Modulatory role of L-carnitine against microcystin-LR-induced immunotoxicity and oxidative stress in common carp.

Microcystin-LR (MCLR), one of the most popular microcystins (MCs) found in many field water bodies around the world, poses great health risks to animals and humans. In the present study, healthy common carp (initial weight 24.8 ± 2.3 g) were randomly assigned to five groups. Group I was fed on normal diet as control. Group II was maintained on normal diet and received MCLR intraperitoneal injection (150 µg kg-1 BW). Common carp in groups III, IV, and V were daily pretreated with L-carnitine (LC) at doses of 0.5, 1.0, and 2.0 g kg-1 of the diet for 4 weeks prior to MCLR intraperitoneal injection. The results showed that MCLR alone led to a significant downregulation in immune response, including serum complement C3, lysozyme, and bactericidal activity. However, oxidative stress response: catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and lipid peroxidation (LPO) levels were significantly increased. Similarly, gene expressions of inflammatory IL-1ß, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) were also upregulated after challenged with MCLR. However, LC pretreated group caused a significant elevation in immune response (C3, lysozyme, and bactericidal activity) and gene expressions of inflammatory IL-1ß, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) after MCLR stress. Antioxidant activities (CAT, SOD, GSH, GPx, and LPO) were returned to background levels at 96 h after MCLR challenge. Strikingly, LC supplementation at 2.0 g kg-1 has been considered the optimum for common carp since it exhibited enhancement of immune response and antioxidant activity over the level 0.5 and 1.0 g kg-1, and even better than that of control level. It was concluded that LC as a functional feed additive significantly inhibited the progression of MCLR-induced immunotoxicity and oxidative stress in common carp.

Effects of Ala-Gln feeding strategies on growth, metabolism, and crowding stress resistance of juvenile Cyprinus carpio var. Jian.

The present study was conducted to evaluate the effects of different L-alanyl-l-glutamine (Ala-Gln) feeding strategies on the growth performance, metabolism and crowding stress resistance related parameters in juvenile Jian carp (Cyprinus carpio var. Jian) under crowded condition (80 g/L). Juvenile Jian carp (initial weight 26.1 ± 0.6 g) were distributed into five groups which fed with graded concentrations (0% or 1.0%) of Ala-Gln for eight weeks. Control group (I, 0/0) fed with control diet (0% Ala-Gln) throughout the feeding trial. The other four groups employed different control and experimental diet feeding strategies ranging from two weeks control diet fed and two weeks experimental diet (1% Ala-Gln) fed (II, 0/2) to eight weeks experimental diet fed (V, 4/4). Results revealed that Mean weight gain (MEG) under all different feeding strategies of Ala-Gln were significantly higher than that of the control group (p < 0.05), and MEG of group II (201.90%) was even higher than that of group IV (184.70%). Liver glycogen and blood total protein of groups II, III and V were significantly higher than that in groups I and IV (p < 0.05). The highest level of serum thyroxine (10.07 ng/ml), insulin-like growth factor-I (52.40 ng/ml) and insulin (9.73 µ IU/mL) were observed in group V. However, diet supplemented with Ala-Gln did not affect the levels of serum glucose, cortisol and catecholamine in fish. The mRNA expression of GR1a, GR1b and GR2 were also significantly changed in Ala-Gln supplementation groups compared with control group (p < 0.05). After fish intraperitoneally injected with virulent Aeromonas hydrophila, the fish survival rates were significantly increased in all Ala-Gln supplementation groups compared with control group (p < 0.05). Results from the present experiment showed the importance of dietary supplementation of Ala-Gln in benefaction of the growth performance, metabolism and crowding stress resistance in Jian carp breeding. The optimal feeding strategy was alternatively fed with control diet and then experimental diet at an interval of two weeks for juvenile Jian carp under crowded condition.

Peg-Asparaginase-Associated Pancreatitis in Chemotherapy-Treated Pediatric Patients: A 5-Year Retrospective Study.

