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本期专题执行主编简介
2020, 51(3): 1-1.
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Abstract:
Primary aldosteronism (PA) is the most common cause of secondary hypertension. The diagnosis procedure of PA includes screening, confirmatory diagnosis and subtype classification. International and national guidelines recommended plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to detect possible cases of PA, and one or more tests (fludrocortisone suppression test, saline infusion test, oral sodium loading test, or captopril challenge test) to confirm ARR positive patients. Adrenal venous sampling (AVS) is also recommended as the best method to distinguish unilateral and bilateral adrenal disease when surgical treatment is feasible and desired by the patient. However, many studies find that each of the above diagnostic method has shortcomings. Recently, more and more studies are attempting to explore new methods with higher diagnostic efficiency and more conveniences, including new screening tests, new confirmatory diagnostic tests, new imaging and pathological histology methods. In our studies, the regression model, which included upright PAC, upright PRA, and lowest potassium, is superior to ARR for PA screening; the blood potassium and the ratio of blood potassium to blood sodium after the saline infusion test are not suitable for PA subtyping. This article will review the advances and progress in PA diagnosis.
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Objective To investigate the the feasibility and diagnostic efficiencyvalue of different screening indexesmethods for screening primary aldosteronism (PA). Methods The clinical data of 499 patients with PA and 479 patients with essential hypertension diagnosed from Jan. 2009 to Dec. 2018 were retrospectively analyzed. The diagnostic performance of different screening indexs was compared by plotting receiver operating characteristic curves (ROC). Results The area under the ROC curve (AUC) of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) was greater than that of the ratio of the upright PAC to the angiotensin Ⅱ (AT-Ⅱ) (AA2R), upright PRA, upright PAC, supine ARR, and lowest blood potassium (P<0.05). The AUC of logistic regression model was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). There was no significant difference in AUC between decision tree model and upright ARR (94.1% vs. 94.6%, P>0.05). In the test set, the AUC difference between the logistic regression model and the decision tree model was not statistically significant (96.3% vs. 94.1%, P > 0.05). The calibration curve of the logistic regression model is closer to the 45 ° line, and the consistency between the prediction probability and the actual probability of the logistic regression model is better than that of the decision tree model. Conclusion For the screening of PA, upright ARR seems to be the best single screening index, while AA2R (radioimmunoassay) is not recommended. The diagnostic efficacy of logistic regression model including upright PAC, PRA and lowest blood potassium is better than that of single upright ARR.
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Objective To explore the electrolyte characteristics between different types of primary aldosteronism (PA), especially the value of serum potassium and the ratio of sodium to potassium after saline infusion test (SIT) in differential diagnosis of PA. Methods The clinical data was collected from 135 patients who received screening for the causes of hypertension from Jan. 2009 to Dec. 2018 in West China Hospital. The patients were divided into two groups: essential hypertension group (EH group, 34 patients) and primary aldosteronism group (PA group, 101 patients). PA patients were divided into aldosterone-producing adenoma group (APA group, 60 patients) and idiopathic hyperaldosteronism group (IHA group, 41 patients). To analyze the value of serum potassium and the ratio of sodium to potassium after SIT in the differential diagnosis of PA with receiver operating characteristic (ROC) curve. Results Compared with EH group, the serum potassium level of APA group was lower either before or after SIT (P<0.01). The ratio of sodium to potassium before and after SIT in APA group were higher than that in EH group (P<0.05). There were no differences between APA group and IHA group in the level of serum potassium and the ratio of sodium to potassium before SIT. The level of serum potassium after SIT in APA group was lower than that in IHA group (P<0.01), and the ratio of sodium to potassium was higher (P<0.05). The area under ROC curve (AUC) of serum potassium level and the ratio of sodium to potassium after SIT were 0.641 and 0.646, respectively, while the AUC of aldosterone level was 0.788. The optimal cut-off value of serum sodium level was 3.56 mmol/L, with a sensitivity and specificity of 46.7% and 85.4%. The optimal cut-off value of ratio of sodium to potassium was 39.09, with 53.3% and 80.5% in sensitivity and specificity. Conclusion The serum potassium and the ratio of sodium to potassium after SIT has limited diagnostic value for its low sensitivity in differential diagnosis of PA.
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Objective To summary the clinical diagnosis and treatment of primary aldosteronism (PA) in West China Hospital (WCH) of Sichuan University during 2009-2018. Methods This study enrolled the patients diagnosed as PA and admitted in WCH of Sichuan University from January 2009 to December 2018. The information of the patients including epidemiological and clinical data, diagnosis and treatment as well as therapeutic outcomes were collected and analyzed. Results A total of 853 patients with 1 248 diagnostic cases were included in the analysis, and the diagnosis cases of PA increased year by year from 2009 to 2018. Most patients (74.33%) were confirmed the diagnosis in the Department of Endocrinology and Metabolism and then admitted to the hospital. PA was more frequent in female than in male, with a ratio of female to male about 1.34∶1. Hypertension was the most common chief complaint, in contrast, the proportion of fatigue and/or numbness as the symptoms of hypokalemia was declining. More and more patients were diagnosed because of imaging examination founding adrenal incidentoma. After 2016, more and more patients were diagnosed by recumbent saline suppression test and captopril challenge test, and the number of adrenal venous sampling to classify PA subtypes was increasing to help choosing different treatment options. The proportion of surgical treatment decreased year by year, and more and more patients adopted medical treatment or transferred to surgery with combined treatment instead of simple operation. Conclusion During the past 10 years, remarkable progress was made in the diagnosis and treatment of PA. Hypertension was the most important clinical manifestation of PA, so the screening of PA in hypertensive patients should be strengthened. Adrenal incidentaloma has become prevalent manifestation of PA with an increasing trend, which needs more attention in clinical practice.
