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Objective:To investigate the mechanism of human placenta derived mesenchymal stem cells (hPMSCs) in the inhibition of TNF-α secretion in CD4 + IFN-γ + T cells (Th1) through CD73/nuclear factor-erythroid 2-related factor 2(Nrf2) pathway to reduce liver injury in mice with graft versus-host disease (GVHD). Methods:Flow cytometry (FCM) was used to analyze the expression of TNF-α in Th1 cells and the expression of PD-1 on CD4 + IFN-γ + TNF-α + T cells (TNF-α + Th1 cells) isolated from peripheral blood and liver tissues of mice with GVHD. Hematoxylin-hosin (HE) staining, Masson staining and immunofluorescence staining were used to observe the pathological changes in liver tissues of GVHD mice in each group. HE staining was also used to observe the pathological changes in skin and lung tissues of GVHD mice. A nonconditional protocol to induce the differentiation of peripheral blood mononuclear cells (PBMCs) into Th1 cells in vitro was established. The proportion of TNF-α + Th1 cells and the mean fluorescence intensity (MFI) of Nrf2 and phosphorylated nuclear factor-kappa B (p-NF-κB) in this T cell subgroup were detected. Results:Compared with the normal control group, the proportion of TNF-α + Th1 cells and the expression of PD-1 on this T cells in peripheral blood and liver tissues of mice in the GVHD high group increased significantly ( P<0.01). The proportion of TNF-α + Th1 cells in peripheral blood and liver tissues decreased after hPMSCs treatment ( P<0.001), but the expression of PD-1 on this T cell subset was promoted in peripheral blood and liver tissues ( P<0.01, P<0.001). However, the intervention effects of shCD73 on TNF-α + Th1 cells in peripheral blood and liver tissues were significantly weakened ( P<0.05, P<0.01). Liver histopathological analysis showed that the proportion of TNF-α + Th1 cells in liver was positively correlated with Suzuki′s score, collagen area and the MFI of α-SMA ( P<0.001). Similarly, histopathological analysis of skin and lung tissues also showed that the proportion of TNF-α + Th1 cells in peripheral blood was positively correlated with skin Marina score and lung Shukai Qiao score ( P<0.001). In vitro experiment also showed that hPMSCs down-regulated the proportion of TNF-α + Th1 cells ( P<0.01) and up-regulated the expression of PD-1 on them ( P<0.05). Further analysis showed that hPMSCs could enhance the MFI of Nrf2 ( P<0.05) and weaken the MFI of p-NF-κB ( P<0.01) in TNF-α + Th1 cells. Conclusions:hPMSCs could up-regulate the expression of PD-1 through CD73/Nrf2 pathway to inhibit the formation of TNF-α + Th1 cells, thereby alleviating liver injury in GVHD mice.
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Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.
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Objective:To investigate the risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer, and application value of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 228 patients with stage Ⅱ-Ⅲ colon cancer who underwent radical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to June 2016 were collected. There were 118 males and 110 females, aged from 25 to 87 years, with a median age of 62 years. All patients underwent open or laparoscopic-assisted radical resection of colon cancer. Observation indicators: (1) postoperative tumor recurrence; (2) risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer; (3) development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. Follow-up using outpatient examination and telephone interview was performed to detect postoperative 3-year tumor recurrence up to June 2019. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the Pearson chi-square test or Fisher exact probability. Multivariate analysis was performed using Logistic stepwise regression analysis. The independent risk factors were included into R 3.6.1 software to construct a nomogram prediction model. The receiver operating characteristic curve (ROC) was drawed, and the area under curve (AUC) was used to evaluate discrimination of the nomogram prediction model. The calibration chart with R software was used to evaluate consistency of the nomogram prediction model. Results:(1)Postoperative tumor recurrence: 53 of 228 patients had postoperative tumor recurrence including 19 cases with locoregional recurrence and 34 cases with distant metastasis. Of the 34 patients with distant metastasis, there were 14 cases with liver metastasis, 7 cases with lung metastasis, 4 cases with brain metastasis, and 9 cases with multiple metastasis or isolated metastasis in other sites. The time to recurrence was 12 months (range, 6-19 months). (2) Risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer:results of univariate analysis showed that bowel obstruction, preoperative carcinoembryonic antigen (CEA) level, ascites, vascular invasion were related factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( χ2=4.463, 13.622, 10.914, 5.911, P<0.05). Pathological N stage was also a related factor for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( P<0.05). Results of multivariate analysis showed that preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 were independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( odds ratio=3.129, 3.071, 7.634, 3.439, 15.467, 95% confidence interval as 1.328-7.373, 1.047-9.007, 1.103-52.824, 1.422-8.319, 3.498-68.397, P<0.05). (3) Development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer: based on preoperative CEA level, ascites, vascular invasion and pathological N stage of multivariate analysis, a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was developed using R 3.6.1 software. The nomogram score was 41.7 for preoperative CEA level >5 μg/L, 41.0 for ascites, 74.2 for vascular invasion, 45.1 and 100.0 for pathological N stage as stage N1 and N2, respectively. The total of different scores for risk factors corresponded to the probability of postoperative recurrence. The ROC of nomogram for recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was drawed,with the AUC of 0.805(95% confidence interval as 0.737-0.873, P<0.05). The calibration chart showed a good consistency between the probability of recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer predicted by nomogram and the actual probability of postoperative recurrence. Conclusions:Preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 are independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. The nomogram prediction model contributes to prediction of the recurrent risks after radical resection of stage Ⅱ-Ⅲ colon cancer.
