Cytokines' gene expression, humoral immune and biochemical responses of common carp (Cyprinus carpio, Linnaeus, 1758) to transportation density and recovery in brackish water

A Phase I Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Tripegfilgrastim (Dulastin®) after Single Administration in Pediatric Patients

A prospective randomized controlled trial was conducted to study the effectiveness and safety of intravenous different doses tranexamic acid (TXA) in single-level unilateral minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). The patients treated with single-level unilateral MIS-TLIF between September 2019 and October 2020 were enrolled and randomly classified into low-dose TXA (LD) group (n=39), high-dose TXA (HD) group (n=39), and placebo-controlled (PC) group (n=38). The LD, HD, and PC groups received intravenous TXA 20 mg/kg, TXA 50 mg/kg, the same volume of normal saline at 30 minute before skin incision after general anesthesia, respectively. There was no significant difference on baseline characteristics and preoperative laboratory results among 3 groups (P>0.05), including age, gender, body mass index, surgical segments, hematocrit (HCT), hemoglobin (HGB), prothrombin time (PT), international normalized ratio (INR), D-dimer, fibrin degradation products (FDP), activated partial prothromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea. The intraoperative blood loss (IBL), postoperative drainage volume, operation time, total blood loss (TBL), hidden blood loss (HBL), blood transfusion, hematological examination indexes on the first day after operation, and the incidence of complications within 1 month were compared among the 3 groups. There were 3, 2, and 4 patients in the LD, HD, and PC groups who underwent autologous blood transfusion, respectively, and there was no allogeneic blood transfusion patients in the 3 groups. There was no significant difference in IBL, postoperative drainage volume, and operation time between groups (P>0.05). The TBL, HBL, and the decreased value of HGB in LD and HD groups were significantly lower than those in PC group (P<0.05), and TBL and HBL in HD group were significantly lower than those in LD group (P<0.05); the decreased value of HGB between LD group and HD group showed no significant difference (P>0.05). On the first day after operation, D-dimer in LD and HD groups were significantly lower than that in PC group (P<0.05); there was no significant difference between LD and HD groups (P>0.05). There was no significant difference in other hematological indexes between groups (P>0.05). All patients were followed up 1 month, and there was no TXA-related complication such as deep venous thrombosis of lower extremity, pulmonary embolism, and epilepsy in the 3 groups. Intravenous administration of TXA in single-level unilateral MIS-TLIF is effective and safe in reducing postoperative TBL and HBL within 1 day in a dose-dependent manner. Also, TXA can reduce postoperative fibrinolysis markers and do not increase the risk of thrombotic events, including deep venous thrombosis and pulmonary embolism.

Tumor clearance, T-cell fitness, and minimal residual disease (MRD) outcomes in patients with relapsed/refractory multiple myeloma (RRMM) treated with cevostamab plus pomalidomide and dexamethasone: Biomarker analyses from CAMMA 1 Arm B

Humans are exposed to pyrethroid-based pesticides through agricultural produce. In this study, male Wistar rats were orally treated for 9 to 12 months with a mixture of pyrethroids that is equivalent to one-fifth (high dose; HD) or one-twenty fifth (low dose; LD) of the amount of pyrethroids present in the cereals and rice consumed by an average Indian. In rats treated for 9 months, the spermatogenesis-associated genes Abp, Ar, Cd9, Dax1, Dazap1, Ddx3y, Gdnf, Gfra1, Grth, Inhb, Ovol1, P1, Plzf, Pygo2, Scf, Tgfb1, Tp1, Tp2, and Vim1 were downregulated in both LD and HD groups. In rats treated for 12 months Gdnf, Hsf2, Inhb, Tgfb1, Thy1, and Ybx2 expression was downregulated in both LD and HD groups. Steroidogenesis-associated genes 17-β-Hsd, Gata4, Hmgcr, Hmgcs1, Pde4b, and Tspo gene expression were reduced in both LD- and HD-treated groups treated for 9 months. In 12-month-treated rats, Creb1 expression decreased in both LD and HD groups. The epigenetic reprogramming-associated genes, Dnmt1, Dnmt3a, Dnmt3b, Hdac10, Hp1bp3, Kat3a Kat3b, Mch2ta, Ncoa7, and Sirt1 were downregulated in both HD and LD groups of 9-months-treated rats. In rats treated for 12 months, Hdac10, Mch2ta, Ncoa7, and Sirt1 messenger RNA levels decreased in both the HD and LD groups. Thus, we demonstrate that long-term exposure to a mixture of pyrethroids caused aberrations in the transcriptome of factors involved in sperm production and development.

