Aim To investigate the relationship between the brain targeting effect and P-glycoprotein(P-gp)expression level of Danshensu borneol ester(DBE)and the combination use of sodium Danshensu and borneol(SDSS-B).Methods The liquid chromatography mass spectrometry(LC-MS)method was applied to investigate the accumulation of Danshensu(DSS)in rat brain tissues after intravenous injection of DBE,SDSS-B and SDSS.Also their effect on regulating the expression level of P-gp in rat hippocampus was investigated using Western blot.Results The brain targeting effect of DBE,SDSS-B was qualitatively analyzed through the brain distribution of DSS,and the result was DBE(SDSS-B)>SDSS(P<0.01).Meanwhile,the brain distribution of DBE group was slightly lower than SDSS-B group at 15 min,while at 30 min DBE was higher than that of SDSS-B.DBE demonstrated a better slow release property compared to SDSS-B.Western blot analysis indicated that DBE,SDSS-B were more effective in inhibiting the expression of P-gp than SDSS in rat hippocampus(P<0.01 vs control or SDSS group),and the lowest P-gp expression was obtained with(47.58±2.28)％and(46.54±1.41)％at 45 min after administration of DBE or SDSS-B.Once the administration time was extended to 60 min,the inhibitory effect on P-gp expression of DBE was stronger than SDSS-B[(85.04±1.42)％vs(95.29±0.98)％].However,no significant inhibition of P-gp expression in rat hippocampus was found throughout the treatment of SDSS(P>0.05 at 5,15,45,60 min,vs control group).Conclusion An attenuated expression level of P-gp can be realized by DBE and SDSS-B,which is advantageous to their brain targeting.

BACKGROUND:There is a great difference of grade size of macrobead in various joint diseases; therefore, it can be used to determine state of joint diseases initially.OBJECTTVE : To explore the physical properties of synovial fluid nano-particles and their correlations with the occurrence of knee osteoarthritis (KOA).DESIGN: Controlled experimental study based on synovial fluid samples.PARTICIPANTS: A total of 99 synovial fluid samples were collected from normal subjects and KOA patients with various KOA severities. Among them, 41 were normal synovial fluids, 58 were KOA.METHODS: Synovial fluid samples from individuals with and without KOA were obtained. Using the technology of quasi-elastic laser scattering, nano-particle size and its distribution were estimated, and the dynamic/static light scattering spectrometric analyzer allowed the measurement of particles Zeta potentials. A correlation analysis between the particle size, Zeta potentials and the onset of KOA was attempted.MAIN OUTCOME MEASURES:① Grade size and distribution of microsome in synovial fluid;② Zeta potentials and distribution of microsome in synovial fluid; ③ grade size and clinical correlation of microsome in synovial fluid.RESULTS: ① The mean nano-particle diameter in the synovial fluid of KOA patients were significantly greater than those of normal joints [(297±84), (63±23) nm, P ＜ 0.001]. The distribution curve of KOA synovial fluid nano-particle size was normal knee and (-15.84 ±3.34) mV of KOA patients, and there was a significant difference (P ＜ 0.001). This suggestedthat the Zeta potentials in the synovial fluid of KOA patients were significantly greater than those of normal joints. ③ The average particle size and Zeta potential of synovial fluid strongly correlated with the integrity of the joint of KOA (rp =0.797 2,0.631 9, P＜ 0.01).CONCLUSION: The nano-particle size and Zeta potential of synovial fluid are significantly correlated with the development of KOA, and this can reflect the severity of KOA.

BACKGROUND: People have concerned with the effect of fibroblast growth factor biological protein sponge on the repairing effect of traumatic ulcer.OBJECTIVE: To observe the repairing effect of fibroblast growth factor biological protein sponge on the repairing effect of traumatic ulcer and its possible adverse reactionDESIGN: Grouping comparison observation.SETTING: Staff Room of Physiology, Medical College of Jinan University PARTICIPANTS: Totally 40 cases of traumatic ulcer accepted the treatment in the First Hospital of Jinan Univerity between March 2004 and May 2005 were recruited. Patients with diabetes mellitus and infection on the whole body were excluded. Traumatic ulcer lay in the shank. Patients were randomly divided into experimental group and control group with 20 in each group.INTERVENTIONS: In the experimental group (n=20), sterilized fibroblast growth factor biological protein sponge was used and in the control group (n=20), sterilized petrolatum gauze dressing was used on the wound.Change the gauze dressing once per day until the wound healed. Drugs,which affected wound growth, were not used on the whole body and at the local part. Wound healing status was evaluated 1, 2 and 3 weeks after changing the drugs (The secretion of a wound was divided into: nothing, a little, middling, a great deal. frontier reaction of wound was divided into:nothing, slight, middling, severe.). Pigment deposition and scar was recorded after wound healing.MAIN OUTCOME MEASURES: Healing time of ulcer, healing course of the wound and adverse reaction of the patients in the two groupsRESULTS: Totally 40 patients of the two groups entered result analysis.Wound healing status after treatment of the patients in the two groups: The rate of wound healing in 3 weeks in the experimental group was significantly higher than that in the control group [95% (19/20),55% (11/20),χ2=8.533,P ＜ 0.05]. Wound secretion and peripheral inflammatory reaction of the wound in the experimental group was obviously milder than that of the control group; there was no obvious adverse reaction and scar of the wound found in the two groups.CONCLUSION:FGF biological protein sponge can promote the healing of traumatic ulcer; shorten the healing time without scar and adverse reaction.This dressing is convenient, safe, and non-irritative.

