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ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.
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Objective:To evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) for rectal cancer with lateral lymph node metastasis (LLNM).Methods:From January 2016 to December 2022, 103 rectal cancer patients with LLNM were enrolled. The patients were divided into SIB-IMRT group (52 cases) and conventional chemoradiotherapy (CRT) group (51 cases) using the random number table method. The dose was 50 Gy for the pelvis with 60 Gy of SIB-IMRT for the LLNM in the SIB-IMRT group. The dose was 50 Gy for the pelvis in the CRT group. The primary endpoint was the lateral recurrence rate. The efficacy and adverse reactions of the two groups were compared.Results:The adverse reactions and surgical complications after neoadjuvant radiotherapy were comparable between the two groups. The response rates of LLNM treatment were 76.9% and 56.9%, respectively, in the two groups ( χ2=4.69, P=0.03). The SIB-IMRT group and CRT group had a local recurrence rate of 7.7% and 25.5% ( χ2=5.92, P=0.015), respectively, and a lateral recurrence rate of 3.8% and 23.5% ( χ2=8.49, P=0.004), respectively. Univariate analysis showed that the SIB-IMRT, short axis of lateral lymph nodes <5 mm after radiotherapy, and negative result in the postoperative lymph node pathological examination were factors associated with lateral recurrence. Multivariable regression analysis demonstrated that the SIB-IMRT ( HR=6.42, 95% CI: 1.40-29.49) and short axis of lateral lymph nodes <5 mm after radiotherapy ( HR=0.17, 95% CI: 0.04-0.66) were independent factors associated with lateral recurrence. The two groups had a 3-year disease-free survival of 73.25% and 62.6% ( P>0.05), respectively, and a 3-year overall survival of 87% and 82.5% ( P>0.05), respectively. Conclusions:The SIB-IMRT is safe and effective for rectal cancer with LLNM. The short axis of lateral lymph nodes <5 mm after neoadjuvant radiotherapy and SIB-IMRT is an independent risk factor for lateral recurrence.
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Objective To investigate the expression of serum long non-coding RNA MEG3 and microRNA(miR)-195-5p in patients with severe necrotizing pancreatitis and their relationship with the severity and prognosis of severe necrotizing pancreatitis.Methods A total of 122 patients with acute pancreatitis admitted to Cangzhou Central Hospital from October 2020 to January 2023 were selected as the research objects.Ac-cording to the severity of the disease,the patients were divided into severe necrotizing pancreatitis(severe group,53 cases)and non-severe necrotizing pancreatitis(non-severe group,69 cases).According to the prog-nosis of alternate ending with severe necrotizing pancreatitis can be divided into good prognosis group(38 ca-ses)and poor prognosis group(15 cases).At the same time,50 healthy people who underwent physical exami-nation in the hospital during the same period were selected as the control group.The clinical data and serum levels of lncRNA MEG3 and miR-195-5p in each group were compared.Spearman correlation analysis was used to analyze the relationship between serum levels of lncRNA MEG3,miR-195-5p and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)and Ranson scores.Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in patients with severe necrotizing pancreatitis.The receiver operating characteristic(ROC)curve was used to analyze the value of lncRNA MEG3 and miR-195-5p in eval-uating the prognosis of patients with severe necrotizing pancreatitis.Results There was no significant differ-ence in age,gender,body mass index,underlying disease and etiology between severe group and non-severe group(P>0.05).Compared with the non-severe group,APACHEⅡ and Ranson scores were significantly in-creased in the severe group(P<0.05).Compared with the control group,the serum levels of lncRNA MEG3 and miR-195-5p in the non-severe group and the severe group were decreased(P<0.05),and the serum levels of lncRNA MEG3 and miR-195-5p in the severe group were lower than those in the non-severe group(P<0.05).Spearman correlation analysis showed that serum levels of lncRNA MEG3 and miR-195-5p in AP pa-tients were negatively correlated with APACHEⅡ and Ranson scores(P<0.05).Multivariate Logistic re-gression analysis showed that APACHEⅡ and Ranson scores and serum levels of lncRNA MEG3 and miR-195-5p were independent risk factors for poor prognosis in patients with severe necrotizing pancreatitis(P<0.05).ROC curve results showed that the area under the curve(AUC)of lncRNA MEG3 and miR-195-5p for evaluating the poor prognosis of patients with severe necrotizing pancreatitis was 0.767 and 0.777,respectively,the sensitivity was 86.7%and 80.0%,and the specificity was 49.9%and 45.8%,respectively.The AUC of combined e-valuation was 0.982,and the sensitivity and specificity were 86.7%and 78.8%,respectively.Conclusion The serum levels of lncRNA MEG3 and miR-195-5p are related to the severity and prognosis of severe necrotizing pancreatitis,which can evaluate the severity and predict the prognosis of severe necrotizing pancreatitis.
