ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

Objective To explore the impact of change in oxygen concentration on the expression of angiopoietin-like protein 8(ANGPTL8)by endothelial cells(HPAECs)of human pulmonary artery,and the role and mecha-nism of ANGPTL8 in pulmonary hypertension(PH).Methods HPAECs were treated under hypoxic and hyperoxic conditions,and the expression level of ANGPTL8 was detected using Western blot and PCR.The changes in endo-thelial-mesenchymal transition(EndMT)and ERK signaling pathway activity were analyzed.Simultaneously,new-born rats were exposed to hyperoxia to develop a bronchopulmonary dysplasia(BPD)model.The expression of ANGPTL8 protein and changes in the ERK signaling pathway in lung tissue were observed.Results Under hypoxic condition,the protein expression of ANGPTL8 in HPAECs was significantly increased accompanied by inhibition of the ERK signaling pathway.ANGPTL8 promoted the EndMT process induced by hypoxia(P<0.05)and silencing the expression of ANGPTL8 resulted in a partial reversal of EndMT.The protein expression of ANGPTL8 was decreased in hyperoxia-exposed HPAECs and rat lung tissues accompanied by the activation of the ERK signaling pathway(P<0.05).Conclusions ANGPTL8 is highly sensitive to the change of oxygen concentration in HPAECs and closely correlated to its expression level and to the activity of ERK signaling pathway.This result suggests that ANGPTL8 may have potential regulatory effects on the development of PH.

Purpose To investigating the pathological characteristics of the heart and spleen in a Kawasaki disease(KD)model induced by candida albicans watersoluble fraction(CAWS)and to provide a research basis for the pathological mechanisms of KD.Methods Intraperitoneal injection of CAWS was used to establish a KD model in C57BL/6 mice.Specimens of the heart,aorta,and spleen were collected to measure body weight and the weights of the heart and spleen.HE staining was utilized to examine the morphological alterations in the heart,aorta,and spleen.The expression levels of the ma-ture macrophage marker(F4/80),TNF-α,and IL-1β in the spleen were measured using qRT-PCR and immunofluorescence.its clinical pathological characteristics were analyze and relevant literatures were reviewed.Results Compared to the control group,there were no significant differences in the heart and body mass of the model group mice,but their spleen mass signif-icantly increased(P＜0.05).In the myocardial interstitium of model group mice,there was infiltration of mononuclear cells,disorder of the elastic fibers in the aortic wall along with mucoid degeneration,disruption of the splenic red and white pulp struc-ture,and significant macrophage infiltration.In the model group mice,the mRNA levels and immunofluorescence staining inten-sity of spleen F4/80(2.58-fold,P＜0.000 1),TNF-α(1.43-fold,P＜0.001),and IL-1β(3.62-fold,P＜0.000 1)were significantly higher than those in the control group.Conclusion Mice with KD models induced by CAWS can exhibit patholog-ical alterations akin to KD in the heart and aorta,significant en-largement of the spleen,infiltration by macrophages,with ele-vated expressions of TNF-α and IL-1β.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective:To investigate the influencing factors of post-dialysis hypertension in maintenance hemodialysis (MHD) patients.Methods:This study was a cross-sectional and retrospective study. The patients receiving hemodialysis from January 9, 2017 to January 14, 2017 in 5 hemodialysis centers of Beijing area were selected. Post-dialysis hypertension was defined as an event characterized by an average increase of more than 15 mmHg in post-dialysis mean artery pressure (MAP) compared to intradialytic 3 h MAP during 3 consecutive hemodialysis sessions. Post-dialysis stable blood pressure was defined as an event characterized by an increase of less than 15 mmHg or a decrease of less than 10 mmHg in post-dialysis MAP compared to intradialytic 3 h MAP, with the exception of patients with post-dialysis hypertension and post-dialysis hypotension. The patients were divided into hypertension group and stable blood pressure group based on whether they had post-dialysis hypertension, and the differences of clinical data between the two groups were compared. The influencing factors of post-dialysis hypertension were analyzed by multivariate unconditional logistic regression.Results:A total of 491 MHD patients were enrolled in this study, including 65 patients (13.2%) in the hypertension group, 406 patients (82.7%) in the stable blood pressure group and 20 patients (4.1%) in the hypotension group. The age, blood calcium before dialysis and the proportion of patients using 1.75 mmol/L Ca 2+ dialysate in the hypertension group were higher than those of the stable blood pressure group, and pre-dialysis serum intact parathyroid hormone and pre-dialysis serum uric acid in the post hypertension group were lower than those of the stable blood pressure group (all P<0.05). The age, pre-dialysis serum intact parathyroid hormone, pre-dialysis serum calcium, pre-dialysis serum uric acid, dialysate Ca 2+ concentration of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and post-dialysis serum calcium, pre-dialysis total serum cholesterol, application of β receptor blocker, gender of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. Multivariate logistic regression analysis showed that using 1.75 mmol/L Ca 2+ dialysate was the independent influencing factor of post-dialysis hypertension (with using 1.50 mmol/L Ca 2+ dialysate as reference, OR=2.930, 95% CI 1.282-6.694, P=0.011). The age and pre-dialysis serum calcium of statistical differences between hypertension group and stable blood pressure group ( P<0.05), and pre-dialysis serum sodium and pre-dialysis serum uric acid of univariate analysis ( P<0.1) were included into the logistic regression equation as covariates. The older age ( OR=1.046, 95% CI 1.000-1.093, P=0.049) and higher pre-dialysis serum calcium ( OR=21.847, 95% CI 2.111-226.075, P=0.010) were the independent influencing factors of post-dialysis hypertension when the 1.50 mmol/L Ca 2+ dialysate was used. Conclusions:The independent influencing factor of post-dialysis hypertension is using 1.75 mmol/L Ca 2+ dialysate, while the independent influencing factors of post-dialysis hypertension are the older age and the higher pre-dialysis serum calcium level when the dialysate Ca 2+ concentration was 1.50 mmol/L.

