Rhodium-Promoted C-H Activation/Annulation between DNA-Linked Terminal Alkyne and Aromatic Acid: A Finding from the Selection Outcomes.

Inspired by previous selection outcomes, we investigated and developed a rhodium-promoted C-H activation/annulation reaction of DNA-linked terminal alkynes and aromatic acids. This reaction exhibits excellent efficiency with high conversions and a broad substrate scope. Most importantly, the unique DEL-compatible conditions provide a better scenario for yielding an isocoumarin scaffold compared to conventional organic reaction conditions, and this newly developed on-DNA method has confirmed its feasibility in preparing DNA-encoded libraries.

Progressive Dual Priori Network for Generalized Breast Tumor Segmentation.

To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance. The source code and open data can be accessed at https://github.com/wangli100209/PDPNet.

The roles of nuclear orphan receptor NR2F6 in anti-viral innate immunity.

Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.

Dyadic coping and associated factors in women with high-risk pregnancy and their spouses: Do they interact?

OBJECTIVE: The objective of this study was to examine the present situation of dyadic coping in pregnant women with high-risk pregnancy and their spouses, as well as the relevant factors and the interactions between partners. METHODS: From October 2022 to September 2023, a cross-sectional survey was undertaken, involving 460 pairs of pregnant women with high-risk pregnancy who were hospitalized for childbirth and their accompanying spouses. These participants completed self-assessments on dyadic coping, marital satisfaction, perceived stress, and self-efficacy through the completion of paper questionnaires. The collected data was then subjected to analysis utilizing correlation analysis and multiple linear regression. The actor-partner interdependence model (APIM) was then developed using the structural equation modeling(SEM) to test the binary association. FINDINGS: Pregnant women preferred to utilize stressful communication, whereas their spouses employed supportive and delegated coping. Both external (such as education level, employment status, and medical insurance) and internal (such as marital satisfaction, perceived stress, and self-efficacy) factors were associated with pregnant women's dyadic coping. Education level and internal factors were also associated with the spouses' dyadic coping. In contrast to spouses, who can only have a partner effect on pregnant women through marriage satisfaction, all pregnant women's internal elements played the partner effect on the spouses' dyadic coping. IMPLICATIONS: The study's findings help identify populations with inadequate coping ability. Promoting marital satisfaction, self-efficacy, and reducing perceived stress are associated with enhancing the dyadic coping ability of pregnant women with high-risk pregnancy and their spouses. It also suggests that antenatal care should intervene with pregnant women with high-risk pregnancy and their spouses as a whole, and emphasize collaborative coping and effective mutual support between couples rather than spousal support alone.

PLA2G12A protects against diet-induced obesity and insulin resistance by enhancing energy expenditure and clearance of circulating triglycerides.

Secreted phospholipase A2s are involved in the development of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease, which have become serious and growing health concerns worldwide. Integration of genome-wide association study and gene co-expression networks analysis showed that the secreted phospholipase A2 group XIIA (PLA2G12A) may participate in hepatic lipids metabolism. Nevertheless, the role of PLA2G12A in lipid metabolism and its potential mechanism remain elusive. Here, we used AAV9 vector carrying human PLA2G12A gene to exogenously express hPLA2G12A in the liver of mice. We demonstrated that the overexpression of hPLA2G12A resulted in a significant decrease in serum lipid levels in wild-type mice fed with chow diet or high-fat diet (HFD). Moreover, hPLA2G12A treatment protected against diet-induced obesity and insulin resistance in mice fed a HFD. Notably, we found that hPLA2G12A treatment confers protection against obesity and hyperlipidemia independent of its enzymatic activity, but rather by increasing physical activity and energy expenditure. Furthermore, we demonstrated that hPLA2G12A treatment induced upregulation of ApoC2 and Cd36 and downregulation of Angptl8, which contributed to the increase in clearance of circulating triglycerides and hepatic uptake of fatty acids without affecting hepatic de novo lipogenesis, very low-density lipoprotein secretion, or intestinal lipid absorption. Our study highlights the potential of PLA2G12A gene therapy as a promising approach for treating obesity, insulin resistance and T2DM.

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel by genetic mutations causes the inherited disease cystic fibrosis (CF). CF lung disease that involves multiple disorders of epithelial function likely results from loss of CFTR function as an anion channel conducting chloride and bicarbonate ions and its function as a cellular regulator modulating the activity of membrane and cytosol proteins. In the absence of CFTR activity, abundant mucus accumulation, bacterial infection and inflammation characterize CF airways, in which inflammation-associated tissue remodeling and damage gradually destroys the lung. Deciphering the link between CFTR dysfunction and bacterial infection in CF airways may reveal the pathogenesis of CF lung disease and guide the development of new treatments. Research efforts towards this goal, including high salt, low volume, airway surface liquid acidosis and abnormal mucus hypotheses are critically reviewed.

