Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.

Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination

Analysis of the population structure and genetic diversity of the red swamp crayfish (Procambarus clarkii) in China using SSR markers

BACKGROUND: Procambarus clarkii produces high-quality, delicious meat that is high in protein, low in fat, and rich in calcium and phosphorus. It has become an important aquatic resource in China. Our objectives are (i) to analyze the level of genetic diversity of P. clarkii populations; (ii) to explore the genetic differentiation (Gst); and (iii) to propose appropriate strategies for the conservation. RESULTS: In this study, Shannon's index (I) and Nei's gene diversity index (H) for P. clarkii were high (I = 0.3462 and H = 0.2325 on average and I = 0.6264, H = 0.4377 at the species level) based on the SSR markers. The expected heterozygosity value of 17 microsatellite loci in 25 crayfish populations was 0.9317, the observed heterozygosity value was 0.9121, and the observed number of alleles per locus was 2.000; and the effective number of alleles per locus was 1.8075. Among the P. clarkii populations, the inbreeding coefficient within populations (Fis) was 0.2315, overall inbreeding coefficient (Fit) was 0.4438, genetic differentiation coefficient among populations (Fst) was 0.3145 and gene differentiation (Gst) was 0.4785 based on SSR analyses. The cluster analysis results obtained by unweighted pair-group method with arithmetic mean (UPGMA) analysis, principal coordinate analysis (PCoA) and STRUCTURE analysis were similar. A mantel test showed that the isolation-by-distance pattern was not significant. CONCLUSIONS: The high Gst among P. clarkii populations is attributed to genetic drift and geographic isolation. The results indicated that more P. clarkii populations should be collected when formulating conservation and aquaculture strategies.

A functional polymorphism in the paired basic amino acid-cleaving enzyme 4 gene confers osteoarthritis risk in a population of Eastern China.

Paired basic amino acid-cleaving enzyme 4 (PACE4), a proprotein convertase, is involved in the activation of aggrecanases (ADAMTS-4 and ADAMTS-5) in osteoarthritic and cytokine-stimulated cartilage. Activated aggrecanases cause aggrecan degradation and thus, contribute to osteoarthritis (OA). In this study, we investigated the association between PACE4 gene polymorphisms and OA risk. One single-nucleotide polymorphism (rs4965833) in the PACE4 gene was genotyped in 432 OA patients and 523 healthy controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expression of PACE4 in blood samples from 90 OA patients (30 for each genotype). The relative expression level of PACE4 mRNA was higher in the GG genotype as compared to the AA/AG group. Moreover, the PACE4 rs4965833 polymorphism was associated with increased risk of OA, especially among individuals aged ≥55 years and with a body mass index ≥25. There was no significant association between the PACE4 rs4965833 polymorphism and clinical parameters of OA patients, such as erythrocyte sedimentation rate, C-reactive protein, Visual Analog Scale for pain and Lequesne's index. In conclusion, the rs4965833 polymorphism in the 3'-UTR of PACE4 is associated with OA susceptibility.

Development and evaluation of a training model for paracentetic suprapubic cystostomy and catheterization.

OBJECTIVES: Minimally invasive paracentetic suprapubic cystostomy is a technique that should be learned by all surgical trainees and residents. This study aimed to develop a self-made training model for paracentetic suprapubic cystostomy and placement of the suprapubic catheter and then to evaluate its effectiveness in training fourth-year medical students. METHODS: Medical students were divided into an experimental group receiving comprehensive training involving literature, video, and model use and a control group receiving all the same training protocols as the experimental group except without hands-on practice using the model. Each student's performance was video-recorded, followed by subjective and objective evaluations by urology experts and statistical analysis. RESULTS: All students completed the surgical procedures successfully. The experimental group's performance scores were significantly higher than those of the control group (median final performance scores of 91.0 vs. 86.8, respectively). Excellent scores were achieved by more students in the experimental group than in the control group (55% vs. 20%), and fewer poor scores were observed in the experimental group than in the control group (5% vs. 30%). CONCLUSIONS: Based on its cost-effectiveness, reusability, and training effectiveness, this paracentetic suprapubic cystostomy training model is able to achieve goals in teaching practice quickly and easily. Use of the model should be encouraged for training senior medical students and resident physicians who may be expected to perform emergent suprapubic catheter insertion at some time.

