Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

The Role of SF1 and SF2 Helicases in Biotechnological Applications.

Helicases, which utilize ATP hydrolysis to separate nucleic acid duplexes, play crucial roles in DNA and RNA replication, repair, recombination, and transcription. Categorized into the major groups superfamily 1 (SF1) and superfamily 2 (SF2), alongside four minor groups, these proteins exhibit a conserved catalytic core indicative of a shared evolutionary origin while displaying functional diversity through interactions with various substrates. This review summarizes the structures, functions and mechanisms of SF1 and SF2 helicases, with an emphasis on conserved ATPase sites and RecA-like domains essential for their enzymatic and nucleic acid binding capabilities. It highlights the unique 1B and 2B domains in SF1 helicases and their impact on enzymatic activity. The DNA unwinding process is detailed, covering substrate recognition, ATP hydrolysis, and conformational changes, while addressing debates over the active form of UvrD helicase and post-unwinding dissociation. More importantly, this review discusses the biotechnological potential of helicases in emerging technologies such as nanopore sequencing, protein sequencing, and isothermal amplification, focusing on their use in pathogen detection, biosensor enhancement, and cancer treatment. As understanding deepens, innovative applications in genome editing, DNA sequencing, and synthetic biology are anticipated.

Hepatic microcirculatory disturbance in liver diseases: intervention with traditional Chinese medicine.

The liver, a complex parenchymal organ, possesses a distinctive microcirculatory system crucial for its physiological functions. An intricate interplay exists between hepatic microcirculatory disturbance and the manifestation of pathological features in diverse liver diseases. This review updates the main characteristics of hepatic microcirculatory disturbance, including hepatic sinusoidal capillarization, narrowing of sinusoidal space, portal hypertension, and pathological angiogenesis, as well as their formation mechanisms. It also summarized the detection methods for hepatic microcirculation. Simultaneously, we have also reviewed the characteristics of microcirculatory disturbance in diverse liver diseases such as acute liver failure, hepatic ischemia-reperfusion injury, viral hepatitis, non-alcoholic fatty liver disease, hepatic fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Finally, this review also summarizes the advancement in hepatic microcirculation attributed to traditional Chinese medicine (TCM) and its active metabolites, providing novel insights into the application of TCM in treating liver diseases.

Combination therapy consisting of transarterial chemoembolization, lenvatinib, and programmed cell death protein 1 blockade for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case series study and literature review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava carcinoma tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors (TKIs) is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and one patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in one and three patients, respectively. Treatment-related adverse events of any grade occurred in of 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in one patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

Kopsileuconines A-D: bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.

Three dimensional analysis of factors affecting the prognosis of calcaneal fractures.

PURPOSE: Analyzing the correlation between patients' basic information, three-dimensional parameters after calcaneal fractures, and the prognosis of calcaneal fractures. METHODS: A retrospective analysis was conducted on 43 patients with calcaneal fractures who underwent surgical treatment in the Foot and Ankle Surgery, Xi'an Honghui Hospital, from September 2019 to August 2022. Patient demographics including gender and age were collected, as well as the preoperative posterior articular surface collapse area, number of fracture fragments, length, width, height, and volume of the calcaneus obtained from preoperative three-dimensional imaging. Patients were followed up for VAS, AOFAS, and SF-36 scores. Correlation analysis was performed on the obtained data. RESULTS: All 43 included patients received complete follow-up, including 40 males and 3 females, with an average follow-up time of 35.37 ± 10.73 months, and an average age of 43.98 ± 12.08 years. All patients' VAS, AOFAS, and SF-36 scores at the last follow-up showed no correlation with patient age, gender, or the area of posterior articular collapse, number of fracture fragments, length, width, height, or volume of the calcaneus. CONCLUSIONS: The prognosis of calcaneal fractures is unrelated to three-dimensional factors such as patient age, gender, length, width, height, volume of the calcaneus, area of the posterior joint, and number of fracture fragments.

