Bioinspired and biomimetic strategies for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.

Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types.

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

Prognostic implication of UBE2C + CD8 + T cell in neoadjuvant immune checkpoint blockade plus chemotherapy for locally advanced esophageal cancer.

BACKGROUND: Immune checkpoint blockers (ICBs) plus chemotherapy as neoadjuvant therapy for patients with esophageal cancer (EC) has gained substantial attention. This study aimed to investigate the early and mid-term outcome of neoadjuvant ICBs plus chemotherapy and discover immune-associated predictors of major pathological response (MPR) for locally advanced EC. METHOD: Patients with locally advanced EC who received neoadjuvant ICBs plus chemotherapy were retrospectively included between June 2019 to December 2021. Conjoint analysis of Bulk-RNA seq (GSE165252) and scRNA seq (GSE188900) were used to investigate potential prognostic factors and immunological mechanisms, then multiplexed immunofluorescence was applied to validate. RESULTS: 76 patients were included. A total of 21 (27.6 %) patients achieved MPR, with 13 (17.1 %) attaining a pathological complete response. Over a median follow-up of 1.8 years, 6 (7.9 %) patients died and 21 (27.6 %) experienced disease recurrence within 0.6 to 2.1 years after surgery. The overall survival rate and recurrence-free survival rate were 93.3 + 2.9 % and 84.8 + 4.2 % at 12 months, 90.8 + 3.7 % and 67.1 + 6.4 % at 24 months, and 90.8 + 3.7 % and 62.9 + 7.2 % at 36 months, respectively. Patients achieving MPR had a significantly lower risk of recurrence compared to non-responders (9.5 % vs 34.5 %, P = 0.017). Analysis of bulk-RNA seq and scRNA-seq revealed that UBE2C and UBE2C + CD8 + T cells were adverse prognostic factors. Immunohistochemistry demonstrated that the non-MPR group had a higher infiltration of UBE2C + immune cells than MPR group after neoadjuvant treatment. Multiplexed immunofluorescence confirmed that infiltrating UBE2C + CD8 + T cells in MPR group were significantly fewer than non-MPR group after neoadjuvant treatment, indicating their poor prognostic role for EC. CONCLUSIONS: Neoadjuvant ICBs plus chemotherapy shows promising efficacy in locally advanced EC, with MPR being a significant predictor of lower recurrence risk. Immunological analyses identified UBE2C + CD8 + T cells as adverse prognostic factors, suggesting their potential as biomarkers for patient stratification and treatment response.

miR-22-3p in the rostral ventrolateral medulla promotes hypertension through inhibiting ß-arrestin-1.

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that ß-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in ß-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the ß-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of ß-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by ß-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced ß-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting ß-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of ß-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of ß-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the ß-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of ß-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting ß-arrestin-1 in the RVLM.

The Application of Mesenchymal Stem Cells in Future Vaccine Synthesis.

Vaccines have significant potential in treating and/or preventing diseases, yet there remain challenges in developing effective vaccines against some diseases, such as AIDS and certain tumors. Mesenchymal stem cells (MSCs), a subset of cells with low immunogenicity, high proliferation potential, and an abundant source of extracellular vesicles (EVs), represent one of the novel and promising vaccine platforms. This review describes the unique features and potential mechanisms of MSCs as a novel vaccine platform. We also cover aspects such as the safety and stability of MSCs that warrant future in-depth studies.

Direct prediction of gas adsorption via spatial atom interaction learning.

Physisorption relying on crystalline porous materials offers prospective avenues for sustainable separation processes, greenhouse gas capture, and energy storage. However, the lack of end-to-end deep learning model for adsorption prediction confines the rapid and precise screen of crystalline porous materials. Here, we present DeepSorption, a spatial atom interaction learning network that realizes accurate, fast, and direct structure-adsorption prediction with only information of atomic coordinate and chemical element types. The breakthrough in prediction is attributed to the awareness of global structure and local spatial atom interactions endowed by the developed Matformer, which provides the intuitive visualization of atomic-level thinking and executing trajectory in crystalline porous materials prediction. Complete adsorption curves prediction could be performed using DeepSorption with a higher accuracy than Grand canonical Monte Carlo simulation and other machine learning models, a 20-35% decline in the mean absolute error compared to graph neural network CGCNN and machine learning models based on descriptors. Since the established direct associations between raw structure and target functions are based on the understanding of the fundamental chemistry of interatomic interactions, the deep learning network is rationally universal in predicting the different physicochemical properties of various crystalline materials.

