Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of pathological and physiological processes including proliferation and apoptosis, so this family of transcription factors appears to be a promising target for future drug discovery for cancers.This review presents the research progress of FOXO proteins as a target for cancer therapy.

Increasing clinical evidence shows that modern lifestyle interrupting circadian rhythm contributes to the prevalence of obesity and diabetes.Recent genetic animal models further support the interaction of circadian rhythms and metabolic state.Circadian clock is not limited to be in central nervous system,and is also present in nearly all cells of the body,which constitute hierarchically circadian systems.The molecular circadian clock is evolved to allow organisms to anticipate and prepared for predictable,daily changes in the environment and regulates cellular and tissue function by driving patterns of gene expression and enzymatic activity.At present,basic science in this field has progressed at an extraordinary pace and is expected to continue unraveling the mechanisms linking circadian clocks to metabolism,which is important for understanding the pathophysiology of metabolic diseases such as obesity and diabetes,and provides a conceptual basis for the prevention and therapeutics of these diseases.

Objective To investigate the efficacy and safety of long guidewire exchange technique in performing cerebral angiography via radial artery approach.Methods The clinical data of 257 patients,who received cerebral angiography during the period from June 2014 to May 2016 at Daxing Hospital of Capital Medical University,Beijing,China,were retrospectively analyzed.Among the 257 patients,186 had type Ⅱ or type Ⅲ aortic arch.According to the different looping technologies for Simmons-2 catheter used in the performance of cerebral angiography,these 186 patients were divided into the study group (n=90) and the routine group (n=96).The success rate of radial artery puncturing,the success rate of Simmons-2 catheter looping formation,the success rate of supra-arch arterial catheterization,the time spent for angiography,the radiation exposure time,complications,etc.were recorded.Results The success rate of radial artery puncturing was 100％ in both groups.The success rate of Simmons-2 catheter looping formation in the study group was 97.8％,which was significantly higher than 72.9％ in the routine group (P＜0.05).The success rates of catheterization for the left subclavian artery,left common carotid artery and right carotid artery in the study group were 97.8％,97.8％ and 97.8％ respectively,which were remarkably higher than 72.9％,72.9％ and 72.9％ respectively in the routine group (P＜0.05).No statistically significant difference in the success rates of catheterization for right subclavian artery and for right vertebral artery existed between the two groups (P＞ 0.05).The time spent for angiography in the study group and the routine group was (22.5±9.4) min and (28.3±8.3) min respectively.The radiation exposure time in the study group was (8.9±4.5) min,which was obviously lower than (12.6±6.5) min in the routine group (P=0.017 and P=0.035,respectively).The incidences of complications in the study group and the routine group were 4.4％ and 5.2％ respectively,the difference was not statistically significant (P＞0.05).No severe complications,such as intracranial arterial embolie events,puncture bleeding,arterial occlusion,etc.,occurred in all patients of both groups.Conclusion The use of long guidewire exchange technology can improve the success rate of Simmon-2 catheter looping formation and the success rate of supra-arch arterial catheterization,it can also shorten the time for angiography procedure and reduce the radiation exposure time.This technique is very effective with higher safety.Therefore,this long guidewire exchange technique should be used as a common method for cerebral angiopraphy via radial artery approach in patients with type Ⅱ or type Ⅲ aortic arch.

Objective:To establish an animal model in goats for curved mandibular regeneration by distraction osteogenesis(DO).Methods:Four goats were used.Internally installed curved mandibular distractors were activated 6 days after mandibular osteotomy on the mandibular angles or mandibular symphyses at a rate of l mm/d for 25~34 days.The mandibles were examined by roentgenography.Results:The arched defects of the mandibles in the 4 goats were reconstructed by regenerated bone by the end of DO.Conclusion:Internally installed curved distractor may be used for osteogenesis in the repaire of the arched mandibular defects.

