.

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.

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.

ObjectiveTo explore the effectiveness of traditional Chinese medicine （TCM） chronic disease management programme in preventing postoperative recurrence of colorectal polyps. MethodsThe clinical data of 447 postoperative colorectal polyp patients were retrospectively collected， and the patients were divided into an exposure group and a control group taking the acceptance of TCM chronic disease management programme as exposure factor， and the polyp recurrence rate as the main outcome indicator， comparing the differences in baseline characteristics， outcome events， and safety assessment between the two groups， and conducting correlation analysis between the length of medication and polyp recurrence. Multifactorial logistic regression was used to analyse the effects of receiving the TCM chronic disease management programme （TCM treatment and life management for spleen deficiency and dampness stasis syndrome， dampness and stasis obstruction in collaterals syndrome， and intestinal dampness and heat syndrome）， gender， age， co-morbidities， TCM syndrome， and dietary and exercise factors on the outcome events. ResultsAmong 257 postoperative patients with colorectal polyps， there were 172 in the exposure group and 85 in control group. The recurrence rate of polyps in exposure group was 22.7% （39/172）， while the recurrence rate in control group was 57.6% （49/85）， and the difference between groups was statistically significant （P＜0.01）. The diameter of recurrent polyps in exposure group （median= 4.0 mm） was smaller than that in control group （median= 5.0 mm， P＜0.01）. The correlation analysis between the duration of medication taking and the recurrence of polyps in the spleen deficiency and dampness stasis syndrome group showed Phi value as -0.345 （P＜0.001）； the correlation analysis within the group of dampness and stasis obstruction in collaterals syndrome showed Phi value as -0.361 （P＜0.05）， indicating a negative correlation between the duration of medication taking and polyp recurrence. The results of multivariate logistic regression analysis indicated that the positive effect of accepting TCM chronic disease management programme on preventing polyp recurrence is statistically significant （OR=0.224， P＜0.01）. ConclusionAccepting TCM chronic disease management programme for colorectal polyps can help reducing the recurrence rate after polyp surgery， which is a protective factor for patients to the outcome event.

Objective To observe the association between afterschool physical exercise and sleep quality among preschool children,and to explore the proper afterschool physical exercise model for better sleep quality.Methods A cross-sectional study was conducted.From Apr to Jun 2024,a total of 1 430 children from three public kindergartens in Minhang district were enrolled to participate in the survey.Parents were invited to complete the basic sociodemographic information,afterschool physical exercise information and the Children's Sleep Habits Questionnaire.One-way ANOVA and linear mixed effects models were used to explore the relationship between afterschool exercise and sleep quality.Results A total of 1 430 questionnaires were sent out and 1 384 were recovered with a recovery rate of 96.78%.Among them 1 366 were valid,with an effective rate of 95.52%.The average age of the children was(5.19±0.87)years old with gender ration of 1.07∶1(male:female).The prevalence of poor sleep quality was 80.60%(regarding a CSHQ total score>41 as cutoff).A one-way ANOVA indicated that time on afterschool physical exercise was significantly associated with sleep duration,Night waking,and sleep onset delay(P<0.05).After adjusting for age,gender,the only child or not,main caregiver,and parental education and occupation,linear mixed effects models showed that engaging in afterschool physical activity for at least 180 mins per week has a statistically significant predictive effect on sleep duration scores(β=-0.50,z=-4.52,95%CI:-0.72,-0.28,P<0.001),night waking scores(β=-0.16,z=-2.34,95%CI:-0.29,-0.02,P=0.020),and sleep onset delay scores(β=-0.14,z=-2.35,95%CI:-0.26,-0.02,P=0.019).Conclusion Afterschool exercise was significantly associated with sleep quality among preschool children in Minhang district of Shanghai.The time≥180 min on afterschool exercise per week in preschool children was significantly positively associated with maintaining sleep duration,reducing night wakings and shortening the latency to fall asleep.The habit of afterschool exercise and the time on afterschool exercise should be emphasized by parents and the society to improve sleep quality among preschool children.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.