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS.

BACKGROUND: Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated. AIM: To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression. METHODS: Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis. RESULTS: The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC. CONCLUSION: This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Ephrin-A4 Ligand (EFNA4) Predicts Poor Prognosis of Hepatocellular Carcinoma and Promotes Tumor Proliferation.

Background/Aims: Primary hepatocellular carcinoma (HCC) is one of the most lethal tumor diseases in the world. Receptor tyrosine kinases (RTKs) are thought to play a vital role in HCC and Ephrin-A4 ligand (EFNA4) is a membrane-bound molecule that can activate RTKs through erythropoietin-producing hepatocellular (Eph) receptors. However, the specific role of EFNA4 remains unknown. The aim of our study was to explore the prognostic value of EFNA4 expression in HCC. Methods: Bioinformatics analyses were conducted to probe the expression levels and prognostic value of EFNA4 in HCC. The quantitative real-time polymerase chain reaction, immunohistochemical and western blot were used to confirm the expression of EFNA4 in paired clinical specimens of HCC. Colony formation assay was used to confirm the proliferation of tumor cell. Results: The expression of EFNA4 is generally elevated in various cancers. Especially, EFNA4 was upregulated in tumor tissue and associated with clinical stage in HCC patients. HCC patients with lower levels of EFNA4 possessed better survival and progression-free survival times. Colony formation assay indicated that the overexpression of EFNA4 promoted tumor cell proliferation. Conclusion: These results demonstrated that EFNA4 played as an oncogenic gene and a prognostic biomarker for HCC patients.

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects.

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. The review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy.

The effectiveness of problem-based learning compared with lecture-based learning in surgical education: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to systematically evaluate the impact of problem-based learning (PBL) and lecture-based learning (LBL) teaching models on students' learning in surgical education. METHODS: We systematically searched the publications related to the application of PBL and LBL in surgical courses in PubMed, Embase, Web of Science and Cochrane Library databases, the last retrieval time is September 20, 2022. After screening the literature according to the inclusion and exclusion criteria, extracting data and evaluating the methodological treatment of the included studies, Stata 17.0 software was used to perform meta-analysis. RESULTS: Nine studies were included totally. The results showed that compared with LBL, PBL was superior in clinical competence (SMD = 0.81, 95% CI: 0.12 ~ 1.49, P = 0.020) and student satisfaction (SMD = 2.13, 95% CI: 1.11 ~ 3.15, P < 0.0001) with significant differences. But the comprehensive scores (SMD = 0.26, 95% CI: -0.37 ~ 0.89, P = 0.421) and theoretical knowledge (SMD=-0.19, 95% CI: -0.71 ~ 0.33, P = 0.482) to PBL and LBL had no significant difference. CONCLUSION: This study showed that the PBL teaching model is more effective than the LBL teaching model in surgical education on the aspects of enhancing clinical competence and student satisfaction. However, further well-designed studies are needed to confirm our findings.

A case of Marine Lenhart syndrome with Hashimoto's thyroiditis that mimicked thyroid carcinoma.

BACKGROUND: Marine Lenhart syndrome is a rare disease and causes refractory hyperthyroidism. So far, little evidence on the combination of both Marine Lenhart syndrome and Hashimoto's thyroiditis is available. We suspect that Marine Lenhart syndrome when combined with Hashimoto's thyroiditis might have its particular features, which are not exactly the same as those of the isolated Marine Lenhart syndrome. CASE PRESENTATION: A 56-year-old middle-aged man presented with recurrent hyperthyroidism, and Graves' disease combined with Hashimoto's thyroiditis was considered. Radionuclide imaging showed a hot nodule, but ultrasonography suggested the possibility of malignancy with a category of 4B according to the Chinese-Thyroid Imaging-Reporting and Data System (C-TIRADS) model. Fine needle aspiration cytology (FNAC) revealed eosinophilic follicular lesions with papillary features, and prompted that papillary thyroid carcinoma could not be excluded. Partial thyroidectomy was performed and the nodule was proven to be benign by histopathology. The final diagnosis was atypical Marine Lenhart syndrome with Hashimoto's thyroiditis. CONCLUSIONS: Marine Lenhart syndrome combined with Hashimoto's thyroiditis has its particular characteristics, showing some signs mimicking malignancy. Limitations of ultrasonography and FNAC in diagnosis should be noted in these scenarios.

