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The Monte Carlo N-Particle (MCNP) is often used to calculate the radiation dose during computed tomography (CT) scans. However, the physical calculation process of the model is complicated, the input file structure of the program is complex, and the three-dimensional (3D) display of the geometric model is not supported, so that the researchers cannot establish an accurate CT radiation system model, which affects the accuracy of the dose calculation results. Aiming at these two problems, this study designed a software that visualized CT modeling and automatically generated input files. In terms of model calculation, the theoretical basis was based on the integration of CT modeling improvement schemes of major researchers. For 3D model visualization, LabVIEW was used as the new development platform, constructive solid geometry (CSG) was used as the algorithm principle, and the introduction of editing of MCNP input files was used to visualize CT geometry modeling. Compared with a CT model established by a recent study, the root mean square error between the results simulated by this visual CT modeling software and the actual measurement was smaller. In conclusion, the proposed CT visualization modeling software can not only help researchers to obtain an accurate CT radiation system model, but also provide a new research idea for the geometric modeling visualization method of MCNP.
الموضوعات
Radiation Dosage , Software Design , Tomography, X-Ray Computed/methods , Software , Algorithms , Phantoms, Imaging , Monte Carlo Methodالملخص
Objective To investigate the clinical value of high-resolution magnetic resonance imaging(HR-MRI)combined with nomogram model in predicting the risk factors of positive circumferential resection margin(CMR)in rectal cancer surgery.Methods A retrospective analysis was conducted on preoperative data from 107 rectal cancer patients who underwent surgery and were confirmed by pathology.SPSS 2 5.0 software was used for univariate statistical analysis of potential risk factors for positive CRM,and after independent risk factors were selected,multivariate logistic regression analysis was performed to classify the risk factor categories.R software(4.2.0 version)was used to establish the nomogram model,and a curve was drawn to evaluate the model.The receiver operating characteristic(ROC)curve was used to show specificity and sensitivity,the area under the curve(AUC)was used to evaluate discriminative ability,the calibration curve was used to evaluate calibration,the decision curve analysis(DCA)was used to evaluate clinical benefit,and the model was internally validated using the Bootstrap method.Results Tumor located in the lower rectum[P=0.01,odds ratio(OR)=8.71],maximum diameter of tumor perpendicular to the intestinal tube(≥18.86 mm±5.32 mm)(P=0.01,OR=1.24),extramural vascular invasion(EMVI)(P<0.01,OR=0.03),and mesorectal lymph node metastasis(P=0.01,OR=0.15)were independent risk factors for positive CRM in rectal cancer.The nomogram model established based on these factors had a training set AUC of 0.921(sensitivity 0.83,specificity 0.93),a validation set AUC of 0.912(sensitivity 0.87,specificity 0.82),a Bootstrap internal validation corrected AUC of 0.92,and a consistency index(C-index)of 0.92,indicating good discriminative ability,calibration,and clinical benefit value.Conclusion HR-MRI combined with nomogram model predicted that tumor located in the lower rectum,maximum diameter of tumor perpendicular to the intestinal tube ≥(18.86±5.32)mm,EMVI,and mesorectal lymph node metastasis are closely related to positive CRM in rectal cancer.
