Objective To explore a novel method for early lung cancer screening based on exhaled breath analysis. Methods This study enrolled patients with suspected pulmonary malignancies and healthy individuals undergoing physical examinations at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Qingchun and Qiantang campuses) from September 2023 to June 2024. Enrolled subjects were categorized into a lung cancer group, a benign nodule/tumor group, and a healthy control group. Exhaled breath samples were collected using a sensor array constructed from multiple graphene composite materials to capture breath fingerprints. Based on the collected data, screening and diagnostic models for lung cancer were developed and their performance was evaluated. Results A total of 4 580 subjects were included. Among them, 3 195 were pathologically diagnosed with pulmonary malignancies, including 1 394 males and 1 801 females with a mean age of (58.93±12.37) years, 599 were diagnosed with benign nodules/tumors including 339 males and 260 females with a mean age of (57.10±11.06) years, and 786 were healthy controls with no pulmonary nodules detected on chest CT including 420 males and 366 females with a mean age of (29.75±9.32) years. There were 4 031 patients in the training set and 549 patients in the external testing set. The screening model for high-risk populations (distinguishing patients with lung cancer/high-risk pulmonary nodules from healthy individuals) demonstrated excellent performance, with an area under the receiver operating characteristic curve (AUC) of 0.926. At the optimal Youden’s index (cutoff threshold of 63.5%), the external testing set achieved a specificity of 85.2%, a sensitivity of 88.4%, and an accuracy of 86.8%. The diagnostic model (distinguishing patients with lung cancer/premalignant lesions from those with benign pulmonary nodules/healthy individuals) achieved an AUC of 0.818. At its optimal Youden’s index (cutoff threshold of 47.0%), the external testing set showed a specificity of 71.7%, a sensitivity of 77.3%, and an accuracy of 74.5%. Conclusion The non-invasive breath analysis platform based on a sensor array, developed in this study, can achieve rapid and relatively accurate lung cancer screening by analyzing breath fingerprints. This confirms the feasibility of this technology for early lung cancer screening and holds promise for facilitating the early detection and intervention of lung cancer.

It is believed that Shengyang Yiwei Decoction （升阳益胃汤， SYD） is effective in regulating the flow of Qi （气）， and can treat various diseases caused by the disorder of the spleen and stomach Qi. In clinical practice， based on the pathological characteristics of children often having insufficient spleen， and adhering to the principle of treating different diseases with the same method， the focus is placed on the core pathogenesis of spleen and stomach Qi disharmony. We use SYD in various pediatric conditions such as allergic rhinitis， post COVID-19 condition， urethral syndrome， and dysfunctional uterine bleeding in adolescence， and emphasize the treatment is flexibly tailored to the symptoms.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Objective To explore the expression level of plasma miRNA in patients with swallowing and cognitive dysfunction after ischemic stroke and its correlation with the severity of dysfunction.Methods A retrospective analysis was conducted on the clinical data of 109 patients with ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University and the First Affiliated Hos-pital of Fujian Medical University from January 2023 to March 2024.The expression levels of plasma miR-140-5p,miR-17-5p,and miR-103a-3p were detected by RT-qPCR.The swallowing function was evaluated by the Wada Drinking Water Test and the Functional Oral Feeding Scale,and the cognitive function of stroke pa-tients was evaluated by the modified Rankin Scale(mRS)classification.According to the mRS rating criteria,the patients were divided into the good functional outcome group(grade≤2,n=50)and the poor functional outcome group(grade≥3,n=59).Analyzed the correlation between miRNA expression levels and the degree of functional impairment,compared the clinical characteristics of patients with different mRS grades,and used the receiver operating characteristic(ROC)curve and the area under the curve(AUC)to analyze the efficacy of miRNA in predicting the functional outcome of mRS evaluation.Results The results of Spearman correla-tion analysis showed that the expression level of miR-17-5p was negatively correlated with the classification of the Wada Drinking Water Test(r=-0.317)and the classification of the Functional Oral Feeding Scale(r=-0.457,P<0.05).Compared with the good functional outcome group,the poor functional outcome group had a lower proportion of males,shorter disease course,and higher expression level of miR-103a-3p,the differ-ences were statistically significant(P<0.05).The results of ROC curve analysis showed that miR-103a-3p(AUC=0.709,95%CI:0.611-0.808)had the ability to distinguish functional outcomes in mRS evaluation.However,miR-140-5p(AUC=0.514,95%CI:0.405-0.624)and miR-17-5p(AUC=0.527,95%CI:0.414-0.637)did not have the ability.Conclusion The expression level of plasma miR-17-5p is related to the severi-ty of dysphagia in patients in the recovery period of ischemic stroke,and miR-103a-3p is helpful for judging the functional outcomes of patients in the recovery period of ischemic stroke.

