BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

Objective To observe the value of residual neural network(ResNet)-101-feature pyramid network(FPN)model based on CT for differentiating benign and malignant lung nodules.Methods Totally 2 040 lung nodules in 2 000 patients were retrospectively enrolled,including 1 150 benign and 890 malignant nodules.The nodules were divided into training set(n=1 632)and test set(n=408)at the ratio of 8∶2,the former including 881 benign and 751 malignant ones,while the latter including 269 benign and 139 malignant ones,respectively.Taken ResNet-101 as the backbone network,combined with FPN,a classification model was established based on chest CT,and the efficiency of this model alone and combined with evaluation of physicians for differentiating benign and malignant lung nodules were evaluated.Results Among 269 benign lung nodules in test set,ResNet-101-FPN model alone correctly diagnosed 214 nodules(214/269,79.55%),while combined with evaluation of physicians correctly diagnosed 230 ones(230/269,85.50%).For 139 malignant nodules in test set,ResNet-101-FPN model alone correctly diagnosed 124 nodules(124/139,89.21%),while combined with evaluation of physicians correctly diagnosed 131 ones(131/139,94.24%).The sensitivity,accuracy and precision of ResNet-101-FPN model combined with evaluation of physicians for distinguishing benign and malignant lung nodules were all higher,while the specificity of the combination was lower than those of ResNet-101-FPN model alone,but the differences were not significant(all P＞0.05).Conclusion ResNet-101-FPN model could be used to distinguish benign and malignant lung nodules based on CT.Combining with evaluation of physicians could improve diagnostic efficiency of this model.

Objective To explore the value of CT derived fractional flow reserve(CT-FFR)combined with pericoronary adipose tissue(PCAT)fat attenuation index(FAI)in predicting major adverse cardiac events(MACE)in patients with obstructive coronary heart disease(CHD).Methods A total of 149 patients with obstructive CHD who underwent coronary computed tomography angiography(CCTA)examination were analyzed retrospectively.The patients were divided into MACE group and non-MACE group according to the occurrence of MACE.The clinical data,CCTA characteristics,CT-FFR,PCAT volume and FAI differences between the two groups were compared.Multiple logistic regression analysis was used to screen the independent predictors of MACE.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the efficiency of a single independent predictor and its joint prediction of MACE.Results CT-FFR≤0.8 and right coronary artery(RCA)FAI(RCA-FAI)were independent risk factors for MACE in patients with obstructive CHD.The AUC of CT-FFR≤0.8 and RCA-FAI to predict MACE in patients with obstructive CHD were 0.773 and 0.766,respectively,while of their combination was 0.865.Conclusion Compared with single imaging parameters,the combined imaging parameters of CT-FFR and RCA-FAI can significantly improve the predictive efficiency of MACE in patients with obstructive CHD.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

In clinical application, a microneedle system that continuously delivers drugs is of great value for the delivery of some vaccines and hormone drugs. In this study, a controlled-release chitosan-based microneedle array (PVA/CS-MN) was designed, combining microneedle patches with drugs for controlled-release of drugs. Here we report the optimization of the preparation process of PVA/CS-MN. The appearance, morphology, mechanical properties, dissolution and swelling properties, and in vitro penetration properties of the MN arrays were characterized. The PVA/CS-MN prepared by the optimal process showed good morphology and mechanical properties. PVA/CS-MN can smoothly open microchannels on the skin and achieve controllable dissolution and swelling functions. Ascorbic acid (l-ascorbic acid) was used as a model drug to prepare a Vc-PVA/CS-MN. In vitro transdermal diffusion experiments showed that the Vc-PVA/CS-MN released about 57% of the drug within 1 h. About 66.7% of the drug was slowly released within 12 h, and a total of 92% of the drug was released after 7 days. The controllable sustained-release properties and excellent drug delivery efficiency of PVA/CS-MN provide a new option for sustained transdermal drug delivery.
Ascorbic Acid ; Chitosan ; Delayed-Action Preparations ; Drug Delivery Systems ; Hormones ; Vaccines

Objective:To explore the effects of information-motivation-behavior (IMB) model combined with solution focused approach (SFA) in primary large liver cancer (PLLC) .Methods:From January 2017 to January 2018, this study selected 123 PLLC patients of the Affiliated Cancer Hospital of Zhengzhou University as subjects by convenience sampling. All of patients were divided into group A ( n=61) and group B ( n=62) with the random number table. Group A carried out the routine nursing model, while group B implemented the IMB model combined with the SFA. The intervention effects were evaluated with the Quality of Life-Liver Cancer (QOL-LC) , the Chinese Strategies Used by People to Promote Health (C-SUPPH) and the Herth Hope Index (HHI) . Results:Among those PLLC patients between two groups, there were no statistical differences in the scores of QOL-LC, C-SUPPH and HHI on admission ( P>0.05) . The scores of QOL-LC, C-SUPPH and HHI of PLLC patients in group B at discharge, 15 days after discharge were higher than those in group A with statistical differences ( P<0.05) . Conclusions:In the process of clinical intervention for PLLC patients, scientific and reasonable IMB model combined with SFA based on patients' condition can improve the scores of QOL-LC, C-SUPPH and HHI which is one of the subsidiary intervention for improving the whole therapeutic effects and has good application as well as promotion values.

