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 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.

Objective:To investigate the association between hepatic echinococcus granulosus infection and necrosis with gene polymorphism of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), and to identify the related factors at the gene level.Methods:A total of 106 patients with hepatic echinococcosis who underwent surgical treatment in the department of hepatobiliary surgery, People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2020 were selected. Patients with necrosis caused by hepatic echinococcus granulosus infection were selected as the observation group, and patients without necrosis caused by hepatic echinococcus granulosus infection were selected as the control group, with 53 cases in each group. The serum levels of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-10 (-592, -1082) and TNF-α (rsl800630) were detected by polymerase chain reaction (PCR). The levels of IL-10 and TNF-α and their gene polymorphisms were analyzed.Results:The levels of serum IL-10 and TNF-α in the observation group were significantly higher than those in the control group (all P<0.05); There was significant difference in genotype and allele frequency of IL-10 (-592, -1082) and TNF-α (rsl800630) (all P<0.05). The serum IL-10 level of CC genotype patients with IL-10 gene -592C/A locus in the observation group was higher than that of CA+ AA genotype patients, with statistically significant difference ( P<0.05). The serum IL-10 level in patients with TT genotype at -1082T>A of IL-10 gene in the observation group was higher than that in patients with TA+ AA genotype, with statistically significant difference ( P<0.05). The serum TNF-α level in patients with CC genotype at rsl800630C/A locus of TNF-α gene in the observation group was higher than that in patients with CA+ AA genotype, with statistically significant difference ( P<0.05). Conclusions:The changes of IL-10 (-592, -1082) and TNF-α (rsl800630) gene polymorphisms may be associated with hepatic echinococcus granulosus infection and necrosis.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Objective To investigate the feasibility and safety of modified percutaneous left atrial appendage occlusion (PLAAO) under transthoracic echocardiographic (TTE) guidance without general anesthesia instead of transesophageal echocardiographic guidance.Methods A total of 14 patients who met the inclusion criteria underwent modified PLAAO guided by TTE instead of TEE without general anesthesia.Regular clinical follow-up observations of PLAAO-related major adverse events were done in the perioperative period.Results All patients were successfully implanted with left atrial appendage occluder device (Watchman) without device-related serious complications.Immediately occlusion success rate was 100％.No major adverse events occurred during hospitalization and follow-up.The mean operation time was 108 ± 22 min(range 75-150 min)and the mean radiation exposure time was 15.8 ± 7.6 min(range 8-32 min).Conclusion Modified PLAAO guided by TTE instead of TEE without general anesthesia may be safe and effective.This method simplifies the operation process and is favorable for PLAAO application.But this modified PLAAO is still needed to be validated in more patients.

Objective To evaluate the significance of contrast medium (CM) volume and estimated glomerular filtration rate (CM/eGFR) in predicting contrast-induced nephropathy (CIN) after PCI. Methods A total of 307 patients after PCI were enrolled from Nanfang Hospital from May 2014 to October 2015. The patients were divided into the CIN group(n = 29) and the non-CIN group(n = 278) according to whether CIN within 72 hours after PCI. The baseline renal function was assessed by the sCr and CyC, respectively. Results Twenty-nine patients (9.4%, 29/307) developed CIN. There were significant differences in Age, CM、NTpro-BNP、IABP、 Periprocedural Hypotension、Preprocedural sCr/CyC between two groups (P < 0.05, respectively). The result of multivariate logistic regression analysis showed that Age, Cardiac function ≥Ⅲ level, IABP, use CCB, CM/eGFRMDRD, CM/eGFRCyC were independent risk predictors for CIN, respectively. Receiver Operating Characteristic (ROC) curve analysis showed that the area under the curve of CM/eGFRMDRD(AUC = 0.838) was superior to CM/eGFRCyC (AUC = 0.805) without significant difference. The sensitivity and specificity were 79.3%and 76.3%(Cut-off Point = 2.094), respectively. Conclusion Both the CM/eGFRMDRD and CM/eGFRCyC may be good methods to determine maximum CM before PCI and to predict CIN after PCI currently, without significant differences between these two predictors.

Anemia, Iron-Deficiency ; Humans

Objective To research the expression of Neuritin in gastric cancer .and the relationship between the expression of Neuritin with the occurrence and development of gastric cancer .Methods Collected 58 surgical specimens of gastric cancer from 2010 to 2013 in the first affiliated hospital of Shihezi University ,immunohistochemistry was used to examine the expression of Neu-ritin in gastric cancer and normal tissues near the cancer of the stomach .Results Immunohistochemical staining showed that Neu-ritin was moderately or highly expressed in 96 .55% (56/58) of gastric cancer ,and Neuritin was moderately or highly expressed in 94 .83% (55/58) of normal tissues near the cancer .There was no statistically significantly difference between two groups (P>0 .05);Neuritin was highly expressed in 82 .76% (48/58) of gastric cancer ,and Neuritin was highly expressed in 15 .52% (9/58) of normal tissues near the cancer ,differences between the two groups had statistically significantly (P<0 .05) .Expression of Neuritin was not correlated with gender ,age ,TNM stage ,infiltration depth ,lymph node metastasis ,differentiated degree ,the pathologic type or distant metastasis(P> 0 .05) .Conclusion The Neuritin expression level between gastric cancer and normal tissues near the cancer exist differences .There is overexpression of neuritin in gastric cancer .