This study aimed to investigate the predictive value of dobutamine stress echocardiography (DSE) at varying doses for myocardial viability, with a particular emphasis on the impact of β-adrenergic blockers on myocardial viability in patients with ischemic cardiomyopathy (ICM). A total of 189 patients with ICM underwent DSE. Based on the dosage of dobutamine, patients were randomly divided into three groups: low-dose group (LD, 10µg/kg/min, n = 63), medium-dose group (CD, 20µg/kg/min, n = 63), and high-dose group (HD, 30 µg/kg/min, n = 63). All patients received β-blockers 1min after the DSE examination. Changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), radial strain (RS), and radial strain rate (RSr) during left ventricular systole (LVS) were analyzed, along with secondary effects and myocardial viability in the LD-β, CD-β, and HD-β groups. During the postoperative dobutamine injection, HR, SBP, and DBP in the LD, CD, and HD groups were significantly higher compared to pre-injection levels (p<0.05), with DBP in the HD group being notably higher than in the LD and CD groups (p<0.05). After intravenous injection of metoprolol, all indicators significantly decreased in the LD and CD groups (p<0.05). The rates of RS and RSr in the CD and HD groups were significantly lower than those in the LD group (p<0.05). The proportion of normal wall motion viability (VWM) post-injection was significantly higher than pre-injection levels (p<0.05), with the CD group surpassing the LD group (p<0.05). The use of β-adrenergic blockers demonstrated that the sensitivity, specificity, and accuracy of myocardial viability in the LD, CD, and HD groups were all superior to those of the control group (p<0.05), with the CD group exhibiting the highest diagnostic performance (p<0.05). The incidence of arrhythmias in the HD group was 20.3%, compared to 7.9% in the LD group (χ2 = 6.78, p = 0.034). Additionally, the occurrence of cardiovascular events in the HD group was 17.2%, significantly higher than the 6.3% observed in the LD group (χ2 = 6.21, p = 0.045). Moderate-dose DSE exhibited the optimal diagnostic performance in assessing myocardial viability in patients with ICM. Furthermore, the use of β-blockers effectively enhances the sensitivity and accuracy of the diagnosis, providing important practical guidance for the clinical evaluation of myocardial viability.

Ptcy Versus High Dose of ATG in HLA-Mismatched Unrelated Stem Cell Transplantation for Hematological Malignancies

We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients. The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified. Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014). A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.

To assess the growth-promoting effect of different doses of growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2) in GH deficiency (GHD) of hypothalamic origin, 43 prepubertal children aged between 4.3 and 18.9 years (mean 10.4 +/- 2.9 years) were randomly assigned to three treatment regimens: low-dose GHRH(1-29)-NH2 (LD group; n = 15), high-dose GHRH(1-29)-NH2 (HD group; n = 12) and GH (GH group; n = 16). The LD group received GHRH(1-29)-NH2 at 30 micrograms/kg/day s.c. in three daily doses, the HD group received 60 micrograms/kg/day s.c. in three daily doses and the GH group received GH, 0.1 IU/kg/day s.c. once daily. All children were treated for a period of 6 months. Evaluation included anthropometry, bone age, intravenous and subcutaneous GHRH(1-29)-NH2 tests and determination of insulin-like growth factor I (IGF-I) levels. An increase in height velocity of 2 cm/year or more was observed in all except two children. Height velocity during treatment was lowest in the LD group, but comparable in the HD and GH groups. An increase in height SDS for bone age occurred only in the GH-treated group. GH responses to intravenous GHRH(1-29)-NH2 showed a priming effect of the LD GHRH(1-29)-NH2 treatment, while a decrease in response occurred in the GH-treated group. Following a subcutaneous test dose of one-third of the daily dose of GHRH(1-29)-NH2, GH levels remained unchanged in both the LD and HD groups. There was accumulation of GHRH immunoreactivity over time in the HD group, but there was no correlation between measured GHRH and GH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

