ObjectiveTo explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease （ESRD） patients complicated by frailty. MethodsA total of 84 patients with ESRD were enrolled and divided into the frailty group （31 cases） and non-frailty group （53 cases） according to the Chinese version of the Tilburg Frailty Indicator （TFI）. Cranial magnetic resonance imaging （MRI） data， neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients， and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. ResultsLogistic regression analysis showed that high blood urea nitrogen level， depression， malnutrition， and sleep disturbance were risk factors for frailty in patients with ESRD （P<0.05）， while a higher level of education served as a protective factor （P<0.05）. Compared with the non-frailty group， the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network （P<0.05）. ConclusionHigh levels of blood urea nitrogen， depression， malnutrition， and sleep disorders can increase the risk of frailty in patients with end-stage renal disease （ESRD）， while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network （SMN） and visual network （VN）， which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.

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.

To address the growing challenge of an increasing number of elderly lung cancer patients amidst China's aging population and to fill the gap in quality control standards for surgical treatment in this special population, this study aimed to develop a standardized surgical evaluation system for elderly lung cancer patients tailored to China's national conditions. The system was established through a literature review, integrated the pathophysiological characteristics of elderly patients, and was constructed following review, feedback, and revision by experts from multiple thoracic surgery centers. Employing a 100-point scoring system, it comprises three primary domains: physical infrastructure and geriatric adaptability foundational conditions (10 points); management level and perioperative care models (20 points); and technical proficiency and clinical outcomes (70 points). The system places a strong emphasis on geriatric adaptability, proposing specific, quantifiable indicators for age-friendly facility modifications, control of elderly-specific complications, multidisciplinary collaboration, and standardized perioperative management. It provides a convenient and measurable assessment tool for quality control in the surgical treatment of elderly lung cancer in China, which is expected to promote the standardization and homogenization of diagnosis and treatment.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

[摘 要] 目的：开发靶向成纤维细胞活化蛋白（FAP）的CAR-T细胞，评价其通过重塑肿瘤微环境（TME）抑制乳腺癌生长的能力。方法：将识别FAP不同抗原表位的纳米抗体VHH1和VHH2串联，设计两种胞外识别区排列顺序不同的FAP-CAR1（VHH1-Linker-VHH2）和FAP-CAR2（VHH2-Linker-VHH1），构建以二价FAP抗体为胞外识别域的CAR，将其分别克隆至逆转录病毒载体并完成病毒包装。分离小鼠淋巴细胞，经抗CD3/CD28抗体激活后进行转导，制备FAP-CAR1-T和FAP-CAR2-T细胞。通过实时无标记动态细胞分析（RTCA）、流式细胞术（FCM）评估FAP-CAR-T细胞的靶向杀伤活性，ELISA检测其激活后IL-2分泌水平。分别用FAP-CAR1-T细胞（FAP-CAR-T组）、HER2-CAR-T细胞（HER2-CAR-T组）及未转导T细胞（Mock-T组）治疗4T1-HER2荷瘤小鼠，分析FAP-CAR-T对肿瘤生长的抑制作用，并通过免疫组织化学（IHC）检测肿瘤组织中T细胞浸润情况。进一步通过转录组分析差异表达基因。结果：FAP-CAR1-T与FAP-CAR2-T细胞体外扩增稳定，CAR阳性率 > 60%。两者均能特异、高效杀伤过表达鼠源FAP的小鼠成纤维细胞NIH3T3-mFAP，且FAP-CAR1-T细胞在扩增和分泌IL-2方面优于FAP-CAR2-T细胞，因此选用FAP-CAR1-T细胞进行后续体内实验。在小鼠4T1-HER2皮下移植瘤模型中，FAP-CAR-T治疗组小鼠肿瘤生长速度显著低于Mock-T组（P < 0.05），与HER2-CAR-T组肿瘤生长速度相当（P > 0.05）；与Mock-T组相比，FAP-CAR-T治疗组小鼠肿瘤组织中CD3+ T细胞浸润增加，胶原沉积面积减少（P < 0.001或P < 0.01）。转录组分析结果显示，FAP-CAR-T组相较Mock-T组的差异表达基因富集于细胞外基质、免疫应答等GO条目及ECM-受体相互作用等KEGG通路。结论：FAP-CAR-T细胞通过特异性靶向FAP相关基质细胞，重塑肿瘤微环境，显著抑制乳腺癌生长，且在肿瘤体积控制上与HER2-CAR-T细胞相比无统计学差异。

Hemorrhoids are common anorectal diseases with complex pathogenesis, and there is still a lack of ideal experimental animal models for research on their prevention and treatment. In this paper, Chinese and English databases are searched with the keywords "hemorrhoids" and "animal model", and 36 relevant studies are finally included. The shortcomings of existing hemorrhoid animal models in integrating the clinical disease and syndrome characteristics of traditional Chinese and Western medicine are systematically analyzed, and the consistency of various models with clinical practice is evaluated. The studies are divided into four categories according to modeling methods: chemical modeling, physical modeling, biological modeling, and combined modeling. The clinical consistency of modeling is evaluated in combination with the diagnostic points of hemorrhoids in traditional Chinese and Western medicine. The results show that there are significant differences in the reproduction of clinical indicators by different modeling methods. According to clinical consistency, the models can be divided into three grades: high-consistency models are mainly based on combined modeling methods (such as induction by carrageenan combined with norepinephrine hydrochloride), which can more comprehensively simulate core pathological changes such as venous congestion and local inflammation; moderate-consistency models adopt single chemical or physical intervention (such as local inflammation induced by croton oil or vein ligation), which can only reproduce part of the pathological process; low-consistency models mostly adopt direct stimulation, with limited research value for pathological characteristics. Existing animal models have obvious advantages in replicating Western medical structural lesions of hemorrhoids, but they still have obvious defects in simulating the chronic disease course and stably reproducing the characteristics of traditional Chinese medicine syndromes, and a unified standard has not yet been formed for the traditional Chinese medicine evaluation system of models. In conclusion, it is still necessary to further explore the construction of high-quality integrated disease and syndrome animal models for hemorrhoids in traditional Chinese and Western medicine. Future research should integrate the theories of traditional Chinese and Western medicine, adopt multi-factor chronic modeling strategies, and establish a standardized comprehensive evaluation system covering macroscopic signs and microscopic indicators. This paper provides a reference for constructing standardized integrated disease and syndrome animal models of hemorrhoids that conform to the pathological changes of Western medicine and take into account the characteristics of traditional Chinese medicine syndromes, with the aim of providing more effective experimental tools for research on the pathogenesis of hemorrhoids and their integrated prevention and treatment with traditional Chinese and Western medicine.