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AIM: To analyze the changes of serum homocysteine(Hcy), vitamin B12(VitB12)and folic acid in the serum of patients with diabetic retinopathy(DR), and to explore their significance in the occurrence and development of DR.METHODS: A case-control study was designed. A total of 95 patients with DR(DR group), 94 patients with diabetes mellitus(DM group)treated in endgcrinology department and 87 patients with age-related cataract(normal control group)from the ophthalmology department of Shenzhen People's Hospital between July 2021 and January 2022 were selected. Fasting venous blood was collected and serum was separated. The concentration of Hcy in serum was detected by enzyme linked immunosorbent assay(ELISA), and chemiluminescence immunoassay was used to detect the concentration of VitB12 and folic acid. Pearson linear correlation analysis was used to evaluate the correlation between Hcy and clinical parameters. Multivariate linear regression analysis was used to evaluate the main factors which affect Hcy level. Receiver operating characteristic(ROC)curve was designed to analyze the diagnostic value of serum Hcy, VitB12 and folic acid in DR.RESULTS: The concentration of serum Hcy in DR group was 16.52±3.54 μmol/L, which was significantly higher than that in DM group(10.86±3.47 μmol/L)and control group(6.84±1.39 μmol/L; all P<0.05); The concentration of VitB12 in the serum of the control group was 501.79±108.95 pmol/L, which was higher than that in DM group(478.57±57.85 pmol/L)and DR group(455.88±181.49 pmol/L), but the difference was not statistically significant(P=0.054); The concentration of folic acid in serum of control group was 10.31±2.43 nmol/L, which was higher than that of DM group(9.94±1.90 nmol/L)and DR group(7.27±2.79 nmol/L), and the difference between DR group and DM group was statistically significant(P<0.05); In DR group, Hcy expression was weakly positively correlated with triglyceride and low density lipoprotein(r=0.208, P=0.043; r=0.240, P=0.019). Multivariate linear regression showed that low density lipoprotein was an important factor which affect the expression of Hcy in DR patients. ROC curve shows that Hcy has important value in the diagnosis of DR.CONCLUSIONS: Hcy, VitB12 and folic acid are differentially expressed in DR group, DM group and normal control group. Hcy may be involved in the pathogenesis of DR, and it has important value in the diagnosis of DR. In addition, low density lipoprotein is also an important factor which affects the expression of Hcy.
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BACKGROUND@#Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys.@*METHODS@#In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining.@*RESULTS@#15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI.@*CONCLUSION@#Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
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Humans , Mice , Animals , Transcriptome/genetics , Ligands , Kidney/metabolism , Acute Kidney Injury/metabolism , Ischemia/metabolism , Reperfusion Injury/metabolism , Sequence Analysis, RNA , Adaptor Proteins, Signal Transducing/metabolism , Tumor Suppressor Proteins/metabolismالملخص
Natural killer (NK) cells, as an essential part of innate immunity, can directly identify and kill tumor cells after being activated by the synergistic action of surface inhibitory receptors and activated receptors. It can secrete cytokines to recruit dendritic cells (DCs), induce DCs maturation and enhance adaptive immune response. It can target cancer stem cells (CSCs) and circulating tumor cells (CTCs) to inhibit cancer metastasis. NK cells have a unique inflammatory tendency, which can respond to cytokines and chemokines released from tumor sites and migrate to tumor sites, making them occupy an important advantage in cancer targeted therapy. The research on cancer targeted therapy of NK cells as drug delivery carriers, NK cell membrane-coated biomimetic nanoparticles, and NK cell extracellular vesicles (NKEVs) has attracted more and more attention. The article will focus on the mechanism of NK cells inhibiting cancer, and summarize the research progress of cancer targeted therapy of NK cells.
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Objective: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.Methods:The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. Results:A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95%CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95%CI 0.591 to 1.976, P=0.801).Conclusion: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
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OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
الموضوعات
Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Antibodies, Antineutrophil Cytoplasmic/analysis , China/epidemiology , Kidney Failure, Chronic/complications , Lymphocytes , Peroxidase , Retrospective Studiesالملخص
Background: Inflammatory bowel disease (IBD) is a recurrent disease with unknown etiology. Psychological disorders such as anxiety, depression and fear are commonly seen in IBD patients and seriously reduce the quality of life. Aims: To investigate the current status of fear of progression in patients with IBD and its relationship with the quality of life. Methods: IBD patients admitted to the Department of Gastroenterology, Xijing Hospital, Air Force Medical University from October 2020 to December 2020 were enrolled consecutively. The demographic data and clinical data on disease course and severity were collected. A questionnaire survey was conducted by using Fear of Progression Questionnaire-Short Form (FoP-Q-SF) and the MOS 36-Item Short-Form Health Survey (SF-36). Results: A total of 225 IBD patients were enrolled, including 146 cases of ulcerative colitis (UC) and 79 cases of Crohn's disease (CD). The mean score of FoP-Q-SF was 34.89±9.70. Using 34 points as the cut-off value, 53.3% of the IBD patients were identified as fear of progression. The FoP-Q-SF score in CD patients was significantly higher than that in UC patients (36.92±10.47 vs. 33.80±9.11, P<0.05). Fear of progression was positively correlated with the disease activity and severity in both UC and CD patients (all P<0.05), whereas age was negatively correlated with fear of progression (P<0.05). In patients with FoP-Q-SF score equal or greater than 34 points, scores of 5 health concepts of SF-36 scale, including physical functioning, role-physical, role-emotional, mental health, and general health were significantly lower than those with FoP-Q-SF score less than 34 points (all P<0.05). In addition, the quality of life was also affected by age, education level and length of disease course. Conclusions: Fear of progression is prevalent in IBD patients and may affect the quality of life, and is correlated with disease type (UC/CD), age and activity and severity of the disease.
