Xiaoyu Han

Induction of Apoptosis by Berberine in Hepatocellular Carcinoma HepG2 Cells via Downregulation of NF-κB.

Hepatocellular carcinoma (HCC) is highly resistant to traditional chemotherapeutic approaches, which causes difficulty in the development of effective drugs for the treatment of HCC. Berberine, a major ingredient of Rhizoma coptidis, is a natural alkaloid used in traditional Chinese medicine. Berberine exhibits potent antitumor activity against HCC due to its high efficiency and low toxicity. In the present study, we found that berberine sensitized HepG cells to NF-κB-mediated apoptosis. Berberine exhibited a significant antiproliferation effect on the HepG2 cells and promoted apoptosis. Both qRT-PCR and immunofluorescence staining revealed that berberine reduced the NF-κB p65 levels in HepG2 cells. Moreover, p65 overexpression rescued berberine-induced cell proliferation and prevented HepG2 cells from undergoing apoptosis. These results suggest that berberine inhibits the growth of HepG2 cells by promoting apoptosis through the NF-κB p65 pathway.

Hypersplenism: History and current status.

Hypersplenism is a common disorder characterized by an enlarged spleen which causes rapid and premature destruction of blood cells. This review summarizes the history of hypersplenism, discuss its classification and pathogenesis, and examines its diagnosis and treatment options. We performed a comprehensive literature search using PubMed, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) database, reviewed hypersplenism-related articles and summarized the major findings. According to its etiological causes, hypersplenism is characterized by splenomegaly and peripheral cytopenias. It can be classified into three categories: i) primary hypersplenism; ii) secondary hypersplenism; and iii) occult hypersplenism. A number of mechanisms causing hypersplenism have been identified, and mainly involve retention in the spleen, phagocytosis, and autoimmunity. Treatment options for hypersplenism include etiological treatment, non-surgical treatment, total splenectomy and liver transplantation. In any case, treatment should be individualized for each patient.

Analysis of Peripheral Blood Cells Due to Adults Posthepatitic Cirrhotic Portal Hypertension and Their Postoperative Prognosis

Objectives: To explore the constituent ratio of peripheral blood cells changes in patients with splenomegaly due to posthepatitic cirrhotic portal hypertension and its postoperative prognosis, and to grade the peripheral cytopenias. Methods: Data of 366 cases of splenomegaly due to posthepatitic cirrhotic portal hypertension were collected and analyzed. Results: Thirty-six patients (9.8%) had a normal blood cell count and 330 patients had peripheral cytopenias, in which mono-lineage cytopenias accounted for 30% (99/330), bi-lineage cytopenias accounted for 35.8% (118/330) and tri-lineage cytopenias accounted for 34.2% (113/330). There were significant statistical differences (P 3 points, respectively. The prognosis revealed significant differences between the three grades (P<0.05). Conclusions: Peripheral cytopenias can influence postoperative prognosis. Thrombocytopenia is a major factor influencing postoperative prognosis and grading is of great significance in analyzing the condition of inpatients and guiding their treatment.

Prognostic Risk Factors for Surgery in Patients with Cirrhotic PortalHypertension

Background: In the clinical management of cirrhotic portal hypertension, surgery is often necessary; however, the operative mortality rate is high. Methods: Data from 161 patients who underwent surgery for cirrhotic portal hypertension were analyzed, and 24 potential predictors of surgical outcome were assessed. A Kruskal Wallis rank sum test was used for single-factor comparisons, and multivariate logistic regression for multi-factor comparisons to identify risk factors for poor surgical outcomes and calculate their scores. Results: Six predictors of poor surgical outcomes were identified: postoperative bleeding within 30h of >2L, with a score of 3; severe liver atrophy (an anteroposterior diameter of the left lobe of ≤55 mm and an oblique diameter of the right lobe ≤ 110mm), with a score of 3; a base excess of 2 L, with a score of 2; and a red blood cell count of <3G/L, with a score of 1. For patients with a good outcome (n=147), all patients had a score of ≤ 3, except one patient who had a score of 4. With respect to patients that died (n=14), all had a score of ≥ 5, except one patient who had a score of 4. A significant difference was observed between the two groups (P<0.05). The mortality was 100% in patients with a score of ≥ 7. Conclusions: Six risk factors for poor surgical outcomes were identified in this study. Operative mortality appears to be significantly increased in patients with a score of 5-6. Surgery should be contraindicated in patients with a score of ≥ 7. To reduce mortality, close attention should be paid to preoperative and intraoperative treatment and prevention to achieve a score of <4.