Target organ damage in untreated hypertensive patients with primary aldosteronism.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity.

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Stem Cell-Derived Extracellular Vesicles: Promising Therapeutic Opportunities for Diabetic Wound Healing.

Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care.

Three-dimensional Ni foam supported Pt/NiFe LDH catalyst with enhanced oxygen activation for room-temperature formaldehyde oxidation.

Room-temperature catalytic oxidation of formaldehyde (HCHO) has been extensively investigated due to its high efficiency, convenience, and environmental friendliness. Herein, nickel-iron layered double hydroxide (NiFe LDH) nanosheets were synthesized in-situ on a nickel foil (NF) using a facile one-step hydrothermal method, followed by the deposition of ultra-low content (0.069 wt%) of Pt nanoparticles through NaBH4 reduction. The resulting three-dimensional (3D) hierarchical Pt/NiFe-NF catalyst exhibited exceptional activity for the complete decomposition of formaldehyde to carbon dioxide (CO2) at room temperature (∼95 % conversion within 1 h), as well as remarkable cycling stability. The 3D porous structure of Pt/NiFe-NF provides fast transport channels for the diffusion of gas molecules, making the active catalyst surfaces more accessible. Moreover, abundant hydroxyl groups in NiFe LDH serve as adsorption centers for HCHO molecules to form dioxymethylene (DOM) and formate intermediates. Furthermore, electronic interactions between NiFe LDH and Pt enhance the adsorption and activation of O2 on Pt surfaces, leading to the complete decomposition of intermediates into non-toxic products. This work presents new insights into the design and preparation of Pt-based 3D hierarchical catalysts with surface-rich hydroxyl groups for the efficient removal of indoor HCHO.

[Using Cloud Healthcare to Improve Home Learning Efficacy in Congenital Heart Disease Infants].

BACKGROUND: During the COVID-19 pandemic, visitation restrictions in line with infection control policies curtailed opportunities for family members to learn essential caregiving skills in the intensive care unit. This limitation decreased satisfaction among family members, possibly indicating their increased difficulties in care due to the lack of face-to-face guidance. Thus, increasing family member understanding of and ability to apply learning content without direct interaction presents a significant and urgent challenge. Moreover, because of lack of caregiving confidence, some family members may be reluctant to facilitate the discharge of critically ill patients, causing delays in discharge planning. These challenges underscore the obstacles faced by nursing health education during the pandemic. PURPOSE: This study was designed to utilize cloud technology to enhance the knowledge and skills of families caring for infants with congenital heart disease at home and to assess their satisfaction with the associated homecare learning platform. RESOLUTION: Based on our hospital's cloud-based health education platform, a series of personalized instructional video materials was developed for families of infants with congenital heart disease. These materials cover comprehensively the entire treatment process, from diagnosis to post-discharge home care skills, for these patients. To facilitate autonomous learning, the videos in this series were made accessible to the families anytime, anywhere via personal devices such as smartphones and tablets. Concurrently, a chatbot tool was integrated to provide guidance on inpatient care for infants with congenital heart disease, including fundamental aspects of newborn care, with the aim of equipping parents and caregivers with the knowledge and skills necessary to provide basic post-discharge care. To ensure the families acquired personalized care skills, after completing the learning modules, practical bedside training sessions incorporating knowledge and skills assessments were organized for family members. RESULTS: After project implementation, the average knowledge score for family members increased significantly from 79.1 to 100 (perfect score). The proportion of family members proficient in executing caregiving techniques autonomously also rose impressively from 30% to 95%. Furthermore, average overall satisfaction with cloud-based technology-assisted caregiving learning among the family members rose 31.4% from 3.5 to 4.6. CONCLUSIONS: This project represents a viable solution to providing clinical nursing guidance independent of the constraints of time and location, and effectively enhances homecare-skill-related learning outcomes in family members, especially with regard to caring for infants with congenital heart disease.

The dyadic associations among self-efficacy, dyadic coping, and health-related quality of life between high-risk pregnant women and spouses: a cross-sectional study.

AIM: Health-related quality of life(HRQoL) is essential for high-risk pregnant women and their spouses. This study aimed to explore the dyadic associations (including actor and partner effects) among self-efficacy, dyadic coping, and HRQoL of high-risk pregnant women and their spouses and examine the mediating effect of dyadic coping. METHODS: This cross-sectional study recruited participants from two Grade A tertiary hospitals in China from October 2022 to September 2023. A questionnaire including the Chinese version of the General Self-Efficacy Scale, Dyadic Coping Inventory, and 12 Short Form Health Survey Scales was used for the survey. The actor-partner interdependence mediation model was constructed to test dyadic associations and mediating effects. RESULTS: In the actor effects, self-efficacy was positively associated with dyadic coping and HRQoL (P < 0.05). Regarding partner effects, pregnant women's self-efficacy was positively associated with spouses' dyadic coping and physical health (P < 0.05). Dyadic coping partially mediated the relationship between self-efficacy and HRQoL for both groups(P < 0.05). CONCLUSION: The HRQoL of high-risk pregnant women and their spouses requires urgent attention. Enhancing self-efficacy and dyadic coping in these couples is related to their improved physical and mental health. Healthcare professionals should consider interactions between couples and include them together in perinatal care. Intervention programs for couples or families based on existing positive psychology and dyadic interventions may work together to improve the HRQoL of couples.

Inhibition of NOTCH4 sensitizes FLT3/ITD acute myeloid leukemia cells to FLT3 tyrosine kinase inhibition.

Internal tandem duplication mutations of FLT3 (FLT3/ITD) confer poor prognosis in AML. FLT3 tyrosine kinase inhibitors (TKIs) alone have limited and transient clinical efficacy thus calling for new targets for more effective combination therapy. In a loss-of-function RNAi screen, we identified NOTCH4 as one such potential target whose inhibition proved cytotoxic to AML cells, and also sensitized them to FLT3 inhibition. Further investigation found increased NOTCH4 expression in FLT3/ITD AML cell lines and primary patient samples. Inhibition of NOTCH4 by shRNA knockdown, CRISPR-Cas9-based knockout or γ-secretase inhibitors synergized with FLT3 TKIs to kill FLT3/ITD AML cells in vitro. NOTCH4 inhibition sensitized TKI-resistant FLT3/ITD cells to FLT3 TKI inhibition. The combination reduced phospho-ERK and phospho-AKT, indicating inhibition of MAPK and PI3K/AKT signaling pathways. It also led to changes in expression of genes involved in regulating cell cycling, DNA repair and transcription. A patient-derived xenograft model showed that the combination reduced both the level of leukemic involvement of primary human FLT3/ITD AML cells and their ability to engraft secondary recipients. In summary, these results demonstrate that NOTCH4 inhibition synergizes with FLT3 TKIs to eliminate FLT3/ITD AML cells, providing a new therapeutic target for AML with FLT3/ITD mutations.

Cancer cell membrane-camouflaged biomimetic nanoparticles for enhancing chemo-radiation therapy efficacy in glioma.

Glioblastoma multiforme (GBM) presents significant challenges in treatment, with current standard-of-care approaches offering limited efficacy and survival benefits. This necessitates the development of innovative therapeutic strategies to enhance treatment outcomes. Nanotechnology has emerged as a promising avenue in cancer therapy, offering targeted drug delivery and enhanced therapeutic efficacy. Polymeric nanoparticles, particularly those based on Poly (lactic-co-glycolic acid) (PLGA), have gained traction as drug carriers due to their biocompatibility and controlled release properties. However, their interception by macrophages poses challenges to effective drug delivery. Superparamagnetic iron oxide (SPIO) nanoparticles have shown promise as radiosensitizers, enhancing the efficacy of radiotherapy through the generation of reactive oxygen species (ROS). Moreover, cell membrane biomimetic drug delivery systems have garnered attention for their ability to improve biocompatibility and targeting capabilities. Leveraging these concepts, our study introduces a novel multifunctional platform, GM@P (T/S), comprising polymeric nanoparticles coated with cancer cell membrane. By encapsulating temozolomide (TMZ) and SPIO nanoparticles within GM@P (T/S), we aim to synergistically enhance the cytotoxic effects of chemotherapy and radiotherapy against GBM while overcoming limitations associated with conventional treatments. This innovative approach holds promise for addressing the unmet clinical needs in GBM therapy and advancing towards more effective and personalized treatment strategies.

[Research status and prospects of probiotics in functional gastrointestinal disorders in infants and toddlers]. / ç›Šç”ŸèŒåœ¨å©´å¹¼å„¿åŠŸèƒ½æ€§èƒƒè‚ ç— ä¸­çš„ç ”ç©¶çŽ°çŠ¶åŠå±•æœ›.

Functional gastrointestinal disorders (FGIDs) are common digestive system diseases in children, which can severely affect the growth and development of infants and toddlers. Probiotics therapy, as a relatively safe treatment method, have attracted the attention of researchers. However, their effectiveness in treating FGIDs in infants and toddlers is still unclear. This article reviews the mechanisms of probiotics in treating FGIDs in infants and toddlers, explores the reasons for the inconsistency in various research results, and aims to provide assistance for the clinical treatment of FGIDs in infants and toddlers and future research.

Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription.

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

Draconibacterium aestuarii sp.nov., a Glycolipid-Producing Bacterium Isolated from Tidal Flat Sediment and Emended Description of the Genus Draconibacterium.

A facultatively anaerobic, Gram-negative, curved rod-shaped bacterium (4.0-17.0 µm long, 0.6-0.9 µm wide), designated Z1-6T, was obtained from tidal flat sediment collected from YueAo village in Zhoushan, Zhejiang, People's Republic of China. Strain Z1-6T occurred at 15-45 °C (optimum 28-32 °C), pH 6.0-9.0 (optimum 7.0-7.5), and in the presence of 1-5% (w/v) NaCl (optimum 1-2%). The strain contained iso-C15:0 and antesio-C15:0 as the major fatty acids. An unsaturated menaquinone with seven isoprene units (MK-7) was the predominant respiratory quinone. The polar lipids included phosphatidylethanolamine (PE), one aminophospholipid (APL), two phospholipids (PL1 and PL2), three glycolipids (GL1, GL2, and GL3), and two unidentified lipids (L1 and L2). The genomic DNA G+C content of strain Z1-6T was 39.2%, and the genome size was 6.4 Mb. The strain showed the highest average nucleotide identity (ANI) value of 73.5-74.6%, digital DNA-DNA hybridization (dDDH) value of 19.3-20%, average amino acid identity (AAI) value of 72.0-73.1% with the members of genus Draconibacterium. Phylogenetic analysis based on 16S rRNA gene sequences and genome revealed that strain Z1-6T formed a distinct branch in the clade of the genus Draconibacterium. Based on the phenotypic, phylogenetic, chemotaxonomic analyses and genomic data, strain Z1-6T represents a novel species of the genus Draconibacterium, for which the name Draconibacterium aestuarii sp. nov. (The type strain Z1-6T = MCCC 1K07533T = KCTC 92310T) is proposed.

Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis.

Objective: To evaluate the efficacy of different combinations of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: We obtained relevant randomized controlled trials (RCTs) from databases such as PubMed, Embase, Web of Science, and The Cochrane Library up to May 31, 2023. The analysis of clinical prognostic factors was performed using R 4.2.3 and STATA 15.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events of grade 3-5 severity (Grade ≥3 TRAE). Results: A total of 17 randomized controlled trials (RCTs) were conducted between 2012 and 2023, involving 7792 patients. These trials evaluated 11 different treatment methods. The results of these trials showed that in terms of overall survival (OS) and progression-free survival (PFS), the combination of tislelizumab with chemotherapy and the combination of camrelizumab with chemotherapy were particularly effective. Moreover, when compared with other combination therapies, pembrolizumab combined with chemotherapy showed superiority in terms of disease control rate (DCR) and objective response rate (ORR). Subgroup analyses further demonstrated that the addition of immune checkpoint inhibitors (ICIs) to chemotherapy significantly improved PFS and OS in patients without liver metastasis and in those with brain metastasis. Additionally, carboplatin-based combination therapy was found to confer favorable survival benefits in terms of PFS, while cisplatin-based combination therapy showed the most favorable outcomes in terms of OS. The results of subgroup analyses for overall survival (OS) showed that the combination of immunotherapy and chemotherapy yielded positive outcomes in specific subgroups. These subgroups were characterized by PD-L1 Tumor Proportion Score (TPS) of 50 % or higher, usage of anti-PD-1 medications, age below 65, male gender, smoking history, and non-squamous cell carcinoma histology. Superior effectiveness was demonstrated only in extending the progression-free survival (PFS) of female patients and patients with squamous carcinoma. Meanwhile, other patient cohorts did not show the same level of improvement. Conclusions: Tislelizumab, camrelizumab or pembrolizumab combined with chemotherapy may be the optimal first-line treatment strategies for NSCLC.