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The disorder of brain-gut interaction is an important cause of irritable bowel syndrome (IBS), but the dynamic characteristics of the brain remain unclear. Since there are many shortcomings for evaluating brain dynamic nature in the previous studies, we proposed a new method based on slope calculation by point-by-point analysis of the data from functional magnetic resonance imaging, and detected the abnormalities of brain dynamic changes in IBS patients. The results showed that compared with healthy subjects, there were dynamic changes in the brain for the IBS patients. After correction by false discovery rate (FDR), significant abnormalities were only found in two functional connections of the right posterior cingulate gyrus linked to left middle frontal gyrus, and the right posterior cingulate gyrus linked to left pallidus. The above results of the brain dynamic analysis were totally different from those of the brain static analysis of IBS patients. Our findings provide novel complementary information for illustrating the central nervous mechanism of IBS and may offer a new direction to explore central target for patients with IBS.
الموضوعات
Humans , Brain/diagnostic imaging , Brain Mapping , Gyrus Cinguli/diagnostic imaging , Irritable Bowel Syndrome/diagnostic imaging , Magnetic Resonance Imagingالملخص
BACKGROUND@#Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.@*METHODS@#We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.@*RESULTS@#Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.@*CONCLUSION@#This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.
الموضوعات
Humans , Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Gene Expression , Kidney/metabolism , SARS-CoV-2 , Sequence Analysis, RNA , Single-Cell Analysis , Urinary Bladder/metabolismالملخص
OBJECTIVE@#To explore the influence of intraoperative urine volume on postoperative acute kidney injury (AKI) and the independent risk factors of AKI.@*METHODS@#This was a retrospective cohort study recruiting patients who received selective pulmonary resection under general anesthesia in Peking University First Hospital from July, 2017 to June, 2019. The patients were divided into the AKI group and the control group according to whether they developed postoperative AKI or not. Firstly, univariate analysis was used to analyze the relationship between perioperative variables and postoperative AKI. Secondly, receiver operating characteristic (ROC) curve was used to explore the predictive value of intraoperative urine output for postoperative AKI. The nearest four cutoff values [with the interval of 0.1 mL/(kg·h)] at maximum Youden index were used as cutoff values of oliguria. Then univariate analysis was used to explore the relationship between oliguria defined by these four cutoff values and the risk of AKI. And the cutoff value with maximum OR was chosen as the threshold of oliguria in this study. Lastly, the variables with P < 0.10 in the univariate analysis were selected for inclusion in a multivariate Logistic model to analyze the independent predictors of postoperative AKI.@*RESULTS@#A total of 1 393 patients were enrolled in the study. The incidence of postoperative AKI was 2.2%. ROC curve analysis showed that the area under curve (AUC) of intraoperative urine volume used for predicting postoperative AKI was 0.636 (P=0.009), and the cutoff value of oliguria was 0.785 mL/(kg·h) when Youden index was maximum (Youden index =0.234, sensitivity =48.4%, specificity =75.0%). Furthermore, 0.7, 0.8, 0.9, 1.0 mL/(kg·h) and the traditional cutoff value of 0.5 mL/(kg·h) were used to analyze the influence of oliguria on postoperative AKI. Univariate analysis showed that, when 0.8 mL/(kg·h) was selected as the threshold of oliguria, the patients with oliguria had the most significantly increased risk of AKI (AKI group 48.4% vs. control group 25.3%, OR=2.774, 95%CI 1.357-5.671, P=0.004). Multivariate regression analysis showed that intraoperative urine output < 0.8 mL/(kg·h) was one of the independent risk factors of postoperative AKI (OR=2.698, 95%CI 1.260-5.778, P=0.011). The other two were preoperative hemoglobin ≤120.0 g/L (OR=3.605, 95%CI 1.545-8.412, P=0.003) and preoperative estimated glomerular filtration rate < 30 mL/(min·1.73 m2) (OR=11.009, 95%CI 1.813-66.843, P=0.009).@*CONCLUSION@#Oliguria is an independent risk fact or of postoperative AKI after pulmonary resection, and urine volume < 0.8 mL/(kg·h) is a possible screening criterium.
