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

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a peripheral retinal disease characterized by subretinal hemorrhage and/or subretinal pigment epithelial hemorrhage or exudation. It is often misdiagnosed as age-related macular degeneration, polypoidal chorioretinopathy or choroidal melanoma. With the development of multimodal imaging, PEHCR has different features under different examinations, such as B-scan ultrasound, fluorescein fundus angiography, optical coherence tomography and so on, which contributes to differention from other diseases. Clinical treatments for the disease include intravitreal injection of retinal photocoagulation therapy, anti-vascular endothelial growth factor, pars plana vitrectomyand so on, but there is still no universal consensus. In order to gain a deeper understanding of the clinical features, treatment options and prognosis of PEHCR, minimize missed diagnoses and misdiagnoses, and improve treatment efficiency, further research is required.

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 effect of pre-pregnancy age, alanine aminotransferase (ALT), blood glucose (GLU) level on premature birth. Methods Based on the free pre-marital health check-ups and pre-pregnancy eugenic health check-ups in Dongguan, the examination results of the subjects were obtained and the pregnancy outcomes were followed up. Logistic regression models were used to analyze the relationship between women^’s pre-pregnancy age, ALT, and GLU levels and the incidence of premature birth. Results A total of 18 150 subjects were included in this study, and the overall incidence of premature birth was 6.06% (1,099/18,150). The women^’s pre-pregnancy age 30 to 34 (RR=1.26, 95% CI:1.07～1.48), age>34 (RR=1.82, 95% CI:1.52～2.18), ALT≥40 U/L (RR=1.40, 95% CI: 1.09～1.80) and GLU>6.1 mmol/L(RR=1.74, 95% CI: 1.01～2.97) were the influencing factors of premature birth. Conclusion Older women, abnormal serum alanine aminotransferase level and hyperglycemia had an impact on the occurrence of premature birth, which has important guiding significance for health education of eugenics before pregnancy.

Objective To investigate the biomechanical properties and clinical effects of the unilateral/bilateral percutaneous vertebroplasty (PVP) on the treatment of osteoporotic vertebral compression fractures in elderly patients. Methods The finite element models of the unilateral/bilateral percutaneous vertebroplasty (PVP) in osteoporotic vertebral compression fractures were established to evaluate changes in strain and stress of the fractured vertebra after surgery. Eighty patients with osteoporotic vertebral compression fractures underwent unilateral or bilateral PVP were collected for retrospective analysis. The operation time,intraoperative fluoroscopy times,injected bone cement volume, bone cement leakage rate and visual analogue scales (VAS) score between the two groups were analyzed. Results The maximum strain and stress in unilateral PVP group were 1.18 times and 1.15 times of those in bilateral PVP group,respectively.The operation time and intraoperative fluoroscopy times in unilateral PVP group were obviously smaller than those in bilateral PVP group (P<0.001). There was no statistical significance in the injected bone cement volume, bone cement leakage rate, and VAS score between the two groups (P>0.05).Conclusions The biomechanical effect of unilateral PVP was similar to that of bilateral PVP. The puncture needle localization of unilateral PVP for treating elderly patients with osteoporotic vertebral compression fractures had the advantage of less operation time and limited X-ray exposure.

OBJECTIVETo evaluate the application of small intestine double stoma and succus entericus reinfusion in the patients with severe intra-abdominal infection.

METHODSTen patients with high intestinal perforation from February 2005 to November 2014 were enrolled in the study. All the cases received emergency operation. Small bowel with intestinal perforation was resected, and double stoma was applied in the proximal and distal small intestine. When abdominal infection under control, total enteral nutrition was successfully administered from nasogastric tube. The succus entericus from the proximal intestine was collected and transfused back to the distal intestine. Stool was collected and fecal nitrogen, fat and carbohydrate contents were determined. Related serum protein levels were measured.

RESULTSAs compared to pre-reinfusion, the absorption rate of carbohydrate [(90.9±7.8)% vs. (82.7±15.2)%], fat [(87.6±6.4)% vs. (59.1±10.8)%], and nitrogen [(82.4±9.8)% vs. (67.2±15.4)%] increased after succus entericus reinfusion (P<0.05). The serum protein levels increased significantly as well[fibronectin: (285.6±3.6) vs. (157.0±22.6) mg/L, P<0.01; transferrin: (4.86±0.21) vs. (3.60±0.25) g/L, P<0.05; pre-albumin: (291.3±112.5) vs. (199.1±53.3) mg/L, P<0.05].

CONCLUSIONSmall intestine double stoma and succus entericus reinfusion are effective in improving the absorption of carbohydrate, fat and nitrogen in the patients with severe intra-abdominal infection.