Aim To study the effect of sibutramine hydrochloride on hypothalamus orexin system gene in high-fat dietary obesity rats.Methods SD rats were fed with high-fat diet to induce obesity model.Then,the rats were divided into two groups,the treatment group with sibutramine(8 mg?kg-1,ig)and control group with NaCl(ig)for 4 weeks.All rats' weight,blood fat and glucose were measured,prepro-orexin and its receptors mRNA expression in the hypothalamus were assessed by semi-quantity RT-PCR.Results Sibutramine not only decreased the obesity rats' weight and the level of serum lipid and glucose,but also increased the level of prepro-orexin mRNA expression in obesity rats.There was no difference in mRNA expression of both orexin receptors in each group.Conclusions Sibutramine hydrochlorid has an anti-obesity effect in high-fat obesity rats,which may be related to the increase of prepro-orexin gene mRNA expression level.

Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.
Cell Transdifferentiation ; Humans ; Induced Pluripotent Stem Cells ; Pluripotent Stem Cells ; Regenerative Medicine ; trends ; Stem Cells

Replenishing the insulin-producing β cell mass is considered to be a hot topic in the field of diabetes treatment.It has long been known that pancreatic β cells are generated primarily by self-duplication in adults.However,insulin resistance can induce dramatic compensatory β cell mass expansion in the pancreas.Therefore,it is of great value to investigate the etiology and pathogenesis of β cell proliferation under insulin resistance.The recent study has shown that betatrophin,a protein secreted by the liver,modulates β cell growth in response to insulin resistance.We published one article in Diabetes Care titledIncreased circulating levels of betatrophin in newly diagnosed type 2 diabetic patientsto elaborate the relationship between diabetes and betatrophin.

Objective To investigate the relationship of STAT3 with expressions of MMP-2,MMP-9 and TIMP-1 and with epithelial-mesenchymal transition (EMT) in breast cancer cells,and to explore the clinical significances.Methods The mRNA of STAT3 and the protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 of breast cancer cells in 84 patients with breast cancer were determined by real-time RT-PCR technique and immunohistochemical method in paraffin-embedded specimensm respectively.Normal breast tissues adjacent to breast cancer were taken as controls.Results mRNA expression of STAT3 was significantly higher in breast cancer tissues than in controls (t=4.513,P＜ 0.001).Protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 were higher in breast cancer tissues than in controls (all P＜ 0.05).There were positive correlations between pSTAT3 expression and the expressions of MMP-2,MMP-9 and TIMP-1 in breast cancer tissues (all P＜0.05).The higher levels of pSTAT3 and MMP-2 were associated with poorer differentiation and more lymph node metastasis of breast cancer (both P＜0.05).The positive expression of MMP-9 was correlated with lymph node metastasis (P＜0.05),but not with histological grading (P＞0.05).The positive expression of TIMP-1 had no associations with histological grading and lymph node metastasis (both P＞0.05).There were no significant differences in the protein expressions level of pSTAT3,MMP-2,MMP-9 and TIMP-1 between different ages and different breast tumor sizes (all P＞0.05).Conclusions The increased expression of STAT3 in breast cancer cells is closely correlated with the increased expressions of MMP-2,MMP-9 and STAT3 inhibitor TIMP-1.The activation of STAT3 gene can mediate EMT by inducing the protein expressions of MMP-2,MMP-9,which promotes the invasion and metastasis of breast cancer.

Aim To study influence of PTEN inhibitors ( PIC) on high glucose induced endothelial cell senes-cence Methods ( 1 ) HUVECs were cultured in ECM medium. Cell viability was determined by CCK-8. Cells were randomly divided into control group ( C ) , high glucose group ( HG ) , high glucose +10 nmol · L-1 PIC group ( HG +10 nmol · L-1 PIC ) , high glu-cose+100 nmol · L-1 PIC group ( HG +100 nmol · L-1 PIC) . Cell apoptosis was examined by flow cytom-etry. Senescence Detection Kit was performed by SA-β-gal Cytochemical staining. The expression levels of genes and protein ( p16 and Pten ) were detected by real-time PCR and Western blot. Results The prolif-eration rate was markedly decreased in HG group com-pared with C group, and this phenomenon was reversed by PTEN inhibitors . Cell apoptosis was significantly increased in HG group compared with C group, and a-gain these changes were blocked by PIC. The expres-sion levels of genes ( PTEN) were significantly higher in HG group compared with C group. The frequency of senescent ( SA-β-Gal-positive ) cells and the expres-sion level of senescence genes ( p16 ) were significantly higher in HG group compared with C group, and these changes were blocked by PIC. Conclusion These re-sults show that PTEN inhibitors ( PIC ) delays cellular senescence that is promoted under high glucose condi-tion.