BACKGROUND: Asparaginase-associated pancreatitis (AAP) is one of the most common complications occurring in patients with asparaginase-treated acute lymphoblastic leukemia (ALL). Peg-asparaginase (peg-asp), a chemically recombined asparaginase with lower hyposensitivity and better patient tolerance, is now approved as the first line asparaginase formulation in ALL chemotherapy regimens. Due to the differences in pharmacokinetic characteristics and administration procedure between l-asp and peg-asp, this study aimed to investigate the clinical manifestations of peg-asp-associated pancreatitis. METHOD: Patients with peg-asp-associated pancreatitis diagnosed within a 5-year period (July 2014 to July 2019) were identified and retrospectively studied. The clinical manifestations, laboratory findings, and imaging results of patients with AAP were analyzed. AAP patients were further classified into mild/moderate and severe groups based on criteria used in previous studies. Clinical outcomes were compared between groups. RESULTS: A total of 38 patients were enrolled in this study. The underlying disease included ALL (n=35) and lymphoma (n=3). The majority of patients developed AAP during the first phase, called remission induction (n=26, 68.4%), after a median of 2 peg-asp doses (range: 1-11). The DVLP regimen (n=23) is the most common peg-asp regimen used in AAP patients. Abdominal pain occurred after a median of 14.5 days (range: 1-50) from the last peg-asp administration, accompanied by abdominal distension (n=14), nausea (n=17), vomiting (n=21), and fever (n=19). Serum amylase elevation was reported in all AAP patients, of whom 65.8% (n=25) exhibited an elevation in the level of this enzyme three times the upper normal level, fulfilling the Atlanta criteria. The level of serum lipase (median days of elevation=23 days, range: 4-75) was significantly elevated compared with that of serum amylase (median days of elevation=9 days, range: 2-71) and persisted at a markedly high level after the level of serum amylase returned to normal. Common local complications included abdominal ascites (n=10) and peripancreatic fluid collection (n=8). Approximately 42.1% (n=16) of patients with severe AAP experienced systemic complications (septic shock or hypovolemic shock) or severe local complications (pseudocyst), among whom 5 failed to recover. Approximately 84.8% (n=28/33) of the remaining patients resumed chemotherapy; among them, peg-asp formulation in 30.3% (n=10/33) of these patients was adjusted, while asparaginase treatment in 39.4% (n=13/33) was permanently discontinued. Five patients experienced an AAP relapse in later stages of asparaginase treatment. Comparison between mild/moderate and severe AAP patients showed a statistically significant difference in the number of pediatric intensive care unit stays (p=0.047), survival rate (p=0.009), AAP prognosis (p=0.047), and impacts on chemotherapy (p=0.024), revealing a better clinical outcome in mild/moderate AAP patients. CONCLUSION: Early recognition and management of AAP is essential in reversing the severity of AAP. The existing AAP criteria had a low strength in determining the severity of pediatric AAP. A well-defined AAP definition could help distinguish patients with high anticipated risk for redeveloping AAP and ALL relapse, in order to prevent unnecessary withdrawal of asparaginase. Our study could serve as a basis for conducting future large cohort studies and for establishing an accurate definition of pediatric AAP.

[Exploration of the Role of Tumor Suppressor Genes Foxo1 and PTEN in the Tumorigenesis of Mouse Natural Killer-Cell Lymphoma].

