Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis / 中华肝脏病杂志

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

Observation on therapeutic alliance with UDCA and glucocorticoids in AIH-PBC overlap syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the efficacy of ursodeoxycholic acid (UDCA) combined with glucocorticoids in the treatment of autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome.</p><p><b>METHODS</b>19 patients with AIH-PBC overlap syndrome were divided randomly into two groups: initiate combined group and initiate UDCA-monotherapy group. Biochemical responses and pathological features before and after treatment were analyzed retrospectively with student's t test, Wilcoxon rank sum test and Fisher's exact method.</p><p><b>RESULTS</b>In the initiate combination group, biochemical responses in terms of AIH features (ALT decline to normal, IgG is less than or equal to 16 g/L) and PBC features (ALP decline ≥ 40% or to normal) were achieved. In UDCA-monotherapy group, no statistical difference existed in biochemical responses before adding glucocorticoids, whereas the levels of ALT, AST, GLB and IgG decreased significantly when combined with glucocorticoids. No statistical difference of rates of biochemical responses eixted between the two groups, whereas variance could be seen in different pathological stages. Alleviation of inflammatory infiltration after therapy appeared in 3 patients.</p><p><b>CONCLUSION</b>Combination therapy of UDCA with glucocorticoids could be suitable for AIH-PBC overlap syndrome. Early treatment is of benefit for achieving better biochemical response and pathological improvement.</p>

A new monoclonal antibody selectively distributes on hepatocellular membrane / 中华肝脏病杂志

<p><b>OBJECTIVE</b>Screening monoclonal antibodies selectively distribute on hepatocellular membrane by hybridoma technology and exploring their relationship with liver diseases.</p><p><b>METHODS</b>Plasma membrane vesicles of rat hepatocytes were prepared using density gradient centrifugation and BALB/c mice were immunized with the membrane vesicles. Monoclonal antibodies were made with hybridoma technology. The immunizing valences and monoclonal antibodies were detected and screened by ELISA. Mh7 antigen was identified by immunoprecipitation method. Liver tissues of carbon tetrachloride injured rat models and diabetic rat models were used to detect the pathology value of mh7-antigen.</p><p><b>RESULTS</b>Hepatocellular membrane vesicles were obtained successfully. Several monoclonal antibodies were yielded by hybridoma technology. Immunofluorescence and pre-embedding immunogold-silver cytochemistry confirmed that mh7-antigen was a membrane molecule and with a 200KD molecular weight. Immunohistochemistry results indicated mh7 selectively distributed on hepatocellular membrane. Results with rat models demonstrated that mh7-antigen was dramatically reduced in fatty degenerated hepatocyte of carbon tetrachloride injured rat models and distributed as straps in diabetic rat models.</p><p><b>CONCLUSIONS</b>Mh7 is a new hepatocellular membrane monoclonal antibody and may closely related with liver diseases.</p>

A two-year follow-up study on the efficacy of ursodeoxycholic acid on primary biliary cirrhosis in different stages / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the therapeutic effect of primary biliary cirrhosis(PBC) in different stages with ursodeoxycholic acid (UDCA).</p><p><b>METHODS</b>91 patients with PBC were divided into 4 periods based on levels of liver test and symptoms. Clinical manifestations, biochemical changes and pathological changes were observed for 2 years on UDCA therapy.</p><p><b>RESULTS</b>The levels of alkaline phosphatase (ALP) and glutamyltranspetidase (GGT) at the second PBC period were declined by 51.9% and 67.3% respectively after a 6-month UDCA therapy. The biochemical responses were 81.25% (Paris criteria) and 93.75% (Barcelona criteria). The levels of ALP and GGT at the third PBC period were declined by 48.8% and 46.6% after 6 months of UDCA therapy, and the biochemical responses were 36.84% (Paris criteria) and 57.89% (Barcelona criteria). Symptoms like fatigue, pruritus and jaundice after UDCA therapy were better than before. Same results also appeared at the fourth period. 11 patients in different periods underwent pathological examinations before and after UDCA therapy and no progression found in the first and the second periods, however difference found in the third and the fourth periods with the lymphocyte infiltration was less than before UDCA treatment.</p><p><b>CONCLUSION</b>Good biochemical responds appear in patients at the second, third and forth periods after UDCA therapy, in which the second period is best. Symptoms could be improved after UDCA treatment. Early UDCA therapy is benefit for slowing down the progression of liver pathology.</p>