Grading of Peripheral Cytopenias due to Splenomegaly and Hepatitis BCirrhotic Portal Hypertension

Background: Splenomegaly due to hepatitis B cirrhotic portal hypertension is common in clinical practice, and it is often complicated by monolineage or multilineage cytopenias. We attempted to answer the following questions based on our 20 years of observation and research: can peripheral cytopenias be graded and what are the effects of peripheral cytopenia grades on clinical outcomes? Objectives: This study aimed to investigate the grading of peripheral cytopenia in patients with splenomegaly due to hepatitis B cirrhotic portal hypertension and its effect on clinical outcomes. Methods: Data from 330 patients with splenomegaly due to hepatitis B cirrhotic portal hypertension were collected from January 1991 to December 2011. All data were analysed with SPSS 13.0. Univariate and multivariate analyses were performed. The various forms of cytopenia were scored and graded according to the F value of the multiple linear regression equation. Depending mainly on the severity, cytopenia was graded as mild, moderate, or severe, and was given a total score of 3 points, respectively. Their relationships with clinical outcomes on follow up (cured, improved, no change or dead) were then compared. Results: All patients in this study were treated with splenectomy +/- devascularization or total porto-systemic shunting operation. Of 330 patients, 99 (30%) patients had monolineage cytopenia, 118 (35.8%) bilineage cytopenia, and 113 (34.2%) trilineage cytopenia. On univariate analysis, severity of erythropenia was related to a significant difference in surgical outcome on intra-group comparison (P<0.05). On multivariate analysis, thrombocytopenia was related to a significant difference in surgical outcome when compared with leukopenia and erythropenia (P<0.05). A significant difference in surgical outcome existed among the three grades (mild, moderate, and severe) of cytopenia (P<0.05). Conclusion: Peripheral cytopenias had significant impact on clinical outcomes. The more severe the cytopenias, the worse the surgical outcomes. Thrombocytopenia was a major factor affecting surgical outcomes. The thrombocytopeniabased three-level grading of cytopenia provided a basis for analyzing individual patients, planning treatment, and assessing prognosis in clinical practice.

Causes of peripheral cytopenia in hepatitic cirrhosis and portal hypertensive splenomegaly

The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia were retrospectively analyzed to investigate the causes of peripheral cytopenia, as well as the proportion of the causes in these patients. All patients underwent splenectomy. Before operation, these patients had one or more types of peripheral cytopenia (cumulative cytopenia: 390 patient-times). After splenectomy, blood counts in 79.2% (309/390) returned to normal, while in 15.9% (62/390) they increased but failed to reach to normal levels, and in 4.9% (19/390) they became lower than before the operations. For the last group of patients (n = 19), long-term follow-up showed that blood counts returned to normal in five patients. In other words, in 80.5% [(309 + 5)/390 or 314/390] of patient-times, the peripheral cytopenia was due to hypersplenism, in 15.9% it was due to a combination of factors, and in 3.6% [14/390] it had nothing to do with the hypersplenism. Thus, hypersplenism is a major cause, but not the only cause, of peripheral cytopenia in patients with hepatic cirrhosis and portal hypertensive splenomegaly, and splenectormy is an effective treatment for these patients. Impact statement For a long time, the development of peripheral cytopenias as a complication to cirrhotic portal hypertension has been attributed to hypersplenism; however, this has never been fully demonstrated. Dameshek summarized that hypersplenism should be diagnosed by the presence of four conditions: (a) mono- or multi-lineage peripheral cytopenias; (b) compensatory hyperplasia of bone marrow; (c) splenomegaly; and (d) correction of cytopenias after splenectomy. We retrospectively analyzed the clinical data from 183 surgical patients, and found that 80.5% of peripheral cytopenias was caused by hypersplenism, 16% by a combination of factors, and 3.5% by other factors unrelated to hypersplenism. As the first quantitative findings in this field, our results verify that hypersplenism is a major, but not exclusive, cause of peripheral cytopenias, and provides important clinical evidence for investigating the cause of peripheral cytopenias.