Development and evaluation of a training model for paracentetic suprapubic cystostomy and catheterization

OBJECTIVES: Minimally invasive paracentetic suprapubic cystostomy is a technique that should be learned by all surgical trainees and residents. This study aimed to develop a self-made training model for paracentetic suprapubic cystostomy and placement of the suprapubic catheter and then to evaluate its effectiveness in training fourth-year medical students. METHODS: Medical students were divided into an experimental group receiving comprehensive training involving literature, video, and model use and a control group receiving all the same training protocols as the experimental group except without hands-on practice using the model. Each student's performance was video-recorded, followed by subjective and objective evaluations by urology experts and statistical analysis. RESULTS: All students completed the surgical procedures successfully. The experimental group's performance scores were significantly higher than those of the control group (median final performance scores of 91.0 vs. 86.8, respectively). Excellent scores were achieved by more students in the experimental group than in the control group (55% vs. 20%), and fewer poor scores were observed in the experimental group than in the control group (5% vs. 30%). CONCLUSIONS: Based on its cost-effectiveness, reusability, and training effectiveness, this paracentetic suprapubic cystostomy training model is able to achieve goals in teaching practice quickly and easily. Use of the model should be encouraged for training senior medical students and resident physicians who may be expected to perform emergent suprapubic catheter insertion at some time.

The rs878081 polymorphism of AIRE gene increases the risk of rheumatoid arthritis in a Chinese Han population: a case-control study.

The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.

MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment.

Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221-3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA-34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA-451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders.

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment

Aberrant expression of microRNAs (miRNAs) has been shown to be involved in early observations of depression. The aim of this study was to determine if serum levels of miRNA-451a, miRNA-34a-5p, and miRNA-221-3p can serve as indicators of disease progression or therapeutic efficacy in depression. We collected data from 84 depressed patients and 78 control volunteers recruited from the medical staff at the West China Hospital. Depression severity was rated using the 24-item Hamilton Depression Scale (HAMD). Serum miRNA-451a, miRNA-34a-5p, and miRNA-221-3p levels were determined in samples from the depressed patients before and 8 weeks after antidepressant treatment as well as in samples from controls. Compared with the controls, the patients had lower miRNA-451a levels, higher miRNA-34a-5p and miRNA-221-3p levels, and increased HAMD scores whether they underwent antidepressant treatment or not. Eight weeks after antidepressant treatment, the patients exhibited increased miRNA-451a levels, decreased miRNA-34a-5p and miRNA-221-3p levels, and reduced HAMD scores. The serum level of miRNA-451a was negatively correlated with HAMD scores of the patients, while the serum levels of miRNA-34a-5p and miRNA-221-3p were positively correlated with HAMD scores whether the patients underwent antidepressant treatment or not. Paroxetine was markedly effective in 50 patients who also displayed an increased level of miRNA-451a but reduced levels of miRNA-34a-5p and miRNA-221-3p. In contrast, paroxetine was moderately effective or ineffective in 34 patients. In conclusion, depressed patients had lower serum miRNA-451a but higher serum miRNA-34a-5p and miRNA-221-3p, and these miRNAs are potential predictors of the efficacy of antidepressants.

The rs878081 polymorphism of AIRE gene increases the risk of rheumatoid arthritis in a Chinese Han population: a case-control study

The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.