Treatment of focal bone defect in postoperative nonunion with autologous red bone marrow injection / 中国骨伤

<p><b>OBJECTIVE</b>To observe the clinical effect of autologous red bone marrow injection in treating focal bone defect in postoperative nonunion.</p><p><b>METHODS</b>Thirteen patients with focal bone defect in postoperative nonunion (7 cases in tibia, 2 cases in femur, 4 cases in humerus), including 8 males and 5 females with the mean age of 32.5-years-old (ranging from 15 to 60 years). The bone defects were treated with autologous red bone marrow injection (1 time per 2 weeks, 5 times in total) and the X-rays of AP and LP were observed.</p><p><b>RESULTS</b>Thirteen patients were followed up from 6 to 12 months with an average of 7.5 months. According to results of X-ray pictures, 13 cases obtained bone defect recovered completely, and the average time of union was 4 months.</p><p><b>CONCLUSION</b>Autologous red bone marrow injection has ascendancy such as less wound and clear clinical effect, which can accelerate bone healing and promotes functional recovery of limb. It is a good method to treat focal bone defect in postoperative nonunion.</p>

Surgical treatment of 72 cases of ascending aortic aneurysm / 中南大学学报(医学版)

OBJECTIVE@#To summarize the experience of clinical diagnosis and surgical treatment of ascending aortic aneurysm.@*METHODS@#The clinical data of 72 cases of ascending aortic aneurysm were retrospectively analyzed. Of the 72 cases, 36 suffered Mafanos syndrome, 35 suffered aortic dissection, and 1 multiple aortic pseudo-aneurysm. All the patients received artificial vessel replacement or repair under middle or low temperature of cardiopulmonary bypass. Two patients received coronary artery bypass grafting, 2 received aortic valve replacement,and 1 received artificial patch repair.@*RESULTS@#Eight patients died and the others recovered without nervous system complications and were discharged.@*CONCLUSION@#Expedient confirmatory diagnosis, prompt surgical therapy, and efficient therapy during the peri-operative period are helpful to achieve a successful outcome.

Indications and effect of the intra-aortic balloon pump in 38 patients during the cardiac surgery / 中南大学学报(医学版)

OBJECTIVE@#To review the indications and effect of the intra-aortic balloon pump (IABP) in 38 patients during the cardiac surgery.@*METHODS@#From June 2004 to August 2007, 38 patients were performed IABP in the cardiac surgery, including 28 coronary artery bypass grafting (CABG) and 10 valve replacements. The intra-operation prophylactic use of IABP was in 5 cases, the use of IABP for weaning from cardiopulmonary bypass (CPB) during the cardiac surgery was in 22 cases, and the rest use of IABP was after the operation in the intensive care unit. Low molecular weight heparin was used for IABP anticoagulation.@*RESULTS@#Thirteen died out of the 38 IABP patients. The total IABP success rate was 66%.The IABP success rate in CABG was 82%, and 20% in the valve replacement. The patients with intra-operation prophylactic use of IABP all recovered, and 16 recovered out of the 22 patients with IABP uses for weaning from CPB, and 6 recovered out of the 11 patients with post-operation IABP application. No severe complications related to IABP occurred.@*CONCLUSION@#IABP has better effect in CABG patients than in valve replacements. Effect of the prophylactic use of IABP is better than both the IABP use for weaning from CPB or the post-operation IABP application. For IABP anticoagulation, low molecular weight heparin is the better alternative than routine heparin, and the proper ACT is controlled at 150-170 s.

Liver support therapy with molecular adsorbents recirculating system in liver failure: a summary of 252 cases from 14 centers in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure.</p><p><b>METHODS</b>This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV.</p><p><b>RESULTS</b>MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%.</p><p><b>CONCLUSIONS</b>MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.</p>

Surgical treatment of total anomalous pulmonary venous connection / 中南大学学报(医学版)

OBJECTIVE@#To summarize the surgical treatment of total anomalous pulmonary venous connection (TAPVC).@*METHODS@#We retrospectively analyzed 49 patients with TAPVC as follows: 37 patients with supra-cardiac type in which 35 received anastomoses between the rear wall of the left atrium and the common pulmonary vein and the other 2 received anastomoses between the rear edge of the left atrium roof and the common pulmonary vein; another 12 patients with cardiac type who were incised the upper edge of coronary sinus, connected the common junction of pulmonary veins with the left atrium to form a new left atrium, and repaired the atrial septal defect with a pericardial patch.@*RESULTS@#Forty-six patients recovered and 3 patients died. Thirty-eight patients were followed-up from 3 months to 8 years. The rest patients got fluent pulmonary vein drainage and their heart function resumed to NYHA I.@*CONCLUSION@#TAPVC patients should be operated on immediately at definite diagnosis. The fluency of the common pulmonary vein-left atrium anastomoses and proper postoperative care can ensure a satisfactory outcome.