Distribution characteristics of cells in splenomegaly due to hepatitis B-related cirrhotic portal hypertension and their clinical importance:

Objectives To investigate peripheral cytopenia in patients with splenomegaly due to hepatitis B-related cirrhotic portal hypertension (HBRCPH) by comparing blood cell counts from enlarged spleens with peripheral blood. Methods This prospective study involved patients undergoing splenectomy at the Nangfang Hospital from June 2013 to December 2015. Blood cell counts from peripheral blood were compared with those from splenic blood taken during splenectomies. Results Clinical data were available from 30 patients. White blood cell (WBC), red blood cell (RBC) and platelet counts were statistically significantly lower in peripheral blood compared with splenic blood. After splenectomy, peripheral blood cell counts increased significantly compared with pre-operative levels. Platelet and WBC counts in the lower spleen were significantly higher than those in the porta lienis (middle segment) and upper spleen. Conclusions In patients with splenomegaly due to HBRCPH, the counts of three blood cell lineages were significantly higher in the spleen than in peripheral blood. Splenectomy can aid the return of peripheral blood cell counts to normal levels. The most significant retention of platelets and WBCs occurred in the lower spleen which may be useful information for surgeons performing partial splenectomies.

Peripheral Blood Cells Changes After Two Groups of Splenectomy and Prevention and Treatment of Postoperative Complication

Objective: This study aimed to investigate the changes in peripheral blood cells after two groups of splenectomy in patients with traumatic rupture of the spleen and portal hypertension group, as well as causes and prevention and treatment of splenectomy related portal vein thrombosis.Methods: Clinical data from 109 patients with traumatic rupture of the spleen who underwent splenectomy in our hospital from January 2001 to August 2015 were retrospectively analyzed, and compared with those from 240 patients with splenomegaly due to cirrhotic portal hypertension who underwent splenectomy over the same period.Results: After splenectomy, peripheral platelet (PLT) count was significantly increased in both groups (P 0.05), while the white blood cell (WBC) count was significantly decreased (P 0.05), respectively, which was alleviated with urokinase.Conclusion: The significant increase of peripheral PLT count in both groups after splenectomy might be caused by the removal of the site that stored blood cells. The more significant increase of PLT in the traumatic rupture group might be related to a constant production and release of thrombopoietin by the normal liver into blood circulation. The lack of increase of RBC count in the traumatic rupture group indicated no storage of RBCs in the spleen, and the significant increase of WBC count was related to the control of inflammation. The significant increase of WBC and RBC counts in the portal hypertension group was related not only to the elimination of spleen storage, but also to the elimination of hypersplenism. Postoperative routine anticoagulant and thrombolytic therapy could prevent and treat portal vein thrombosis.

Spontaneous remission of obstructive jaundice in rats: Selection of experimental models

The aim of the present study was to evaluate the prevalence and causes of spontaneous remission of obstructive jaundice in rats. Healthy male and female Wistar rats (180–220 g) were randomly assigned to receive common bile duct ligation (CBDL) and transection (group A), CBDL only (group B), or CBD dissection without ligation or transection (control group C; n=36 in each group). There was a difference in eye and skin jaundice prevalence between groups A and B from 14 days after surgery. The level of total bilirubin (TB) did not continue to increase in group A and began to decrease in the majority of rats in group B (P<0.05 vs. group B). At day 21 after surgery, the TB level returned to normal in group B and no significant difference was observed compared with group C. At day 21 after surgery, significant dilatation of bile ducts above the ligature was observed in group A following cholangiography with 38% meglumine diatrizoate and this contrast agent did not spread to other sites. Slight dilatation of the proximal bile ducts was observed in group B and the contrast agent entered the intestinal lumen through the omental ducts adhering to the porta hepatis. After 14 days of surgery, there were 36 rats in group A and B, and 17 rats exhibited spontaneous regression of jaundice. Overall, 47.2% (17/36) of rats experienced spontaneous remission of obstructive jaundice, 82.4% (14/17) of which underwent ligation only. The spontaneous remission of jaundice may have been caused by shunting through very small bile ducts or omental ducts adhering to the porta hepatis. If a model of biliary obstruction is to be established in future research, a model of CBDL and transection is preferable. In this case, jaundice reduction surgery should be performed 14 days after establishment of the model.