Objective: To investigate the safety and feasibility of laparoscopic remedial surgery in patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. Methods: The clinical and follow-up data of 12 patients who didn′t reach the cure criterion of early colorectal cancer and then underwent endoscopic resection was collected. The clinicalpathological features and remedial indications were analyzed to evaluate the effects of laparoscopic remedial surgery. Results: The average number of lymph nodes in the lymph node dissection was 15 during remedial surgery, and 3 of them had lymph node metastasis. Among the 3 patients with residual cancer, two cases were poorly differentiated, 1 case was moderately differentiated, 1 case was positive for basal margin, and 1 case had vascular invasion. No lymph node metastasis occurred in the 9 patients who had no residual cancer. Among these, 8 cases were moderately differentiated, 1 case was poorly differentiated and 2 cases had positive basal margin. The average follow-up duration was 40 months and all 12 patients were in a state of survival at the last follow-up. During the follow-up of the 3 patients with residual cancer, 1 patient received adjuvant chemotherapy with unknown prognosis; 1 patient received postoperative adjuvant radiochemotherapy, and lung metastasis occurred; 1 patient did not receive any treatment after surgery and survived for 33 months. Conclusions Laparoscopic remedial surgery is a safe and feasible remedy for patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. However, the choice of remedial strategy for colorectal carcinoma needs further investigation for patients with no vascular invasion, high degree of differentiation, and negative basal margin.

Objective To investigate the effect and mechanism of Yiqi Shuxin pills in the treatment with viral myocarditis(VMC).Methods 56 cases of VMC in our hospital were randomly divided into the experimental group and the control group,28 cases in each group.The patients in the control group were with routine treatment,and these in the experimental group were treated with Yiqi Shuxin pills based on the control group.The clinical effects between the two groups were compared, and the changes of miR, myocardial enzyme spectrum and immunity were compared before and after treatment.Results The total effective rate was 92.86% in the experimental group and was 72.57% in the control group,there was statistical significance between the two groups(P<0.05);There was no significant difference between the two groups before treatment at miR-1,miR-133,miR-21,CK-MB, cTnI,LDH,CD3 +,CD4 +,CD8 +,NK in serum;The content of miR-1,miR-133,CD3 +,CD4 +,CD8 +,NK after treatment in the two groups were higher than before treatment(P <0.05),miR-21,CK-MB,cTnI and LDH were lower than before(P <0.05);The improvement of these indicators in the experimental group was superior to that in the control group(P<0.05).Conclusion Yiqi Shuxin pills could improve the therapeutic effect of VMC,the mechanism maybe related to improving the circulation of blood miR and enhance cellular immune function.

Objective To investigate clinical effect and mechanism of Yudanrongxin pills in the treatment of patients with acute myocardial infarction ( AMI) .Methods 86 cases of AMI in our hospital from February 2014 to February 2015 were selected and divided into the observation group and the control group, with 43 cases in each group.The patients in the control group were treated with conventional therapy, while patients in observation group were treated with Yudanrongxin pills on the basis of the control group.The related inflammation factors, indicators of myocardial injury and heart function index were compared between two groups before and after treatment.Results Compared with before treatment, in both two groups after treatment, the serum inflammatory factors including high-sensitivity C-reactive protein(hs-CRP), IL-6,soluble vascular cellular adhesion molecule-1 (sVCAM-1), TNF-αand P-selectin decreased, the myocardial injury criterion including creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), myocardial troponin I (cTnI) and myoglobin (Mb) decreased,the cardiac function indexes of left ventricular end systolic volume (LVESV) and left ventricular end diastolic volume (LVEDV) decreased and left ventricular ejection fraction (LVEF) increased (P<0.05).Compared with control group, the hs-CRP,IL-6,sVCAM-1,TNF-α,P-selectin,CK-MB,LD,cTnI and Mb in observation group were lower(P<0.05).The degree of improvement at cardiac function was better than that in control group (P<0.05).Conclusion Yudanrongxin pills could better improve cardiac function in treatment with AMI, its role was relative to inhibition of inflammatory factors and myocardial protection against injury.