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Humans , Acute Kidney Injury/etiology , Lung , Oliguria/etiology , Postoperative Complications/etiology , Postoperative Period , Retrospective Studies , Risk Factorsالملخص
OBJECTIVE@#To investigate whether DNMT1 protein induces retinoblastoma proliferation by silencing MEG3 gene.@*METHODS@#Two retinoblastoma cell lines (HXO-RB44 and SO-RB50) and a normal human retinal pigment epithelial (RPE) cell line were transfected with the plasmid pcDNA-DNMT1 or si-DNMT1 for up-regulating or interference of DNMT1 expression, and with pcDNA-MEG3 or si-MEG3 for up-regulating or interference of MEG3 expression. Western blotting was used to detect the changes in the expression of DNMT1 protein in the transfected cells, and CCK-8 and EdU assays were used to detect the changes in cell proliferation. Real-time quantitative PCR (qRT-PCR) was performed to detect MEG3 expression in SO-RB50 and HXO-RB44 cells after transfection, and the methylation level of MEG3 gene promoter after interference of DNMT1 expression was detected using methylation-specific PCR.@*RESULTS@#SO-RB50 and HXO-RB44 cells showed significantly increased expression of DNMT1 protein as compared with normal RPE cells ( < 0.05). In HXO-RB44 cells, transfection with pcDNADNMT1 resulted in significantly increased expression of DNMT1 protein, enhanced cell proliferation ability, and significantly reduced expression of MEG3 ( < 0.05). In SO-RB50 cells, transfection with si-DNMT1 significantly reduced the expression of DNMT1 protein, suppressed the cell proliferation, and increased MEG3 expression ( < 0.05). Interference of DNMT1 significantly reduced the methylation level of MEG3 gene promoter. After reversing the regulatory effect of DNMT1 on MEG3 gene, DNMT1 protein showed significantly weakened ability to regulate retinoblastoma cell proliferation ( < 0.05).@*CONCLUSIONS@#In retinoblastoma cells, the up-regulation of DNMT1 protein induces promoter methylation and inactivation of MEG3 gene and eventually leads to abnormal cell proliferation.
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Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/mover 30 min-utes on days 1 and 8,and oral S-1 at a dose of 40-60 mg twice daily from days 1 to 14,repeated every 3 weeks.All patients received at least two cycles of chemotherapy. Results A total of 60 patients were included,13(22%) achieved partial remission,37(61%) had stable disease,and 10(17%) experienced progressive disease.The median progression-free survival was 7 months(95% CI=6-10 months) and the median overall survival was 12 months(95% CI=9-20 months).Both univariate and multivariate analyses of prognostic factors showed primary resection was significant in predicting shorter progression-free survival and lung metastasis was significant for shorter overall survival.The most common grade 3-4 toxicities were neutropenia(27%) and leukopenia(18%). Conclusion Gemcitabine combined with S-1 is an effective regimen with manageable toxicities in the treatment of advanced pancreatic cancer and can be used as first-line therapy.
