The evolutionarily conserved Notch family widely exists in vertebrates and invertebrates and plays crucial roles in several biological processes such as embryogenesis, cell proliferation, apoptosis, as well as the differentiation and function of immune cell.Being different from Th1 and Th2 cell subsets, Th17 cells are new subset of CD4+ T cells and can secrete many kinds of cytokines, such as IL-17, IL-17F, IL-21 and IL-22.Recently, Th17 cells are considered to play important roles in asthma, rheumatic arthritis, systemic lupus erythematosus and malignant tumor.This review focuses on the research progress of Notch signaling pathway and its regulatory roles on Th17 cells.

Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

BACKGROUND:Reconstruction with remnant preservation can enhance tendon-bone healing. However, the study limits on the histological level, and there is a lack of research based on the modular biological level.
OBJECTIVE:To investigate whether anterior cruciate ligament reconstruction with remnant preservation can enhance tendon-bone healing.
METHODS:Seventy-two New Zealand rabbits were randomly al ocated to three groups (n=24 per group), fol owed by cruciate ligament reconstruction without remnant (group A), with remnant preservation (femoral tensioning and augmented suture) (group B) and with remnant preservation (graft passing remnant anterior cruciate ligament sheath) (group C), respectively.
RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that the tendon-bone healing in the groups B and C surpassed that in the group A, and group B was better than group C. Real-time PCR revealed that the expression level of osteoprotegrin mRNA and the osteoprotegrin/receptor activator of nuclear factor-κB ligand (RANKL) ratio were greater in the groups B and C than in the group A, and highest in the group C, while the expression levels of RANKL mRNA in the groups B and C were lower than that in the group A. In conclusion, these two kinds of anterior cruciate ligament reconstruction methods with remnant preservation can enhance tendon-bone healing, which have obtained most obvious achievements in the anterior cruciate ligament reconstruction in the graft passing anterior cruciate ligament remnant sheath that may be related to the up-regulation of osteoprotegrin mRNA and down-regulation of RANKL mRNA.

Objective To investigate the relationship between the expression of BRCA1 in breast cancer tissues and the sensitivity to docetaxel chemotherapy.Methods The expression of BRCA1 was detected by immunohistochemical method and the new adjuvant chemotherapy containing docetaxel chemotherapy regimen (TEC)was given.The relationship between BRCA1 expression and efficacy of neoadjuvant chemotherapy with docetaxel was studied.Results The rate of complete response,partial response,stable disease and progress disease was 22.6％,71.7％,5.7％,and 0％ respectively in breast cancer patients with positive BRCA1 expression and 11.8％,58.9％,27.4％,and 2.0％ in breast cancer patients with negative BRCA1 expression.The difference between the 2 groups had statistical significance.Conclusion BRCA1 expression has a positive relationship with sensitivity to chemotherapy regimen containing docetaxel chemotherapy regimens (TEC),and can be used as a good marker for predicting efficacy of chemotherapy and screening agents.

Objective To study the role of src-suppressed C kinase substrate (SSeCKS) in the secretion of tumor necrosis factor (TNF-α) in rat pulmonary micro-vascular endothelial cells (PMVEC) induced by lipopolysaccharide (LPS).Methods Wistar rat PMVEC cultured in vitro were randomly (random number) divided into several groups (n =4) as per exposure to given dosage of LPS for different lengths of time and to different dosages of LPS for given length of time.After PMVEC exposed to 10 mg/L LPS for 1 hour (h),3 h,6 h,12 h and 24 h or 0.1 mg/L,1 mg/L and 10 mg/L LPS for 24 h,the levels of TNF-αin the supernatant of culture medium were examined by the method of enzyme linked immunosorbent assay (ELISA).Another PMVEC was pre-treated by protein kinase C (PKC) inhibitor bis-indolylmaleimide (BIM) for 0.5 h or had the transfection of SSeCKS-specific small interfering RNA (siRNA) for 48 h before 10 mg/L LPS challenge for 24 h,and subsequently the supernatant was also examined by ELISA.One-way analysis of variance (ANOVA) was employed for statistical analysis by SPSS version 10.0 to compare values among all groups.A significant difference was presumed as a probability value ＜ 0.05.Results After PMVEC incubated with 0.1 mg/L,1 mg/L and 10 mg/L LPS for 24 hours,the levels of TNF-αsecreted were (253.70 ± 23.55),(327.88 ± 37.25),(403.20 ± 36.22),respectively,which were higher than that in un-stimulated PMVEC (82.28 ± 22.56,all P =0.000).After 10 mg/L LPS challenge for one hour,the level of TNF-αin the supernatant of PMVEC raised substantially (170.11 ±49.22),peaked at the time of 6 h (404.82 ± 13.78),then persisted at a higher level until 24 h (395.67 ± 36.23) than that in un-stimulated PMVEC (84.60 ± 23.61,P =0.001,0.000,0.000,respectively).After PMVEC pre-incubated with BIM,the level of LPS-induced TNF-αdecreased obviously (200.44 ± 27.39 vs.402.28 ± 31.07,P =0.000).Compared with LPS challenged PMVEC (407.28 ± 32.64),depletion of endogenous SSeCKS in PMVEC after inhibited by SSeCKS-siRNA significantly attenuated increase in the level of LPS-induced TNF-α (195.20 ± 13.28,P =0.000).Conclusions Down-activation of SSeCKS and PKC can inhibit the secretion of TNF-αin PMVEC induced by LPS,relieving the inflammatory response of PMVEC.

