OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To investigate the changes in the severity of mitral regurgitation in patients with large atrial septal defects after surgery.Methods:This study conducted a retrospective analysis using a self-controlled method on 145 patients with secundum atrial septal defects greater than 2 cm who underwent surgical treatment in the Department of Cardiology and Macrovascular Surgery at The First Affiliated Hospital of Anhui Medical University from January 2021 to October 2023. Among these patients, 74 underwent surgical closure, while 71 underwent surgical repair. Data including general information, defect size, number of surgeries of various types, preoperative transthoracic echocardiogram results, and follow-up results from the first and most recent transthoracic echocardiograms after discharge for all patients were collected. The Friedman test was used to compare the degree of mitral regurgitation before surgery and at the first and most recent follow-up after discharge. The differences in the severity of mitral regurgitation in patients before and after surgical treatment were analyzed.Results:Among the 145 patients, there were 25 males and 110 females, with an average age of (36 ± 14) years, height of (163.4 ± 8.2) cm, and body weight of (59.5 ± 10.5) kg. The diameter of the defect was (2.49 ± 0.35) cm. Before surgery, the severity of mitral regurgitation was classified as none, mild, and moderate (including mild to moderate) for 57 patients (39.3%), 83 patients (57.2%), and 5 patients (3.4%), respectively. The average follow-up duration was (324 ± 153) days. At the first follow-up after discharge, the severity of mitral regurgitation was none, mild, and moderate for 50 patients (34.5%), 87 patients (60.0%), and 8 patients (5.5%), respectively. At the most recent follow-up after discharge, the severity of mitral regurgitation was none, mild, and moderate for 30 patients (20.7%), 89 patients (61.4%), and 26 patients (17.9%), respectively. Compared with the preoperative severity of mitral regurgitation, the most recent follow-up showed worsening in 65 patients (44.8%) and improvement in 22 patients (15.2%). The mean rank sums for the three degrees of mitral regurgitation were 1.83, 1.91, and 2.26, with a statistically significant difference ( χ2 = 25.36, P = 0.001). Pairwise comparisons indicated that the most recent follow-up after discharge showed worsening compared with the preoperative severity of mitral regurgitation ( P < 0.05) and that it also worsened compared with the first follow-up after discharge ( P < 0.05). Conclusions:In patients with secundum atrial septal defects greater than 2 cm, undergoing surgery solely for atrial septal defects may result in the potential worsening of mitral regurgitation after the procedure.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To explore the application effects of the solution-focused approach combined with empathic nursing in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) .Methods:A total of 96 AMI patients who underwent PCI in the Department of Cardiology at Cangzhou Central Hospital from March 2020 to March 2023 were selected using convenience sampling. They were randomly assigned to an experimental group ( n=48) and a control group ( n=48) using a random number table. The control group received routine nursing care, while the experimental group received a solution-focused approach combined with empathic nursing. Medication adherence, coping strategies, and patient satisfaction were compared between the two groups. Results:After the intervention, medication adherence and satisfaction scores in the experimental group were significantly higher than those in the control group, and the differences werestatistically significant ( P<0.05) . Additionally, the experimental group scored higher in confrontation coping, and lower in avoidance and resignation coping than the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The combination of a solution-focused approach and empathic nursing can effectively improve medication adherence, coping strategies, and patient satisfaction in AMI patients after PCI.