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Objective To investigate the effects of peptidoglycan (PGN) with different concentrations on Toll-like receptor 2 (TLR2),Toll-like receptor 4 (TLR4) expression in corneal epithelial cells of mice.Methods Corneal epithelial cells of c57 mice were cultured in vitro.Cells were divided into blank control group and 10 mg · L-1 group,30 mg · L-1 gruop and 80 mg · L-1 group (treated by different concentration of PGN for 12 hours).In the meantime,the cells in 30 mg · L-1 group were cultured for different times(named 12 hours group,24 hours group,36 hours group).Expressions of TLR2 and TLR4 mRNA and protein in different group were measured by RT-PCR and flow cytometry.Results Compared with control group (1.00 ± 0.14,1.00 ± 0.01),the expression of TLR2,LR4 mRNA in 10 mg · L-1 group (4.35 ± 0.46,3.53 ± 0.50),30 mg · L-1 group (8.06 ±0.72,5.31 ±0.34),80 mg · L-1 group (2.93 ±0.46,2.23 ±0.04) were increased,the differences were statistically significant (all P < 0.05).Compared with control group,the expression of TLR2,TLR4 protein in different concentration group and 12 hour group were increased,the differences were statistically significant (all P < 0.05).Conclusion PGN can up-regulate both mRNA and protein expression of TLR2 and TLR4 in corneal epithelial cells of mice,suggest that TLR2 and TLR4 in the corneal epithelial cell can recognize some exogenous pathogen and regulate the inflammatory reaction,which are closely related to the occurrence and development of infectious keratitis.
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Objective To explore the efficiency of sunitinib in Chinese pancreatic neuroendocrine tumors (pNET) patients. Methods Advanced pNET patients who had accepted sunitinib treatment in the oncology department of PUMC Hospital from January 2009 to June 2015 after disease progression were enrolled in this study. Data collection included clinicopathological characteristics,medical therapies and outcomes. Results Eighteen pNET patients were collected. The overall response rate (ORR) was 27.7% and the disease control rate (DCR) was 83.3%. Nine patients received sunitinib as the first-line therapy and 9 as the second/post-second line. The median progression-free survival (mPFs)(12 month vs. 12 month;HR:0.92,95%CI:0.31-2.75,P=0.88),ORR (22.2% vs.33.3%;Χ(2)=0.055,P=0.98),and DCR (88.9% vs.77.8%;Χ(2)=0.4,P=0.98)showed no significant difference between first-line therapy and post-second line therapy. The mPFS of Ki-67≥10% and Ki-67<10% group patients was not significantly different (8 months vs. 13 months;HR:1.13,95% CI:0.34-3.77,P=0.845). The commonly reported adverse events included bone marrow suppression,diarrhea,roteinuria,hypertension,and rash. Conclusions First-line or second/post-second line sunitinib treatment has certain antitumor activity in Chinese patients with advanced pNET. The efficiency and commonly reported adverse events of Sunitinib are consistent with the known Western data.
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Humans , Antineoplastic Agents , Therapeutic Uses , Disease-Free Survival , Indoles , Therapeutic Uses , Pancreatic Neoplasms , Drug Therapy , Pyrroles , Therapeutic Usesالملخص
Objective To investigate the alterations of peripheral blood T lymphocyte subsets in patients with sepsis and septic acute kidney injury, and explore the clinical significance.Methods Fifty-five patients with sepsis and forty-three patients with septic acute kidney injury were enrolled in this study. At the same period, thirty healthy subjects were enrolled as the control group.T lymphocyte subsets inclu-ding CD3 +T, CD4 +T, CD8 +T cells, and CD4 +T/CD8 +T in peripheral blood were detected by flow cy-tometry, and acute physiology and chronic health evaluation Ⅱ( APACHE Ⅱ) were graded within twenty-four hours after admission.Then, correlation of the APACHEⅡscores and T lymphocyte subsets was ana-lyzed.Results In the septic acute kidney injury group, peripheral blood CD3 +T, CD4 +T cell percenta-ges, and CD4 +T/CD8 +T ratio were significantly lower than those in the control group and the sepsis group (all P <0.05).In the septic acute kidney injury group with stage 3, CD3+T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio in the patients were significantly lower than those in stage 1 and stage 2 ( all P <0.05).In the septic acute kidney injury group,CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ra-tio were significantly lower in dead group than those in survival group (all P <0.05).APACHEⅡscores in patients with sepsis were significantly negatively correlated with peripheral blood CD4 +T cell percentages and CD4 +T/CD8 +T ratio ( r =-0.645,-0.492, allP <0.05).Conclusions There are varying de-grees of cellular immune imbalance in patients with sepsis and septic acute kidney injury, characterized by decline of circulating CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio.CD4 +T cell percenta-ges and CD4 +T/CD8 +T ratio are closely related to the severity and prognosis of septic acute kidney injury.