Objective To evaluate the combination of transvaginal conventional ultrasonography and shear wave elastography ( SWE) on the diagnosis of endometrial cancer ,and establish a predictive Logistic regression model . Methods Clinical information collection ,transvaginal conventional ultrasonography ,and SWE check were performed in 112 patients w ho were post‐menopausal vaginal bleeding with ≥5 mm thick endometrium . T he Emax and Emean of Young′s modulus for the endometrium were obtained . Pathology was used as the gold standard ,ROC curve was plotted ,which could be used to evaluate the Young′s modulus on the diagnostic effectiveness on endometrial cancer . Single factor analysis and bring logistic regression methods were applied to assess the values of the clinical variables ,transuaginal conventional ultrasonography variables ,and Young′s modulus in the identification of endometrial cancer . Results In 112 cases of endometrial lesions diagnosed by pathology ,there were 84 cases of benign lesions ( benign group) and 28 cases of cancer( malignant group) . Both Emax and Emean in malignant group were larger than benign group [ (53 .00 ± 16 .07) kPa vs ( 31 .99 ± 13 .89) kPa ,( 27 .25 ± 9 .28) kPa vs ( 19 .94 ± 10 .37) kPa ,all P ＜0 .001] . In the logistical regression analysis ,body mass index ,endometrial thickness ,blood flow grading and Young′s modulus were identified as independent risk factors for endometrial cancer . T he accuracy ,sensitivity and specificity of the logistic regression model in the prediction of endometrial cancer were 89 .29% ,82 .14% , and 91 .67% , respectively . T he area under the ROC curve was 0 .928 . Conclusions T ransvaginal conventional ultrasonography combined SWE technique has an important value in the diagnosis of endometrial cancer .

Objective To estimate cervical stiffness during late pregnancy with virtual touch tissue quantification technique(VTQ) and investigate the value of predicting the outcome of labor induction. Methods Cervical length in pregnancy women at 35 -41 weeks′gestation was measured through perineum ultrasound examination before labor induction,and then VTQ was applied to measure shear wave velocity (SWV)values in region of interest(ROI),the maximum,minimum and average of SWV values were obtained from multiple SWV measurement under the VTQ mode. The outcomes of labor induction were tracked and Bishop scores were recorded,vaginal delivery and cesarean delivery groups were compared using Student′s t-test for continuous variables. ROC curve was plotted to analyze the correlation between parameters and the outcome of labor induction and to determine the most accurate SWV value and cut-off value for diagnosis.Univariate and multivariate logistic regression analysis were used to determine which of the following parameters were significant predictors of the outcome of labor induction. Results The SWV mix,SWV max and SWV mean of vaginal delivery and cesarean section were (0.92 ± 0.13)m/s,(1.37 ± 0.14)m/s,(1.13 ± 0.10)m/s and (1.03 ± 0.13)m/s,(1.74 ± 0.42)m/s,(1.36 ± 0.11)m/s,respectively, there were significant differences between vaginal delivery and cesarean section(all P < 0.05).Based on ROC curve analysis,the SWV mean value in cervix was the best value for predicting the outcome of labor induction.The cut-off value of SWV mean value was 1.23 m/s,the sensitivity,specificity and Youden index were 93.8%,83.4%,0.77,respectively.The SWV value and cervical length were closely correlated to the outcome of labor induction,especially the SWV value according to multivariate logistic analysis. Conclusions VTQ can assess the cervical stiffness with SWV values during pregnancy,and it may have an application value of predicting the outcome of labor induction.