BackgroundDandelion is becoming an exploitable alternative to the widely prohibited antibiotics in the poultry production. This research aimed to investigate the effects of dandelion on the growth performance and intestinal barrier function of broiler chickens maintained under standard condition of management. One-hundred and sixty 1-day-old Arbor Acres (AA) male broiler chickens were randomly divided into four groups, with five replicates of eight birds each. The birds were fed a basal diet supplemented without (control group, [CON]) or with 500 (low dose [LD]) or 1000 (high dose [HD]) mg/kg dandelion or with 250 mg/kg chlortetracycline 20% premix (CTC) for 42 days, including the starter phase (d 1 to 21) and the grower phase (d 22 to 42). Body weight (BW) of each bird and feed consumption of each replicate were measured at d 21 and d 42. The ileal tissues were collected on day 21 and 42 to determine expression of genes coding for tight junction protein and mucin as well as ELISA analysis for immune factor. The ileal digesta was collected for microbiota and short chain fatty acids analysis.ResultsCompared with CON group, during day 1–21, the average daily feed intake (ADFI) and feed/gain ratio (F/G) of LD group were lower (P < 0.05); during day 22–42, the F/G of LD and CTC group tended to be lower (P = 0.07); during the overall phase, the ADFI of HD and CTC groups were decreased (P < 0.05), and the F/G of dandelion and CTC groups tended to be decreased (P = 0.07). On day 21, the relative mRNA expression of claudin, occludin-1 and mucin1 in dandelion groups were up-regulated (P < 0.05), and the ZO-1 mRNA expression in CTC group was increased (P < 0.05); on day 42, the claudin and mucin1 transcripts in LD group and ZO-1 transcripts in HD and CTC group were up-regulated (P < 0.05), while the occludin-1 and mucin1 transcripts in CTC group was significantly down-regulated (P < 0.05). In addition, the contents of TNF-α in dandelion groups were lower than that in CTC group (P < 0.05). In the analysis of ileal microbiota, on day 21, decreased α-diversity was observed in HD and CTC groups (P < 0.05). Meanwhile, on day 21, the relative abundance of Firmicutes in dandelion groups tended to be higher (P = 0.09), the relative abundance of Lactobacillus in LD and CTC group were increased (P < 0.05), while Bacteroidete, Bacteroides, and Alistipes relative abundance in dandelion and CTC groups were decreased (P < 0.05). On day 42, the Actinobacteriota relative abundance in CTC group tended to be higher (P = 0.05), and Lysinibacillus relative abundance of CTC group was higher (P = 0.02). Compared with CON group, on day 21, the propionic acid and butyric acid content in CTC group were higher, the butyric acid content in HD group was lower (P < 0.10).ConclusionIn summary, dietary dandelion supplementation at 500 mg/kg of diet enhanced growth performance of broilers by improving the intestinal barrier function. Dandelion can be supplemented in the diet as an antibiotics alternative to enhance production in poultry industry.

