Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

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

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective: To explore the impact of donor reentry experience, specifically among those with a single reactive serological result who completed the reentry process, on their willingness to return for future blood donation, and to examine the mediating roles of blood donation knowledge and trait anxiety. Methods: A cross-sectional survey was conducted between November and December 2025. A total of 386 blood donors from the Changsha Blood Center were categorized into a reentry group (n=123) and a control group (n=263). Data on demographic characteristics, blood donation knowledge (BDKQ), trait anxiety (STAI-T), and blood donation return intention (BDRIS) were collected via questionnaires. SPSS 27.0 and AMOS 28.0 were used for statistical analyses, including independent-samples t-test, one-way ANOVA, multiple linear regression, and path analysis for mediating effect testing. Results: There were statistically significant differences in age, occupation, education level, monthly income and donation frequency between the reentry group and the control group (all P<0.05). The reentry group scored significantly higher in blood donation knowledge and blood donation return intention than the control group (both P<0.05). The mean BDRIS score was 11.51±3.62, indicating a relatively high intention to return. Blood donation knowledge was significantly negatively correlated with trait anxiety (r=-0.15, P<0.05) and positively correlated with blood donation return intention (r=0.19, P<0.05); trait anxiety was significantly negatively correlated with blood donation return intention (r=-0.33, P<0.05). Significant differences in BDRIS scores were found based on group (reentry vs control), age, and number of previous donations (all P<0.05). Multiple linear regression showed that BDKQ positively predicted BDRIS (β=0.11, P<0.05), while STAI-T negatively predicted BDRIS (β=-0.27, P<0.05). Path analysis further revealed that the reentry experience had no direct effect on the intention to return. However, it exerted a positive influence through two indirect pathways: 1) a simple mediating effect via increased blood donation knowledge (β=0.17, accounting for 25.0% of the total effect), and 2) a chain mediating effect through "increased blood donation knowledge → decreased trait anxiety" (β=0.05, accounting for 8.1% of the total effect). The model fit indices reached the ideal fitting criteria. Conclusion: The donor reentry experience does not directly enhance the intention to return for blood donation. Rather, it may exert an indirect positive influence by increasing blood donation knowledge and through the sequential pathway of "increased knowledge → decreased trait anxiety". Blood collection institutions should leverage the reentry process as an opportunity for education and psychological support to improve donor retention rate.

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.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden， which has garnered significant national attention and prompted their inclusion in public health project management systems. However， credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City， Sichuan Province， remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City， Sichuan Province， and to analyze influencing factors of disease stabilization among patients under standardized care， so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023， data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City， the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017， respectively， which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022， the regular medication adherence rate was 71.80% for schizophrenia， 55.26% for paranoid psychosis， and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization： age of 18~39 years （OR=0.613， 95% CI： 0.409~0.918）， age of 40~65 years （OR=0.615， 95% CI： 0.407~0.931）， urban residence （OR=0.587， 95% CI： 0.478~0.720）， and regular medication adherence （OR=0.826， 95% CI： 0.702~0.973）. Risk factors for disease fluctuation included poor （OR=1.712， 95% CI： 1.436~2.040）， non-inclusion in care-support programs （OR=1.928， 95% CI： 1.694~2.193）， non-participation in community rehabilitation （OR=2.255， 95% CI： 1.930~2.634）， and intermittent medication adherence （OR=3.893， 95% CI： 2.548~5.946）. ConclusionThe stability rate， standardized management rate， and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age， household registration status， economic condition， medication compliance， and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. ［Funded by Luzhou Science and Technology Plan Project （number， 2022-ZRK-186）］

Objective: This study aims to explore the influencing factors, formation mechanisms, and treatment methods of labial protuberance in the anterior maxilla during orthodontic treatment, providing a reference for clinical practice. Method: This study reports a case where the absence of upper anterior teeth 11 and 21, and the retraction tilting movement of teeth 12 and 22, resulted in labial protuberance and gingival hyperplasia. Alveolar osteoplasty and gingivoplasty were performed. The specific changes in the alveolar bone during the retraction of the anterior teeth and the characteristics of its remodeling were analyzed. Combined with relevant literature, the factors influencing the formation of labial protuberance in orthodontic patients, mechanisms, and methods for prevention and treatment were summarized. Results: After periodental surgery follow-up for 6 months, the gingival color and shape of teeth 12 and 22 were good, the labial alveolar bone was normal, and the overall condition was stable. A review of the literature showed that labial protuberance is more common in adult orthodontic patients, and the distance (>4 mm) and speed of retraction of anterior teeth are related to its formation, with the main mechanism likely being differential remodeling of the alveolar bone. In adult patients, the number of active osteoblasts and osteoclasts in the alveolar bone decreases, along with a reduction in metabolic activity and overall cellular activity, which diminishes the reactivity of the alveolar bone. After treatment of anterior teeth retraction, there is insufficient labial bone resorption. Moreover, the lack of mechanical stress-mediated periodontal ligament in the interdental space leads to reduced bone remodeling stimulation in this area, resulting in thickening of the labial alveolar bone of the upper anterior teeth. The remodeling rates of cortical and trabecular bone differ, with active trabecular bone proliferation near the tooth root surface and slow cortical bone resorption near the outer surface, which ultimately results in increased bone thickness at the labial cervical region. Specific case analysis indicates that the retraction distance of the upper anterior teeth in this case was about 6 mm. The alveolar bone at the missing sites of teeth 11 and 21, lacking periodontal ligament stimulation, showed less remodeling and absorption, likely appearing as hyperplasia. The prevention of labial bone protrusion mainly involves controlling the speed and distance of retraction of anterior teeth. Smaller labial protuberances generally do not require treatment, but those affecting function and aesthetics can be addressed with periodontal alveolar osteoplasty. Conclusion After the retraction of anterior teeth in orthodontics, a prominent, hard bone protuberance on the labial side can sometimes occur, which may be due to differential remodeling efficiency in different regions of the alveolar bone. For bone protuberance that influences aesthetics or function, periodontal alveolar osteoplasty can be a reliable option.

Background/Aims: The World Health Organization set the goal of eliminating hepatitis C virus (HCV) by 2030, with 80% and 65% reductions in HCV incidence and mortality rates, respectively. We aimed to evaluate the health benefits, cost-effectiveness and return on investment (ROI) of HCV elimination. Methods: Using an HCV transmission compartmental model, we evaluated the benefits and costs of different strategies combining screening and treatment for Chinese populations. We identified strategies to achieve HCV elimination and calculated the incremental cost-effectiveness ratios (ICERs) per disability-adjusted life year (DALY) averted for 2022–2030 to identify the optimal elimination strategy. Furthermore, we estimated the ROI by 2050 by comparing the required investment with the economic productivity gains from reduced HCV incidence and deaths. Results: The strategy that results in the most significant health benefits involves conducting annual primary screening at a rate of 14%, re-screening people who inject drugs annually and the general population every five years, and treating 95% of those diagnosed (P14-R4-T95), preventing approximately 5.75 and 0.44 million HCV infections and deaths, respectively, during 2022–2030. At a willingness-to-pay threshold of $12,615, the P14-R4-T95 strategy is the most cost-effective, with an ICER of $5,449/DALY. By 2050, this strategy would have a net benefit of $120,997 million (ROI=0.868). Conclusions Achieving HCV elimination in China by 2030 will require significant investment in large-scale universal screening and treatment, but it will yield substantial health and economic benefits and is cost-effective.