Objective To investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) in hematogenous spread of hepatocellular carcinoma after hepatic ischemia reperfusion in mice and its mechanism.Methods One hundred and sixty mice were randomly divided into 4 groups,sham,control,Rosiglitazone(R group) and Rosiglitazone + GW9662 (R + GW).The mice models with hepatic ischemia reperfusion combined with portal vein metastasis of hepatocellular carcinoma were well established.Serum ALT level,expressions of MMP-9,NF-κB and PPARγ,hepatic replacement area (HRA) and survival of mice were compared.Results (1) The median survival in sham group was 16.3 d,R group 12.1 d,control group 9.6 d,R + GW group 8.7 d.(2) Impact on portal venous metastasis:compared with left hepatic lobe (ischemic hepatic lobe) of control group,the HRA was significantly decreased in the left hepatic lobe of sham group (29.1％ vs.13.2％,P ＜0.05).Tumor load was higher in control group than R group (29.1％ vs.13.0％,P ＜ 0.05).(3) Serum ALT level:after 2 h,8 h and 24 h hepatic ischemia reperfusion injury (HIRI),the ALT levels in control group [(1 134.2 ± 320.5) U/L],R group [(1 017.3 ± 365.9)U/L] and R + GW group [(1 344.0 ± 304.3) U/L] were all higher than sham group [(20.6 ± 7.8) U/L],P ＜0.05.With 8 and 24 h HIRI,ALT levels were highest in R + GW group [(4 101.7 ± 462.2) U/L,(3 730.8 ± 582.7) U/L],following by control group [(3 649.1 ± 440.1) U/L,(2 226.7 ± 442.7) U/L],andRgroup [(1691.9±398.6)U/L,(1 109.2±237.4)U/L],P＜0.05.(4) MMP-9 expression:after 8 h HIRI,MMP-9 expression level was predominantly elevated in control group than R group [(41.3 ± 10.7) vs.(4.7 ± 1.1),P ＜ 0.05].Similarly,MMP-9 expression was higher in R + GW group than both control and R groups [(166.9 ± 7.9) vs.(41.3 ± 10.7) and (4.7 ± 1.1),P ＜ 0.05].(5) Expressions of PPARγand NF-κB:in the control group,PPARγ expression emerged after 2 h HIRI,and reached the peak with 8 h HIRI,decreased significantly with 24 h HIRI.NF-κB expression elevated with time,and at the peak with 24 h HIRRI.In R + GW group,the PPARγ expression was similar to control group and high expression of NF-κB were detected at all three endpoints.In R group,marked expression of PPARγ was observed after 2 h HIRI,and reached to peak after 24 h HIRI.NF-κB showed weakly positive expression after 2 h HIRI.Conclusions Rosiglitazone could significantly reduce hematogenous spread of hepatocellular carcinoma after hepatic ischemia reperfusion in mice.This may be attributed to NF-κB expression inhibition by PPARγ up-regulation and decreased MMP-9 production after pretreatment with Rosiglitazone.

Objective To investigate the expression of CDX2 in different subtypes of intestinal metaplasia (IM) and gastric cancer,and its relationship with Helicobacter Pylori (H.pylori) infection.Methods The expressions of CDX2 protein were detected with immunohistochemical method in 42 cases of chronic atrophic gastritis (CAG),46 cases of CAG with IM,34 cases of paracancerous IM and 50 cases ofgastric cancer.The IM was divided into three subtypes by HID-AB staining:27 cases of IM Ⅰ,23 cases of IM Ⅱ,and 30 cases of IM Ⅲ.H.pylori infection was detected with one minute rapid urease test,serum H,pylori IgG of ELISA method and HE staining in 80 caese of IM,which were divided into 46 cases of H.pylori-posi-tive groups and 34 cases of H.pylori-negative groups.Results The positive rates of H.pylori infection in IM Ⅰ,IM Ⅱ andIM Ⅲ were 66.67％,65.22％ and 43.34％,respectively,and there was no significant difference among different subtypes ofIM (x2=3.953,P＞0.05).The positive rates of CDX2 expression in IM Ⅰ,IM Ⅱ and IM Ⅲ were 85.19％,69.57％ and 36.67％,respectively,and IM Ⅲ were significant lower than IM Ⅰ,IM Ⅱ (x2 =13.899,P＜0.001;x2 =5.638,P=0.018),and there was no significant difference between IM Ⅰ and IM Ⅱ.Comparing of different types of IM group and gastric cancer group showed that the positive rates of CDX2 expression in IM Ⅰ,IM] were significant higher than in gastric cancer group (x2 =14.517,P＜0.001;x2 =5.509,P＜0.05),but there was no significant difference between IM Ⅲ and gastric cancer group (x2 =0.088,P＞0.05).The positive rates of CDX2 expression in H.pylori-positive groups was significant higher than in H.pylori-negative groups in all of.IM (76.09％ vs 44.12％,x2 8.525,P=0.004).Comparing between different subtypes of IM showed that the positive rates of CDX2 expression in H.pylori-positive groups was significant higher than in H.pylori-negative groups in IM Ⅲ (P=0.023),but there was no significant difference between IM Ⅰ and IM Ⅱ (P＞0.05).There was also no significant difference of CDX2 expression between H.pylori-positive groups and H.pylori-negative groups in gastric cancer.Conclusion H.pylori infection may affect the progression of IM and gastric carcinogenesis by affecting the expression of CDX2 in different subtypes of IM.

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