Hematopoietic stem cells (HSCs) are tissue specific stem cells that replenish all mature blood lineages during the lifetime of an individual. Hematopoietic cell clusters in the aorta of vertebrate embryos play a pivotal role in the formation of the adult blood system. Recently, people have learned a lot about the embryonic HSCs on their development and homing. During their differentiation, HSCs are regulated by the transcription factors, such as Runx1 and Notch signaling pathway, etc. MicroRNAs also regulate the self-renewal and differentiation of hematopoietic stem/progenitor cells on the post-transcriptional levels. Since the onset of circulation, the formation of HSCs and their differentiation into blood cells, especially red blood cells, are regulated by the hemodynamic forces. It would be of great significance if we could treat hematologic diseases with induced HSCs in vitro on the basis of fully understanding of hemotopoietic stem cell development. This review is focused on the advances in the research of HSCs' development and regulation.
Blood Cells ; cytology ; Cell Differentiation ; Embryonic Stem Cells ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Signal Transduction ; Transcription Factors ; physiology

With the improvement of living conditions,people pay more attention to food sanitation,following which the incidence rate of food allergy is higher and higher.Food allergy threatens public health seriously.It is caused mainly by dominance of T helper type 2-based immune responses,which breaks the dynamic balance of Th1/Th2 immune responses and resultes in over secreting of IL-4,IL-5 and IL-13,production of specific antibody IgE,degranulation of mast cells,alteration of intestinal microflora and so on.At present,a lot of investigations have been reported,of which the probiotics therapy attracted more attention.As the indigenous flora,probiotics could not only prevent and treat food allergy but could also modulate immune responses and recover the dynamic balance of it via secreation of cytokines such as IFN-?,IL-10,TGF-?.

Background Recent researches show that oxidative stress is involved in the progress of keratoconus.Nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway plays a critical role in the defense against oxidative stress,but its function in keratoconus is unclear.Objective To investigate the differences of Nrf2-ARE signaling activation and matrix degenerating enzymes between keratoconus and normal corneal stromal cells.Methods Corneal stromal cells were isolated from keratoconus and normal cornea by using dispase and collagenase digestion.The cells were treated with hydrogen peroxide (H2O2) to mimic in vivo oxidative stress condition.Reactive oxygen species (ROS) production was measured by fluorescence substrate DCHF-DA incubation.Nrf2 level and the expression of Nrf2-ARE downstream antioxidant genes were analyzed by Western blot and real-time quantitative-PCR(RT-qPCR).The activity of matrix degenerating enzymes,including urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR) system and matrix metalloproteinase-2 (MMP-2) were assessed by Western blot and gelatin zymography respectively.Results In normal culture,keratoconus corneal stromal cells assumed increased basal ROS and Nrf2 level when compared with normal cells(t =18.155,P＜0.01).However,after H2O2 treatment,the keratoconus corneal stromal cells showed increased ROS production,while decreased Nrf2 translocation and no significant difference in expression levels of Nrf2-ARE downstream antioxidant genes (Nrf2:t =62.123,P＜ 0.01 ; (nicotinamide adenine dinucleotide phosphate quinine oxidoreductase-1 [NQO-1]:t =2.209,P =0.092 ; hemo oxygenase-1 [HO-1]:t =0.293,P =0.784 ; superoxide dismutase [SOD2]:t =0.749,P =0.495).The contents of uPA-uPAR and the activity of MMP-2 also showed a higher level in keratoconus corneal stromal cells than normal cells,with significant differences between them (t =19.164,15.458,4.818,all at P＜0.01).Conclusions The defect of Nrf2-ARE signaling activation exists in the keratoconus corneal stromal cells,and correlats with the abnormal expression level of stromal degeneration enzymes,which suggests that the defect of Nrf2-ARE signaling activation may be involved in the progression of keratoconus.

Objective:To systematically evaluate the clinical efficacy of programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors versus traditional first-line regimens for the treatment of solid tumors.Methods:Databases including PubMed, Embase and Cochrane Library were searched for literatures from the date of their establishment to October 2018 with the key words including "PD-1/PD-L1, solid tumors, melanoma, non-small cell lung cancer, renal cell carcinoma, immunotherapy" . The randomized controlled trial or non randomized controlled trial of high quality about PD-1/PD-L1 inhibitors and traditional fist-line regimens for the treatment of solid tumors were received and enrolled. Patients underwent PD-1/PD-L1 inhibitors immunotherapy were allocated into treatment group, patients underwent traditional first-line regimens treatment were allocated into control group. Two reviewers independently screened literatures, extracted data and assessed the risk of bias. Count data were described as odds ratio ( OR) and 95% confidence interval (95% CI). The heterogeneity of the studies included was analyzed using the I2 test. Funnel plot was used to test potential publication bias if the studies included≥5, and no test was needed if the studies included<5. Results:(1) Document retrieval: a total of 11 available randomized clinical trials were included. There were 5 161 patients, including 2 677 in the treatment group and 2 484 in the control group. (2) Results of Meta analysis. ① There was a significant difference in the objective response rate between the treatment group and the control group ( OR=4.49, 95% CI: 3.01-6.68, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ② There was no significant difference in the disease control rate between the treatment group and the control group ( OR=1.53, 95% CI: 1.01-2.32, P=0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ③ There was a significant difference in disease stability rate between the treatment group and the control group ( OR=0.49, 95% CI: 0.33-0.73, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ④ There was no significant difference in disease progression rate between the treatment group and the control group ( OR=0.71, 95% CI: 0.45-1.15, P>0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies, suggesting that publication bias had little influence on results of Meta analysis. ⑤ There were significant differences in overall incidence of adverse events and incidence of adverse events not less than three levels between the treatment group and the control group ( OR=0.53, 0.54, 95% CI: 0.38-0.74, 0.31-0.93, P<0.05). The bilateral symmetry was presented in the funnel plot based on the 11 studies, suggesting that publication bias had little influence on results of Meta analysis. Conclusion:Compared with traditional first-line regimens treatment, PD-1/PD-L1 inhibitors immunotherapy can improve the objective response rate and decrease the incidence of adverse events.