Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis.

Background and Aims: Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Methods: Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Results: Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). Conclusions: CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

Engineering nanotheranostic strategies for liver cancer.

The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years, and the medicine-based outlook of patients is poor. Given great ideas from the development of nanotechnology in medicine, especially the advantages in the treatments of liver cancer. Some engineering nanoparticles with active targeting, ligand modification, and passive targeting capacity achieve efficient drug delivery to tumor cells. In addition, the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment. Considering clinical use of local treatment of liver cancer, in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy, radiotherapy, and ablation therapy. Furthermore, novel therapies including gene therapy, phototherapy, and immunotherapy are also applied as combined therapy for liver cancer. Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity, and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors, including drug-resistant tumors. Phototherapy is also applied in surgical procedures, chemotherapy, and immunotherapy. Combination strategies significantly enhance therapeutic effects and decrease side effects. Overall, the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.

Tenofovir and telbivudine combination therapy rapidly decreases viral loads in immune-tolerant chronic hepatitis B patients awaiting assisted reproduction: an open-label, randomized, controlled study.

BACKGROUND: Immune-tolerant chronic hepatitis B (CHB) patients awaiting assisted reproduction (AR) are required to initiate antiviral therapy because of laboratory safety concerns. The antiviral therapy in this group has not been well assessed. We sought to explore the efficacy and safety of the combination therapy (COM) of tenofovir (TDF) and telbivudine (LdT). PATIENTS AND METHODS: In this open-label, randomized, controlled study, we enrolled and randomized hepatitis B virus e-antigen (HBeAg)-positive CHB patients awaiting AR into the study COM group and the control (TDF) group. The COM group received combination therapy of TDF and LdT, and the TDF group received a single treatment of TDF. The patients were followed up for at least 48 weeks. The primary endpoint was the proportion of patients with undetectable HBV DNA level at week 12. RESULTS: A total of 121 patients were recruited into the COM group (n=60) and the TDF group (n=61). The percentages of patients with undetectable HBV DNA levels were 90.0% (54/60) in the COM group and 67.2% (41/61) (P=0.002) in the TDF group at week 12; the percentages were 96.6% (58/60) in the COM group and 85.2% (52/61) in the TDF group at week 48 (P=0.028), respectively. HBeAg seroconversion occurred in 5/60 (8.3%) patients in the COM group and 2/61 (3.3%) patients in the TDF group at week 48 (P=0.233). CONCLUSION: TDF and LdT combination therapy shows a rapid antivirological response in immune-tolerant CHB patients awaiting AR, which provide an alternative for this group at AR centers. However, the HBeAg seroconversion rate is unsatisfactory in the short term.

Prognostic factors for renal allograft survival in patients with immunoglobulin A nephropathy: a case control study.

The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.

BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause.

BACKGROUND: The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. RESULTS: Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). CONCLUSIONS: BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.

Isolation of brefeldin A from Eupenicillium brefeldianum broth using macroporous resin adsorption chromatography.

Brefeldin A (BFA) is a macrolide lactone antibiotic, possessing antitumor, antiviral, antifungal activities. In this work, a separation strategy involving one-step macroporous resin adsorption chromatography combined with crystallization was established for BFA purification from Eupenicillium brefeldianum CCTCC M 208113 fermentation broth. Among six macroporous resin adsorbents tested, the non-polar resin HZ830 had the best adsorption and desorption performance. The static equilibrium adsorption data fitted well with the Freundlich equation, and the adsorption kinetic followed the pseudo-second order model. Through experimental optimization of column adsorption and desorption, BFA in purity of 90.4% (w/w), 92.1% (w/w) yield was obtained by a one-step macroporous resin adsorption chromatography, using a stepwise elution protocol. Furthermore, high purity (>99%, w/w) of BFA crystals were prepared from E. brefeldianum CCTCC M 208113 fermentation broth in an overall recovery of 67.0% (w/w), using a combination of adsorption chromatography packed with non-polar macroporous adsorbent HZ830 and crystallization in acetone.

Digital subtraction angiography and computed tomography angiography of predominant artery feeding pancreatic body and tail.

BACKGROUND: Recently a considerable number of promising clinical trials have been designed to perform infusion of stem cells by pancreatic arterial intervention to improve the endocrine function of the pancreas for better diabetes control. It is necessary to investigate the pancreatic body and tail (PBT) arterial system for human islets located mostly in the PBT and identify the predominant artery or arteries. However, the arterial system in the PBT is complicated and variable. In this study we comprehensively investigated the anatomical characteristics of arteries feeding the PBT. RESEARCH DESIGN AND METHODS: One hundred two patients with diabetes underwent 64-slice computed tomography angiography (CTA) and digital subtraction angiography (DSA). The target artery was catheterized, and DSA was performed to show the PBT. All images were documented for later analysis. RESULTS: DSA demonstrated that the feeding arteries for the PBT included the dorsal pancreatic artery (DPA) alone (n = 51 [50%]), combined DPA and great pancreatic artery (GPA) (n = 22 [21.6%]), GPA alone (n = 16 [15.7%]), and transverse pancreatic artery (TPA) (n = 11 [10.8%]). DPA was observed to originate from the initial segment of the splenic artery (n = 34 [46.6%]), common hepatic artery (n = 17 [23.3%]), or superior mesenteric artery (n = 14 [19.2%]). The GPA was mostly from the middle (n = 36 [94.7%]), and only two were found to originate from the initial segment of the splenic artery. The TPA (n = 11) was from either the pancreatoduodenal artery (n = 5 [54.5%]) or the gastroduodenal artery (n = 4 [36.4%]). In most case, the predominant artery of the PBT (95.1%, 97 of 102) could be revealed by 64-slice CTA. CONCLUSIONS: The origins and identities of the predominant artery in the PBT are variable. DSA is superior to CTA for preoperative imaging in arterial intervention therapy.

