[Experimental study on the inhibition of the NLRP3 signaling pathway with Shengsan Jiedu Huayu decoction to alleviate inflammatory injury in rats with acute-on-chronic liver failure].

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1ß content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1ß, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1ß and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1ß, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1ß, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

[Mechanism of action of Jieduhuayu granules for remission of oxidative stress in hepatocytes].

Objective: To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells. Methods: Human liver L02 oxidative injury model was established with 0.1 mmol/ L H(2)O(2) intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H(2)O(2), H(2)O(2) + JDHY (0.5 mg/ml), H(2)O(2) + JDHY (1 mg/ml), and H(2)O(2) + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results: Compared with the normal group, the cell proliferation activity (P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H(2)O(2) group were all significantly reduced (P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased (P < 0.05). Compared with H(2)O(2) group, the cell proliferation activity (P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H(2)O(2) + JDHY (1 mg/ml) and H(2)O(2) + JDHY (1.5 mg/ml) group (P < 0.05) were all significantly increased (P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased (P < 0.05). Conclusion: Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

[Clinical significance of low-dose CT performed for three consecutive years in diagnosis of lung nodules in coal mine workers with 20 working years].

Objective: To investigate the clinical significance of low-dose CT (LDCT) in coal mine workers with relatively long working years. Methods: A total of 907 coal mine workers with ≥20 working years were enrolled, among whom there were 863 male and 44 female workers with a mean age of 49.5 years. Digital radiography (DR) was performed for these workers in 2013, and LDCT was performed for three consecutive years from 2014 to 2016. Results: A total of 32 workers were found to have lung nodules by DR in 2013, while in 2014, 269 workers were found to have non-calcified lung nodules by LDCT, and there was a significant difference in the number of workers with lung nodules (χ(2)=233.73, P<0.005) . There was also a significant difference in the detection rate of nodules between the workers with different working years of dust exposure (χ(2)=6.648, P=0.00) . The male workers had a significantly higher detection rate of nodules than the female workers (χ(2)=5.690, P=0.017) . There was no significant difference in the number of nodules between workers with different types of work (χ(2)=16.985, P=0.05) . There were 443 lung nodules in total, among which 71.56% were solid nodules and 55.75% had a size of ≤4mm; malignant nodules were confirmed by surgery in 6 (0.66%) of the 907 workers after baseline LDCT. LDCT reexamination in 2015 and 2016 found new nodules in 8 workers and enlarged nodules in 3 workers, and there was no significant change in the number of nodules with a size of ≤4 mm. Conclusions: It is necessary to perform high-risk population screening for coal mine workers by LDCT. The follow-up strategies for nodules with a size of ≤4mm are the same as those for negative results; annual reexamination is recommended for nodules with a size of >4-8 mm, and clinical treatment should be considered for nodules with a size of >8 mm.

The combination of polymorphisms within MCP-1 and IL-1beta associated with ulcerative colitis.

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment to sites of inflammation. Raised level of MCP-1 has been widely demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC), suggesting an important role of MCP-1 in the pathogenesis of UC. The -2518A/G polymorphism in the promoter region of MCP-1 gene affecting its transcriptional activation has been reported recently. In order to assess the potential role of this polymorphism in UC, we examined its distribution in 162 unrelated UC patients and 203 healthy controls. In addition, considering the gene regulatory association between interleukin-1beta (IL-1beta) and MCP-1, we further examined whether the gene polymorphisms between MCP-1 and IL-1beta exert synergetic effects on risk of UC. Our results show that the distribution of MCP-1 genotype or allele frequencies between UC patients and controls was not significantly different; however, the association between the polymorphism of MCP-1 -2518 GG and the polymorphism of IL-1beta-511 T in UC patients is significant (OR 2.062, 95% CI 1.034-4.113, P = 0.038). This is the first report describing the association between MCP-1 polymorphism and UC, and our data suggest that the MCP-1 -2518 polymorphism itself does not represent an independent genetic risk factor for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1beta can increase UC risk significantly, which might help us understand the molecular mechanism underlying the development of UC.

Effects of laparoscopically-assisted vaginal hysterectomy compared with abdominal hysterectomy on immune function.

This study evaluated the effects of laparoscopically assisted vaginal hysterectomy (LAVH) and abdominal hysterectomy (AH) on the immune system. Between May 2007 and July 2008, 84 women with uterine myoma were randomized in a double-blind manner to undergo LAVH (n = 42) or AH (n = 42). Plasma levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), T-lymphocyte CD3(+), CD4(+) and CD8(+) subpopulations, and natural killer (NK) cells were measured 24 h before and 24 h and 72 h after surgery. The IL-6, TNF-alpha and CRP levels in both groups increased significantly after surgery compared with pre-operative levels, and were significantly lower in the LAVH versus the AH group. Post-operative CD3(+) and CD8(+) T-cell counts in the AH group decreased significantly compared with pre-operative levels, whereas in the LAVH group they decreased but not to a statistically significant degree. Post-operative CD4(+) T-cell counts in the AH group also decreased significantly at 24 h after surgery, but were significantly increased at 72 h. In conclusion, LAVH does not significantly affect immune function compared with AH, suggesting the preservation of post-operative immunity, however further clinical studies are necessary.

The duration and plantar pressure distribution during one-leg stance in Tai Chi exercise.

BACKGROUND: Tai Chi exercise improved the balance control and muscle strength of the lower extremities. The aim of this study is to quantify the one-leg stance duration and plantar pressure distribution during the one-leg stance in Tai Chi and to try to elaborate on its probable effects on the ability to balance on one leg. METHODS: Sixteen experienced Tai Chi practitioners participated in this study. The Novel Pedar-X insole system was used to record the plantar forces during the execution of a set of 42-form Tai Chi movements and during normal walking. The one-leg stance duration and plantar pressure distribution during the one-leg stance were analyzed. FINDINGS: In Tai Chi exercise, the total duration spent in the one-leg stance was less (p<0.05), the duration of each one-leg stance was longer (p<0.01) and the medial-lateral displacement of the centre of pressure was greater (p<0.05) than during normal walking. The peak pressure and pressure-time integral of the second and third metatarsal heads and the fourth and fifth metatarsal heads were significantly greater (p<0.05) than those of other plantar regions during the one-leg stance in normal walking, whereas the peak pressure and pressure-time integral of the first metatarsal head and the great toe were significantly greater (p<0.05) than those of other plantar regions during the one-leg stance in Tai Chi exercise. INTERPRETATION: The longer duration of each one-leg stance and the plantar pressure distribution characteristics during the one-leg stance in Tai Chi exercise may be associated with an improved ability to balance on one leg. The findings may provide useful information toward the development of strengthening programs, strategies for the prevention of falls, and the promotion of a physically active lifestyle.