Objective To evaluate the movement function of the left ventricular short-axis with parameters (velocity, acceleration and relatively force) measured with improved anatomical M-mode ultrasound. Methods Sixteen patients with myocardial ischemia coronary heart disease who had taken percutaneous transluminal coronary intervention (PCI) were enrolled. All patients were divided into two groups: group A, single major vascular stenosis (n=8);group B, more major vascular stenosis (n=8). M-mode curves of short-axis sections at mitral valve level, papillary level and apical level were recorded, then the peak myocardial velocities, acceleration and force of the systolic phase, early-diastole phase and end-diastole phase were measured at the post processing station. Results The variety ranges of average velocity and acceleration of the three levels during systolic phase were higher than that during diastole phase. The changing rate of velocity and acceleration in group B was higher than that in group A. Conclusion The new parameters that are measured and calculated with anatomical M-mode ultrasound can reflect the movement functions of coronary heart disease patients taken PCI.

Objective:To study the colonization ability of Streptococcus oligofermentans (S.oligofer-mentan)in the condition of high sucrose in oral cavity of rats.Methods:In this study,48 SPF-SD rats aged 21 days were selected.From 24th to 27th days,the rats were fed with water of antibiotic and fed with high glucose diet continuously.On the 28th day,the rats were divided into four groups randomly,12 rats per group.From the 28th day to 30th day,the first group (SMgroup)was inoculated with S.mutans,the second group (SO group)with S.oligofermentan,the third group (SO+SM group)with mixture of S. mutans and S.oligofermentan,the control group not with any bacteria.On the next day and the 10th day after inoculation of bacteria,the samples of dental plaque of the rats were acquired by scrubbing occlu-sal,buccal and lingual surfaces of bilateral mandibular molars with sterile swabs.The samples of SM group were inoculated on MSB and BHIS,of SO group on MSAE,of SO+SMgroup on MSB,MSAE and BHIS,of the control group on MSB and MSAE.S.mutans were screened and calculated on MSB,the suspected colonies of S.oligofermentan were screened and identified by the analysis of 16S rDNA.Re-sults:On the next day,the detection rate of S.oligofermentan was 33.3% (4/12)in the group of SO;in the group of SO+SM,the detection rate of S.oligofermentan was 0,the detection rate of S.mutans 100.00%,and the proportion of S.mutans 14.70%±4.53%;in the group of SM,the detection rate of S.mutans was 100.00%,the proportion of S.mutans 12.42%±4.27%.On the 10th day,in the group of SO,the detection rate of S.oligofermentan was 0;in the group of SO+SM,the detection rate of S.oligofermentan was 0,the detection rate of S.mutans 100.00%,and the proportion of S.mutans 15.78%±5.10%;in the group of SM,the detection rate of S.mutans was 100.00%,and the propor-tion of S.mutans 17.08%±5.75%.Conclusion:In the condition of the experiment where high glucose was maintained in the oral cavity in rats,S.oligofermentan appeared transiently and couldn’t colonize in the rats.