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Objective To investigate the clinical characteristics of aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) complicated with obstructive sleep apnea hypopnea syndrome (OSAHS) and the effect of OSAHS on renin-angiotensin-aldosterone system (RAAS) in APA and IHA patients. Methods The clinical data of 127 patients with primary aldosteronism (PA) diagnosed from May 2010 to Aug. 2019 were retrospectively analyzed. There were 70 cases of APA, 53 cases of IHA. Another 4 cases were primary adrenal hyperplasia (PAH), so not included into further analysis. According to the results of polysomnography, the 123 patients of APA or IHA were divided into OSAHS group (96 cases) and non-OSAHS group (27 cases ). The patients with OSAHS were divided into mild, moderate and severe subgroups based on apnea hypopnea index (AHI).The clinical characteristics, biochemical parameters, plasma renin activity, aldosterone levels, and the ratio of aldosterone to renin activity (ARR) in the patients of APA and IHA complicated with OSAHS were compared with those of the patients without OSAHS. Results There were 49 OSAHS cases (49/70, 70.0%) in APA patients. and 47 OSAHS cases (47/53, 88.7%) in IHA patients. The age, male ratio, body mass index (BMI), waist circumference, triglyceride, blood uric acid, and blood creatinine in APA patients with OSAHS were higher than those in APA patients without OSAHS (P<0.05), while high-density lipoprotein and estimated glomerular filtration rate (eGFR) were lower (P<0.05). Compared to the patients without OSAHS, IHA-OSAHS patients had higher BMI and waist circumference (P<0.05). Moderate/severe OSAHS-APA patients exhibited higher plasma renin activity levels and lower ARR values than the APA patients with no/mild OSAHS (P<0.05). There were no significant differences in plasma renin activity, aldosterone levels, and ARR values between moderate/severe OSAHS-IHA group and no/mild OSAHS-IHA group. Conclusion The prevalence of OSAHS is significantly higher in the patients with PA than normal population, and OSAHS may aggravate glycose, lipid and uric acid metabolism in PA patients. Moderate/severe OSAHS can increase renin levels and decrease ARR values in APA patients, but has no significant effect on RAAS in IHA patients.
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Objective TRAIL-Mu3 was obtained by mutating the N-terminus of human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene to an eight continuous arginine sequence. The present study was designed to explore the antitumor effect of this soluble mutant protein and the underlying mechanisms. Methods The inhibitory effect of TRAIL-Mu3 on the proliferation of lung cancer cell lines NCI-H460, A549, NCI-H1299 and calu-1 was tested by CCK8 assay. The apoptotic rates of A549 and NCI-H460 treated by TRAIL-Mu3 were detected by flow cytometer (FCM). The expressions of apoptosis related proteins death receptor (DR) 4, DR5, Caspase-3, Caspase-8 and X-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. Moreover, a subcutaneous xenograft tumor mouse model of NCI-H460 was established and treated with TRAIL-Mu3 daily or every other day or three times a week. The expressions of DR4, DR5, Caspase-3, Caspase-8 and XIAP were detected by immunohistochemical staining. Results The in vitro study demonstrated that as compared to the TRAIL, the TRAIL-Mu3 was more toxic and pro-apoptotic by up-regulation of the expression and activity of DR4, Caspase-3 and Caspase-8. Also, the animal study showed a similar antitumor effect between treatment with TRAIL-Mu3 every other day and three time a week, which was better than daily use. All treatments significantly suppressed the growth of xenograft tumor, increased the expression or activity of DR4 and Caspase-3, and down-regulated the expression of XIAP (P<0.05). Conclusion TRAIL-Mu3 could improve antitumor activity in vivo and in vitro through elevating DR4 expression, activating Caspase-3/-8, and inhibiting XIAP activation.
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Objective To investigate the effects of short hairpin RNA (shRNA) on the proliferation, invasion, apoptosis and tumor formation of non-small cell lung cancer cisplatin-resistant cell line (A549/DDP) via silencing of colon cancer associated transcript 2 (CCAT2). Methods TA549/DDP cells were transfected with shRNA-CCAT2 (sh-CCAT2) or shRNA-negative control (shRNA-NC), and untransfected A549/DDP cells were used as the control group. CCAT2 mRNA expression in three groups of A549/DDP cells was detected by quantitative real-time PCR (qRT-PCR). The proliferation of three groups of A549/DDP cells treated with different mass concentrations of DDP (0-8 mg/L) was detected by MTT. According to the proliferation experiment results, 2 mg/L was selected as DDP concentration for subsequent experiments. The effects of 2 mg/L DDP treatment on the proliferation, apoptosis, and invasion ability of each group of cells (with untreated A549/DDP cells as the control group) were tested by clone formation experiments, flow cytometry analysis and Transwell experiments. The expression levels of cell proliferation marker proteins (Ki67, PCNA), apoptosis marker proteins (Caspase-3, Caspase-9) and invasion marker proteins (VEGF, MMP-14) were detected by Western blot. Nude mice were injected subcutaneously with A549/DDP cells, A549/DDP cells transfected with shRNA-NC or A549/DDP cells transfected with sh-CCAT2. DDP was intraperitoneally injected at the concentration of 2 mg per kilogram of mice body weight totally for 7 times with an interval of 3 d. A control group was injected subcutaneously with A549/DDP cells, and an equal volume of normal saline instead of DDP was injected intraperitoneally. The tumor volume was detected every 5 d for a total of 30 d. Mice were sacrificed and tumor tissues were taken out 30 d later. CCAT2 mRNA expression level in tumor tissues was detected by RT-PCR, and tumor cell apoptosis was detected by TUNEL staining. Results Compared with the control group and the shRNA-NC transfection group, the expression level of CCAT2 mRNA was decreased in sh-CCAT2 transfected A549/DDP cells (P<0.01). The decrease degree of cell proliferation was more pronounced after treating with 2 to 8 mg/L of DDP (P<0.01). Compared with the control group, in the three groups that treated with DDP, the formation of clones and the expression of proliferation marker proteins Ki67 and PCNA were reduce (P<0.01), while the rate of apoptosis and the expression of apoptosis marker proteins Caspase-3 and Caspase-9 were increased (P<0.01). Also, the number of invasion cell and the expression of invasion marker proteins VEGF and MMP-14 were reduced in the three groups that treated with DDP (P<0.01). Among the three groups of DDP-treated cells, the changes in sh-CCAT2 transfected cells was the most obvious (P<0.01). Compared with the control group, the tumor volume of the three DDP treatment groups was smaller and the differences were statistically significant at 30 d (P<0.01). The expression of CCAT2 mRNA was decreased in tumor tissues (P<0.01), while apoptosis increased (P<0.01). Among the three DDP treatment groups, the A549/DDP cell group transfected with sh-CCAT2 showed the most notable changes (P<0.01). Conclusion sh-CCAT2 can inhibit the proliferation of A549/DDP cells, induce apoptosis and reduce the cell invasion ability, thereby inhibiting the growth of A549/DDP cells.