Objective To investigate the correlation of serum interleukin-6 (IL-6) and C-reactive protien (CRP) lev?els with left atrial thrombus and severe spontaneous echocontrast (SEC) in patients with atrial fibrillation (AF). Methods A case-control study of patients with atrial fibrillation (n=76) was carried out. All patients were divided into control group (n=45) and study group (n=31) according to their conventional echocardiography performance. Serum IL-6 and CRP were exam?ined in both groups. Results The levels of serum IL-6 in patients with thrombus and severe SEC were (324.13±42.86) ng/L and (332.29±53.17) ng/L, respectivly which is higher than that in patient without thrombus or without severe SEC (108.75± 25.43) ng/L and (93.59 ± 27.82) ng/L respectively. In parallel, CRP levels in patients of thrombus and severe SEC were (66.97 ± 17.65) mg/L and (71.81 ± 20.19) mg/L respectively which is higher than that in patients without thrombus or without severe SEC (17.28±6.52) mg/L and (16.76±8.73) mg/L respectively. All differences were of statistically significant(P<0.05). Conclusion Increase of serum IL-6 and CRP as well as high systemic inflammatory state correlate with left atrial thombus and severe SEC in patients with AF.

Objective To evaluate the application of small intestine double stoma and succus entericus reinfusion in the patients with severe intra-abdominal infection. Methods Ten patients with high intestinal perforation from February 2005 to November 2014 were enrolled in the study. All the cases received emergency operation. Small bowel with intestinal perforation was resected, and double stoma was applied in the proximal and distal small intestine. When abdominal infection under control, total enteral nutrition was successfully administered from nasogastric tube. The succus entericus from the proximal intestine was collected and transfused back to the distal intestine. Stool was collected and fecal nitrogen, fat and carbohydrate contents were determined. Related serum protein levels were measured. Results As compared to pre-reinfusion, the absorption rate of carbohydrate [(90.9±7.8)% vs. (82.7± 15.2)%], fat [(87.6±6.4)% vs. (59.1±10.8)%], and nitrogen [(82.4±9.8)% vs. (67.2±15.4)%] increased after succus entericus reinfusion (P<0.05). The serum protein levels increased significantly as well[fibronectin:(285.6±3.6) vs. (157.0±22.6) mg/L, P<0.01﹔transferrin:(4.86±0.21) vs. (3.60± 0.25) g/L,P<0.05﹔pre-albumin:(291.3±112.5) vs. (199.1±53.3) mg/L, P<0.05]. Conclusion Small intestine double stoma and succus entericus reinfusion are effective in improving the absorption of carbohydrate, fat and nitrogen in the patients with severe intra-abdominal infection.

Objective To evaluate the application of small intestine double stoma and succus entericus reinfusion in the patients with severe intra-abdominal infection. Methods Ten patients with high intestinal perforation from February 2005 to November 2014 were enrolled in the study. All the cases received emergency operation. Small bowel with intestinal perforation was resected, and double stoma was applied in the proximal and distal small intestine. When abdominal infection under control, total enteral nutrition was successfully administered from nasogastric tube. The succus entericus from the proximal intestine was collected and transfused back to the distal intestine. Stool was collected and fecal nitrogen, fat and carbohydrate contents were determined. Related serum protein levels were measured. Results As compared to pre-reinfusion, the absorption rate of carbohydrate [(90.9±7.8)% vs. (82.7± 15.2)%], fat [(87.6±6.4)% vs. (59.1±10.8)%], and nitrogen [(82.4±9.8)% vs. (67.2±15.4)%] increased after succus entericus reinfusion (P<0.05). The serum protein levels increased significantly as well[fibronectin:(285.6±3.6) vs. (157.0±22.6) mg/L, P<0.01﹔transferrin:(4.86±0.21) vs. (3.60± 0.25) g/L,P<0.05﹔pre-albumin:(291.3±112.5) vs. (199.1±53.3) mg/L, P<0.05]. Conclusion Small intestine double stoma and succus entericus reinfusion are effective in improving the absorption of carbohydrate, fat and nitrogen in the patients with severe intra-abdominal infection.

Objective To discuss the risk factors of free wall rupture (FWR) in acute ST-segment elevation myocardial infarction (STEMI) patients. Methods We retrospectively reviewed all patients (n=1247) with STEMI hospitalized in CCU from January 2005 to July 2010. Results FWR occurred in 29 patients(2.3%). Of these 1247 patients, 128 (10.2%) patients received thrombolytic therapy, 623 (50.0%) patients underwent primary PCI. Compared to No-FWR group, FWR group has signiifcant differences in age (62.4±6.4 y vs. 66.6±8.3 y, P<0.05), hypertenion (29.7%vs. 21.8%, P>0.05), diabetes mellitu (55.2%vs. 23.5%, P=0.022), presence of heart failure on admission (Killip≥Ⅱ) ( 16.4%vs. 34.0%, P<0.05), Peak value of hCRP[20.33 (15.02, 81.25) vs. 43.35 (16.56, 126.78)], no-history of pervious MI (10.3%vs. 18.4%, P=0.018). Multivariate logistic regression showed that age (≥70 years old), Killip≥Ⅱ, hCRP ( > 100 mg/L) and thrombolytic therapy were independent risk factors of FWR. Conclusions STEMI patients with advanced age, Killip≥Ⅱ, hCRP and thrombolytic therapy were more vulnerable of FWR.