Objective To target at the NKG2A-HLA-E inhibitory axis,a pluripotent stem cell(iPSC)-derived geneti-cally engineered natural killer cells(NK cells)with NKG2A knockout(NKG2A KO-iNK)were prepared and then their tumor-killing efficacy was evaluated in vitro.Methods NKG2A was knocked out in iPSCs using gene-editing technology.These cells were then differentiated into NKG2A KO-iNK cells.Surface markers at each differentiation stage were analyzed by flow cytometry.Western blot confirmed NKG2A knockout,and flow cytometry assessed expres-sion of activating receptors(NKG2D)and natural cytotoxicity receptors(NKp30,NKp44,NKp46)in NKG2A KO-iNK cells.Cytotoxic activity against tumor cell lines with varying human leukocyte antigen E(HLA-E)expression level was evaluated via lactate dehydrogenase(LDH)release assay.Results Co-transfection of iPSCs with Cas9 pro-tein and three small-guide RNAs(sgRNAs)targeting at exons 1 and 2 of the KLRC1 gene(encoding NKG2A)suc-cessfully generated monoclonal NKG2A-knockout iPSCs(NKG2A KO-iPSCs)with a single T-base insertion in exon 1.During iPSC differentiation into NK cells,CD34 expression reached 30％-50％at the embryoid body(EB)stage(day 8),while CD56 and CD 16 expression exceeded 80％by day 28.Western blot confirmed complete NKG2A knockout in NKG2A KO-iNK cells.Flow cytometry revealed comparable expression level of activating receptor NKG2D and cytotox-icity receptors(NKp30,NKp44,NKp46)between NKG2A KO-iNK and wild-type iNK(WT-iNK)cells.The LDH assay results indicated that the cytotoxic activity of NKG2A KO-iNK cells against the HLA-E highly-expressed B-cell precursor leukemia cell line Nalm6 cells was significantly higher than that of WT-iNK cells,while there was no signif-icant difference between them and human myeloma cell line H929 cells with low HLA-E expression and human hepa-tocellular carcinoma cell line HepG2 cells with almost no HLA-E expression.Interferon-γ(IFN-γ)pretreatment up regulated HLA-E expression in Nalm6 cells,further amplifying NKG2A KO-iNK-mediated cytotoxicity.Conclusions By disrupting the NKG2A-HLA-E inhibitory axis,NKG2A KO-iNK cells exhibit markedly enhanced in vitro cytotoxic-ity against HLA-E-high tumor cells.This result highlights their potential function as a novel adoptive cell therapy strategy for cancers reliant on HLA-E-mediated immune evasion.

Objective To investigate the therapeutic effect of combination treatment of transcatheter arterial chemoembolization(TACE),micro wave ablation(MW A)and targeted immunotherapy for hepatocellular carcinoma(HCC).Methods The clinical data of HCC patients,who were admitted to the Affiliated Central Hospital of Jiangnan University of China to receive TACE from August 2016 to August 2023,were retrospectively analyzed.Based on the inclusion criteria,a total of 252 patients were included in this study.According to the therapeutic scheme,the patients were divided into combination group(receiving TACE,MWA,targeted therapy and immunotherapy,n=41),and control group(receiving TACE alone,n=211).The overall survival(OS)and progression-free survival(PFS)of the two groups were statistically analyzed.After propensity score matching at 1∶1 ratio,the clinical effects of the two groups were analyzed.According to different data,t-test,test,Kaplan-Meier curve,logarithmic rank test,Cox regression analysis,or Cox proportional risk model analysis was used to make statistical analysis.Results Multivariate regression analysis showed that tumor number,maximum diameter,invasion of large vessels,tumor capsule,AFP level,glutamic oxalacetic transaminase,BCLC stage and Child-Pugh stage were the independent risk factors for patient survival.Imaging response and combination treatment were the protective factors for survival.After propensity score matching,a total of 37 pairs of patients were obtained,and the baseline data were comparable between the groups.The differences in OS and PFS between the two groups were statistically significant.Combination treatment of TACE,MWA,targeted therapy and immunotherapy could significantly prolong OS and PFS in HCC patients.Conclusion Compared with TACE alone,combination use of TACE,MWA,targeted therapy and immunotherapy is a more effective therapeutic scheme for HCC,it can remarkably and effectively improve OS and PFS in HCC patients.

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans ; Receptors, Antigen, T-Cell, gamma-delta ; Immunotherapy, Adoptive ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy*