Non-small cell lung cancer(NSCLC)accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide.Firstly,this review explores the limitations of conventional therapies,chemotherapy,radiotherapy,and surgery,focusing on the development of drug resistance and significant toxicity that often hinder their efficacy.Thereafter,advancements in targeted therapies,such as immune checkpoint inhibitors(ICIs)and tyrosine kinase inhibitors(TKIs),are dis-cussed,highlighting their impact on improving outcomes for patients with specific genetic mutations,including c-ros oncogene 1 receptor tyrosine kinase(ROS1),anaplastic lymphoma kinase(ALK),and epidermal growth factor receptor(EGFR).Additionally,the emergence of novel immunotherapies and phytochemicals is examined,emphasizing their potential to overcome therapeutic resistance,particu-larly in advanced-stage diseases.The review also delves into the role of next-generation sequencing(NGS)in enabling personalized treatment approaches and explores the clinical potential of innovative agents,such as bispecific T-cell engagers(BiTEs)and antibody-drug conjugates(ADCs).Finally,we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide. Firstly, this review explores the limitations of conventional therapies, chemotherapy, radiotherapy, and surgery, focusing on the development of drug resistance and significant toxicity that often hinder their efficacy. Thereafter, advancements in targeted therapies, such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), are discussed, highlighting their impact on improving outcomes for patients with specific genetic mutations, including c-ros oncogene 1 receptor tyrosine kinase (ROS1), anaplastic lymphoma kinase (ALK), and epidermal growth factor receptor (EGFR). Additionally, the emergence of novel immunotherapies and phytochemicals is examined, emphasizing their potential to overcome therapeutic resistance, particularly in advanced-stage diseases. The review also delves into the role of next-generation sequencing (NGS) in enabling personalized treatment approaches and explores the clinical potential of innovative agents, such as bispecific T-cell engagers (BiTEs) and antibody-drug conjugates (ADCs). Finally, we address the socioeconomic barriers that limit the accessibility of these therapies in low-resource settings and propose future research directions aimed at improving the long-term efficacy and accessibility of these treatments.

Objective:To explore the prognostic value of monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in assessing patients with heart failure with reduced ejection fraction (HFrEF).Methods:Patients with HFrEF (LVEF<40%) admitted to the TEDA International Cardiovascular Disease Hospital between 2 January 2019 and 15 January 2023 were selected. The MHR levels were recorded at admission in patients with HFrEF who were followed up regularly for 12 months. The major adverse cardiovascular events (cardiac death and readmission for heart failure) were defined as poor prognosis. Multivariate Cox regression was used to analyze factors associated with poor prognosis. The receiver operator characteristic (ROC) curves were used to assess the diagnostic value of MHR for poor prognosis. The DeLong test was used to analyze whether there was a difference in the effectiveness of MHR and BNP for detecting poor prognosis. The critical value grouping for poor prognosis was evaluated by MHR, and survival analyses were performed using Kaplan-Meier.Results:A total of 286 subjects were enrolled in the study, including 206 males and 80 females, with a median age ( Q1, Q3) of 67 (58, 74) years. Multivariate Cox regression showed that MHR ( HR=1.482, 95% CI:1.015-2.164) and BNP ( HR=1.001, 95% CI:1.000-1.001) were associated with poor prognosis in patients with HFrEF. The area under the ROC curve for the adjunctive diagnostic value of MHR, BNP and the combination of both for poor prognosis in patients with HFrEF was 0.709, 0.738 and 0.769, respectively. The critical values were 0.486, 1 090 pg/ml and 0.41, respectively. The DeLong test showed no differences in the validity of MHR, BNP and their combination for detecting poor prognosis. Kaplan Meier survival analysis of 12-month follow-up showed that the time for poor prognosis in HFrEF patients with MHR>0.486 group (8.645 months) was significantly shorter than that in MHR≤0.486 group (10.296 months, P<0.001), and the risk of poor prognosis in MHR>0.486 group was 2.843 times higher than that in MHR≤0.486 group ( HR=2.843, 95% CI:1.867-4.327). Conclusion:MHR can be an indicator of poor prognosis in patients with HFrEF.