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<p><b>OBJECTIVE</b>To investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women.</p><p><b>METHODS</b>The expression of PTEN, p-AKT, and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method). The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors.</p><p><b>RESULTS</b>(1) Of the 71 cases of endometrial carcinoma, 65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC). PTEN loss of expression was found in 63.4% (45/71) of tumors, and more commonly occurred in EEC (66.2%, 43/65) than that in NEEC (2/6, P = 0.18). Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases, P = 0.07). In ER negative subgroup, the patients with PTEN loss of expression (12 cases) had longer survival than those with normal PTEN expression (7 cases; P = 0.04). (2) The frequency of PIK3CA mutation was 41.2% (14/34) with a hot mutation spot at T544 in exon 9. PIK3CA mutations more commonly occurred in EEC (44.8%, 13/29) than in NEEC (1/5, P > 0.05). The mutations at exon 9 more commonly occurred in EEC, well- and moderately-differentiated EEC, and tumors at early stage (P > 0.05). On the contrary, in tumors at early stages, the frequency of mutations in exon 20 (14.3%, 4/28) was significantly lower than that at late stages (4/6, P = 0.01). (3) p-AKT was positive in 59.2% (42/71) of tumors that were more frequently found in EEC (60.0%, 39/65) than that in NEEC (3/6, P = 0.68). However, the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0%, 21/28; 53.6%, 15/28) and poorly-differentiated EEC (3/9, P = 0.02). Moreover, p-AKT expression was significantly correlated with positive ER (r = 0.339, P = 0.00).</p><p><b>CONCLUSIONS</b>Endometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis. PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis. The function of PTEN loss and p-AKT expression may vary according to different hormone status.</p>
الموضوعات
Adult , Aged , Female , Humans , Middle Aged , Carcinoma, Endometrioid , Genetics , Metabolism , Pathology , General Surgery , Class I Phosphatidylinositol 3-Kinases , Endometrial Neoplasms , Genetics , Metabolism , Pathology , General Surgery , Exons , Follow-Up Studies , Hysterectomy , Mutation , Neoplasm Invasiveness , Neoplasm Staging , PTEN Phosphohydrolase , Metabolism , Phosphatidylinositol 3-Kinases , Genetics , Metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Receptors, Estrogen , Metabolism , Receptors, Progesterone , Metabolism , Signal Transduction , Survival Rateالملخص
Tn order to set up a mouse model of myelofibrosis (MF) induced with high dose recombinant human erythropoietin (rhEPO). 60 mice were collected and divided into EPO and control groups, the former was injected with rhEPO and the latter with normal saline intraperitoneally. 5 mice from each group were executed on day 6, 30, 60, 90, 120 and 150 respectively. Their WBC count, Hb level, MCV, RDW and platelet amount were measured by automatic blood cell analyzer; CD34(+) cell ratio in bone marrow were analyzed by flow cytometry; liver and spleen coefficients were measured; pathological changes of liver, spleen, femur were observed by HE staining and reticular fibers staining; cortex thickness, femoral canal diameter and lumbar spine density were determined by computerized tomography (CT). The results indicated that as compared with normal control group in EPO induced group, WBC count was increased slightly in whole period, but without statistic significance (p > 0.05), Hb level and RDW increased at day 6 and 30 significantly (p < 0.05), MCV increased at day 6 significantly (p < 0.05), but platelet amount decreased significantly at all time points (p < 0.05). Most mice in EPO-induced group had hepatomegalia and their liver and spleen coefficient increased significantly at day 60 (p < 0.05), while most mice had splenomegaly and its coefficient was increased significantly at all time-points (p < 0.05). CD43(+) cell ratio of EPO group increased significantly in whole period (p < 0.05). CT scanning displayed femoral cortical thickening, medulla canal narrowing and lumbar spine density increasing at day 150, meanwhile, HE staining and reticular fiber staining showed the fatty degeneration or vacuolization in liver, splenomegaly with megakaryocytic proliferation, femur bone marrow fibrosis and osteosclerosis. It is concluded that the mouse induced by high dose of rhEPO displays the myelofibrosis associated with splenic extramedullary hemopoiesis, and this study is useful to establish a practical MF model, and to explore its pathological mechanism.
