Objective: To investigate the effects and mechanisms of inositol hexaphosphate(IP6)on cell cycle of HT-29 human colon carcinoma cell line. Method: HT-29 cells were exposed to various concentrations of IP6 for certain time. The effect of IP6 on cells proliferation was evaluated by MTT assay. Flow cytometric analysis was performed for cell cycle progression. Immunocytochemical stain was used to detect the expression of p53 and p21 protein. Results: A significant dose-dependent as well as time-dependent growth inhibition was observed in IP6-treated HT-29 cells, and associated with an increase in G1 arrest; Different concentrations of IP6 decreased the abnormal expressions of p53 gene and strongly increased the expression of p21. Conclusions: IP6 had an inhibitory effect on proliferation of HT-29 cells .and its mechanisms might be related to many factors, such as inhibiting the abnormal expression of p53 gene, inducing the expression of cell cycle inhibitor p21 which block the cell cycle.

Objective To study the effect and mechanism of the neurological function recovery in rats with spinal cord injury (SCI) rats after the transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells (BMSC), and to investigate the suitable engraftment time.Methods The BMSC at 3rd passage were differentiated into neural stem cells (NSC), and immunofluorescence staining was used to identify the NSC. The oriented-induced cells were labeled with Brdu 3 days before they were transplanted, and they were slowly injected into the injured site of the SCI rats. The SCI rats were randomly divided into group Ⅰ (transplantation at first week postinjury), group Ⅱ (transplantation at 2nd week postinjury) and control group (the operation was the same as group Ⅰ, but the cell suspension was replaced by the equal volume of normal saline). The BBB scores after transplantation were recorded. The distribution and differentiation of transplanted cells were observed by using immunofluorescence staining with antibodies against Brdu combined with Nestion and Brdu combined with NF200. NF200 immunofluorescence staining was used to show the regeneration of nerve fibers. The pathological changes of the injured site were observed by HE staining.Results The nestin expression was positive after the BMSC were differentiated for 3 days, and if the induced spherical cells were cultured continuously, the different levels of NF200 and GFAP were found. BBB scores in group Ⅰ and group Ⅱ were significantly higher than in control group (P<0.05), especially in group Ⅰ. The immunofluorescence showed that a large number of Brdu and Nestin double-positive cells and some Brdu and NF200 double-positive cells filled the injured site and linked the two sides of the injured area in group Ⅰ and group Ⅱ, and the lesion area of the spinal cord was reduced as compared with control group (P<0.05). More importantly, further reduction in lesion area and improvement in neurological function were observed in group Ⅰ.Conclusion The BMSC can be differentiated into NSC. The transplantation of the NSC could effectively promote the nerve function recovery after SCI, and the effect of transplantation at first week postinjury was better than at 2nd week postinjury.

Objective:To evaluate the quality of the current foreign clinical practice guidelines (CPG) on obstetric venous thromboembolism (VTE), providing reference for standardizing the prevention and treatment of domestic VTE clinical practice.Methods:The GPGs for the management of obstetric VTE published abroad from inception to July 2020 were electronically searched. Two researchers independently evaluated the quality of the included guidelines in accordance with the internationally recognized guideline evaluation tool, AGREE Ⅱ.Results:A total of 12 guidelines, 2 recommendations and 1 consensus for obstetric VTE were included, covering 3 continents and 9 countries, and the published time span was 2009-2020. The standardized scores of the six domain (scope & purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability and editorial independence) included in the guidelines were: 99.44%, 62.78%, 70.35%, 95.74%, 68.80% and 76.94% respectively, and the scores in each domain were ≥ 50.00%, indicating that the included CPGs were of good quality. Except for the domain scope & purpose, the ranges of the other five domains were ≥ 50.00%, suggesting that the quality of the CPGs differed significantly. Among the 15 included CPGs, 4 CPGs were level A (recommended), 11 CPGs were level B (recommended after being revised), and there was no CPG in level C (not recommended). The difference in the recommended content of obstetric VTE management mainly focused on the risk assessment, drug type, dosage and period.Conclusions:The overall quality of the CPGs for obstetric VTE management is high, while the quality of the CPGs varies greatly. In addition, there are differences in the recommended content of obstetric VTE management. More high-quality researches are required to provide evidence-based support for the improvement of the CPGs.