Objective:To investigate the changes in the severity of mitral regurgitation in patients with large atrial septal defects after surgery.Methods:This study conducted a retrospective analysis using a self-controlled method on 145 patients with secundum atrial septal defects greater than 2 cm who underwent surgical treatment in the Department of Cardiology and Macrovascular Surgery at The First Affiliated Hospital of Anhui Medical University from January 2021 to October 2023. Among these patients, 74 underwent surgical closure, while 71 underwent surgical repair. Data including general information, defect size, number of surgeries of various types, preoperative transthoracic echocardiogram results, and follow-up results from the first and most recent transthoracic echocardiograms after discharge for all patients were collected. The Friedman test was used to compare the degree of mitral regurgitation before surgery and at the first and most recent follow-up after discharge. The differences in the severity of mitral regurgitation in patients before and after surgical treatment were analyzed.Results:Among the 145 patients, there were 25 males and 110 females, with an average age of (36 ± 14) years, height of (163.4 ± 8.2) cm, and body weight of (59.5 ± 10.5) kg. The diameter of the defect was (2.49 ± 0.35) cm. Before surgery, the severity of mitral regurgitation was classified as none, mild, and moderate (including mild to moderate) for 57 patients (39.3%), 83 patients (57.2%), and 5 patients (3.4%), respectively. The average follow-up duration was (324 ± 153) days. At the first follow-up after discharge, the severity of mitral regurgitation was none, mild, and moderate for 50 patients (34.5%), 87 patients (60.0%), and 8 patients (5.5%), respectively. At the most recent follow-up after discharge, the severity of mitral regurgitation was none, mild, and moderate for 30 patients (20.7%), 89 patients (61.4%), and 26 patients (17.9%), respectively. Compared with the preoperative severity of mitral regurgitation, the most recent follow-up showed worsening in 65 patients (44.8%) and improvement in 22 patients (15.2%). The mean rank sums for the three degrees of mitral regurgitation were 1.83, 1.91, and 2.26, with a statistically significant difference ( χ2 = 25.36, P = 0.001). Pairwise comparisons indicated that the most recent follow-up after discharge showed worsening compared with the preoperative severity of mitral regurgitation ( P < 0.05) and that it also worsened compared with the first follow-up after discharge ( P < 0.05). Conclusions:In patients with secundum atrial septal defects greater than 2 cm, undergoing surgery solely for atrial septal defects may result in the potential worsening of mitral regurgitation after the procedure.

Objective:To explore the application effects of the solution-focused approach combined with empathic nursing in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) .Methods:A total of 96 AMI patients who underwent PCI in the Department of Cardiology at Cangzhou Central Hospital from March 2020 to March 2023 were selected using convenience sampling. They were randomly assigned to an experimental group ( n=48) and a control group ( n=48) using a random number table. The control group received routine nursing care, while the experimental group received a solution-focused approach combined with empathic nursing. Medication adherence, coping strategies, and patient satisfaction were compared between the two groups. Results:After the intervention, medication adherence and satisfaction scores in the experimental group were significantly higher than those in the control group, and the differences werestatistically significant ( P<0.05) . Additionally, the experimental group scored higher in confrontation coping, and lower in avoidance and resignation coping than the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The combination of a solution-focused approach and empathic nursing can effectively improve medication adherence, coping strategies, and patient satisfaction in AMI patients after PCI.

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

The surveillance data of new cases of acute myocardial infarction (AMI) from January 1, 2013, to December 31, 2021, in Tengzhou City, Shandong Province, were used to analyze the incidence rate of AMI and its change trend among residents. The age and gender standardized incidence rate was calculated based on the 7th National Population Census 2020. The Cochran-Armitage trend test was used to analyze the trend of onset time and age. From 2013 to 2021, the crude and standardized incidence rate of total AMI in Tengzhou City declined from 130.07/100 000 and 161.12/100 000 to 76.15/100 000 and 72.77/100 000 ( Z=-13.785 and -20.822, both P<0.001). The crude and standardized incidence rates of males were higher than those of females. In 2016, males aged 45-54 years old and females aged 35-64 years old increased by 33.33%, 103.65%, 106.30%, and 95.75% compared to 2015, and the differences were statistically significant ( χ2=6.512, 4.965, 25.115, and 46.004, all P<0.05). The incidence rate of AMI in men aged<35 and 35-44 years old had an upward trend. From 2013 to 2021, the incidence rate of AMI decreased by 55.15% in urban areas and 36.59% in rural areas ( Z=-8.529 and -11.235, both P<0.001).

Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.