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Objective To study the relationship between down-regulated expression of X linked inhibitor of apoptosis protein (XIAP) gene and the reversal effect of taxol-resistance by using siRNA interference technology in the taxol-resistant ovarian cancer. Methods Randomly assigned the nude mice into six groups (6 in each group) . Group A: normal saline; Group B: taxol; Group C: siRNA-NC+normal saline; Group D: siRNA-NC+taxol; Group E: siRNA XIAP+normal saline; Group F: siRNA XIAP+taxol. Each group was dealt with the corresponding processing depending on the agreed protocol and the transplanted tumors had a multi-point injection with reagents related siRNA, one time every 3 days, 9 times (27 d) in total. Taxol (2 mg/kg) was used in the intraperitoneal injection, 0.2 mL every time, once a week, for four weeks. After 27 d of siRNA treatment, xenograft volumes and qualities were measured and the inhibitory rate was calculated; RNA expression levels and protein levels of XIAP gene in xenografts were detected respectively by real-time fluorescent quantitative PCR and Western blot. Apoptosis of the transplanted tumor cells was examined by TUNEL method. Results Among the six groups, the proliferation of transplanted tumor in Group F was the slowest, and the tumor inhibition rate was the highest compared with control Group A, followed by Group E, and the tumor inhibition rate was the lowest in Group C. Group F and E expressed the lowest XIAP mRNA and protein expressions (P<0.05, vs. the other 4 groups) .The apoptosis rate was highest in Group F, followed by Group E, and lowest in Group A and C (P<0.05). Conclusion XIAP siRNA has synergy with taxol in taxol-resistant ovarian cancer cells.
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Objective To investigate the effects of ubiquitin-like PDH and ring finger domain 1 (UHRF1) on the expression ratio of estrogen receptor (ER) α/ERβ, and to explore the experimental mechanism of UHRF1 affecting the proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma. Methods The protein and mRNA expressions of UHRF1, ERα and ERβ in normal thyroid Nthy-ori3-1 cells and thyroid papillary carcinoma BCPAP cells were detected by Western blot and qRT-PCR. BCPAP cells were treated with Scrambled siRNA and UHRF1 siRNA, respectively. The expressions of ERα and ERβ mRNAs were detected by qRT-PCR. MTT and Transwell were used to determine the proliferation, invasion and migration in each group of BCPAP cells. Results Compared with Nthy-ori3-1 cells, the expressions of UHRF1 and ERα proteins and mRNAs in BCPAP cells were significantly up-regulated (P<0.05), while the expressions of ERβ protein and mRNA were significantly down-regulated (P<0.05). Compared with the control group and Scrambled siRNA group, the expression of ERα mRNA in BCPAP cells transfected with UHRF1 siRNA was significantly decreased (P<0.05), while the expression of ERβ mRNA was significantly increased (P<0.05). The proliferation, invasion and migration of BCPAP cells transfected with UHRF1 siRNA were significantly decreased (P<0.05). Conclusion UHRF1 upregulates ERα/ERβ expression ratio and promotes proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma.
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Objective The purpose of this study is to investigate the injury of liver and kidney tissues in overload pressure induced cardiac hypertrophy/heart failure mice model and the changes of macrophage activation level. Methods 6-8 week-old C57BL/6 mice were subjected to transverse aortic constriction (TAC) surgery to establish the cardiac hypertrophy/heart failure mouse model induced by pressure overload, while the aortic was not ligated in the Sham group. At 4 weeks and 8 weeks after TAC, the mice of each group were subjected to echocardiography and blood collection. And mice were sacrificed to collect samples of the heart, liver, and kidney tissues. The contents of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and serum creatinine (Scr) in Sham group and two operation groups were determined. The histological changes of liver, heart and kidney tissues were observed by HE staining, and the expression of the marker of macrophage activation, F4/80 protein, was detected in the heart, liver and kidney tissue by immunohistochemical staining. Results Cardiac hypertrophy occurred at 4 weeks after TAC operation in C57BL/6 mice and developed into heart failure at 8 weeks after TAC. The echocardiography showed that, compared with the Sham group, the left ventricular end-diastolic posterior wall thickness (LVPWd) and the left ventricular internal diameter in diastole (LVIDd) were significantly increased, while the left ventricular ejection fraction (EF) and the left ventricular fractional shortening (FS) were significantly decreased (P<0.05) in the 4-week-TAC group and 8-week-TAC group. The plasma content of ALT, AST, TBil and Scr in the 4-week-TAC group and 8-week-TAC group were significantly higher than those in the Sham group (P<0.05). HE staining showed obvious liver pathological changes in TAC mice, such as vacuolation, mild hepatic sinusoid congestion and inflammatory infiltration in mice post 4 weeks after surgery, and such liver injury was worse in mice post 8 weeks after surgery. Besides, there was a slight damage in renal tissue shown by HE staining, such as slight glomerular injury and slight bleeding. F4/80 protein immunohistochemical staining results demonstrated that the activation of macrophages in the heart and liver in the 4-week-TAC group and 8-week-TAC group was significantly increased than that in the sham group (P<0.05), but there was no significant difference in kidney tissues in groups. Conclusion Macrophages are involved in the process of liver and kidney injury in cardiac hypertrophy/heart failure.