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Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.
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Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. The purpose of this study was to examine the correlation between metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) expression in HCC cell lines of different metastatic potentials and such metastatic phenotypes as orientation chemotaxis and adhesion. MTDH/AEG-1 expression was detected by RT-PCR and western blotting in HCC cell lines (HepG2, Huh7, Sk-HEP-1, MHCC-97H). Distribution of MTDH/AEG-1 was observed by immunofluorescence staining and confocal laser scanning microscopy. The abilities of orientation chemotaxis and adhesion and the index of interaction between HCC cell lines and microvascular endothelial cell lines (MVECs, including HUVECs and HPMECs) were measured by chemotaxis assay and adhesion assay, respectively. The results showed that MTDH/AEG-1 protein expression was significantly higher in high metastatic potential cancer cell lines (Sk-HEP-1, MHCC-97H) than in low metastatic potential cell lines (HepG2, Huh7) (P<0.05). The MTDH/AEG-1 protein was localized in the perinuclear region of HCC cells. Furthermore, the abilities of orientation chemotaxis and adhesion of HCC cells to HPMECs were increased as compared with those of HCC cells to HUVECs (P<0.05). The abilities of orientation chemotaxis and adhesion were much stronger in Sk-HEP-1 and MHCC-97H cells with MTDH/AEG-1 highly expressed than in HepG2 and Huh7 cells with MTDH/AEG-1 lowly expressed (P<0.05). These results suggested that the expression of MTDH/AEG-1 gene in HCC cell lines of different metastatic potentials was closely positively related to the abilities of orientation chemotaxis and adhesion of HCC cells. It was deduced that MTDH/AEG-1 might play a pivotal role in the lung-specific metastasis of HCC, which may be mediated through orientation chemotaxis and adhesion abilities of HCC cells. MTDH/AEG-1 may serve as a potential therapeutic target for HCC.
Sujets)
Humains , Carcinome hépatocellulaire , Anatomopathologie , Adhérence cellulaire , Molécules d'adhérence cellulaire , Métabolisme , Lignée cellulaire tumorale , Polarité de la cellule , Chimiotaxie , Cellules HepG2Résumé
Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. The purpose of this study was to examine the correlation between metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) expression in HCC cell lines of different metastatic potentials and such metastatic phenotypes as orientation chemotaxis and adhesion. MTDH/AEG-1 expression was detected by RT-PCR and western blotting in HCC cell lines (HepG2, Huh7, Sk-HEP-1, MHCC-97H). Distribution of MTDH/AEG-1 was observed by immunofluorescence staining and confocal laser scanning microscopy. The abilities of orientation chemotaxis and adhesion and the index of interaction between HCC cell lines and microvascular endothelial cell lines (MVECs, including HUVECs and HPMECs) were measured by chemotaxis assay and adhesion assay, respectively. The results showed that MTDH/AEG-1 protein expression was significantly higher in high metastatic potential cancer cell lines (Sk-HEP-1, MHCC-97H) than in low metastatic potential cell lines (HepG2, Huh7) (P<0.05). The MTDH/AEG-1 protein was localized in the perinuclear region of HCC cells. Furthermore, the abilities of orientation chemotaxis and adhesion of HCC cells to HPMECs were increased as compared with those of HCC cells to HUVECs (P<0.05). The abilities of orientation chemotaxis and adhesion were much stronger in Sk-HEP-1 and MHCC-97H cells with MTDH/AEG-1 highly expressed than in HepG2 and Huh7 cells with MTDH/AEG-1 lowly expressed (P<0.05). These results suggested that the expression of MTDH/AEG-1 gene in HCC cell lines of different metastatic potentials was closely positively related to the abilities of orientation chemotaxis and adhesion of HCC cells. It was deduced that MTDH/AEG-1 might play a pivotal role in the lung-specific metastasis of HCC, which may be mediated through orientation chemotaxis and adhesion abilities of HCC cells. MTDH/AEG-1 may serve as a potential therapeutic target for HCC.