With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.

OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA)).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimicNC(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe2+increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.