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Objective To investigate the effects of AMPKα1/Nrf2/heme oxygenase-1 (HO-1) pathway mediated by galantamine hydrobromide lycoremine (Gal) on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in rats with myocardial ischemia reperfusion (I/R). Methods A myocardial ischemia reperfusion injury rat model was established, and the rats were randomly divided into 5 groups: Control group, I/R model group, Gal 1 mg/kg group, Gal 2 mg/kg group and Gal 4 mg/kg group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular wall thickness (LVWT), and left ventricular short-axis shortening rate (FS) were detected by doppler ultrasound. Hematoxylin eosin staining was used to detect the pathological damage of myocardial tissue. The expression of Caspase-3 was detected by immunohistochemistry. Protein expression levels of CCAAT/enhancer-binding protein homologous protein (CHOP), cleaved Caspase-12, growth arrest and DNA damageinducible protein 34 (GADD34), immunoglobulin heavy-chain-binding protein (BiP), α-smooth muscle actin (α-SMA), Collagen Ⅰ, AMPKα1, Nrf2, and HO-1 were measured by western blot, and AMPK inhibitor Compound C was added for verification. Results Compared with the I/R model group, the grade of pathological damage of myocardial tissue in each group of Gal was improved, and cleaved Caspase-3 positive expression rate and Caspase-3 mRNA level were significantly reduced (P<0.05) as well. The results showed that LVWT, FS and LVEF in Gal 2 mg/kg and Gal 4 mg/kg groups were significantly increased (P<0.05), LVEDV and LVESV were significantly reduced (P<0.05) compared with I/R model group. CHOP, cleaved Caspase-12, α-SMA, Collagen Ⅰ, AMPKα1, Nrf2, HO-1 protein levels were significantly reduced (P<0.05), and GADD34 and BiP protein levels were significantly increased (P<0.05) in Gal 2 mg/kg and Gal 4 mg/kg groups. Conclusion The regulation of AMPKα1/Nrf2/HO-1 pathway mediated by Gal on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in myocardial ischemia reperfusion rats.
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Objective To observe the relationship between the mechanism of bone marrow stem cell mobilization mediated the myocardial fibrosis inhibition in rats and the non-classical pathway mediated by transforming growth factor-β (TGF-β). Methods Twenty two Wistar rats were subcutaneously injected with isoproterenol (Iso) to establish the model of myocardial fibrosis, and then were randomly divided into control group and granulocyte colony-stimulating factor (G-CSF)-treat group (GT group). The rats in GT group were subcutaneously injected with recombinant human granulocyte stimulating factor for 5 days, and the control group was injected with normal saline. After 4 weeks, the myocardial structure was observed by pathological staining, the content of serum B type natriuretic peptide (BNP) was detected by ELISA , the expression of type Ⅲ collagen was detected by immunohistochemistry staining and the protein expression level of typeⅠcollagen, TGF-β, transforming growth factor kinase 1 (TAK1), mitogen-activated protein kinase kinase (MKK) and p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot. Results Compared with the control group, the serum BNP level, Masson staining collagen deposition, collagen area ratio and the expression of typeⅠcollagen, TGF- β, TAK1, MKK3 and p38MAPK in the GT group were lower than those in the control group. Conclusion Bone marrow stem cell mobilization can alleviate the degree of myocardial fibrosis in rats, which is related to the inhibition of TGF- β/TAK1/MKK/p38MAPK pathway.
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Objective To study the alterations of endoplasmic reticulum (ER) stress and mitochondrial damage after acute myocardial infarction (AMI). Methods A total of 40 SD rats were used in this study and 32 of them were subjected to AMI by ligation of left anterior descending artery. The rats were sacrificed and the heart tissues were collected after 1 h, 2 h, 4 h and 6 h of AMI (n=8 per group). The mRNA levels of activating transcription factor 6 alpha (ATF6) and immunoglobulin heavy chain binding potein (BiP), as well as the expression of mitochondrial DNA (mtDNA) in cytoplasm were detected by RT-PCR. The ATP levels in the cardiomyocytes were detected by a commercial ATP assay kit. Results The mRNA levels of ATF6 and BiP were significantly increased after 1 h of AMI, which were maintained at high level from 2 h of AMI to the end of the experiment (P<0.05). The ATP concentrations in the cardiomyocytes were significantly elevated after 1 h of AMI but remarkably decreased after 4 h and 6 h of AMI (P<0.05). The release of mtDNA in cytoplasm was significantly increased after 2 h of AMI, followed by further elevations at 4 h and 6 h after AMI (P<0.05). Conclusion Mitochondrial damage is secondary to ER stress in AMI.