Detection of KRAS mutation using plasma samples in non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The aim of this study was to investigate the diagnostic accuracy of KRAS mutation detection using plasma sample of patients with non-small cell lung cancer (NSCLC). Methods: Databases of Pubmed, Embase, Cochrane Library, and Web of Science were searched for studies detecting KRAS mutation in paired tissue and plasma samples of patients with NSCLC. Data were extracted from each eligible study and analyzed using MetaDiSc and STATA. Results: After database searching and screening of the studies with pre-defined criteria, 43 eligible studies were identified and relevant data were extracted. After pooling the accuracy data from 3341 patients, the pooled sensitivity, specificity and diagnostic odds ratio were 71%, 94%, and 59.28, respectively. Area under curve of summary receiver operating characteristic curve was 0.8883. Subgroup analysis revealed that next-generation sequencing outperformed PCR-based techniques in detecting KRAS mutation using plasma sample of patients with NSCLC, with sensitivity, specificity, and diagnostic odds ratio of 73%, 94%, and 82.60, respectively. Conclusion: Compared to paired tumor tissue sample, plasma sample showed overall good performance in detecting KRAS mutation in patients with NSCLC, which could serve as good surrogate when tissue samples are not available.

Stoma-site approach single-port laparoscopic versus conventional multi-port laparoscopic Miles's procedure for low rectal cancer: A prospective, randomized controlled trial.

OBJECTIVE: The aim of this study was to compare perioperative outcomes of patients with low rectal cancer after stoma-site approach single-port laparoscopic Miles procedure or conventional multi-port laparoscopic Miles procedure, as well as to evaluate the safety and efficacy of stoma-site approach single-port laparoscopic surgery in low rectal cancer. METHODS: Between September 2020 and September 2021, 51 low rectal cancer patients scheduled for Miles procedure at the Department of Gastrointestinal Surgery of Affiliated Hospital of North Sichuan Medical College were randomly assigned to the single-port laparoscopic surgery group (SPLS) and the multi-port laparoscopic surgery (MPLS) group. The perioperative outcomes were compared between the two groups. RESULTS: In this study, 25 patients underwent SPLS and 26 underwent MPLS. All patients completed the study, and there were no perioperative deaths in either group. Observation indicators such as intraoperative bleeding (39 mL vs. 41 mL), number of lymph nodes (20.12 ± 3.29 vs. 21.84 ± 3.74), average hospital stay (7.15 ± 1.52 vs. 7.64 ± 1.66), and time to flatulence (2.5d vs. 2.5d) showed no significant differences between the SPLS and MPLS groups (p > 0.05). However, the operation duration (180 min vs. 118 min) and perioperative complications showed statistically significant differences between the two groups (p < 0.05). In addition, patients in the SPLS group had significantly higher satisfaction scores than those in the MPLS group (p < 0.05). CONCLUSION: For patients with low rectal cancer requiring Miles surgery, stoma-site approach single-port laparoscopic surgery has comparable safety and efficacy to multi-port laparoscopic surgery.

PTP1B knockdown alleviates BMSCs senescence via activating AMPK-mediated mitophagy and promotes osteogenesis in senile osteoporosis.