OBJECTIVE: To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma. METHODS: NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1fl/fl) as well as floxed PTEN alleles (PTENfl/fl) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1△NKPTEN△NK. The growth and development of the mice and tumor formation were observed. The flow cytometry was used to detect the percentages of NK cells in main lymphatic organs. B16F10 metanoma model of tumor metastasis was utilized to investigate NK cell-mediated tumor surveillance in vivo after NK cells special deletion of Foxol and PTEN. RESULTS: The mouse model with NK cell-special Foxo1 and PTEN double knockout was established. Compared with control group (Foxo1fl/flPTENfl/fl mice), Foxo1△NKPTEN△NK mice were born alive and appeared to be healthy over a period of 46 weeks. No spontaneous tumor formation was observed at this stage. There were no significant differences in NK cell percentages of gated lymphocytes from various organs including blood, bone marrow, peripheral lymph node and spleen between Foxo1△NKPTEN△NK mice and Foxo1fl/flPTENfl/fl mice [PB: 4.76%±0.46% vs 4.17%±0.64% (P＞0.05, n=8); BM: 1.13%±0.23% vs 1.31%±0.10% (P＞0.05, n=8) ; LN: 0.50%±0.10% vs 0.85%±0.20% (P＞0.05, n=8); SP: 4.41%±0.65% vs 3.50%±0.24% (P＞0.05, n=8)]. B16F10 melanoma metastasis model of tumor was established, No differences in median survival time were observed in the 2 types of mice (P＞0.05, n=13). CONCLUSION: The simultaneous deletion of the Foxo1 and PTEN genes may not plays significant role in the tumorigenesis of mouse natural killer-cell lymphoma and NK cell-mediated tumor surveillance in vivo.

[Retrospective Analysis of Clinical Features and Prognosis of 84 Patients with Extranodal NK/T Cell Lymphoma in One Center].

OBJECTIVE: To investigate the clinical characteristics, treatment and prognostic factors of patients with extranodal NK/T cell lymphoma. METHODS: The clinical data of patients with extranodal NK/T cell lymphoma admitted in the Hospital Affiliated to the Academy of Military Medical Science from June 2006 to June 2016 were retrospectively analyzed. The clinical features, therapeutic efficacy and prognosis-related factors were clarified. RESULTS: A total of 84 patients with extranodal NK/T cell lymphoma with complete clinical data were collected, with a median follow-up of 21 months (1-123 months), the overall survival (OS) and progression free survival (PFS) were 58.9% and 52.1% years, respectively. Univariate analysis showed that anemia, the copy number of EBV-DNA, LDH level, IPI score, ECOG score, Ann Arbor staging, complete remission after the initial therapy were statistically significant for both OS and PFS of the patients, and chemotherapy regimens were only statistically significant for PFS. Multivariate analysis showed that complete remission after the initial therapy, LDH level and ECOG score were statistically significant for both OS and PFS in patients with NK/T cell lymphoma. CONCLUSION: LDH level, ECOG score and complete remission after the initial therapy are independent prognostic factors for patients with extranodal NK/T cell lymphoma.

[Clinical observation of 100 patients with malignant lymphoma treating with different preconditioning regimens followed by autologous hematopoietic stem cell transplantation].

This study was designed to compare the curative effect, prognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphoma (ML). The clinical data of 100 ML patients (Sep 1992 to Aug 2010 in 307 Hospital) were retrospectively analyzed, and were divided into two groups by different preconditioning regimens: the high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group. The overall survival (OS) rate, progress free survival (PFS) rate and adverse effect were analyzed. The results showed that until Feb 2011, the median follow-up was 33.5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1.0×1.0(9)/L in high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group were (6.0 ± 0.4) d and (8.2 ± 0.4) d, platelet up to > 20.0×1.0(9)/L in two groups were (7.1 ± 0.8) d and (11.4 ± 2.5) d (P < 0.05). The 3-year OS rate of the two groups were 67.3% and 68.9%. 5-year OS rates of two groups were 62.8% and 60.6%, 10-year OS rates of two groups were 57.6% and 56.2% respectively; 3-year PFS of two group were 63.6% and 63.2%, 5-year of two group were 59.4% and 58.3%, 10-year of two group were 50.8% and 55.3% respectively (P > 0.05). Meanwhile, the incidence of fever, infection, bleeding, secondary cancer between two groups was not significant different (P > 0.05). It is concluded that the hematopoietic reconstitution of high-dose chemotherapy/radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However, there is no significant difference in curative effect and prognosis between the two groups.