Adenovirus-mediated human interleukin 24 (MDA-7/IL-24) selectively suppresses proliferation and induces apoptosis in keloid fibroblasts.

Keloids are fibroproliferative dermal lesions characterized by the proliferation of fibroblasts and the formation of excess scar tissue, for which no effective treatment exists. We transfected a replication-incompetent adenovirus vector expressing green fluorescent protein and interleukin-24 gene (Ad-GFP/IL-24) into keloid fibroblasts (KF) and normal dermal fibroblasts (NDF) in vitro to investigate the suppression effects by observation on cell lines growth, apoptosis, mitosis cycle, etc. The expression of GFP and IL-24 mRNA confirmed that Ad-GFP/IL-24 was transfected into KF and NDF successfully. The expression level of secreting IL-24 protein detected by enzyme-linked immunosorbent assay in Ad-GFP/IL-24-treated KF and PBS-treated NDF was higher than controls; treatment with Ad-GFP/IL-24 in KF induced growth suppression (71.83% ± 6.67%, P < 0.05 to 9.79% ± 3.34%, P < 0.01), apoptosis (24.2% ± 3.08% to 66.51% ± 5.29%, P < 0.01) and increased the percentage of the G2/M phase (42.26% ± 6.44%, P < 0.01) in KF but not in NDF. The data showed that the exogenous IL-24 gene could selectively inhibit human KF proliferation and induce significant apoptosis.

The long-term outcomes of pediatric kidney transplantation: a single-centre experience in China.

To explore the long-term outcomes of paediatric kidney transplantation and the effects of renal allograft on growth, education, employment, marriage and procreation. Twenty-seven children with ESRD received the renal allograft from 1985 to 2001. The patient and kidney survival rate, renal function, growth and employment, etc., were reviewed retrospectively. The average follow-up period was 10.3 +/- 4.4 yr. The one-, three-, five- and 10-yr graft survival rates were 96.3%, 88.9%, 81.5% and 66.7%, respectively, and the corresponding patient survival rates were 100%, 92.6%, 85.2% and 68.8%. The body weight gain was 4-10 kg in one-yr post-operative and the height increased 0-2 cm for girls and 2-5 cm for boys. A total of 44.4% of the recipients accomplished their education above junior high school. The employment rate was 46.2% in males, and 57.2% in females. Twelve patients were married. Non-adherence occurred in 30% of the recipients. Forty percent of the surviving recipients developed complications. Seven patients died. More attention should be paid to non-adherence of medications and more supports from the society are required to improve the life quality of paediatric recipients, especially in employment and education.

[Advanced oxidation protein products in diabetic nephropathy patients and its relation with superoxide dismutase, glutathione peroxidase, neopterin].

OBJECTIVE: To determine the changes of advanced oxidation protein products (AOPP) in diabetic nephropathy (DN) patients, as well as its relationship with superoxide dismutase (SOD), glutathione peroxidase (GPx) and neopterin (NPT). METHODS: By the concentration of urinary albumin excretion rate (UAER) and creatinine (Cr), 85 diabetes mellitus (DM) patients were divided into 4 groups as non-DN group (DM), early-staged DN group (DN3), significant DN group (DN4) and end-staged DN group (DN5). The concentration of the serum AOPP was measured by ameliorated method introduced by Wikto-Sarsat, while SOD by Xanthine oxidase test, GPx by [5,5'Dithio-bis (2-Nitrobenzoic aicd) ] (DTNB) reaction test and NPT by ELISA. RESULTS: AOPP in Group DN5 [(117.8 +/- 64.8) [micromol/L] and Group DN4 [ (80.0 +/- 23.0) micromol/L] were significantly higher than those in Group DM [(58.2 +/- 17.7) micromol/L]. There was no significant difference of AOPP between Group DN3 [(72.7 +/-17.2) micromol/L] and Group DM. Serum AOPP negatively correlated with SOD and GPx (r = -0.217 and -0.374 respectively, P < 0.05), while positively correlated with NPT (r = 0.499, P < 0.01). CONCLUSION: DN patient has enhanced protein oxidation than DM patient, which is related to oxidative stress and chronic inflammation in DN.