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Objective Investigate the expression of SRY-related HMG box 11 (SOX11) and paired box domain 5 (PAX5) in patients with mantle cell lymphoma (MCL) and analyze the relationship between them and their clinical significance. Methods Seventy-six formalin-fixed paraffin-embedded (FFPE) samples of patients who were diagnosed with MCL from January 2012 to August 2017 were collected.Fifty-six FFPE samples from patients with diffuse large B cell lymphoma (DLBCL), thirty-eight FFPE samples from patients with follicular lymphoma (FL) and nine FFPE samples from patients with Burkitt's lymphoma (BL) were used as control groups. Real-time quantitative PCR (qRT-PCR) and immunohistochemistry were used to detect the mRNA and protein expressions of SOX11 and PAX5. The association between expressions of SOX11 and PAX5 in patients with MCL was analyzed. On the basis of the median H score of SOX11 and PAX5 protein expressions in patients with MCL, they were divided into high and low expression group, and the relationship between the different groups and patients’ clinical characteristics and prognosis were analyzed. Results The different mRNA expression levels of SOX11 and PAX5 in different lymphoma tissues were statistically significant (P<0.01). The mRNA expression levels of SOX11 and PAX5 in MCL group were higher than those of the control groups, and the differences of those between MCL and DLBCL or FL were statistically significant (P<0.01). However, the differences of those between MCL and BL were not significant (P>0.05). The expression level of SOX11 protein was also higher than those of the control groups (P<0.000 1). However, there was no significant difference in PAX5 protein expression level between the MCL group and the control group, nor the expression levels of SOX11 and PAX5 genes and proteins among the control groups (P>0.05). By analyzing the samples from patients with MCL, we observed a positive relevance between SOX11 and PAX5 both in mRNA expression level (rs=0.714, P<0.000 1) and protein expression level (G=0.407, P=0.01). There was no difference in clinical characteristics and overall survival between the high and low expression group. Conclusion In MCL, there was a positive relevance between the expressions of SOX11 and PAX5. The expression of SOX11 or PAX5 alone has no significant effect on the prognostic stratification of MCL patients.
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Objective To investigate the expression of follistatin related gene (FLRG) in colon cancer and its relationship with clinicopathological features of colon cancer. Methods The cancer tissue, paracancerous tissue and normal tissue were collected from 80 patients with colon cancer who underwent radical operation from December 2018 to December 2019. Immunohistochemistry and Real-time PCR were carried out to examine the expression of FLRG and the clinical implications of FLRG was further analyzed. Results The expression of FLRG in colon cancer tissues was significantly higher than that in paracancerous tissues and normal tissues (P<0.05), and the expression of FLRG in paracancerous tissues was significantly higher than that in normal tissues (P<0.05). There was no significant difference in the expression of FLRG among colon cancer patients with different sex, age, tumor growth location and differentiation degree (P>0.05). The expression level of FLRG in patients with distant metastasis was higher than that in patients without distant metastasis (P<0.05), and the expression level of FLRG in patients with late clinical stage (stage Ⅲ and Ⅳ) was higher than that in patients with earlier clinical stage (stage Ⅰ and Ⅱ) (P<0.05). Conclusion FLRG is up-regulated in colon cancer tissue, which may be involved in the regulation of tumor development. FLRG may be a potential prognostic target.
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Objective To investigate the effect of down-regulation of SND1 expression on senescence of human diploid fibroblasts. Methods Western blot and immunohistochemistry were used to detect the expression of SND1 in young or senescent 2BS cells and aged tissues. Immunofluorescence was conducted to detect the localization of SND1 in young 2BS cells. CCK8 and EDU were performed to detect the proliferation of 2BS. Colony formation analysis was used to evaluate the capacity of colony formation of 2BS. Expression chip and RT-qPCR analysis were performed to detect the change of SASP expression level. β-galactosidase staining was employed to indicate the senescent 2BS cells. Results The expression of SND1 in the senescent 2BS cells was significantly down-regulated compared with in the younger 2BS cells, and in human colon adenomas, its expression was also significantly down-regulated compared with in non-lesion colon tissues. In young 2BS, knockdown of SND1 inhibited the proliferation and colony formation of 2BS, and led to stronger senescence-associated beta-galactosidase staining (SA-β-gal). Expression chip and RT-qPCR analysis indicated that knockdown of SND1 up-regulated the expression of senescence-associated secretory phenotype components (SASP). Conclusions Our data indicated that down-regulation of SND1 regulated human diploid cell senescence by up-regulating the expression of SASP components.
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Objective To observe the effect of ginsenoside Rg1 on the acute lung injury of sepsis in combination with the antibiotic imipenem in a mouse model of sepsis that induced by cecal puncture. Methods C57BL/6 mice were used to establish the model of sepsis. The model mice were randomly divided into model group, imipenem group, ginsenoside Rg1 group, and ginsenoside Rg1+imipenem group, 10 mice in each group. Another 10 mice were set as control group. Sham operation was performed in the mice of control group. Each mice was intraperitoneally injected the corresponding drug in 2 h, 26 h and 50 h after surgery for three times. They were 2 h after surgery, 26 h after surgery and 50 h after surgery. 2 h after the last administration, the oxygenation index of the arterial blood was measured, the lung tissue was taken to measure lung wet/dry ratio (W/D), and HE staining was used to observe the lung inflammation. The ELISA kits were used to detect the levels of interleukin (IL)- 1β, IL-6, tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) inalveolar lavage fluid. Western blot and immunohistochemical staining were used to detect NF-κB p65 expression in lung tissues. Results The drug-administered groups significantly reduced the W/D of the lungs in the septic mice and increased the oxygenation index in the blood (P<0.01), and decreased the inflammation in lung and the levels of IL-1β, IL-6, TNF-α and NF-κB in the alveolar lavage fluid (P<0.01), and decreased the expression of NF-κB p65 in lung tissue (P<0.01). When ginsenoside Rg1 was combined with imipenem, the above indicators were closer to the control group than that in the ginsenoside Rg1 and imipenem groups. Conclusion Rg1 can significantly inhibit lung inflammation in septic mice. It has a better therapeutic effect when combined with antibiotics.
