Objective Streptococcus sanguis is a possible candidate bacterium for the caries replacement therapy, which has no advantages in the acidic environment.The aim of the study was to construct acid-resistant strains of Streptococcus sanguis, determine its acid tolerance, and explore the mechanism of its antagonism against Sterptococcus mutans.Methods By gradually reducing the pH value of the medium, we constructed acid-resistant strains of Streptococcus sanguis, observed their growth and measured their acid tolerance according to their survival rate against lethal pH.We evaluated the competitive relationship between Streptococcus sanguis and Streptococcus mutans by plate experiment and detected the changes of related acid resistance genes by real-time quantitative PCR.Results The growth of Streptococcus sanguis and its acid-resistant strains were limited by the pH value, and that of Streptococcus sanguis was better in either acidic or normal environment.The lethal pH value of Streptococcus sanguis was 3.6, that of its acid-resistant strains was 2.3, and the survival rate of the acid-resistant strains was 66.59% in the pH 3.6 environment.In comparison, the lethal pH value of Streptococcus mutans was 2.5, that of its acid-resistant strains was 2.1, and the survival rate of the acid-resistant strains was 2.55% in the pH 2.5 environment.In the presence of chloramphenicol, the acid-resistant strains could not survive in the original lethal pH.In the sub-lethal pH environment, the expressions of the acid resistance-related genes Groel and Dnak in the acid-resistant strains were significantly up-regulated as compared with those in the original Streptococcus sanguis (P<0.05).Conclusion Streptococcus sanguis has an acid adaptability and can enhance acid resistance in the sub-lethal pH environment.Acid-resistant Streptococcus sanguis in the replacement therapy may provide some new ideas for the treatment of dental caries.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Apolipoproteins E ; blood ; genetics ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Venous Thromboembolism ; blood ; genetics ; Young Adult ; alpha-2-Antiplasmin ; analysis ; genetics

Objective To evaluate the reliability and validity of Bowel Function Index applied to assess the constipation induced by strong opioid drugs for patients with cancer pain.Methods 126 patients with constipation induced by strong opioid drugs for pain caused by cancer were selected.BFI,Patient Assessment of Constipation Symptoms(PAC-SYM) and clinical observations were used to collect data which were conducted for reliability analysis,correlation analysis and tests for several independent samples to evaluate the reliability and validity.Results The internal consistency determined by Cronbach αt was 0.86 for the total BFI score.Significant correlations were found among BFI,PAC-SYM and clinical observations.The BFI total score and each item scores of three groups all showed significant differences.Conclusions The Chinese version of BFI is a simple,valid and reliable,clinically relevant tool to assess the constipation induced by strong opioid drugs for pain caused by cancer.

CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.

OBJECTIVETo investigate the effect of hypoxia on the human pulmonary artery smooth muscle cells two pore domain potassium channels TASK-1 and the regulation of non-receptor tyrosine kinase c-Src in this process.

METHODSThe cultured human pulmonary artery smooth muscle cells (hPASMCs) were divided into: normal group, hypoxia 30 minute group, hypoxia 6 hours group and hypoxia 48 hour group, and hypoxia 48 hour + PP2 group, hypoxia 48 hour + PP3 group, hypoxia 48 hour + bpV group. Flow cytometry was used to analyze the cell cycle, RT-PCR and Western blot technique were carried out to detect the expression changes of TASK-1 mRNA and protein in different groups.

RESULTS(1) Cell Cycle Show: Compared with normal control group, with prolonged hypoxia, the percentages of hPASMCs in S phases of cell cycle were increased. While compared with hypoxia 48 hour group, the percentages of hypoxia 48 hour + PP2 group hPASMCs in S phases of cell cycle were decreased. The expression of TASK-1 mRNA on hPASMCs in acute hypoxia 6 hour group was increased, while the expression of TASK-1 protein on hPASMCs in the acute and chronic hypoxia group was decreased, and the expression of TASK-1 mRNA on hPASMCs in the chronic hypoxia group was decreased; After pre-incubation of a potent and selective inhibitor of the Src family of protein tyrosine kinases PP2, the expression of TASK-1 mRNA and protein in hypoxia 48 hour group was increased, however after pre-incubation of the inhibitor of the Src family of protein tyrosine phosphatase bpV, the expression of TASK-1 protein in hypoxia 48 hour group was decreased.

CONCLUSIONHypoxia promotes human pulmonary artery smooth muscle cell proliferation, and non-receptor tyrosine kinase c-Src may participate in the expression of two pore domain potassium channels TASK-1 regulated by hypoxia. Therefore, we hypothesized that TASK-1 channels and c-Src participatein the acute and chronic hypoxic human pulmonary vasoconstriction.

Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Humans ; Myocytes, Smooth Muscle ; cytology ; Nerve Tissue Proteins ; metabolism ; Potassium Channels, Tandem Pore Domain ; metabolism ; Pulmonary Artery ; cytology ; RNA, Messenger ; Vasoconstriction ; src-Family Kinases ; metabolism

Adult ; Bone Neoplasms ; diagnostic imaging ; therapy ; Combined Modality Therapy ; Curettage ; methods ; Embolization, Therapeutic ; methods ; Female ; Follow-Up Studies ; Giant Cell Tumor of Bone ; diagnostic imaging ; therapy ; Humans ; Male ; Sacrum ; Time ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