OBJECTIVETo summarize the features of clinical manifestations, laboratory tests and imaging findings of patients with cardiac amyloidosis (CA).

METHODSA total of 60 CA patients (including 41 male and 19 female patients) from 4 centers admitted between May, 2012 and November, 2013 were included in the study. The demographic data, medical history, clinical manifestations, laboratory test data, ECG, cardiac ultrasound, and cardiac magnetic resonance (CMR) imaging of the patients were analyzed.

RESULTSTwo-thirds of the 60 CA patients, were middle-aged or elderly men, and 47% of the patients had AL-CA. The clinical manifestations included exertional dyspnea (73%), pedal edema (47%), hypotension (47%), and hypertrophy of the tongue (22%); abnormal laboratory test results included albuminuria (53%) and liver (15%) and kidney (28%) dysfunction; blood routine, urine and serum immunoglobulin quantification and immunofixation electrophoresis could help the screening of AL-CA. Kidney (53%) and liver (15%) involvement was common, and 86% of AL-CA patients had kidney involvement. Typical ECG characteristics included poor R wave progression (35%), low voltage in limb leads (33%), and a pseudo infarct Q wave (30%); the latter two were more frequent in AL-CA. The characteristics of ultrasound findings included left ventricle thickening (100%), left atrial enlargement (87%) and enhanced echo of the myocardial granules(92%), and diastolic dysfunction was obvious in all the CA patients regardless of the systolic function. The DT and E/e' of the mitral annulus could be used as an index to evaluate diastolic dysfunction in early stage of the disease. Left ventricular (LV) global subendocardial late gadolinium enhancement (LGE, 81%) accompanied by right ventricular (RV) and atrial LGE was the typical characteristic of CMR, and the range of LGE in the RV and the two atria was wider in AL-CA than in non-AL-CA. NT-proBNP (97%) and cardiac troponin (53%) in CA patients were both elevated, which helped in diagnosing and assessing the severity of cardiac involvement, according to which 50% of the patients were found to be at a high risk, 43% at an intermediate risk, and 7% at a low risk.

CONCLUSIONThe combination of the features of clinical, laboratory tests and imaging findings of CA have important diagnostic and prognostic value for CA.

Adult ; Aged ; Amyloidosis ; diagnosis ; pathology ; physiopathology ; Cardiomyopathies ; diagnosis ; pathology ; physiopathology ; Electrocardiography ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Magnetic Resonance Imaging ; Male ; Middle Aged

Objective To summarize the features of clinical manifestations, laboratory tests and imaging findings of patients with cardiac amyloidosis (CA). Methods A total of 60 CA patients (including 41 male and 19 female patients) from 4 centers admitted between May, 2012 and November, 2013 were included in the study. The demographic data, medical history, clinical manifestations, laboratory test data, ECG, cardiac ultrasound, and cardiac magnetic resonance (CMR) imaging of the patients were analyzed. Results Two-thirds of the 60 CA patients, were middle-aged or elderly men, and 47%of the patients had AL-CA. The clinical manifestations included exertional dyspnea (73%), pedal edema (47%), hypotension (47%), and hypertrophy of the tongue (22%); abnormal laboratory test results included albuminuria (53%) and liver (15%) and kidney (28%) dysfunction; blood routine, urine and serum immunoglobulin quantification and immunofixation electrophoresis could help the screening of AL-CA. Kidney (53%) and liver (15%) involvement was common, and 86% of AL-CA patients had kidney involvement. Typical ECG characteristics included poor R wave progression (35%), low voltage in limb leads (33%), and a pseudo infarct Q wave (30%);the latter two were more frequent in AL-CA. The characteristics of ultrasound findings included left ventricle thickening (100%), left atrial enlargement (87%) and enhanced echo of the myocardial granules(92%), and diastolic dysfunction was obvious in all the CA patients regardless of the systolic function. The DT and E/e' of the mitral annulus could be used as an index to evaluate diastolic dysfunction in early stage of the disease. Left ventricular (LV) global subendocardial late gadolinium enhancement (LGE, 81%) accompanied by right ventrivular (RV) and atrial LGE was the typical characteristic of CMR, and the range of LGE in the RV and the two atria was wider in AL-CA than in non-AL-CA. NT-proBNP (97%) and cardiac troponin (53%) in CA patients were both elevated, which helped in diagnosing and assessing the severity of cardiac involvement, according to which 50%of the patients were found to be at a high risk, 43%at an intermediate risk, and 7% at a low risk. Conclusion The combination of the features of clinical, laboratory tests and imaging findings of CA have important diagnostic and prognostic value for CA.