Objective: To observe the efficacy and safety of analgesic drugs in the standardized treatment of cancer pain patients at the pain clinic. Methods: The data of 787 cancer pain patients and their corresponding prescriptions for cancer pain were collected from April, 2012 to April, 2013 at the pain clinic. The obtained information comprise of diseases that lead to cancer pain, cause of pain, pain intensity, and efficacy and side effects of medications. Diseases that caused cancer pain include 658 cases with primary malignant lung cancer. Results: Pain was mainly caused by primary lung cancer in 787 cancer-related patients. An analgesic drug, namely, oxycodone hydrochloride, was administered in 54.6% via single drug therapy. The daily dosage range of this drug was 20 to 90 mg/d in 280 cases. About 35.6% of the studied patients with a daily dosage of 90 mg/d or lower had their pain effectively managed. After the treatment, the number of cases with moderate to severe pain was reduced from 437 (55.5%) to 248 (31.5%). The oral administration of opioid oxycodone hydrochloride tablets ranked first among the prescribed drugs for cancer pain, and single-drug therapy was the choice of medication. The majority of patients had satisfactory pain-relief with a daily dosage of less than 90 mg/d upon the administration of oxycodone hydrochloride sustained-release tablets and morphine sulfate controlled-release tablets. Side effects included mild constipation, nausea, vomiting, dizziness, loss of appetite, urinary retention, somnolence, and so on. Intervention treatment was needed in most of the patients. Conclusion: Pain clinic is critical in the administration of standardized treatment for cancer pain in hospitals. The establishment of pain clinic ensures the standardized treatment of cancer pain.

Objective The aim of this study was to evaluate the relationship between hemoglobin ( Hb ) levels and diabetic retinopathy( DR) risk in Chinese patients with type 2 diabetes mellitus( T2DM) . Methods A total of 629 patients who were hospitalized and diagnosed as T2DM were enrolled in the study. The clinical data were collected;All participants underwent an ophthalmic examination, including fundus photographs. They were divided into DR and non-diabetic retinopathy( NDR) groups based on the results of fundus examination. Anemia was defined according to Chinese anemia criteria. The analyses were performed to evaluate the relationships between Hb levels and DR risks. Results The patients with DR had lower hemoglobin levels and a higher prevalence of anemia compared to those without DR. A univariate analysis displayed a significant negative correlation between Hb levels and the rates of DR( P<0.01) . In multivariate linear regression, a 29％ decrease in DR risk was found with a 1 g/dl increase in Hb level(OR=0.713, 95％CI 0.598-0.850, P<0.01). Presence of anemia increased the risk of DR with OR=4.123(95％CI 1.793-9.478, P<0.01) times compared to those who did not have anemia. Conclusion The study indicates a negatire relationship letween Hb levels and DR risk, and a higher Hb levels may reduce the development of DR in T2DM.