Objective:To explore the prognostic value of monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in assessing patients with heart failure with reduced ejection fraction (HFrEF).Methods:Patients with HFrEF (LVEF<40%) admitted to the TEDA International Cardiovascular Disease Hospital between 2 January 2019 and 15 January 2023 were selected. The MHR levels were recorded at admission in patients with HFrEF who were followed up regularly for 12 months. The major adverse cardiovascular events (cardiac death and readmission for heart failure) were defined as poor prognosis. Multivariate Cox regression was used to analyze factors associated with poor prognosis. The receiver operator characteristic (ROC) curves were used to assess the diagnostic value of MHR for poor prognosis. The DeLong test was used to analyze whether there was a difference in the effectiveness of MHR and BNP for detecting poor prognosis. The critical value grouping for poor prognosis was evaluated by MHR, and survival analyses were performed using Kaplan-Meier.Results:A total of 286 subjects were enrolled in the study, including 206 males and 80 females, with a median age ( Q1, Q3) of 67 (58, 74) years. Multivariate Cox regression showed that MHR ( HR=1.482, 95% CI:1.015-2.164) and BNP ( HR=1.001, 95% CI:1.000-1.001) were associated with poor prognosis in patients with HFrEF. The area under the ROC curve for the adjunctive diagnostic value of MHR, BNP and the combination of both for poor prognosis in patients with HFrEF was 0.709, 0.738 and 0.769, respectively. The critical values were 0.486, 1 090 pg/ml and 0.41, respectively. The DeLong test showed no differences in the validity of MHR, BNP and their combination for detecting poor prognosis. Kaplan Meier survival analysis of 12-month follow-up showed that the time for poor prognosis in HFrEF patients with MHR>0.486 group (8.645 months) was significantly shorter than that in MHR≤0.486 group (10.296 months, P<0.001), and the risk of poor prognosis in MHR>0.486 group was 2.843 times higher than that in MHR≤0.486 group ( HR=2.843, 95% CI:1.867-4.327). Conclusion:MHR can be an indicator of poor prognosis in patients with HFrEF.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Objective:To investigate the changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its role in predicting major adverse cardiac events (MACEs) in patients with end-stage heart failure (ESHF) before and after implanted a HeartCon left ventricular assist device (LVAD).Methods:The retrospective study included 30 ESHF patients [23 males and 7 females, aged 54.5 (40.8, 60.0) years], who were admitted to TEDA International Cardiovascular Disease Hospital from September 15, 2020 to June 20, 2023 to receive treatment with HeartCon LVAD implantation. Their clinical data were analyzed and NT-proBNP concentrations in their blood samples were measured preoperatively and during the follow-up period. Patients were followed regularly and MACEs, including cardiac death and rehospitalization for right heart failure, were recorded within 6 months of discharge; Logistic regression was used for prognostic analysis, and Receiver Operator Characteristic (ROC) curves were used to assess the adjunctive diagnostic value of NT-proBNP for poor prognosis in LVAD patients. The cut-off values for diagnosing poor prognosis by NT-proBNP were divided into two groups, and survival analysis was performed by Kaplan-Meier and tested by log rank; Cox regression was performed to analyze whether high levels of NT-proBNP at 6 months of follow-up wsa a risk factor for poor prognosis in patients with LVAD.Results:The median preoperative NT-proBNP level in 30 ESHF patients successfully implanted with HeartCon LVADs was 3 251.0 (1 544.5, 6 401.5) pg/ml. It decreased significantly 7 days postoperatively (3 251.0 vs. 1 815.0 pg/ml, P<0.05), and then the decreasing trend slowed. It decreased to 1 182.0 (620.0, 3 385.3) pg/ml on the 90th post-operative day. The preoperative NT-proBNP>3 251.0 pg/ml group had a longer postoperative hospital stay (47 d vs 33 d, Z=-2.138, P=0.032). Multivariate logistic regression analysis, only NT-proBNP at 7 days postoperatively was found to predict poor prognosis in LVAD patients, with an OR of 1.001 ( P=0.01); ROC curves were analyzed for the adjunctive diagnostic value of 7-day postoperative NT-proBNP levels for poor prognosis (cut-off value of 2 083.0 pg/ml), with an AUC of 0.833 ( P=0.002); The Kaplan-Meier survival analysis showed that the time to MACEs within 6 months was significantly shorter in the group with NT-proBNP>2 083.0 pg/mL on postoperative day 7 than in the group with NT-proBNP≤2 083.0 pg/ml (3.538±0.689 vs. 5.471±0.323 months, P=0.004); Cox regression analysis showed that the risk of MACEs was 4.25 times higher in the 7-day postoperative NT-proBNP>2 083.0 pg/ml group than in the NT-proBNP≤2 083.0 pg/ml group ( HR=4.25, P=0.035). Conclusions:The higher the preoperative NT-proBNP level, the longer the postoperative hospital stay in HeartCon LVAD patients. NT-proBNP levels decrease most significantly on postoperative day 7 and is a risk factor for MACEs. It may be used as a prognostic predictor in ESHF patients with implanted LVADs.