Objective To explore, the effect of different dosage of pulmonary surfactant (PS) on the inci-dence of bronchopulmanary dysplasia. Method Four hundred and three premature infants with hyaline membrane disease were divided into 3 groups according to the dose of PS: low-dose group (L-PS group, ≤ 100 mg/kg, n =188) ,high-dose group(H-PS group, > 100 mg/kg, n = 94) and no-PS group (N-PS group, n = 121). The frac-tional inspired oxygen(FiO2) and ptlmonary oxygenating function before and after 6 hours treatment were observed and the durations of oxygen therapy and mechanical ventilation, frequency of repeated intubafion, length of hospi-talization and the incidence of BPD were compared among the three groups. Results After 6 hours PS administra-tion, the FiO2,oxygen index and duration of oxygen therapy and mechanical ventilation were significantly decreased (P <0.05), while PO2 and the arterio-alveolar partial pressure of oxygen were significantly increased (P <0.05)in the H-PS and L-PS groups, compared with the N-PS group. Compared with the L-PS and N-PS groups,the H-PS group showed a decreased incidence of BPD. Conclusions PS administration could improve the pul-monary oxygenation and prevent the development of BPD, especially in high-dose.

Objective To study the influence of pregnant rats' prenatal chronic stress (PS) on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone (COR) and adreno-cortico-tropic-hormone (ACTH) were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency (EL) to find the platform in the control group was significantly less than that in the PS group in female rat offspring (F =4.533,P ＜ 0.05),and the difference was statistically significant on the 5th day (t =2.788,P ＜ 0.01).EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring (F =6.101,P ＜0.05),and the difference was statistically significant on the second day (t =3.051,P ＜ 0.01).In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar(P ＞ 0.05).The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring(t =3.658,P ＜ 0.01) and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings(t =2.319,P ＜ 0.05).A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group(t =-3.072,P ＜ 0.01).Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.

BACKGROUND: Though there were many experiments addressing repairing osteochondral defects before, faulty restoration occurred at coupling interfaces. OBJECTIVE: To investigate the feasibility of repairing of osteochondral composite defects in rabbit knees with animal-origin osteochondral scaffold combined with bone marrow mesenchymal stem cells (BMSCs)/chondrocytes.METHODS: New Zealand white rabbits were randomly divided into the experimental, control and blank groups and prepared for unilateral knee joint osteochondral defects. Animal-origin osteochondral scaffold combined with BMSCs/chondrocytes, animal-origin osteochondral scaffold and no material was implanted to repair the defects in the experimental, control and blank groups, respectively. Healing condition was evaluated by gross observation, hematoxylin-eosin staining, and toluidine blue staining at 4, 8, and 12 weeks after operation. RESULTS AND CONCLUSION: At 12 weeks after operation, gross observation showed the defects were repaired completely without local depression and the regenerated tissues were fused with surrounding tissues in the experimental group. Hematoxylin-eosin staining and toluidine blue staining revealed that there were many new hyaline cartilages in the cartilage defects in which columnar cells were lined well and cartilage lacuna was obviously, also, there were many bony tissues in the bone defects. The regeneration cartilage, the underlying subchondral bone and host bone were coupled completely. The toluidine blue positive rate and histologic scores of the experimental group were superior to those of the control and blank groups (P < 0.05). It is demonstrated that animal-origin osteochondral scaffold combined with BMSCs/chondrocytes is an ideal method to repair defects between cartilage and the underlying subchondral bone.