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Objective To investigate the epidemic characteristics of pulmonary tuberculosis (TB) in Minhang District of Shanghai, and to provide a scientific basis for TB prevention and control. Methods Data from active TB patients registered in Minhang District of Shanghai from 2009 to 2019 was collected and analyzed using descriptive epidemiological method. Results From 2009 to 2019 the registration rates of TB patients in Minhang district of Shanghai showed a downward trend, with an average annual registration rate of 32.35/100 000, including 3 611 (41.08%) patients who were registered permanent residents of Shanghai and 5 179 (58.92%) patients who were non-permanent residents. The ratio of men to women was 2.04:1. Workers accounted for more cases (22.77%) than other occupations among patients without registered permanent residence, while retirees accounted for the majority of cases (38.60%) among patients with registered permanent residence. Among the TB patients without registered residence, the highest proportion (45.86%) was in the 20-29 years old group, while the highest proportion in permanent residents was in the 50-59 years old group (19.47%). The peak incidence occurred in May in patients without registered permanent residence, while the peak incidence was in June in patients with registered permanent residence. Conclusion It is necessary to strengthen the prevention and control of TB in people without registered permanent residence of Shanghai, and at the same time, to strengthen the prevention and control of TB in old people and students with registered permanent residence of Shanghai.
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Objective To investigate the clinical characteristics, diagnosis and treatment of primary splenic tumors.Methods The clinical data of 47 patients with spleen tumors treated in the First Affiliated Hospital of Medical College, Xi'an Jiaotong University from January 2008 to October 2014 were retrospectively analyzed.Results 28 patients had no symptoms and only on physical examination was a mass found in some patients.There were 12 patients who manifested with upper abdominal discomfort or pain, 2 patients with an epigastric mass, l patient manifested with fever and 2 patients manifested with nausea and vomiting.Preoperative examination showed anemia in 7 patients.Three patients manifested with hypersplenism.Preoperative ultrasonic examination was performed on 39 patients with a diagnostic rate of 89.7%.43 patients underwent CT examination which had a diagnostic rate of 90.7%, MRI was performed in 4 patients and the diagnoses were all correct.Of the 47 patients with splenic tumor, 38 patients had a benign tumor.34 patients were treated by surgery, including 22 patients who underwent open splenectomy, 9 patients laparoscopic splenectomy, 3 patients laparoscopic fenestration of splenic cyst.Malignant tumors were found in 9 patients.Four patients underwent splenectomy, 2 patients were treated by laparoscopic splenectomy.Preoperative examination and postoperative pathological examination showed a benign tumor in 38 patients, including 1 1 patients with a splenic cyst, 6 patients with a cavernous hemangioma, 5 patients with an inflammatory pseudo tumor of spleen (accounting for 57.3% of all the benign tumor).Malignant tumors included 5 patients with malignant lymphoma, 1 patient with splenic angiosarcoma, 1 patient with gastric carcinoma which metastasizes to the spleen, 1 patient with cervical carcinoma metastasizing to the spleen and 1 patient with liver carcinoma metastasizing to the spleen.Adjuvant chemotherapy and (or) radiotherapy after surgery were performed for patients with malignant lymphoma of the spleen.For 2 patients who were diagnosed early, surgery combined with radiotherapy or chemotherapy and immunotherapy were alive for more than 18 months.Conclusions The clinical manifestations of splenic tumors lack specificity.The diagnosis mainly depends on ultrasonic examination, CT and MRI.Early diagnosis, radical operation and comprehensive treatment are important to improve the prognosis of patients with malignant tumors of the spleen.