Transfection of human VEGF165 gene into bone marrow mesenchymal stem cells in rats / 中南大学学报(医学版)

OBJECTIVE@#To create a method for transfecting human vascular endothelial growth factor165 (hVEGF165) gene into bone marrow mesenchymal stem cells (MSCs) in rats.@*METHODS@#MSCs of Wistar rats were isolated by density gradient centrifugation and purified based on their ability of adhesion to plastic. Detections of cell surface antigens, including CD34, CD45, CD44, and SH3, were performed using flow cytometry. MSCs' potential of differentiating into osteoblast and lipoblast in vitro was tested. The vector pcDNA(3.1)-hVEGF165 was transfected into MSCs with the liposome mediated method. The expression of hVEGF165 in the transfected cells was detected by enzyme linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis.@*RESULTS@#The cultured MSCs were CD34-, CD45-, CD44+ , and SH+, which were differentiated into osteoblasts and lipocytes successfully. The expressed hVEGF165 in the transfected rat MSCs was demonstrated.@*CONCLUSION@#The vector pcDNA(3.1)-hVEGF165 is successfully expressed in MSCs.

Angiogenic effect of bone marrow mesenchymal stem cells transfected with human VEGF gene on myocardial infarcts in rats / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the angiogenic effect of the bone marrow mesenchymal stem cells (MSCs) transfected with human vascular endothelial growth factor (VEGF(165)) gene on myocardial infarcts in rats.@*METHODS@#The animal model of heart ischemic was established by ligating the left anterior descending coronary artery in Wistar rats. The ligated rats were divided into 4 groups (n=12 each), and 2 weeks later they were injected hVEGF-transfected MSC at the heart infarct zone (Group A), MSC (Group B), liposome-hVEGF gene plasmid (Group C), and medium (Group D). Four weeks after the injection, the capillary density of the infracted zone and the expression of human VEGF in vivo were examined.@*RESULTS@#Four weeks after the transplantation,the capillary density was significantly greater in Group A than that in Group B and Group D, slightly greater than that in Group C. The highest expression of hVEGF was Group A, and followed by Group C, Group B, and Group D.@*CONCLUSION@#MSC is helpful for the stable expression of hVEGF gene, and is an ideal cellular vehicle for VEGF genes.

Myocardial protective effects of pretreatment with captopril on ischemia-reperfusion myocardium in rabbits / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of pretreatment with captopril on myocardium ischemia-reperfusion injury in atherosclerotic rabbits.@*METHODS@#Thirty-two New Zealand white rabbits were assigned randomly to the normally feed group, cholesterol-feed (CF) group, and cholesterol food plus captopril group (cap-feed group), which were fed for 10 weeks. We examined the changes in the size of the infarct and changes in the myocardium ultrastructure resulting from coronary ischemia/reperfusion. Levels of endothelin (ET) and nitic oxide (NO) were measured in the different experiment stages.@*RESULTS@#The ET levels significantly increased and the content of NO significantly decreased in the CF group compared with those of the cap-feed group. The ultrastructure of myocardium cell was slightly destroyed and the infarct size was significantly smaller in the cap-feed group than the normally feed rabbits and CF rabbits.@*CONCLUSION@#The long-term captopril treatment can lighten the severity of myocardial injury produced by coronary ischemia/reperfusion.

Modified low-potassium dextran solution in heart-lung transplantation / 中南大学学报(医学版)

OBJECTIVE@#To determine the application of modified low-potassium dextran (LPD) solution in heart-lung transplantation.@*METHODS@#We used the modified LPD as the lung flush solution of the donor in the first heart-lung transplantation procedure in Hunan.@*RESULTS@#The patient survived 555 days after the surgery and severe infection, lung disfunction or severe graft rejection never occurred.@*CONCLUSION@#Modified LPD as lung flush solution of the donor during heart-lung transplantation demonstrates an excellent effect of lung protection.