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 analyze the intervention effects of moderate to vigorous classroom physical exercise on psychological sub health among Uyghur junior high school students, providing reference for mental health promotion and intervention in the ethnic group. Methods: From April to July 2022, 647 eighth grade Uighur junior high school students from two middle schools in the Kashgar Prefecture, Xinjiang, were selected using a random cluster digital sampling method. They were randomly assigned to a control group ( n =326) and an intervention group ( n =321). While adhering to the regular curriculum, the intervention group additionally received 12 week, 36 session (every Monday, Wednesday, and Friday afternoon) moderate to vigorous classroom physical exercise intervention (45 minutes per session, including warm up, main exercises, and cool down activities). Self administered psychological sub health was completed through Brief Instrument on Psychological Health of Youths before and after intervention, and the data were analyzed using covariance analysis. Results: Before intervention, there were no statistically significant differences between the control and intervention groups in the total scores for psychological sub health or in the scores for the three dimensions including emotional problems, conduct problems, and social adaptation difficulties ( t =0.76, 0.40, 0.01, 0.94 , all P >0.05). After intervention, the scores of the intervention group s junior high school students on the emotional problems, conduct problems, and social adaptation difficulties dimensions decreased by 0.50, 0.28, and 0.18, respectively, compared with the control group, and all differences were statistically significant ( t =3.35, 3.36, 2.07, all P <0.05). The main effect of the psychological sub health category was statistically significant ( F =60.66, P <0.01, partial η 2=0.09). Compared with the control group, the psychological sub health scores of junior high school students in the intervention group decreased by 0.96 ( t =3.42, P < 0.05 ). Conclusion The 12 week moderate to vigorous classroom physical exercise intervention has a positive effect on the psychological sub health of Uyghur junior high school students.

This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P＜0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P＞0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P＜0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

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.