[Study on the correlation between PPG and HVPG in patients with portal hypertension].

Objective: To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT). Methods: 752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results: Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 (P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg (P<0.001), 0.145, and 0.021 (P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 (P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion: The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

[The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice].

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

Effects of isomaltooligosaccharide and Bacillus supplementation on sow performance, serum metabolites, and serum and placental oxidative status.

This study investigated the effects of isomaltooligosaccharide (IMO) and Bacillus supplementation on sow performance, serum metabolites, and serum and placental oxidative status. Multiparous gestating sows (n = 130) with similar body conditions were randomly allocated to five groups (n = 26) receiving a basal diet (CON group) or a basal diet supplemented with 0.5% IMO (IMO group); 0.5% IMO and 0.02% Bacillus subtilis (IMO + S group); 0.5% IMO and 0.02% Bacillus licheniformis (IMO + L group); or 0.5% IMO, 0.02% Bacillus subtilis, and 0.02% Bacillus licheniformis (IMO + S+L group). There were no significant differences in the litter sizes among all dietary groups. The average piglet birth weight was improved in all treatment groups, and the placental efficiency was greater in the IMO + S and IMO + S+L groups than in the CON group (P < 0.05). The IMO + S+L group had increased the low-density lipoprotein cholesterol and reduced the total cholesterol in umbilical venous serum (P <  0.05). Additionally, the malondialdehyde concentrations were greater in umbilical venous serum of piglets in all treatment groups relative to that in the CON piglets (P <  0.05). The placental total antioxidant capacity was increased in the IMO+L and IMO+S+L groups (P <  0.05). Furthermore, the growth hormone concentration in umbilical venous serum was greater (P <  0.05) in all treatment groups. Overall, IMO and Bacillus supplementation during late gestation resulted in a changed metabolism of sows, improved the placental antioxidant capacity, and increased the growth hormone concentrations in umbilical venous serum, which ultimately improved the piglet birth weight and placental efficiency.

[Binding characteristics of chemosynthetic Ac-SDKP analogue FAM-Aca-SDKP to hepatic stellate cell-T6 cells].

OBJECTIVE: To investigate the binding of the chemosynthetic analogue of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) FAM-Aca-SDKP to hepatic stellate cell-T6 (HSC-T6) cells and basic physical characteristics. METHODS: The Ac-SDKP analogue short-peptide FAM-Aca-SDKP carrying green fluorescence was synthesized chemically. Quantitative real-time PCR was used to evaluate its effect on the secretion of HSC collagen and verify the consistency in the biological effect between FAM-Aca-SDKP and Ac-SDKP. A fluorescence microscope was used to observe the binding between FAM-Aca-SDKP and HSC-T6, and flow cytometry was used to evaluate the time-concentration effect of the binding between FAM-Aca-SDKP and HSC-T6. The t-test or rank sum test was used for the statistical analysis of different types of data. RESULTS: After HSC-T6 was incubated with Ac-SDKP or FAM-Aca-SDKP for 24 hours, the expression of type I collagen in HSC-T6 was increased, when the action time was 0.5 hour, Ac-SDKP and FAM-Aca-SDKP caused a 30%-50% reduction in the expression of type I collagen. After HSC-T6 was incubated with FAM-Aca-SDKP, strong green fluorescence was observed on cell surface under a fluorescence microscope, and after Ac-SDKP was added, Ac-SDKP significantly reduced the fluorescence intensity on cell surface due to competitive inhibition. Flow cytometry showed that when the concentration of FAM-Aca-SDKP was 0-50µmol/L, the rate of fluorescence-positive cells rapidly increased from 0 to 12%; when the concentration was 50-100µmol/L, the rate of fluorescence-positive cells only increased from 12% to 14%; co-incubation with Ac-SDKP significantly reduced the rate of fluorescence-positive cells. The number of positive cells reached the peak at the 45-minute point of the incubation and then decreased gradually. CONCLUSIONS: FAM-Aca-SDKP can bind to the surface of HSC-T6 cells, and this process has ligand-receptor binding characteristics such as competitive inhibition, saturability, and time-concentration effect.