It has been showed that there were obvious obstacle effects of Panax notoginseng replanting. Crop rotation was the main effective technique to overcome the obstacle. To find a reasonable crop rotation system for P. notoginseng, aqueous extracts from root, stem and leaf of P. notoginseng were analyzed for allelopathic effect on three maize varieties (which are often grown in regions where P. notoginseng grown). The main results were as follows: (1) Allelopathic effect of P. notoginseng stem and leaf extracts on the three other tested plants was stronger than that of root extracts; (2) Corn was more vulnerable to the effects of allelochemicals at seedling stage than at germination stage, and the corn root was more sensitive than aerial part to allelochemicals; (3) Lusan No. 3 and Yunrui No. 1 showed resistance to P. notoginseng allelopathy, with respective comprehensive sensitivity indexes (M3) of - 0.089 3 and -0.159 2, while Bainuo No. 1 is sensitive at M3 = -0.261 0. It then can be concluded that Lusan No. 3 and Yunrui No. 1 may be an alternative rotation plants for overcoming P. notoginseng continuous cropping obstacle.
Allelopathy ; Panax notoginseng ; chemistry ; growth & development ; Pheromones ; pharmacology ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Zea mays ; drug effects ; growth & development

Objective To analyze the prognostic factors of patients with leukemia treated with single fraction total body irradiation (SFTBI) followed by hernatopoietic stem cell transplantation (HSCT).Methods From January 2001 to September 2008, 102 patients received HSCT. The differences of the survival rate, relapse rate and incidence of interstitial pneumonia (IP) between groups regarding different genders, ages, pathological types, transplantation methods and TBI parameters were compared and the factors related with the survival rate, relapse rate and incidence of IP were analyzed. Results The followup time ranged from 15 to 1482 days (median, 406 days). The follow-up rate was 95.1%. 86 and 55patients were followed up more than one year and three years. The 1-and 3-year survival rates were 59.0%and 44.0%. In univariate analysis, the 3-year survival rate was signifcantly different between the groups with and without relapse before transplantation (20% vs. 55%, χ2 = 6.33, P = 0. 012), allogeneictranplantation versus autologous tranplantation (39% vs. 68%, χ2 = 8.06, P = 0.005), grade 3 or more acute graft versus host disease (aGVHD) and grade 0 -2 aGVHD (0% vs. 54%, χ2 = 7.52, P = 0.006),with and without relapse after transplantation (19% vs. 58%, χ2 = 10.13, P =0.001), with and without IP (23% vs. 58%, χ2 =8.35, P=0.004). Multivariate analysis showed that grade 3 or more aGVHD was the only statistically significant prognostic factors (χ2 = 12. 74 ,P =0. 000). The l-and 3-year relapse rateswere 30. 0% and 50. 0%. The incidence of relapse was obviously higher in the group with relapse before transplantation than that without (47% vs. 16%, χ2 =7. 32, P=0. 007). Multivariate analysis showed thatrelapse before transplantation was a significant factor predicting relapse after transplantation (χ2 = 9. 39,P =0. 020). The cumulative incidence of IP was 35.0%. The incidence of IP was different between groups with dose homogeneity > 3% and ≤ 3% (27% vs. 4%, χ2 = 5. 21, P = 0. 023), with and without acute parotitis (34% vs. 3%, χ2 = 14. 15, P= 0.000), allogeneic transplantation group and autologous transplantation group (31% vs. 8%, χ2= 7.70, P= 0.006). Multivariate analysis showed that transplantation methods, acute parotitis and dose homogeneity were statistically significant factors in predictingIP (χ2 = 10. 08 , 10. 08 and 7.69 , P = 0. 002 , 0. 002 and 0. 010 , respectively) . Conclusions Patients who develop grade 3 or higher aGVHD have poor prognosis. Dose homogeneity influences the incidence of IP. Patients undergoing allogeneic transplantation are apt to have IP. Acute parotitis is related with IP and might be a predictor.

China ; History, 20th Century ; History, 21st Century ; Pathology ; Periodicals as Topic ; history

Objective To evaluate the efficacy and tolerance of preoperative concurrent chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer.Methods From June 2007 to June 2013,51 untreated patients with histopathologically proven rectal cancer (T3/T4 or N (+))were included in this study.Three-dimensional radiotherapy was delivered to the whole pelvic cavity at 45.0-50.4 Gy/25-28 fractions.Two cycles of chemotherapy with FOLFOX4 or XELOX were given concurrently at weeks 1 and 4 of radiotherapy.Surgery was performed at 4-8 weeks after chemoradiotherapy.Adjuvant chemotherapy with FOLFOX4 or XELOX was given within one month after surgery.The Kaplan-Meier method was used to calculate survival rates,and the log-rank test was used for univariate analysis;the Cox regression model was used for multivariate prognostic analysis.Results Fortynine patients completed the preoperative chemoradiotherapy and surgery.The median follow-up was 2.9 years.The overall sphincter preservation rate was 65％;the overall downstaging rate was 59％.Ten (20.4％) of all patients achieved a pathologic complete response (pCR).Grade ≥3 toxicities occurred in 25％ of all patients,and the overall postoperative complication rate was 31％.The 3-and 5-year sample sizes were 24,12,respectively.The 3-and 5-year overall survival rates were 81％ and 69％,respectively;the 3-and 5-year disease-free survival (DFS) rates were 76％ and 60％,respectively;the 3-and 5-year local recurrence-free survival (LRFS) rates were 78％ and 70％,respectively;the distant metastasis-free survival rates were 82％ and 74％,respectively.The multivariate analysis showed that tumor downstaging was an independent prognostic factor for 5-year DFS and LRFS.Conclusions For locally advanced middle-low rectal cancer,preoperative radiotherapy with concurrent FOLFOX4/XELOX chemotherapy can increase pathologic downstaging rate,pCR rate,and sphincter preservation rate.Patients with tumor downstaging may have a better survival advantage.