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Objective To explore the disparities of hypertension control rate and its affecting factors between plateau and plain regions in Sichuan province. Methods The cross-sectional study was conducted from May to September 2017. We recruited 231 subjects in Jinyang and Chenghua community health service center in Chengdu and 220 subjects in Jiulong County in Ganzi Autonomous Prefecture, Sichuan Province. Demographic characteristics, medical history, family history, lifestyle, cognitive function and medication compliance were collected using a structured questionnaire. Blood pressure and electrocardiogram were measured, and blood samples were collected among participants included in the study. Bivariate logistic regression analysis was used to investigate the affecting factors of hypertension control rate. All the statistical analyses were stratified by plateau and plain regions. Results Hypertension control rate in the plain group was higher than the plateau group (19.05% vs. 8.64%). The logistic regression model showed that the control rate of hypertension was higher among the participants who were 70-80 years old than 40-50 years old in the plain group (OR=4.037, 95%CI: 1.269-12.848). Central obesity (OR=0.480, 95%CI: 0.233-0.987) and high uric acids (OR=0.994, 95%CI: 0.989-0.998) were the risk factors of control rate. In the plateau group, high medication compliance (OR=4.793, 95%CI: 1.407-16.326) and high uric acids (OR=1.008, 95%CI: 1.003-1.012) were the protective factors, and low cognitive function (OR=0.234,95%CI: 0.071-0.767) was risk factor. Conclusion The control rate of hypertension in the plain is higher than that in the plateau. In the plain, the risk factors are central obesity and high uric acids, and aged 40-50 years. In the plateau, the risk factors are poor medication compliance and low cognitive function.
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Objective To understand the status and distribution characteristics of health-related quality of life (HRQOL) of the older generation of migrant workers in Chengdu, and analyze the factors influencing the quality of life of the older generation of migrant workers, so as to provide reference for formulating relevant policies to improve the health of the older generation of migrant workers. Methods From June 2017 to June 2018, the respondent-driven sampling (RDS) method was used to select 1 492 non-registered migrant workers born before 1980 living in Chengdu city. The investigation was performed with questionnaire including demographic characteristics, working status, economic status, disease status, living environment and HRQOL. Results The scores of physical component summary (PCS), mental component summary (MCS) and the total score of HRQOL in the older generation of migrant workers were 50.78±7.54, 50.67±10.24 and 101.45±12.34, respectively. Multiple linear regression analysis showed that older age (standard regression coefficient ()=−0.061, P=0.026), low education level (=−0.053, P=0.038), being unmarried, divorced or widowed (=−0.064, P=0.009), chronic diseases (=−0.156, P<0.001), or two-week illness (=−0.190, P<0.001) were the risk factors of low HRQOL; High income level (=0.069, P=0.013), having a steady job (=0.126, P<0.001), having endowment insurance (=0.055, P=0.027) and satisfactory with the living environment (=0.060, P=0.016) were the contributing factors factors of high HRQOL. Conclusion The HRQOL of the older generation of migrant workers in Chengdu is generally good. More attention should be paid to the migrant workers of older age, having lower income, suffering from chronic diseases, being unmarried/divorced/widowed, and lacking endowment insurance. Appropriate measures should be taken to improve the health status of the key groups.
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Objective To compare the effects of mitochondria staining between specific mitochondrial fluorescent probes and anti-mitochondrial protein antibody in cell and tissue samples. Methods The HepG2 cells fixed by 4% paraformaldehyde were stained with MitoTracker Deep Red (100 nmol/L) or anti-Grp75 antibody (75 nmol/L or 100 nmol/L). The human healthy liver tissue samples fixed by 4% paraformaldehyde were stained with 150 nmol/L MitoTracker Deep Red or anti-Grp75 antibody. The above stained cell and tissue samples were observed using confocal microscopy. Results We found non-specific staining in HeLa cells and obscure mitochondrial image using MitoTracker Deep Red probes, while clear tubular and punctate distribution using anti-Grp75 antibody. In contrast, we observed more specific and better effects of MitoTracker Deep Red probes-stained liver tissue samples as compared to the antibody. Conclusion To visualize mitochondria, the anti-Grp75 antibody staining worked better on cells and the MitoTracker Deep Red probes are more suitable for tissue samples.
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Objective To investigate the establishment of atrial septal defect model with high success rate in pigs with extracorporeal circulation and the method of followed patch repair. Methods Twenty Chinese miniature pigs weighing 45.3-55.7 kg were used, four of which were used for blood donationand the remaining for models. General anesthesia was conducted with intubation. Thoracotomy was performed through the right fourth intercostal space, and the ascending aorta cannulation with a wire-guide technique was carried out. The extra-pericardial method was used for the superior and inferior vena cava cannulation. The ascending aorta was not cross-clamped. After snaring the superior and inferior vena cava, the right atrium was opened on pump. Sutures were preset and a clamp was used to create and expand an interatrial septal hole followed by the implantation of the experimental patch. Results One animal died due to the aortic root torn and hemorrhage while exposing the right atrial appendage. The remaining 15 pigs successfully completed the operation. Among these 15 experimental animals, one had postoperative hypotension. The average pressure was decreased to 38 mmHg (1 mmHg=0.133 kPa), which was corrected by vasoactive agents and fluid resuscitation. One animal had intraoperative cardiac arrest and was resuscitated by heart massage. Fifteen experimental animals were raised for 6 months and all survived. Conclusion The selection of suitable experimental animals like swine and well-established surgical methods could ensure the success establishment of experimental models and patch repairment.
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Objective To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of a rapid-acting insulin analog—insulin aspart (the tested formulation) which was manufactured by The United Laboratories and to evaluate the bioequiavailability to the reference formulation (NovoRapid®) produced by Novo Nordisk in Chinese healthy volunteers. Methods A total of 24 male healthy volunteers were recruited from February to April 2016 to participant in this before-after, single dose, and randomized crossover study. And the experimental observation was conducted on 2 test days respectively with a between-period from 7 to10 d. According to a random number table, the volunteers were divided into group A or B, group A was administrated with tested insulin aspart (IAsp) for the first time and reference NovoRapid® for the second time and group B had the revered order differed from group A. The PK/PD of these insulin analogs were estimated by euglycemic clamp study. Results The relative biological effectiveness (reflecting gloucose-lowing effect) and bioavailability on behalf of plasma-drug concentration were 98.3±18.8% and 97.3%±8.3% respectively. For PK parameters, the 90% confidence interval (CI) of peak plasma insulin concentration (Cmax) and area under the curve of insulin aspart concentration from 0 to 10 hours (AUCIAsp, 0-10 h) of IAsp were 88.8%-106% (equivalent range 70%-143%) and 94.0%-100% (equivalent range 80%-125%) respectively; for PD parameters, the 90%CI of the maximum glucose infusion rate (GIRmax) and AUCGIR, 0-10 h were 95.5%-113% (equivalent range 70%-143%) and 89.9%-104% (equivalent range 80%-125%) respectively, which indicated that IAsp and NovoRapid® was bioequivalent. One of the subjects discovered hyperuricemia without clinical symptoms and the rest had no clinically significant abnormalities in the safety indexes before and after the tests. No hypoglycemic events, allergic reactions, or local injection adverse reaction occurred in this trial. Conclusion The tested IAsp has comparable relative bioavailability to the reference NovoRapid®.