Objective:To explore the correlation between hepatitis B virus (HBV) infection and deep infection after spinal internal fixation surgery and analysis of pathogenic bacteria.Methods:One hundred and eighty-four patients who underwent spinal internal fixation with HBV infection in Xiaogan First People′s Hospital of Hubei Province from January 2013 to January 2019 were selected as the HBV infection group, and 184 patients who underwent spinal internal fixation with non-HBV infection were selected as the non-HBV infection group. The incidence of deep infection and the distribution of pathogenic bacteria were compared between 2 groups. The influencing factors of postoperative deep infection and HBV reactivation in patients with HBV infection were analyzed by single factor analysis and multi-factor Logistics regression analysis.Results:The incidence of deep infection after spinal internal fixation surgery in HBV infection group was significantly higher than that in non-HBV infection group: 19.57% (36/184) vs. 9.24% (17/184), and there was statistical difference ( P<0.01). The pathogenic bacteria of deep infection in both groups were mainly acinetobacter bausinensis, klebsiella pneumoniae, staphylococcus aureus, staphylococcus epidermidis. There was no statistically significant difference in the distribution of pathogenic bacteria between 2 groups ( P>0.05). The deep infection incidences in age ≥ 65 years, operation time ≥ 3 h, intraoperative blood loss ≥ 1000 ml, CD 4+/CD 8+<1.4, total lymphocyte count<0.7 × 10 9/L, liver function abnormalities (AST>40 U/L or ALT>50 U/L), HBV-DNA (+) patients with HBV infection were significantly higher: 27.16%(22/81) vs. 13.59%(14/103), 28.77%(21/73) vs. 13.51%(15/111), 31.15%(19/61) vs. 13.82%(17/123), 29.69%(19/64) vs. 14.17%(17/120), 27.78% (20/72) vs. 14.29%(16/112), 7/18 vs. 17.47%(29/166), 30.43%(21/69) vs. 13.04%(15/115), and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis showed that intraoperative blood loss (≥ 1 000 ml), CD 4+/CD 8+(<1.4), total lymphocyte count (<0.7 × 10 9/L), and HBV-DNA (+) were independent risk factors for deep infection after spinal internal fixation in patients with HBV infection ( P<0.01 or <0.05). The HBV reactivation incidence in age ≥ 65 years, operation time ≥ 3 h, intraoperative blood loss ≥ 1 000 ml, liver function abnormalities, HBV-DNA (+), postoperative deep infection patients with HBV infection were significantly increased: 33.33% (27/81) vs. 18.45% (19/103), 34.25% (25/73) vs. 18.92% (21/111), 34.43% (21/61) vs. 20.33% (25/123), 8/18 vs. 22.89% (38/166), 34.78% (24/69) vs. 19.13% (22/115), 41.67% (15/36) vs. 20.95% (31/148), and there were statistical differences ( P<0.05). Multivariate Logistic regression analysis showed that intraoperative blood loss (≥ 1 000 ml), HBV-DNA (+) and postoperative deep infection were independent risk factors for HBV reactivation after spinal internal fixation in patients with HBV infection ( P<0.05 or <0.01). Conclusions:HBV infection significantly increases the incidence of deep infection after spinal internal fixation surgery, and the independent risk factors are intraoperative blood loss (≥1 000 ml), CD 4+/CD 8+ (<1.4), total lymphocyte count (<0.7 × 10 9/L), and HBV-DNA (+). Spinal internal fixation surgery can cause HBV reactivation, and its independent risk factors are intraoperative blood loss (≥ 1 000 ml), HBV-DNA (+) and postoperative deep infection.