ObjectiveTo investigate the efficacy of bundle treatment on patients with moderate or severe acute respiratory distress syndrome (ARDS).Methods A multicenter prospective observational study comparing the result of historical treatment strategy and bundle treatment was conducted. According to the new Berlin standard of definition, 73 patients with moderate or severe ARDS due to pulmonary factors, age from 18 to 65 years, admitted to Department of Critical Care Medicine of Taian Central Hospital and Handan Central Hospital were enrolled. Thirty-three patients admitted during September 2012 to May 2014 (prospective observation period) were enrolled as the bundle treatment group. Forty patients with matched disease history admitted from January 2010 to August 2012 were enrolled as the control group. The patients in bundle treatment group received bundle treatment based on the treatment strategy of primary diseases. Bundle treatment included restrictive fluid management, respiratory support, high-dose ambroxol combined with Xuebijing injection, prevention of ventilation associated pneumonia (VAP), individualized sedation plan, installation of continuous blood purification treatment for critical patients. A special team was organized to ensure the successful implementation of all bundle measures. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, oxygenation index, duration of mechanical ventilation, the length of intensive care unit (ICU) stay, incidence of VAP, and 28-day mortality 5 days after treatment were compared between two groups.Results There were no significant differences in basic characteristics of patients between the two groups, including gender, age, etiology, severity, etc. (allP> 0.05) with comparability. Compared with the control group, there was no significant difference in APACHEⅡ score 5 days after treatment in bundle treatment group (15.1±2.8 vs. 16.2±3.0,t = 1.618,P = 0.110). Compared with control group, oxygenation index in bundle treatment group was significantly improved [mmHg (1 mmHg = 0.133 kPa): 135.4±34.5 vs. 117.1±34.2,t = -2.273,P = 0.026), the duration of mechanical ventilation was obviously reduced (days: 8.70±2.50 vs. 10.10±2.67,t = 2.308,P = 0.024), incidence of VAP was significantly lower [18.2% (6/33) vs. 32.5% (13/40),χ2 = 5.027,P = 0.025], and 28-day mortality rate was obviously lowered [24.2% (8/33) vs. 37.5% (15/40),χ2 = 4.372,P = 0.037], the length of ICU stay shown no statistical difference (days:10.40±1.94 vs. 11.30±2.34,t = 1.620,P = 0.110).Conclusion Implementation of bundle treatment can significantly shorten the duration of mechanical ventilation, reduce the incidence of VAP, and improve the prognosis of patients.

To investigate the classification and modeling of traditional Chinese medicine (TCM) syndromes in post-hepatitic cirrhosis by partial least-squares (PLS) method, and to study the clinical application of PLS method in TCM research.

Objective To explore the relationship between vascular lesions and benign paroxysmal positional vertigo in the elderly.Methods 74 patients aged 60 years and over with benign paroxysmal positional vertigo in Huanhu Hospital and 80 subjects without vertigo history in the medical examination center of the same hospital were randomly divided into the case group and the control group,respectively.The carotid intima-media thickness (CIMT) and plaque in the carotid artery were detected using high-resolution color duplex ultrasound for evaluating large vascular lesions.At the same time,T1WI,T2WI and diffusion weighted imaging (DWI) were performed with high-field 3.0 T MRI scanner as the detection index of small vascular lesions to compare the difference in severity of lacunar infarction,leukoaraiosis and micro hemorrhage between the two groups.Both indexes were used together to compare the overall difference in the intracranial and extracranial vascular lesions between the two groups.Results Between the case group and the control group,there were significant differences in the CIMT [(0.96±0.21) mm vs.(0.84±0.26) mm,t=3.136,P＜0.05],the detection rate of plaque (89.2％ vs.72.5％,x2 =5.803,P＜0.05),the number of lacunar infarction [(3.48± 1.67) vs.(2.34± 2.06),t=1.994,P＜0.05] and the score of white matter [(4.77±2.15) vs.(3.95±2.04),t=2.430,P＜0.05].There was no significant difference in the positive detection rate of the cerebral microbleeds in the case group and control group (22.9％ vs.17.5％,x2=0.4264,P＞0.05).Conclusions There is a relationship between the benign paroxysmal positional vertigo and intracranial or extracranial vascular lesions in the elderly.Vascular factor may play an important role in the pathogenesis of benign paroxysmal positional vertigo.Not only the atherosclerosis of large and small arteries but also the microcirculation disturbance may be partly attributed to the benign paroxysmal positional vertigo in the elderly.