ARTEMIS: An independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions.

INTRODUCTION: Breast cancer, a heterogeneous disease, is influenced by multiple genetic and epigenetic factors. The majority of prognostic models for breast cancer focus merely on the main effects of predictors, disregarding the crucial impacts of gene-gene interactions on prognosis. OBJECTIVES: Using DNA methylation data derived from nine independent breast cancer cohorts, we developed an independently validated prognostic prediction model of breast cancer incorporating epigenetic biomarkers with main effects and gene-gene interactions (ARTEMIS) with an innovative 3-D modeling strategy. ARTEMIS was evaluated for discrimination ability using area under the receiver operating characteristics curve (AUC), and calibration using expected and observed (E/O) ratio. Additionally, we conducted decision curve analysis to evaluate its clinical efficacy by net benefit (NB) and net reduction (NR). Furthermore, we conducted a systematic review to compare its performance with existing models. RESULTS: ARTEMIS exhibited excellent risk stratification ability in identifying patients at high risk of mortality. Compared to those below the 25th percentile of ARTEMIS scores, patients with above the 90th percentile had significantly lower overall survival time (HR=15.43, 95 % CI: 9.57-24.88, P=3.06 × 10-29). ARTEMIS demonstrated satisfactory discrimination ability across four independent populations, with pooled AUC3-year = 0.844 (95 % CI: 0.805-0.883), AUC5-year = 0.816 (95 % CI: 0.775-0.857), and C-index = 0.803 (95 % CI: 0.776-0.830). Meanwhile, ARTEMIS had well calibration performance with pooled E/O ratio 1.060 (95 % CI: 1.038-1.083) and 1.090 (95 % CI: 1.057-1.122) for 3- and 5-year survival prediction, respectively. Additionally, ARTEMIS is a clinical instrument with acceptable cost-effectiveness for detecting breast cancer patients at high risk of mortality (Pt = 0.4: NB3-year = 0.019, NB5-year = 0.062; NR3-year = 69.21 %, NR5-year = 56.01 %). ARTEMIS has superior performance compared to existing models in terms of accuracy, extrapolation, and sample size, as indicated by the systematic review. ARTEMIS is implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/ARTEMIS/. CONCLUSION: ARTEMIS is an efficient and practical tool for breast cancer prognostic prediction.

Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo. METHODS: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo. RESULTS: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect. CONCLUSION: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Intrarenal venous flow patterns - Guiding fluid management in sepsis with AKI: A case report.

INTRODUCTION: Sepsis often leads to acute kidney injury (AKI), presenting significant challenges in fluid management. This study explores the potential of analyzing intrarenal venous flow (IRVF) patterns to guide tailored fluid therapy, aiming to improve patient outcomes. PATIENT CONCERNS: A patient was admitted to the intensive care unit with symptoms of septic shock, including fever, severe hypotension, and altered mental status, secondary to a perforated ascending colon adenocarcinoma. DIAGNOSIS: The patient was diagnosed with perforated ascending colon adenocarcinoma, septic shock, and AKI. Clinical findings included elevated inflammatory markers and impaired renal function. INTERVENTIONS: The primary therapeutic interventions included surgical resection of the perforated colon, administration of broad-spectrum antibiotics, and fluid resuscitation. Fluid management was guided by continuous monitoring of IRVF, which facilitated precise adjustments to optimize fluid balance and renal perfusion. OUTCOMES: By utilizing IRVF patterns to guide fluid therapy, the patient's circulatory status and renal function significantly improved. The individualized fluid management approach contributed to better stabilization of the patient's condition. LESSONS: This case underscores the potential utility of IRVF patterns in guiding fluid management strategies for patients with sepsis and AKI. The main is the benefit of IRVF-guided fluid therapy in improving patient outcomes. Further research is warranted to validate the efficacy and safety of this approach, with the aim of enhancing clinical outcomes in critically ill patients.

Droplet-based microfluidics for engineering shape-controlled hydrogels with stiffness gradient.