The arrival of the era of precision medicine has opened a new diagnosis and treatment model for heart failure (HF), and the development of various omics technologies has also promoted the research and clinical application of HF precision phenotype. HF patients are affected by many factors such as gender, age, height, weight, drugs, valvular disease, etc. At the same time, its disease course is long and complex, and different HF types and stages also affect the treatment and prognosis of patients. Therefore, a variety of new biomarkers are urgently needed in clinic to meet the needs of individualized HF diagnosis and treatment. With the latest advances in epigenetics, proteomics, metabolomics and microbiology, it provides a beneficial complementary effect of "addition" for the study of HF individual heterogeneity. The existing application problems and limitations of various types of markers are discussed. For the future, the integration of all personalized omics data offers unlimited potential for precision medicine in patients with HF.

Objective:To investigate the association between CITP/MMP-1 ratio and the severity of Myocardial fibrosis (MF) in patients with Chronic Heart failure (CHF) and its diagnostic and prognostic value in patients with MF.Methods:A retrospective study was conducted to select 110 cases [86 males, (56.60±11.15) years old;24 females, (60.06±12.02) years old] who were hospitalized in the Department of Cardiology, Teda International Cardiovascular Hospital from May 18, 2021 to February 30, 2022 and underwent magnetic magnetic examination. Serum CITP and MMP-1 were detected by enzyme-linked immunoassay and CITP/MMP-1 ratio was calculated. Plasma brain natriuretic peptide (BNP) was detected by automatic chemiluminescence analyzer. Anova and non-parametric test were used to compare the difference of indexes among all groups. Spearman analysis was used to analyze the correlation between serum collagen metabolites and the severity of myocardial fibrosis. Logistic regression analysis was performed for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of related indexes. Major adverse cardiac events within 1 year after discharge were recorded, including cardiogenic death, HF rehospitalization, malignant arrhythmia, and myocardial infarction. The risk factors of poor prognosis were analyzed by Cox regression. Patients were divided by the median value of CITP/MMP-1 ratio or the median value of CITP/MMP-1 ratio and BNP. Survival analysis was performed by Kaplan-Meier and Log Rank test was performed.Results:Serum MMP-1 and BNP in LGE (+) group were higher than those in LGE (-) group (1.79 ng/ml > 0.91 ng/ml, Z=-2.924; 503 pg/ml > 367 pg/ml, Z=-1.932; P<0.05); The CITP/MMP-1 ratio in the LGE (+) group was lower than that in the LGE (-) group (3.84 < 10.85, Z=-3.601, P<0.001). MMP-1 in CHF with arrhythmia group was higher than that in CHF group (1.98 ng/ml > 1.25 ng/ml, Z=-2.016), while CITP/MMP-1 ratio was lower than that in CHF group (3.25 < 5.73, Z=-2.751), all P<0.05. CITP/MMP-1 ratio in CHF patients was negatively correlated with the severity of MF ( r=-0.363, P<0.001), and BNP and MMP-1 were positively correlated with the severity of MF ( r=0.267, r=0.264, P<0.05). Serum BNP was positively correlated with collagen metabolite MMP-1 and negatively correlated with CITP/MMP-1 ratio (all P<0.05). Logistic multivariate regression analysis showed that only CITP/MMP-1 was a predictor of myocardial fibrosis, with an OR value of 0.624 ( P=0.005). ROC curve was used to evaluate serum BNP, MMP-1 and CITP/MMP-1 ratio in the diagnosis of myocardial fibrosis in HF patients, with AUC of 0.653, 0.696 and 0.754, respectively. The accuracy of CITP/MMP-1 ratio in diagnosing fibrosis was better than that of BNP by comparing their AUC, and the difference was statistically significant ( Z=-3.808, P<0.001). Cox regression analysis showed that CITP/MMP-1 ≤3.84 was a risk factor for poor prognosis, OR=2.647 ( P=0.009). Kaplan-Meier survival analysis at 1-year follow-up showed that the survival rate of the group with lower CITP/MMP-1 ratio was significantly lower than that of the group with higher CITP/MMP-1 ratio ( P=0.014). The survival rate of CITP/MMP-1 increased and BNP decreased group was higher than that of CITP/MMP-1 decreased and BNP increased group ( P=0.011). Conclusions:The ratio of CITP/MMP-1 can be used as a negative correlation indicator of the degree of cross-linking, which is better than BNP in the evaluation of MF, and has a good auxiliary diagnostic value for myocardial fibrosis in patients with chronic heart failure, and is expected to become a protective indicator for patients with chronic heart failure and be used in clinical evaluation of myocardial fibrosis. CITP/MMP-1 ratio is associated with the incidence of major adverse cardiac events, and CITP/MMP-1 ≤3.84 can be used as a predictor of prognostic adverse cardiovascular events in CHF patients.