The senescence of bone marrow mesenchymal stem cells (BMSCs) is the basis of senile osteoporosis (SOP). Targeting BMSCs senescence is of paramount importance for developing anti-osteoporotic strategy. In this study, we found that protein tyrosine phosphatase 1B (PTP1B), an enzyme responsible for tyrosine dephosphorylation, was significantly upregulated in BMSCs and femurs with advancing chronological age. Therefore, the potential role of PTP1B in BMSCs senescence and senile osteoporosis was studied. Firstly, significantly upregulated PTP1B expression along with impaired osteogenic differentiation capacity was observed in D-galactose (D-gal)-induced BMSCs and naturally-aged BMSCs. Furthermore, PTP1B silencing could effectively alleviate senescence, improve mitochondrial dysfunction, and restore osteogenic differentiation in aged BMSCs, which was attributable to enhanced mitophagy mediated by PKM2/AMPK pathway. In addition, hydroxychloroquine (HCQ), an autophagy inhibitor, significantly reversed the protective effects from PTP1B knockdown. In SOP animal model, transplantation of LVsh-PTP1B-transfected D-gal-induced BMSCs harvested double protective effects, including increased bone formation and reduced osteoclastogenesis. Similarly, HCQ treatment remarkably suppressed osteogenesis of LVsh-PTP1B-transfected D-gal-induced BMSCs in vivo. Taken together, our data demonstrated that PTP1B silencing protects against BMSCs senescence and mitigates SOP via activating AMPK-mediated mitophagy. Targeting PTP1B may represent a promising interventional strategy to attenuate SOP.

Topological optimization of anterior cervical plate (ACP) and its biomechanic characteristics.

BACKGROUND: Currently, quadrilateral anterior cervical plate (QACP) is a highly prevalent ACP. OBJECTIVE: This study aims to design a novel ACP using topology optimization (TOACP). METHODS: A completed model for C1-C7 cervical segments was established and validated. QACP and TOACP cage systems were implanted within two cervical vertebrae models, respectively, and peak stresses and stress distributions for screw, plate, endplate and cage displacement were investigated under differing exercise modes. RESULTS: Stress levels upon QACP screw were maximized for over-extension exercise (243.3 MPa, 3.35% > TOACP screw). Stress level upon TOACP plate was maximized for over-extension exercise (118.2 MPa, 7.26% > QACP screw). Following QACP cage system implantation, stress on endplate and cage displacement were maximized for extension exercise, which were 27.1%, and 6.3% > TOACP cage system, respectively. Finite element analysis results revealed that topological optimization of the plate can effectively reduce screw stress, thereby enhancing cervical segments' stability during surgery. Furthermore, stress on endplate and cage displacement decreased, indicating great potential in cage sinking and fusion enhancement. CONCLUSIONS: Topological optimization of the plate equips the cage system with advantages in clinical applications and biomechanical performance, providing alternative solutions and a theoretical basis for ACP design.

[Macroscopic and mesoscopic biomechanical analysis of the bone unit in idiopathic scoliosis].

To investigate the effects of postoperative fusion implantation on the mesoscopic biomechanical properties of vertebrae and bone tissue osteogenesis in idiopathic scoliosis, a macroscopic finite element model of the postoperative fusion device was developed, and a mesoscopic model of the bone unit was developed using the Saint Venant sub-model approach. To simulate human physiological conditions, the differences in biomechanical properties between macroscopic cortical bone and mesoscopic bone units under the same boundary conditions were studied, and the effects of fusion implantation on bone tissue growth at the mesoscopic scale were analyzed. The results showed that the stresses in the mesoscopic structure of the lumbar spine increased compared to the macroscopic structure, and the mesoscopic stress in this case is 2.606 to 5.958 times of the macroscopic stress; the stresses in the upper bone unit of the fusion device were greater than those in the lower part; the average stresses in the upper vertebral body end surfaces were ranked in the order of right, left, posterior and anterior; the stresses in the lower vertebral body were ranked in the order of left, posterior, right and anterior; and rotation was the condition with the greatest stress value in the bone unit. It is hypothesized that bone tissue osteogenesis is better on the upper face of the fusion than on the lower face, and that bone tissue growth rate on the upper face is in the order of right, left, posterior, and anterior; while on the lower face, it is in the order of left, posterior, right, and anterior; and that patients' constant rotational movements after surgery is conducive to bone growth. The results of the study may provide a theoretical basis for the design of surgical protocols and optimization of fusion devices for idiopathic scoliosis.

Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors. METHODS: A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; P < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; P = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; P < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; P = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; P = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors. CONCLUSION: In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.