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<p><b>OBJECTIVE</b>To evaluate the clinical outcomes of ileal D-pouch anal anastomosis in the treatment of ulcerative colitis (UC) and familial adenomatous polyposis (FAP).</p><p><b>METHODS</b>Clinical and follow-up data of 6 UC patients and 5 FAP patients undergoing proctocolectomy and D-ileum pouch anal anastomosis between October 2014 and March 2015 were retrospectively analyzed. End-to-side anastomosis was firstly performed in ileal cutting end and ileum, then side-to-side anastomosis was operated in closing amphi-loop to construct the D-ileum pouch.</p><p><b>RESULTS</b>The mean age of the patients was 42 years (range 18 to 61 years), 5 patients were female. The duration of surgery was (225±23) min, the operation time to D-ileum pouch was (18±4) min, the volume of D-ileum pouch was (175±15) ml, the blood loss was (110±30) ml. There was no procedure-related death, however rectum perforation occurred in 1 male UC patient during operation. The postoperative hospital stay was 8 to 11 days (mean 8.5 days). The follow-up period was 2 to 7 months (median 3 months). One female FAP patient suffered from anal anastomosis vagina fistula 21 days after operation. No pouch-related fistula, anastomosis or input loop stricture fecal incontinence, and severe pouchitis were recorded. The defecation frequency was 4 to 6 times per day (UC) and 3 to 5 times per day (FAP) 6 months after operation. No night-time fecal leakage was complained in those patients. Wexner incontinence score was 3±2 and GQLI was 114±11 one month after operation. Clinical outcome in the first month was excellent in 10 patients and good in 1 patient.</p><p><b>CONCLUSIONS</b>After total colorectal resection for UC and FAP patients, application of D-ileum pouch can clear ileal stump of pouch and avoid the pouch-associated complications effectively.</p>
الموضوعات
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Adenomatous Polyposis Coli , Anastomosis, Surgical , Colitis, Ulcerative , Colonic Pouches , Fecal Incontinence , Ileum , Pouchitis , Proctocolectomy, Restorative , Rectal Fistula , Retrospective Studies , Vaginaالملخص
ObjectiveObserve the curative effect of Chinese drugs on chronic obstructive lung disease in alleviating period. Method Divide randomly the 62 patients of said disease into treatment group 32 cases and control 30. The control one take multi-enzyme tablets,the treatment one revised Liujunzi Tang,make comparison to the effective rates of them. Result On increasing appetite and improving lung function,the treatment group had total effective rate 87.5%,while the control 33.3%(P
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Objective:To investigate the effects of acupuncture therapy on acute cerebral infarction. Methods: Eighty patients with acute cerebral infarction were randomly divided into a treatment group of 40 cases and a control group of 40 cases. Xuanzhong(GB 39)-through-Sanyinjiao(SP 6) acupuncture was performed as a main treatment. The curative effects were compared between the two groups and the sizes of cerebral infarct, between pretreatment and posttreatment after one course of treatment. Results: The total recovery rate was 88.5% in the treatment group and 57.5% in the control group after one course of treatment. There was a significant difference between the two(P<0.05). The rate of change in the infarct for the better was significantly higher in the treatment group than in the control group. There was also a significant difference(P<0.05). Conclusion: This treatment is an effective method for lowering the rate of apoplectic disability and raising the cure rate.
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Objective To investigate the relationship between hypoxia inducible factor-1?、angiopoietin2 and vascular endothelial growth factor and angiogenesis in hepatocellular carcinoma(HCC).Methods The(expression) of hypoxia inducible factor-1?、angiopoietin2 and vascular endothelial growth factor mRNA was(detected) in 52 HCC surgical specimens.And microvessel density(MVD) in tissue specimens of patients with coexpression of the parameters was examined.Results Of the 52 surgical specimens,36 cases had over(expression) of HIF-?、angiopoietin and VEGF protein,and coexpression of HIF-? and angiopoietin and VEGF mRNA in 38 of 52 cases.The expression of HIF-?、angiopoietin was related with the expression of VEGF(r_1= 0.783,P
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Objective To investigate the diagnosis and treatment of malignant fibrous histiocytoma (MFH) in abdominal cavity. Methods The clinical manifestations, imaging examination, pathology, methodology, effect of treatment and prognosis of 28 MFH patients were retrospectively analyzed. Results Tumors were in the retroperitoneal space in 17 cases, within abdominal cavity in 6, in mesentery in 3 cases, and in the abdominal wall in 2 cases. The clinical symptoms were body weight loss, abdominal pain and mass. B ultrasonography and CT scanning showed mass in the abdomen. 24 cases were with multiplefoci,4 cases were with a single mass. Seventeen cases underwent complete tumor resection,11 cases with partial resection, 16 cases received postoperative chemotherapy and 14 cases with postoperative radiotherapy. The overall survival rate of 1-, 3- and 5- year was 76.9%,26.9% and 3.9%,respectively. Conclusion MFH is most often located in retroperitoneal space, surgical resection was the treatment of choice. The prognosis in patients with MFH might be improved by complete resection combined with chemotherapy or/ and radiotherapy.