Objective To explore the therapeutic effect of olmesartan (OLM) on acute lung injury induced by paraquat (PQ) in rats in order to study its action mechanism.Methods A total of 70 Wister rats wererandomly (random number) divided into 5 groups,namely control group (C group,n =10),poisoning group (PQ group,n =15),rats treated by OLM with low dose (LD group,n =15),moderate dose (MD group,n=15) and high dose (HD group,n =15).PQ (80 mg/kg) was administered by gavage route in PQ group and in OLM groups for paraquat poisoning modelling,while in C group,equivalent normal saline was given instead.The OLM was administered by gastric instillation in OLM treatment groups (LD group:5 mg/kg; MD group:10 ng/kg; HD group:15 mg/kg) 6 hours after paraquat gavage and once a day for 7 days,while in C group and PQ group,normal saline was used instead.All rats were sacrificed 12 hours after the last dose treatment.The levels of glutathione peroxidase (GSH-Px,energy units),superoxide dismutase (SOD,U/mg pro),malondialdehyde (MDA,nmol/mg pro) in lung tissue,and the levels of serum transforming growth factor beta-1 (TGF-β1,pg/mL) and pH,oxygen partial pressure (PaO2) and bicarbonate ions concentration (HCO3-) were determined.Further,the lung coefficient and lung fibrous tissue hyperplasia grading were calculated.Correlation analysis was carried out to explore the correlation among GSH-Px,SOD,MDA,lung coefficient,lung hyperplasia of fibrous tissue and TGF-β1.The lung tissue were prepared for microscopy observation after Hematoxylin-eosin staining method (HE staining) as well.The difference between groups was compared by one-way analysis of variance,and correlation analysis carried out by using Pearson and Spearman rank correlation coefficient.Results The levels of GSH-Px and SOD in lung tissue of PQ and OLM treatment groups were significantly lower than those in C group,while in OLM treatment groups,those were higher than those of PQ group,and the HD group showed most obvious (all P ＜ 0.05).The level of MDA in lung tissue in PQ and OLM treatment groups were significantly highcr than that in C group while in OLM treatment groups,that was lower than that in PQ group,and the HD group showed most obvious (all P ＜ 0.05),and there were no differences between the LD group and MD group (all P ＞ 0.05).The lung coefficient and lung fibrous tissue hyperplasia grading in PQ and OLM treatment groups were significantly higher than those in C group,while in OLM treatment groups,those were lower than those in PQ group,and the HD group showed most obvious (all P ＜ 0.05).The level of serum TGF-β1 in PQ and OLM treatment groups were significantly higher than that inC group,while in OLM treatment groups,that was lower than that in PQ group,and the HD group showed most evident (all P ＜ 0.05),and there were no differences between the LD group and MD group (all P ＞0.05).The pH,PaO2 and HCO3-in PQ and OLM treatment groups were significantly lower than those in C group,while difference between LD and HD groups was also statistical significance (all P ＜ 0.05),while there were no differences between the PQ group and LD group as well as the LD group and MD group (all P ＞ 0.05).The correlation analysis showed GSH-Px and SOD had negative correlation with TGF-β1 [the correlation coefficient (r) were respectively-0.860 and-0.856,all P＜0.05],while MDA,lung coefficient and lung fibrous tissue hyperplasia grading had positive correlation with TGF-β1 (r were respectively 0.800,0.830 and 0.656,all P ＜ 0.05).Lung tissue section showed the degree of alveolar septa widened,alveolar collapse and inflammatory cells infiltration in OLM treatment groups were milder than those in PQ group,and the mildest in HD group.Conclusions OLM can attenuate the pulmonary edema and pulmonary fibrosis caused by paraquat poisoning and maybe it is associated with reducing the expression of TGF-β1 and inhibiting oxidative stress reaction. Key words: Paraquat; Poisoning; Lung injury ; Olmesartan ; Anti-inflammatory; Serum transforming growth factor beta-1

Effects of nicotinamide and sodium butyrate on meat quality and muscle ubiquitination degradation genes in broilers reared at a high stocking density