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Objective To evaluate the effect of perioperative inflammatory indicators on the prognosis of the patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. Methods The clinical data of 231 ICC patients in the West China Hospital of Sichuan University from December 2006 to December 2016 were retrospectively collected. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) and platelet-to-lymphocyte ratio (PLR) of patients during the perioperative period (pre-operation, postoperative day 3 and day 5) were analyzed. The X-tile software was used to determine the optimal cut-off values of NLR, d-NLR and PLR in pre-operation, postoperative day 3 and day 5. Based on the cut-off values, all patients were divided into high level group and low level group, and Kaplan-Meier methods were used to analyze the correlations of NLR, d-NLR and PLR with the disease-free survival (DFS) and overall survival (OS) of patients. Univariate and multivariate Cox regression models were applied to assess the prognostic values of NLR, d-NLR and PLR. Nomogram was established to predict the prognosis for ICC patients, and the predicting accuracy was evaluated by the Consistency index (C-index). Results A total of 231 ICC patients including 115 males and 116 females were enrolled into this study, and the proportion of patients aged <60 years was 57.1%. Among the patients enrolled, 161 patients (69.7%) recurred and 156 patients (67.5%) died after hepatectomy. The median time of DFS and OS were 8.9 and 12.5 months respectively. The Kaplan-Meier curves showed that d-NLR and NLR levels in pre-operation, postoperative day 3 and day 5, together with the preoperative PLR level were correlated with the time of DFS (P<0.05). Meanwhile, d-NLR and PLR levels in pre-operation, postoperative day 3 and day 5, together with the NLR level in pre-operation and postoperative day 3 were correlated with the time of OS (P<0.05). Univariate and multivariate Cox regression model analysis suggested that high level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of poor DFS. High level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of OS. The level of PLR level was not correlated with DFS and OS. The C-index values of nomogram for predicting DFS and OS were 0.738 (95% confidence interval: 0.699-0.777) and 0.778 (95% confidence interval: 0.758-0.818), respectively. Conclusion High level of the preoperative NLR, preoperative d-NLR and NLR on postoperative day 3 in ICC patients indicate poor prognosis, and PLR has no prognostic value for ICC patients after hepatectomy.
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Objective To evaluate the diagnostic value of abnormal prothrombin (DCP) in Alpha-fetoproteins (AFP)-negative (AFP≤20 ng/mL) hepatocellular carcinoma and the relationship between DCP level and Child-Pugh grade, tumor size, TNM stage as well as differentiation. Methods The inpatients diagnosed with hepatitis B-related liver disease were collected from June 2016 to December 2017, The diagnostic efficacy of DCP for AFP-negative HCC was analyzed by ROC. Area under the curve (AUC), the best cut point, sensitivity, specificity, positive predictive value and negative predictive value were calculated. The relationship between DCP levels and the clinical characteristic of HCC was analyzed. Results A total of 459 hepatitis B markers positive patients were included, including 136 cases of hepatocellular carcinoma, 173 cases of hepatitis B cirrhosis and 150 cases of chronic hepatitis B. DCP in AFP-negative hepatocellular carcinoma group was significantly higher than that in non-HCC group (CHB and LC) (P<0.05). The AUC of DCP was 0.858, P<0.05. The optimal cut-off point for the diagnosis of hepatocellular carcinoma was 61 mAU/mL. The corresponding sensitivity, specificity, positive predictive value and negative predictive value were 72.8%, 88.2%, 61.1% and 89.7%, respectively. In different size of hepatocellular carcinoma, DCP level of those with diameter>3 cm was significantly higher than those with diameter≤3 cm (P<0.05). In different TNM stages, DCP level in stage Ⅱ and Ⅲ was significantly higher than that in stage Ⅰ (P<0.05). There was no significant difference of DCP level among different Child-Pugh grades and differentiation (P>0.05). Conclusion DCP has diagnostic value for AFP-negative hepatocellular carcinoma, its level may reflects the degree of tumor progression.
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Objective To study the association of glucose variability and ICU delirium of patients after liver transplantation. Methods This was a retrospective, single-center cohort study. Patients who admitted to ICU after liver transplantation during Aug. 2016 to Dec. 2018 were enrolled. They were divided into two groups accoding to whether they had delirium in ICU. Multivariate logistic regression analysis model was used to analyze the relationship between glucose variability and ICU delirium, and Cochran-Armitage trend test was used to analyze the linear relationship between blood glucose variability levels and the incidence of delirium. Results A total of 242 patients were enrolled, among them, 36 patients had delirium. The occurrence rate of delirium was 14.9% (36/242). Results indicated that glucose variability was an independently risk factor of ICU delirium for liver transplant patients (P=0.045), and delirium was more common in patients with higher glucose variability (fourth quartile vs. first quartile, odds ratio=5.283, 95% confidence interval: 1.092~25.550, P=0.038). Results of Cochran-Armitage trend test indicated that there was a linear relationship between blood glucose variability level and ICU delirium rate, with the increase of glucose variability level, the risk of ICU delirium was increased too (P<0.001). Conclusion Glucose variability was an independently risk factor of ICU delirium in liver transplantation patients.