BACKGROUND: The development of cartilage tissue engineering provides novel ideas for treatment of articular cartilage defects and implements construction of tissue-engineered cartilage in vivo.OBJECTIVE: To investigate the feasibility of constructing tissue-engineered osteochondral composite through bone marrow stem cells(BMSCs) cultured on the poly(lactide-co-glycolic acid) (PLGA), which was modified with collagen and cellular growth factors.METHODS: PLGA was made by phase separation technique, composited with collagen Ⅱ, basic fibroblast growth factor, and transforming growth factor-β1. The BMSCs of passage 3 were cultured on the above scaffolds. Thirty-six SD rats were randomly divided into experimental, control, and blank groups. These three groups received implantation of BMSCs composited with growth factors and collagen-PLGA, implantation of BMSCs composited with collagen-PLGA, and implantation of collagen-PLGA into the muscle, respectively. At 4, 8, and 12 weeks after surgery, cell directional differentiation and growth were examined by gross observation, hematoxylin-eosin staining, toluidine blue staining, collagen Ⅱ staining, and scanning electron microscope.RESULTS AND CONCLUSION: Gross observation showed that there were many chondroid tissues in the experimental group and fibrous tissues in the control and black groups. Stainings and electron microscope revealed that many chondroblasts and a few osteoclasts appeared in the composite of the experimental group. Toluidine blue and collagen Ⅱ stainings were positive in the experimental group and negative in the control and blank groups. These findings demonstrate that PLGA modified with collagen had a good cellular compatibility. BMSCs cultured on PLGA, which was modified with collagen and cellular growth factors, can construct the tissue-angineered osteochondral composite in rats.

Important/potential value of macrolides has been proved in the management of chronic respiratory diseases by increasing basic and clinical trials.Through three face-to-face discussions,10 experts examined important data and drafted this consensus related to macrolides:(1) mechanism of nonantiinfective effects;(2) clinical use in chronic respiratory diseases;(3) cautions of long-term use.The mechanism out of non-antiinfective effects includes anti-inflammatory effect,modifying airway secretion,immune-regulation related to antibacterial effect,corticoid saving effect and anti-viral effect.The efficacy of long-term use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis,chronic rhinosinusitis.It is considerably used in bronchiectasia,cystic fibrosis,severe asthma and chronic obstructive pulmonary disease.Further studies should be conducted in cryptogenic organizing pneumonia and respiratory viral infection.It should be paid attention to its possible adverse effects (including drug interactions,cardiac toxicity,ototoxicity and disturbance of intestinal flora) and drug resistance in long-term use.A Chinese consensus for non-antiinfective effects and clinical use of macrolides is developed for the first time,which aims to expand their rational use and the further research.

Objective To evaluate the clinical efficacy and safety of ritonavir-boosted danoprevir (DNVr) combined with daclatasvir (DCV) in the treatment of patients with genotype 1b chronic hepatitis C (CHC).Methods Thirty-three patients with genotype 1b CHC admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from August 2018 to February 2019 were enrolled.All the patients received DNVr +DCV antiviral treatment.HCV RNA levels were detected before and 2, 4, 12 weeks after treatment, and after drug withdrawal , respectively.Indicators of liver and kidney function and adverse events were observed.ANOVAV of repeated measurement was used to analyze the data. Results The baseline viral loads of 33 patients ranged from 1.12×104 to 1.76×107 IU／mL.Two weeks after treatment the viral loads of all patients were down to the lowest limit of detection (＜500 IU／mL). Serum ALT, AST and TBil levels returned to norml ( F＝58.26, 14.49 and 20.16, all P＜0.05) and sustained virologic response reached 100%12 weeks after drug withdrawal.Three cases had minor adverse reactions during the treatment.Conclusion DNVr combined with DCV can achieve a rapid and strong virological response in the treatment of patients with genotype 1b CHC with good safety.

OBJECTIVETo study the expression of tumorigenesis-related stem cell markers Lgr5 and CD44 in different pathological types of intestinal polyps and their clinical significance in predicting tumorigenesis.

METHODSA total of 145 cases of colorectal polyps, adenomas and cancer tissues were obtained by colonoscopy biopsy. Immunohistochemistry was employed to detect the expression of Lgr5 and CD44 to analyze their relationship with the occurrence and prognosis of colon and rectal cancer.

RESULTSThe expression of CD44 in colon cancer tissue was 95.65%, significantly higher than that in normal mucosa (5%), inflammatory hyperplastic polyps (22.58%), tubular adenomatous polyps (55.26%) and villous polyps (75.76%) (P<0.05). The expression of Lgr5 in colorectal cancer was up to 95.65% while negative in normal colorectal tissue and was 16.12% in inflammatory hyperplastic tissues (P<0.05). The expression rate of Lgr5 was 86.84% in tubular adenoma and 93.94% in villous polyps, both comparable with that in colon cancer (P>0.05). Correlation analysis indicated that the expression of CD44 and Lgr5 were positively correlated with the progression of intestinal polyp tumorigenesis (rs=0.69377, P<0.0001; rs=0.81637, P<0.0001).

CONCLUSIONLgr5 and CD44 are highly expressed in colorectal cancer tissues in close correlation with the clinical and pathological features. The expression profiles of Lgr5 and CD44 represent a distinct feature to differentiate colorectal cancer from normal intestinal mucosa. Lgr5 is more closely correlated with tumor progression of polyps than CD44. This means detecting of the expression of Lgr 5 together with CD44 is important and necessary in clinical diagnosis of patients with early stage colorectal diseases such as polyps and their canceration.

Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Intestinal Polyps ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Receptors, G-Protein-Coupled ; metabolism ; Young Adult