Objective To study the effect of 1,25-dihydroxyvitamin D3 on bone metabolism in diabetic rats and the related molecular mechanism.Methods A total of 45 healthy 6-8 weeks old male Sprague Dawley (SD) rats were treated with streptozotocin.The streptozotocin-induced diabetic rats were randomly assigned to diabetic group (DM),low dose vitamin D treated group(LD),and high dose vitamin D treated group(HD).Another 12 healthy SD rats were used as normol control group(NC).The rats in NC group and DM group were fed with 0.05 ml/d nut oil;those in the LD group and HD group were fed respectively with 0.03 and0.10 μg · kg-1 · d-1 1,25-dihydroxyvitamin D3 dissolved in 0.05 ml nut oil.12 weeks later,serum calcium,phosphorus,osteocalcin,type Ⅰ collagen cross-linked telopeptide (NTX),and 24 h urinary calcium were determined.Right femurs were harvested for pathohistological analysis by hematoxylin-eosin (HE) staining.Expressions of osteoprotegerin,receptor activator nuclear factor κB ligand (RANKL),core binding factor α1(Cbfa1) were detected by immunohistochemical staining.The osteoprotegerin,RANKL,Cbfa1,osteocalcin mRNA levels of bone tissue were performed by realtime quantitative reverse transcription polymerase chain reaction assay.Results (1) Compared with the NC group,serum calcium and 24 h urinary calcium in LD and HD groups were significantly higher (P＜0.05) ; 24 h urinary calcium in DM group was significantly higher than that in NC group (P ＜ 0.05).(2) Serum osteocalcin level in DM and LD groups was significantly lower than that in NC group (P＜0.05) ; there was no significant difference between the serum NTX levels of all groups (P＞0.05).(3) There was no significant difference in the mRNA expression of Cbfa1 in all groups (P＞0.05).The mRNA expression of osteocalcin in DM group was significantly lower than that in NC group (P ＜0.05).The mRNA expression of RANKL in DM group was significantly lower than that in NC group (P＜0.05) ; and that in LD and HD group was significantly higher than that in DM group (P＜0.05),and that in HD group was significantly higher than that in LD group (P＜0.05).The mRNA expression of osteoprotegerin in DM group was significantly lower than that in NC group (P＜0.05).The ratio of RANKL to osteoprotegerin in HD group was significantly higher than that in DM group (P＜0.05).Conclusions Vitamin D may promote bone metabolism in diabetic rats by up-regulating the expressions of osteocalcin and RANKL or in addition to other means. Key words: Diabetes mellitus ; Rats ; Vitamin D ; Bone metabolism

Dietary β-glucan stimulate complement and C-reactive protein acute phase responses in common carp (Cyprinus carpio) during an Aeromonas salmonicida infection

Heredity of stress-related cortisol response in androgenetic common carp ( Cyprinus carpio L.)

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from mismatched unrelated donors (MMUD) carries high risks of non-relapse mortality (NRM) and graft-versus-host disease (GvHD). Post-transplant cyclophosphamide (PTCY) has emerged as an alternative to antithymocyte globulin (ATG) for GvHD prophylaxis. This single-center retrospective study compared PTCY (N=41) to high-dose ATG and low-dose ATG in 155 MMUD alloHSCT recipients. PTCY was associated with better overall survival with a 1-year overall survival of 78.7% versus 56.5% in the PTCY and high-dose ATG groups (P=0.007) and 64.8% in the low-dose ATG group (P=0.059), driven by a significant reduction in NRM (P=0.008), with a 1-year NRM in the PTCY group of 7.7% versus 24.4% in the high-dose ATG group (P=0.031) and 29.8% in the low-dose group (P=0.026). The relapse incidence was similar between the groups (17.5% vs. 25.7% and 16.2% for the PTCY, high-dose ATG and low-dose ATG groups, respectively; P=0.830), despite a better progression-free survival in the PTCY group (P=0.034) with 1-year progression-free survival being 78.4% compared with 50.0% in the high-dose ATG group (P=0.002) and 54.0% in the low-dose group (P=0.041). Day-100 grade II-IV and grade III-IV acute GvHD, as well as 1-year chronic GvHD and moderate/severe chronic GvHD were not significantly different. However, 1-year GvHD-related mortality was lower in the PTCY group (2.6% vs. 14.4% and 14.9% in the high- and low-dose ATG groups, respectively; P=0.018). Infection-related mortality was similar across groups, but cytomegalovirus and Epstein-Barr virus infections were less frequent with PTCY, a finding potentially linked to differences in immune reconstitution. Compared to high-dose and low-dose ATG, PTCY prophylaxis was associated with improved overall survival and progression-free survival as well as lower NRM in MMUD alloHSCT.