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Objective The chest CT findings of the pneumonia patients with coronavirus disease 19 (COVID-19) were summarized to provide an auxiliary diagnostic basis for the early detection of infected patients. Methods Clinical data and CT images of 23 patients diagnosed with COVID-19 in West China Hospital of Sichuan University were retrospectively collected, and the chest CT findings were summarized and analyzed. Result Of the 23 patients, 56.5% (13/23) had bilateral disease, 69.6% (16/23) had lesions distributed along the bronchovascular bundle, 65.2% (15/23) had lesions distributed periphery, 82.6% (19/23) involved in the basal segment of lower lobe, 82.6% (19/23) had ground-glass opacities, 30.4% (7/23) had ground-glass opacities with consolidation, 26.1% (6/23) had reticular changes. In the stage of disease progression, 54.6% (6/11) had an increased number of lesions, and 63.6% (7/11) had the scope of lesions enlarged and density increased. In the remission stage, 25.0% (4/16) had reduced number of lesions, 81.3% (13/16) had scope of lesions reduced, 62.5% (10/16) had density of lesions decreased, and 37.5% (6/16) had fibrosis. Conclusions As an important diagnostic examination method for COVID-19, CT is conducive to the rapid diagnosis of the disease in patients with epidemiological history.
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Objective To analyze the effects of biofeedback combined with task-oriented training on hand function, Gesell's infant development scale score (Gesell) and balance ability in children with spastic cerebral palsy (SCP). Methods 66 children with SCP admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group. The control group (n=33) received conventional rehabilitation treatment, and the observation group (n=33) received biofeedback combined with task-oriented training based on the treatment of control group. After 6-month treatment, Modified Ashworth scale (MAS) score, Berg balance scale (BBS) score, standing and walking function score in gross motor function scale (GMFM), assisting hand assessment scales (AHA) score, Gesell scale score and satisfaction of the children's parents were compared between the two groups. Results The MAS score after treatment was lower than that before treatment in both two groups (P<0.05), and the BBS score after treatment was higher than that before treatment in both two groups (P<0.05). After treatment, the MAS score in the observation group was lower than the control group, and the BBS score in the observation group was higher than the control group (P<0.05). The scores of standing and walking function after treatment were higher than that before treatment in both two groups (P<0.05). After treatment, the scores of standing and walking function in the observation group were higher than the control group (P<0.05). The AHA score and Gesell developmental quotient (DQ) score after treatment were higher than that before treatment in both two groups (P<0.05). After the treatment, the AHA score and Gesell DQ score in the observation group were higher than the control group (P<0.05). The satisfaction rate of rehabilitation treatment in the observation group was higher than the control group (90.91% vs. 60.61%, P<0.05). Conclusion Biofeedback combined with task-oriented training can improve balance ability, spasm relieve, hand function, development level, standing and walking function in the children with spastic cerebral palsy and increase the treatment satisfaction degree of children's guardians.
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Objective To investigate the feasibility and clinical efficacy of transcatheter arterial embolization using hemostatic clips as the guidance in the patients with peptic ulcer bleeding after endoscopic treatment failure. Methods From February 2009 to October 2018, 33 patients with peptic ulcer bleeding who were treated with transcatheter arterial embolization after endoscopic treatment failure were included in the study. Clinical success rate, 30-d mortality rate and complication rate were observed. Results According to Forrest grading of ulcer bleeding on endoscopy, 8 patients (24.2%) were defined as Ⅰa, 14 patients (42.5%) Ⅰb, 4 patients (12.1%) Ⅱa, and 7 patients (21.2%) Ⅱb. There were 8 patients not given endoscopic treatment due to poor vision. In 25 patients who received endoscopic treatment, 7 patients did not achieve primary endoscopic hemostasis and 18 patients had re-bleeding despite successful primary hemostasis. The mean interval time from endoscopic treatment failure to transcatheter arterial embolization was (35.42±67.54) h. All patients underwent arterial angiography, and 18 patients with positive angiographic findings were treated with embolization. Among the 15 patients with negative angiographic findings, hemostatic clip could be observed fluoroscopically in 8 patients and used as guidance for embolization. Prophylactic embolization was performed in 4 out of 7 patients without visualization of clip fluoroscopically. The clinical success rates in negative angiographic findings patients with and without clip guidance were 75.0% and 28.6% respectively. The clinical success rate with positive angiographic findings was 66.7%. The overall clinical success rate and 30-d mortality rate were 60.0% and 20.0% respectively. No complication related to embolization was observed. Conclusion The preliminary clinical study demonstrates that transcatheter arterial embolization with the guidance of clips is effective and safe for patients with peptic ulcer bleeding after endoscopic treatment failure.
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A 33-year-old woman was admitted at 34+4 weeks after embryo transfer and over 5 d of cutaneous pruritus. Over 2 years ago, the patient had a third-generation test tube baby due to Marfan's syndrome and gave birth to a live baby girl at full term. This time, the glucose tolerance test during the prenatal examination indicated that the patient was with gestational diabetes, and the blood glucose fluctuated within the normal range after the medical nutrition management and exercise control. The heart ultrasound examination during pregnancy showed that the aortic sinus was enlarged to 40 mm, and the left ventricular systolic function was normal. The patient was diagnosed as "intrahepatic cholestasis of pregnancy (mild)". After admission, the gestational age was verified to be 37+2 weeks according to the time of embryo transfer, and the diagnostic result was modified to be intrahepatic cholestasis of pregnancy (severe). During the test, the patient complainted back pain, which might interpreted as a sign of aortic dissection. Cesarean section was carried out under multidisciplinary cooperation, during which the amount of bleeding was 600 mL, bilateral uterine artery ligation was performed and a live baby boy was delivered. The body mass of the baby was 3 020 g, and the Apgar scores (1-5-10 min after delivery) were 10-10-10. The postoperative CT angiography showed aortic dissection (Type B). It was found in the follow-up that the patient had no discomforts such as chest tightness and shortness of breath, and recovered well after the delivery.