Effects of monocyte macrophages stimulation on hepatic lipoprotein receptors.

The first series of in vivo experiments were designed to investigate the effects of monocytic macrophages (MM phi) stimulation by zymosan in cholesterol-fed rats. We found that the MM phi stimulation significantly decreased plasma very-low-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol but not high-density lipoprotein-cholesterol. The hepatic and aortic cholesterol levels were also significantly decreased; meanwhile, the biliary total bile acid and fecal sterol excretion were significantly enhanced. These results were beneficial to the prevention and regression of atherosclerosis. The second series of in vitro experiments led to the discovery that zymosan did not have effect on HDL and LDL binding, uptake and degradation of hepatic parenchymal and nonparenchymal cells isolated from normal rats, but did have significant effects on those isolated from cholesterol-fed rats. The experiments of Kupffer cells modulating hepatocytes also demonstrated that hepatocyte HDL receptor activity was significantly enhanced by conditioned medium from acetylated LDL plus zymosan added to Kupffer cells. Bmax of 125I-labeled HDL specific binding was increased from 237.8 to 295.2 ng/mg cell protein. The Ka value was not affected, indicating that there might be an increment in receptor number, but not receptor affinity. Cholesterol-loaded zymosan-stimulated Kupffer cells might secrete a soluble mediator affecting hepatocyte HDL receptor activity. Zymosan and other MM phi-stimulating reagents are promising in the exploration of a new approach for prevention and treatment of hypercholesterolemia and atherosclerosis.

[Use of technique of culturing cells in diffusion chamber in host-mediate for testing chromosomal effects of gossypol acetate on human lymphocytes].

Human peripheral blood lymphocytes were cultured in diffusion chamber in mice after short-term administration of gossypol acetate. The induced chromosomal aberrations of human target cells indiffusion chamber were used as indices of DNA damage. The results showed that the mean frequency of chromosomal aberration of the human lymphocytes in Gossypol-treated mice was slightly higher than that in the control group, but the difference between them was not statistically significant (p 0.05).

[Effects of "compound prescription progestogen no. 1" on induction of sister chromatid exchanges].

PIP: This paper presents the effects of "compound prescription progestogen No. 1" on the induction of sister chromatid exchanges (SCEs) in human lymphocytes in vitro with or without the addition of exogenous activation system S-9 mix. The results of this study showed that progestogen No. 1 15 mcg and 150 mcg/ml medium did not affect the frequency of SCEs with or without exogenous activation system S-9 mix, compared with the normal controls. When cultured lymphocytes were treated with progestogen No. 1, the mean values of SCEs/cell were 5.79 +or- 2.45-7.92 +or- 2.96, ranging from 1-15 SCEs/cell, and those of the controls were 6.56 +or- 3.89-6.68 +or- 3.18, ranging from 2-14 SCEs/cell. The differences between them were not statistically significant (P0.05). When the concentration of progestogen No. 1 was as high as 300 mcg/ml medium, the mean values were 9.76 +or- 3.30-10.36 +or- 2.42, ranging from 5-18 SCEs/cell, which were obviously higher than those of the controls. The differences between them were statistically significant (P0.05). When cyclophosphamide was present (0.5 and 20 mcg/ml medium), the SCEs mean values were 12.27 +or- 4.19-26.36 +or- 7.01, ranging from 5-40 SCEs/cell. They were higher than in the treated (5.79 +or- 2.45-10.36 +or- 2.42) and the controls (5.56 +or- 3.89-6.68 +or- 3.18). The differences between them were all statistically significant (P0.05). Progestogen No. 1 cannot be transformed to mutagen/carcinogen, even if exogenous activation system S-9 mix was added, which showed that using progestogen as a longacting OC, No. 1 is comparatively safe. (author's modified)^ieng