Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Objective::To establish the Chinese population's amniotic fluid deepest vertical pocket (DVP) reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.Methods::This retrospective cohort study, conducted at Peking University Third Hospital from August 2011 to December 2020, used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound. After exclusions, reference curves were developed using 318 women with 3,299 DVP scans, and the data analyzed included maternal demographics, pregnancy outcomes, ultrasound measurements, and neonatal information. DVPs were assessed via ultrasound at regular intervals and grouped by gestational age (GA) for analyses. Linear mixed models were used to create amniotic fluid reference curves. Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests. Logistic regression provided both crude and adjusted odds ratios, adjusting for pre-pregnancy weight, age, ethnicity, parity, and conception mode. Significance was set at P < 0.05 with 95% confidence intervals (CI), and the analyses were conducted using SPSS ver. 26.0 (IBM Corp., Armonk, NY) and SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA) software. Results::DVP increased from the first trimester to a maximum at 26 weeks (95% confidence interval ( CI), 2.7-8.3 cm for twin 1 and 2.8-7.9 cm for twin 2) and then decreased gradually toward term. Differences between twins 1 and 2 were significant after 26 weeks (95% CI for twin 1: 5.3, 5.5; 95% CI for twin 2: 4.4, 4.5; P < 0.010). Polyhydramnios of twin 1 increased the risk of large for GA. Oligohydramnios of twin 1 increased the risk of small for GA. Polyhydramnios of twin 2 increased the risk of small for GA, premature birth, and neonatal complications. Oligohydramnios of twin 2 increased the risk of preeclampsia, hypertensive disorder complicating pregnancy, and premature rupture of membranes. Conclusion::Reference curves for twin amniotic fluid volumes vary by GA and differ between twins, with potential implications for pregnancy outcomes.

Objective::To establish the Chinese population's amniotic fluid deepest vertical pocket (DVP) reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.Methods::This retrospective cohort study, conducted at Peking University Third Hospital from August 2011 to December 2020, used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound. After exclusions, reference curves were developed using 318 women with 3,299 DVP scans, and the data analyzed included maternal demographics, pregnancy outcomes, ultrasound measurements, and neonatal information. DVPs were assessed via ultrasound at regular intervals and grouped by gestational age (GA) for analyses. Linear mixed models were used to create amniotic fluid reference curves. Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests. Logistic regression provided both crude and adjusted odds ratios, adjusting for pre-pregnancy weight, age, ethnicity, parity, and conception mode. Significance was set at P < 0.05 with 95% confidence intervals (CI), and the analyses were conducted using SPSS ver. 26.0 (IBM Corp., Armonk, NY) and SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA) software. Results::DVP increased from the first trimester to a maximum at 26 weeks (95% confidence interval ( CI), 2.7-8.3 cm for twin 1 and 2.8-7.9 cm for twin 2) and then decreased gradually toward term. Differences between twins 1 and 2 were significant after 26 weeks (95% CI for twin 1: 5.3, 5.5; 95% CI for twin 2: 4.4, 4.5; P < 0.010). Polyhydramnios of twin 1 increased the risk of large for GA. Oligohydramnios of twin 1 increased the risk of small for GA. Polyhydramnios of twin 2 increased the risk of small for GA, premature birth, and neonatal complications. Oligohydramnios of twin 2 increased the risk of preeclampsia, hypertensive disorder complicating pregnancy, and premature rupture of membranes. Conclusion::Reference curves for twin amniotic fluid volumes vary by GA and differ between twins, with potential implications for pregnancy outcomes.

Objective To investigate effects of capsaicin on proliferation,migration and invasion of human large cell carcinoma NCI-H460 and discuss the possible mechanisms by which capsaicin inhibits non-small cell lung cancer. Methods NCI-H460 cells were cultured in vitro and treated with capsaicin at various concentrations. Colony formation assay,wound healing assay,and transwell chamber invasion assay were used to detect the effects of capsaicin on proliferation,migration and invasion of NCI-H460 cells. Western blotting was used to detect the protein expression of E-cadherin,N-cadherin,Vimentin and Snail. Results The rate of colony formation of 100,200,300 μmol.L-1 of capsaicin were (91.17±24.38)%,(43.22±12.91)% and (15.71±4.26)%,respectively,the control group was (99.53±21.25)%.the rate of migration of NCI-H460 cells of 25,50, 100 μmol.L-1 of capsaicin were (85.83±17.43)%,(37.92±10.16)% and(21.08±6.39)%,respectively,the control group was (93.04±20.23)%.The number of invasion of NCI-H460 cells of 25,50,100 μmol.L-1 of capsaicin were (99±18.2),(75± 17.9) and( 52 ± 14. 1 ) , respectively, the control group was ( 107 ± 20. 4 ) . The middle and high-dose capsaicincould inhibit proliferation,migration and invasion of NCI-H460 cells ( P<0.05) ,and E-cadherin expression level was significantly up-regulated and N-cadherin, Vimentin, Snail expression level was significantly down-regulated ( P<0. 05 ) . Conclusion Capsaicin can inhibit proliferation,migration and invasion of NCI-H460 cells,the mechanism may be related to up-regulation of E-cadherin and down-regulation of N-cadherin,Vimentin and Snail expression levels.