Current biofabrication strategies are limited in their ability to replicate native shape-to-function relationships, that are dependent on adequate biomimicry of shape, size and spatial heterogeneity, within cell-laden hydrogels. In this study, a diffusion-based microfluidics platform is presented that meets these needs in a two-step process. In the first step, a hydrogel-precursor solution is dispersed into a continuous oil phase within the microfluidics tubing. By adjusting the dispersed and oil phase flow rates, the physical architecture of hydrogel-precursor phases can be adjusted to generate spherical and plug-like structures, as well as continuous meter-long hydrogel-precursor phases (up to 1.75 m). The second step involves the controlled introduction a small molecule-containing aqueous phase through a T-shaped tube connector to enable controlled small molecule diffusion across the interface of the aqueous phase and hydrogel-precursor. Application of this system is demonstrated by diffusing co-initiator sodium persulfate (SPS) into hydrogel-precursor solutions, where the controlled SPS diffusion into the hydrogel-precursor and subsequent photo-polymerization allows for the formation of unique radial stiffness patterns across the shape- and size-controlled hydrogels, as well as allowing the formation of hollow hydrogels with controllable internal architectures. Mesenchymal stromal cells are successfully encapsulated within hollow hydrogels and hydrogels containing radial stiffness gradient. The cells are observed to respond to the microscale spatial heterogeneity as evidenced by increased cell elongation in softer core regions of the hydrogel as compared to the peripheral stiffer hydrogel regions, as well as stiffness-dependent nuclear accumulation of the yes-associated protein mechano-regulator. Finally, breast cancer cells are found to phenotypically switch in response to stiffness gradients, causing a shift in their ability to aggregate, which may have implications for metastasis. The diffusion-based microfluidics will mimic native shape-to-function relationship and provides a platform to further study the roles of micro- and macroscale architectural features that exist within native tissues.

TTI-101 targets STAT3/c-Myc signaling pathway to suppress cervical cancer progression: an integrated experimental and computational analysis.

BACKGROUND: Cervical cancer (CC) is a significant global health concern, demanding the consideration of novel therapeutic strategies. The signal transducer and activator of transcription 3 (STAT3) pathway has been implicated in cancer progression and is a potential target for therapeutic intervention. This study aimed to explore the therapeutic potential of TTI-101, a small molecule STAT3 inhibitor, in CC and investigate its underlying mechanisms. METHODS: Molecular docking studies and molecular dynamics simulations were performed to explore the binding interaction between TTI-101 and STAT3 and assess the stability of the STAT3-TTI-101 complex. Cell viability assays, wound healing assays, colony formation assays, flow cytometry analysis, and gene expression analysis were conducted. In vivo xenograft models were used to assess the antitumor efficacy of TTI-101. RESULTS: The in silico analysis shows a stable binding interaction between TTI-101 and STAT3. TTI-101 treatment inhibits cell viability, clonogenic ability, and cell migration in CC cells. Furthermore, TTI-101 induces apoptosis and cell cycle arrest. Analysis of apoptosis-related markers demonstrated dysregulation of Bax, Bcl-2, and Caspase-3 upon TTI-101 treatment. Moreover, TTI-101 caused G2/M phase arrest accompanied by a decrease in CDK1 and Cyclin B1 at mRNA levels. In the xenograft model, TTI-101 significantly inhibited tumor growth without adverse effects on body weight. CONCLUSION: TTI-101 exhibited anticancer effects by targeting the STAT3/c-Myc signaling pathway, inducing cell cycle arrest, and promoting apoptosis in CC cells. These findings provide valuable insights into the development of novel therapeutic strategies for cervical cancer. Further investigation is warranted to validate the clinical application of TTI-101.

A disulfidptosis-related glucose metabolism and immune response prognostic model revealing the immune microenvironment in lung adenocarcinoma.