Objective To investigate the effect of bone marrow stem cells (BMSCs) transplantation combined with body weight supported treadmill training on neural functional recovery of rats with spinal cord injury.Methods T11 complete spinal cord injury (SCI) was introduced into 40 Sprague-Dawley male rats using an improved simple device,imitating the Allen method.The rats were randomly divided into a stem cell transplantation group,a body weight support treadmill training group,a combined treatment group and a control group,each of 10 assigned according to a random number table.One week after the SCI operation,stem cell transplantation was performed on the rats in the stem cell transplantation group and the combined treatment group.One day before their transplantation,the third passage BMSCs were labeled with 5-ethynyl-2'-deoxyuridine (Edu).The rats in body weight support treadmill training group and combined treatment group were received body weight support treadmill training,while the other two groups were not given any training.At the 1 st,2nd,3rd,4th and 5th week after SCI modeling,Basso-Beattie-Bresnahan (BBB) movement function score was used to evaluate the motor function recovery of all rats.At the 5 th week after SCI,immunohistochemical staining and immunofluorescence staining was applied to detect neural specific markers including the neuron specific enolase (NSE),microtubule associated protein (MAP-1 β) and vimentin (VIM).The survival and differentiation of the transplanted cells,as well as the nerve fiber recovery in the lesion were also observed.Results The average BBB score of the combined treatment group was (6.60 ± 0.97) at the 2nd week after SCI operation,significantly higher than the other 3 groups,while that of the stem cell transplantation group and the body weight support treadmill training group was (5.00 ± 0.67) and (4.80 ± 0.63) respectively,both higher than that of the control group but without significant differences (P ＞ 0.05).In the third week after modeling,however,the value of the stem cell transplantation group rose to (8.00 ± 0.67),significantly higher than that of the body weight support treadmill training group (6.80 ± 0.79).The immuohistochemical staining showed that a variable degree of neural specific markers (NSE,MAP-1 β,VIM) positive cells were observed in the SCI tissues of all groups,with those in the combined treatment group significantly higher than the other 3 groups.The immunofluorescence also found significantly higher fluorescence expression of neural specific protein markers including NSE,MAP-1 βand VIM in the combined treatment group than the rest group,with obvious proliferation and differentiation of nerve fibers.Conclusions Stem cell transplantation combined with partial body weight supported treadmill training can effectively promote the recovery of neural function of rats with spinal cord injury,and the effect is better than solely stem cell transplantation or the weight loss training.

BACKGROUNDMatrix metalloproteinase-9 (MMP-9), endostatin (ES) and vascular endothelial growth factor (VEGF) are important angiogenic regulators for many neoplasms. The aim of this study is to judge clinical and prognostic values of detection of serum MMP-9, ES and VEGF in patients with non-small cell lung cancer (NSCLC).

METHODSSerum levels of MMP-9, ES and VEGF were detected in 92 patients with NSCLC, 50 patients with pulmonary benign disease and 52 healthy controls by ELISA method.

RESULTSThe serum levels of MMP-9, ES and VEGF in NSCLC patients were significantly higher than those in patients with pulmonary benign disease and healthy controls (P=0.000, P=0.000, P=0.000). The sensitivity and specificity of serum MMP-9 was 92.51% and 79.10% with a cutoff value of 117.17 μg/L, 88.32% and 74.25% for ES with a cutoff value of 100.31 μg/L, and 83.40% and 75.63% for VEGF with a cutoff value of 380.32 ng/L. Serum MMP-9 and ES levels were significant prognostic factors for lung cancer patients (P=0.0145, P=0.008). The change of serum MMP-9 level after chemotherapy was a useful indicator of prognosis for NSCLC patients (P=0.0322).

CONCLUSIONSThe serum levels of MMP-9, ES and VEGF are significantly increased in patients with NSCLC. They might be used as prognostic parameters in patients with NSCLC.

