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.

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 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: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 To explore the comprehensive analysis of mRNA/microRNA(miRNA)networks in peripheral blood of patients with schizophrenia.Methods A total of 6 schizophrenic patients treated in a hos-pital from December 2022 to February 2023 were included as the experimental group and 4 volunteers as the control group.Blood samples of the two groups were collected and the mRNA and miRNA expression levels were detected by RNA-seq technique.Finally,the gene set GSE145554 in Gene Expression Omnibus was used for bioinformatics verification analysis.Results Compared with the control group,a total of 2 133 mRNA differences were detected in the experimental group,including 1 410 mRNA up-regulated and 723 mRNA down-regulated.There were 150 differential miRNAs,including 72 up-regulated miRNAs and 78 down-regula-ted miRNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment biological processes and signaling pathways mainly include mammalian target of rapamycin(mTOR)signaling pathway,phos-phatidylinositide 3-kinases(PI3K)-serine/threonine-protein kinase(AKT)signaling pathway,necroptosis,and protein processing in the endoplasmic reticulum endoplasmic reticulum signaling pathways etc.Conclusion PI3K-AKT,mTOR,necroptosis and protein processing in endoplasmic reticulum signaling pathways are in-volved in the occurrence and development of schizophrenia,and provide a new research direction for the pre-vention,diagnosis and treatment of schizophrenia.

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.

Objective:To investigate the relationship between peripheral blood sST2 level and prognosis in patients with heart failure (HFpEF) complicated with hypertension with ejection fraction preservation.Methods:A total of 122 patients with HFpEF hospitalized in Teda International Cardiovascular Hospital and Baoding First Central Hospital from May 5, 2021 to March 9, 2023 were selected. According to whether they were combined with hypertension, they were divided into HFpEF combined with hypertension group (73 cases, 32 males, (67.56±12.06) years old). There were 41 females (70.61±9.95 years old) and 49 males (67.00±11.64 years old) in the HFpEF group alone. There were 24 female patients (70.12±7.49 years old). sST2 levels in peripheral blood were compared between the two groups.HFpEF patients with hypertension were grouped by hypertension grade and prognosis, and the difference of sST2 in different groups was compared. Logistic regression was used for multivariate analysis. ROC curve to evaluate the diagnostic value of sST2 in the poor prognosis of HFpEF patients with hypertension. Patients were followed up regularly and major adverse cardiac events were recorded within 6 months after discharge, including cardiogenic death and heart failure re-hospitalization. The critical value of poor prognosis diagnosed by sST2 was divided into two groups, survival analysis was performed by Kaplan-Meier,and the Log Rank test was performed. Cox regression analysis was performed to determine whether high levels of sST2 were a risk factor for poor prognosis after 6 months of follow-up.Results:There was no significant difference in sST2 in HFpEF combined with hypertension and HFpEF alone ( P>0.05). sST2 was higher in grade 2 and 3 than in grade 1 hypertension (23.83 ng/ml vs. 12.68 ng/ml, Z=-2.778, P=0.005; 22.54 ng/ml vs. 12.68 ng/ml, Z=-2.865, P=0.004); BNP was higher in grade 3 hypertension than in grade 1 hypertension (582.95 pg/ml vs. 154.50 pg/ml, Z=-2.101, P<0.05). sST2 and BNP were higher in the poor prognosis group than in the good prognosis group (30.10 ng/ml vs. 18.95 ng/ml, Z=-2.803; 685.00 pg/ml vs. 347.50 pg/ml, Z=-2.385), all P<0.05. Logistic regression analysis showed that sST2 was a risk factor for poor prognosis ( OR=1.045, P=0.013). The auxiliary diagnostic value of sST2 level in HFpEF patients with hypertension was analyzed by ROC curve (AUC was 0.721, P<0.05). The incidence of cardiac adverse events in sST2>29.12 group was higher than that in sST2≤29.12 group (44.00% vs. 14.58%), and the difference was statistically significant (χ 2=7.657, P=0.006). Kaplan-Meier survival analysis showed that the percentage of patients with no endpoint event in the sST2≤29.12 group was higher than that in the sST2>29.12 group ( P=0.003).Cox regression analysis showed that the risk of endpoint event in sST2>29.12 group was 3.879 times that in sST2≤29.12 group ( OR=3.879, P=0.011). Conclusions:sST2 level can be used as an indicator of poor prognosis in HFpEF patients with hypertension, and can be used to stratify the risk of HFpEF patients. High levels of sST2 are associated with major adverse cardiac events.