Background: Lung adenocarcinoma accounts for the majority of lung cancer cases and impact survival rate of patients severely. Immunotherapy is an effective treatment for lung adenocarcinoma but is restricted by many factors including immune checkpoint expression and the inhibitory immune microenvironment. This study aimed to explore the immune microenvironment in lung adenocarcinoma via disulfidptosis. Methods: Public datasets of lung adenocarcinoma from the TCGA and GEO was adopted as the training and validation cohort. Based on the differences in the expression of disulfidptosis -related genes, a glucose metabolism and immune response prognostic model was constructed. The prognostic value and clinical relationship of the model were further explored. Immune-related analyses were performed according to CIBERSORT, ssGSEA, TIDE, IPS. Results: We verified that the model could accurately predict the survival expectancy of lung adenocarcinoma patients. Patients with lung adenocarcinoma and a low-risk score had better survival outcomes according to the model. Moreover, the high-risk group tended to have an immunosuppressive effect, as reflected by the immune cell components, phenotypes and functions. We also found that the clinically relevant immune checkpoint CTLA-4 was significantly higher in low-risk group (P<0.05), indicating that the high-risk group may suffer worse tumor immunotherapy efficacy. Finally, we found that this model has accurate predictive value for the efficacy of immune checkpoint blockade in non-small cell lung cancer (P<0.05). Conclusion: The prognostic model demonstrated the feasibility of predicting survival and immunotherapy efficacy via disulfidptosis-related genes and will facilitate the development of personalized anticancer therapy.

Testicular choriocarcinoma with pelvic and pulmonary metastases: a case report.

Testicular tumors represent a common form of solid tumor in young men, with choriocarcinoma of the testis being a rare, non-granulomatous germ cell tumor. It accounts for less than 0.3% of all testicular germ cell tumors. Pelvic and pulmonary metastases originating from testicular choriocarcinoma are exceptionally uncommon in men. This study describes a case of a 27-year-old male diagnosed with testicular choriocarcinoma, presenting initially with nausea, vomiting, and abdominal pain. Furthermore, this review encompasses cases of testiclar choriocarcinoma in individuals aged 30 years and below, both in China and internationally, over the past 20 years.

Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study.

BACKGROUND & AIMS: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.

Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.

Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.

Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.

Association between thymus density loss and efficacy in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Background: Although the thymus undergoes degeneration with the advancement of age, recent studies have continuously revealed that the thymus possesses the potential for regeneration and may reverse this aging trend. Furthermore, an increasing number of studies indicate an association between thymus function and immunotherapy. Considering that lung cancer patients typically undergo chest computed tomography (CT) scans during treatment, this provides convenient conditions for us to observe thymic remodeling through imaging data. Therefore, exploring the changes in the thymus on CT images is of great significance for understanding its relationship with the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) patients. This study investigated the CT imaging characteristics of thymic density changes in patients with advanced NSCLC after immunotherapy. The primary objective was to determine whether changes in thymic density are predictors of response to immunotherapy in patients with NSCLC. Methods: A total of 412 patients with advanced NSCLC who underwent immunotherapy were included. Thymic density measurements were taken initially and after immunotherapy, with the annualized change calculated. Comprehensive analysis, including disease progression, survival, and subgroup assessments, was conducted. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Results: The annual change in density of the thymic region ranged from -108 to 108 HU after the initiation of ICIs. Patients were categorized into "loss" or "non-loss" groups (210 vs. 202) based on thymic density changes. Analysis of short-term progression of solid tumors revealed no statistically significant differences in ORR (P=0.55) and DCR (P=0.67) between the two groups. Throughout the entire follow-up period, 41 patients (19.5%) in the "loss" group and 64 patients (31.7%) in the "non-loss" group died. Thymic density reduction was not associated with PFS (P=0.08), but it was positively associated with increased OS (P=0.003). The results were consistent across subgroups. Conclusions: Thymic density changes were observed in nearly all NSCLC patients undergoing immunotherapy, with decreased density associated with longer OS. These findings suggest a potential association between thymic density changes and immune efficacy in NSCLC immunotherapy.