Objective:To investigate the correlation between serum bilirubin level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus of different sexes.Methods:A total of 1 304 patients with type 2 diabetes mellitus were included in this study. The clinical data were collected and fundus examination was performed. According to the results of fundus examination, the patients were divided into DR group and Non-DR (NDR) group. The correlation between the levels of serum total bilirubin, direct bilirubin, indirect bilirubin, and the occurrence of DR was analyzed.Results:The levels of total bilirubin, direct bilirubin, and indirect bilirubin in DR group were significantly lower than those in NDR group. Univariate analysis showed that the levels of total bilirubin and indirect bilirubin were negatively correlated with the occurrence of DR ( P<0.01). There was no significant correlation between the level of direct bilirubin and the occurrence of DR. Smooth curve fitting showed that there was a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in women, while a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in men. The results of multiple regression analysis showed that in men total bilirubin increased by 1 μmol/L, the risk of DR decreased by 8% ( OR=0.92, 95% CI 0.88-0.98, P<0.01). Indirect bilirubin increased by 1 μmol/L, and the risk of DR decreased by 9% ( OR=0.91, 95% CI 0.84-0.96, P<0.01). In women, when total bilirubin<12.8 μmol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR decreased by 17%( OR=0.83, 95% CI 0.72-0.95, P<0.01); When total bilirubin≥12.8 umol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR increased by 10%( OR=1.10, 95% CI 1.01-1.20, P<0.05); When indirect bilirubin<9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR decreased by 20%( OR=0.80, 95% CI 0.68-0.94, P<0.01); When indirect bilirubin≥9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR increased by 13%( OR=1.13, 95% CI 1.01-1.25, P<0.05). Conclusion:This study shows that there is a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in female patients with type 2 diabetes mellitus, and there is a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in male patients. However, there was no significant correlation between direct bilirubin and DR risk.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3) gene in growth hormone deficiency (GHD), and to determine whether the polymorphisms in the EIF2AK3 of children with GHD associate with the efficacy of recombinant human growth hormone (rhGH) therapy.Methods:Five SNPs of EIF2AK3 gene, including rs1805165 (G>T), rs13045 (A>G), rs867529 (C>G), rs11684404 (T>C), rs6547787(T>G) were selected and genotyped by a TaqMan probe method in 104 children with GHD and 269 normal height control children. Among them, 55 children with GHD were treated with rhGH. The height and weight of each patient with GHD after rhGH treatment were collected. Finally, to investigate whether there were differences between the efficacy of rhGH in children with GHD and different genotypes of EIF2AK3 gene polymorphism.Results:(1) The polymorphisms rs13045 and rs867529 of EIF2AK3 gene were associated with the occurrence of GHD ( P<0.05). (2) The haplotypes GACTG and GAGTT composed of SNPs rs1805165, rs13045, rs867529, rs11684404, and rs6547787 of EIF2AK3 gene increased the risk of GHD with OR (95% CI) of 2.05 (1.33-3.17) and 2.62 (1.48-4.65), respectively. The haplotypes GACTT and TGCCG reduced the risk of GHD, with OR (95% CI) of 0.68 (0.48-0.97) and 0.36 (0.23-0.57), respectively. (3) After determination the relationship between different genotypes and efficacy of rhGH with rs13045 and rs867529, it was found that there was no significant difference in height gain between rs13045 genotypes after rhGH treatment ( P>0.05). Compared with CC genotype, there was a less height gain of CG genotype at rs867529 by 0.099 cm for every 30 d( β=-0.099, 95% CI -0.162--0.018, P=0.016). Conclusions:The EIF2AK3 gene polymorphism (rs13045, rs867529) was associated with the occurrence of GHD. The height gain of CG genotype of rs867529 was lower than that of CC genotype in children with GHD treated with rhGH. The EIF2AK3 locus rs867529 genotype was associated with rhGH efficacy.

Objective To explore the effect of right median nerve stimulation ( RMNS) on brain function in healthy subjects . Methods Twenty-eight healthy volunteers were selected as the study′s subjects. RMNS was admin-istered as a task stimulation in a wake-up therapy mode. The subjects were given 30 seconds of stimulation followed by 30 seconds of rest, repeated for 6 times as the block experiment designed, and functional magnetic resonance imaging (fMRI) was performed simultaneously with the task stimulation . The brain activation was analyzed using SPM 12 soft-ware. Results The fMRI showed that RMNS activated primarily the left M1, the premotor cortex (PMC), the bilater-al primary and secondary somatosensory cortexes (S1 and S2), and the left insular lobe. Compared with the resting state, the intensity of BOLD signal in the above activated brain areas changed significantly in RMNS wake-up stimula-tion mode. Conclusion Stimulation of the right median nerve can stimulate the local cerebral cortex and produce a certain wake-up effect by activating the right brain areas related to the motor and sensory functioning of the hand.