Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each corresponding to a specific peripheral immune response pattern. Elucidating these peripheral immune response patterns may facilitate the objective quantification of the degree of vital qi deficiency, prediction of future metastasis risk, and providing an important reference for the individualized clinical implementation of Fuzheng Juandu therapy.

Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.

This study systematically investigated the molecular mechanisms underlying the involvement of mesoderm development-associated genes in melanoma progression through integrated bioinformatics analy-sis and experimental validation.Utilizing the GSVA(gene set variation analysis)algorithm to perform enrichment analysis of 7 752 biological functions in 406 skin cutaneous melanoma(SKCM)cases,we i-dentified for the first time the significant activation of mesoderm development pathways during SKCM pathogenesis.Four core regulatory genes(SMAD4,NODAL,BMPR1A,and ZFP36L1)were screened using LASSO-COX regression analysis and a prognostic risk-scoring system was established.Gene Ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses revealed predomi-nant enrichment of these genes in mRNA metabolic processes and TGF-β signaling pathways.Experimen-tal validation through Quantitative Polymerase Chain Reaction(qPCR),Western blotting,and immuno-histochemistry(IHC)demonstrated that:(1)Downregulation of SMAD4 and BMPR1A in tumor tissues was significantly correlated with poor prognosis(P＜0.05);(2)NODAL promoted tumor invasion and metastasis by regulating epithelial-mesenchymal transition(EMT);(3)High ZFP36L1 expression was associated with enhanced chemotherapy sensitivity.Further analyses revealed significant correlations be-tween core gene expression levels and tumor immune infiltration characteristics as well as immune check-point molecules.By integrating multi-omics analysis with experimental validation,this study elucidates the critical roles of mesoderm development-associated genes in SKCM progression,particularly clarifying the molecular mechanisms through which SMAD4/NODAL/BMPR1A/ZFP36L1 influence tumor biologi-cal behaviors via immune microenvironment regulation and EMT processes.These findings provide novel theoretical foundations for molecular subtyping and targeted therapy in melanoma.

Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.

This study systematically investigated the molecular mechanisms underlying the involvement of mesoderm development-associated genes in melanoma progression through integrated bioinformatics analy-sis and experimental validation.Utilizing the GSVA(gene set variation analysis)algorithm to perform enrichment analysis of 7 752 biological functions in 406 skin cutaneous melanoma(SKCM)cases,we i-dentified for the first time the significant activation of mesoderm development pathways during SKCM pathogenesis.Four core regulatory genes(SMAD4,NODAL,BMPR1A,and ZFP36L1)were screened using LASSO-COX regression analysis and a prognostic risk-scoring system was established.Gene Ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses revealed predomi-nant enrichment of these genes in mRNA metabolic processes and TGF-β signaling pathways.Experimen-tal validation through Quantitative Polymerase Chain Reaction(qPCR),Western blotting,and immuno-histochemistry(IHC)demonstrated that:(1)Downregulation of SMAD4 and BMPR1A in tumor tissues was significantly correlated with poor prognosis(P＜0.05);(2)NODAL promoted tumor invasion and metastasis by regulating epithelial-mesenchymal transition(EMT);(3)High ZFP36L1 expression was associated with enhanced chemotherapy sensitivity.Further analyses revealed significant correlations be-tween core gene expression levels and tumor immune infiltration characteristics as well as immune check-point molecules.By integrating multi-omics analysis with experimental validation,this study elucidates the critical roles of mesoderm development-associated genes in SKCM progression,particularly clarifying the molecular mechanisms through which SMAD4/NODAL/BMPR1A/ZFP36L1 influence tumor biologi-cal behaviors via immune microenvironment regulation and EMT processes.These findings provide novel theoretical foundations for molecular subtyping and targeted therapy in melanoma.