Rare variants at 16p11.2 are associated with common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized clinically by inadequate quantity and quality of serum immunoglobulins with increased susceptibility to infections, resulting in significant morbidity and mortality. Only a few genes have been uncovered, and the genetic background of CVID remains elusive to date for the majority of patients. OBJECTIVE: We sought to seek novel associations of genes and genetic variants with CVID. METHODS: We performed association analyses in a discovery cohort of 164 patients with CVID and 19,542 healthy control subjects genotyped on the Immuno BeadChip from Illumina platform; replication of findings was examined in an independent cohort of 135 patients with CVID and 2,066 healthy control subjects, followed by meta-analysis. RESULTS: We identified 11 single nucleotide polymorphisms (SNPs) at the 16p11.2 locus associated with CVID at a genome-wide significant level in the discovery cohort. The most significant SNP, rs929867 (P = 6.21 × 10(-9)), is in the gene fused-in-sarcoma (FUS), with 4 other SNPs mapping to integrin CD11b (ITGAM). Results were confirmed in our replication cohort. Conditional association analysis suggests a single association signal at the 16p11.2 locus. A strong trend of association was also seen for 38 SNPs (P < 5 × 10(-5)) in the MHC region, supporting that this is a genuine CVID locus. Interestingly, we found that 80% of patients with the rare ITGAM variants have reduced switched memory B-cell counts. CONCLUSION: We report a novel association of CVID with rare variants at the FUS/ITGAM (CD11b) locus on 16p11.2. The association signal is enriched for promoter/enhancer markers in the ITGAM gene. ITGAM encodes the integrin CD11b, a part of complement receptor 3, a novel candidate gene implicated here for the first time in the pathogenesis of CVID.

Effects of Dangguibuxue Tang, a Chinese herbal medicine, on growth performance and immune responses in broiler chicks.

The effects of Dangguibuxue Tang (DBT) on growth performance and immunity response in immunosuppressed broiler chicks were investigated in this study. 240 one-d-old broiler chicks (DaHeng S01) were randomly divided into 4 groups, 2.0% DBT-treatment (A), 0.5% DBT-treatment (B), cyclophosphamide-control (C), and control group (D). From 4 d to 7 d of age, chicks in group A, B and C were given cyclophosphamide (CY) at a dosage of 100mg/kg body weight (BW) daily by intraperitoneal injection to induce immunosuppression. Chicks in group D were given an equal volume of physiological saline daily by intraperitoneal injection and considered normal chicks. Groups A and B were supplemented with 2.0% or 0.5% of DBT in the drinking water from 8 d to 42 d of age. Groups C and D did not receive any additional medication. The results revealed that chicks from group B had lower feed:gain rate (FGR), lower total mortality, higher immunity organ indexes, higher levels of Newcastle disease (ND) antibody and infectious bursal disease (IBD) antibody, higher interleukin-2 and interleukin-6 levels, and greater lymphocyte proliferative responses to concanavalin A (ConA) during the experiment than those from group C. However, no significant difference in the immunity status in the two levels of DBT-treatment was observed. These results indicate that supplementation of 0.5% of DBT can improve both cellular immunity and humoral immunity in immunosuppressed broiler chicks.

Effects of Dangguibuxue Tang, a Chinese herbal medicine, on growth performance and immune responses in broiler chicks

The effects of Dangguibuxue Tang (DBT) on growth performance and immunity response in immunosuppressed broiler chicks were investigated in this study. 240 one-d-old broiler chicks (DaHeng S01) were randomly divided into 4 groups, 2.0% DBT-treatment (A), 0.5% DBT-treatment (B), cyclophosphamide-control (C), and control group (D). From 4 d to 7 d of age, chicks in group A, B and C were given cyclophosphamide (CY) at a dosage of 100mg/kg body weight (BW) daily by intraperitoneal injection to induce immunosuppression. Chicks in group D were given an equal volume of physiological saline daily by intraperitoneal injection and considered normal chicks. Groups A and B were supplemented with 2.0% or 0.5% of DBT in the drinking water from 8 d to 42 d of age. Groups C and D did not receive any additional medication. The results revealed that chicks from group B had lower feed:gain rate (FGR), lower total mortality, higher immunity organ indexes, higher levels of Newcastle disease (ND) antibody and infectious bursal disease (IBD) antibody, higher interleukin-2 and interleukin-6 levels, and greater lymphocyte proliferative responses to concanavalin A (ConA) during the experiment than those from group C. However, no significant difference in the immunity status in the two levels of DBT-treatment was observed. These results indicate that supplementation of 0.5% of DBT can improve both cellular immunity and humoral immunity in immunosuppressed broiler chicks.

Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II).

PURPOSE: Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Eligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2:1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points. RESULTS: In all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable. CONCLUSION Addition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro.

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1ß, TNF-α, and IL-6 in vitro.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.