الموضوعات
Animals , Female , Humans , Mice , Disease Models, Animal , Erythropoietin , Mice, Inbred Strains , Primary Myelofibrosis , Recombinant Proteinsالملخص
<p><b>OBJECTIVE</b>To explore the effects of adenovirus-delivered tissue inhibitor of metalloprotein- ases-3 (Ad-TIMP-3) on the irradiation sensitivity of human papillomavirus (HPV)-positive cervical cancer cells.</p><p><b>METHODS</b>An adenovirus expressing TIMP-3 (Ad-TIMP-3), alone or in combination with irradiation,was used to treat HPV-positive cervical cancer cells HeLa-Luc and CaSki. The effects of Ad-TIMP-3 on the proliferation of HeLa-Luc and CaSki cells were detected with MTT assay. The effect of the combination of Ad-TIMP-3 and X-ray on the proliferation of cells were determined by clone formation assay. Twenty nude mice were equally randomly divided into four groups: normal control group,Ad-TIMP-3 group,X-ray group,and combination group. The size of tumor was measured separately,and tumor growth curves were drawn.</p><p><b>RESULTS</b>Ad-TIMP-3 significantly inhibited the proliferation of HPV-positive cervical cancer cells in a dose-dependent manner. Combination of Ad-TIMP-3 and X-ray significantly decreased the clones of HeLa-Luc and CaSki than Ad-TIMP-3 or X-ray alone (P<0.05). The tumor weights were (0.216±0.098), (0.276±0.073), and (0.044±0.043) g, respectively, in Ad-TIMP-3 group, X-ray group,and combination group, which were all significantly lower than that in normal control group [(0.534±0.218) g] (all P<0.05). In addition,the tumor weight in the combination group was significantly lower than that in Ad-TIMP-3 group and X-ray group (both P<0.05). The tumor inhibition rate was 59.60%, 48.30%, and 91.80% in X-ray group, Ad-TIMP-3 group and combination group, respectively.</p><p><b>CONCLUSIONS</b>Ad-TIMP-3 can effectively inhibit the proliferation of cervical cancer cells. When combined with X-ray,it can remarkably increase the irradiation sensitivity of HPV-positive cervical cancer cells,and thus suppress the tumorigenesis capability of these cells in vivo.</p>
الموضوعات
Animals , Female , Humans , Mice , Adenoviridae , Genetics , Cell Line, Tumor , Cell Proliferation , Genetic Vectors , Mice, Nude , Papillomaviridae , Genetics , Radiation Tolerance , Tissue Inhibitor of Metalloproteinase-3 , Genetics , Transfection , Uterine Cervical Neoplasms , Pathology , Radiotherapy , Virologyالملخص
<p><b>OBJECTIVE</b>To investigate the clinical treatment modality and prognosis of small cell lung cancer(SCLC).</p><p><b>METHOD</b>We retrospectively analyzed the clinical data of 77 SCLC patients who were admitted to our department after 2002.</p><p><b>RESULTS</b>The disease was limited in 43 patients and extensive in 34 patients. For patients with limited SCLC, the 1-year, 2-year, and 5-year survival rate was 80%, 56%, and 21%, respectively. Four patients who had undergone surgical resection were all alive. Among patients who underwent adjuvant chemotherapy followed by radiotherapy, salvage chemotherapy, and salvage chemotherapy followed by radiotherapy, the median of survival period was 51 months, 12 months, and 28 months, respectively. For patients with extensive SCLC, the 1-year and 2-year survival rate was 56% and 25%, respectively. The median of survival period was 14.3 months. Stage was an independent factor in multifactor COX regression. Monofactor COX regression showed that radiotherapy and resection were factors correlated with survival. Brain metastasis had no impact on survival.</p><p><b>CONCLUSIONS</b>Chemotherapy followed by radiotherapy is preferred for limited SCLC, while surgical resection remains questionable for early-stage patients. For extensive SCLC, multi-line chemotherapy may be helpful to improve the overall survival. Stage is an independent factor for predicting the prognosis.</p>