Objective:To investigate the association between peripheral immune function status and lung cancer metastasis,and to identify peripheral blood immune biomarkers for'Deficiency of Vital Qi'assessment in lung cancer metastasis.Methods:A retrospective analysis was conducted on peripheral blood immune markers collected before treatment from lung cancer patients admitted into Shanghai Municipal Hospital of Traditional Chinese Medicine,affiliated to Shanghai University of Traditional Chinese Medicine,between March 2023 and April 2025.Patients were categorized into the non-metastatic and the metastatic groups based on the presence of distant metastasis,and the differences in the expressions of immune cells and cytokines between groups were compared.Peripheral blood immune markers with P<0.05 in univariate analysis were incorporated into a multivariate binary logistic regression model to identify independent predictors of lung cancer metastasis.Results:A total of 193 lung cancer patients were included(101 in the non-metastatic group and 92 in the metastatic group).There were no statistically significant differences between the two groups in terms of gender,age,smoking history,drinking history,or pathological type(all P>0.05).Univariate analysis revealed significant differences in multiple immune markers between the non-metastatic and metastatic groups(all P<0.05),including:lymphocyte count,CD3+,CD4+,and CD8+T,CD19+B cells,absolute counts of CD3-CD16+CD56+NK cells,percentages of Treg cells,CD8+CD28+Treg cells,G-MDSC,and CD3-CD16+CD56+dim NK cells,and levels of cytokine IL-1β,IL-6,and IL-10.Binary logistic regression analysis of differential indicators suggested that the percentage of Treg cells and CD8+CD28+Treg cells in peripheral blood were independent predictors of distant metastasis in lung cancer(OR=1.193,95%CI[1.047,1.36],P<0.01;OR=0.978,95%CI[0.957,0.999],P<0.05).Conclusion:Peripheral blood immune dysfunction is the biological basis for'qi deficiency'in lung cancer metastasis.This study quantitatively demonstrates the correlation between peripheral immune function status and lung cancer metastasis,providing empirical evidence for the theories of'qi deficiency and hidden toxicity'and'metastatic state of tumors'.

Lung cancer is the malignant tumor with the highest incidence and lethality globally.In recent years,emerging immunotherapy based on the immune checkpoint inhibitors,programmed cell death protein-1 and its ligand(PD-1/L1),as a representative,has made revolu-tionary breakthroughs in the field of lung cancer.The indications for this treatment mode have moved from driver-gene-negative advanced or locally advanced lung cancer to adjuvant and neoadjuvant treatment of perioperative lung cancer,and an increasing number of mono-clonal antibodies against PD-1 and PD-L1 has been approved for the treatment of lung cancer.However,with the widespread use of immun-otherapy,the problem of drug resistance has gradually come to the fore.Only a small proportion of the overall lung cancer population re-sponds to immunotherapy,bringing a new round of challenges to lung cancer treatment.In this paper,the clinical status of immunotherapy resistance in lung caner is reviewed,and cutting-edge advances in knowledge of resistance mechanisms and coping strategies are reviewed,with the aim of providing clinicians with ideas and the basis for formulating individualized,precise treatment plans.

Based on the concepts of "people-oriented" in traditional Chinese medicine and "tumor-suppression" in modern medicine， we have combed the studies on the spatial and temporal evolution of tumor metastasis and its biological characteristics in different perspectives， and initially proposed the theory of tumor metastasis from the perspective of the dynamic game between the tumor cells and the body's immune system under the theory of the integration of Chinese and Western medicine， that is， the formation of metastasis is the result of the dynamic evolution of the cancer cells and their surrounding environmental factors in the body over time and space. It is believed that the symptomatic manifestation of metastasis is systematic， the triggering factors of metastasis are constant， and the clinical outcome of metastasis is staged. Accordingly， it is proposed to understand the mechanism of metastasis from the perspective of spatial and temporal dynamics， to establish a clinical and pathological model for identifying metastasis， and to reveal the critical point of metastasis， so as to facilitate the change of the research on tumor metastasis from static to dynamic， and provide ideas for the formulation of metastasis prevention and treatment strategies， and the construction of a new system of metastasis prevention and treatment in the clinical tumor field.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity