Traditional Chinese medicine has a long history of intranasal administration. Compared with the other administration routes, intranasal administration has the benefits of fast absorption, high bioavailability, high brain-targeting and non-invasive. In the past few years we take "Xingnaojing" and "Tongqiao Sanyu formula" as model drug and studied pharmacokinetics of effective components of different polarities. MDCK/MDCK-MDR1 cells were used to simulate blood brain barrier to study the permeate behaviors of different drug and the mechanism of enhancing effects of aromatic medicine. Then a microemulsion (modified by mPEG2000-PLA) was prepared for intranasal administration, and the pharmacokinetics and investigated tissue distribution were studied by fluorescence imaging. The irritation of the drug and different preparations were studied on human nasal epithelial cell (HNEC) cell and living animals. In this paper, we reviewed the achievements and hope that it can provide constructive suggestions for the future research.
Administration, Intranasal ; instrumentation ; methods ; Animals ; Biological Availability ; Blood-Brain Barrier ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Humans

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.
Administration, Cutaneous ; Animals ; Coumaric Acids ; administration & dosage ; pharmacokinetics ; Male ; Needles ; Rats ; Rats, Sprague-Dawley ; Skin Absorption

Objective To evaluate the clinical diagnostic value of prospective electrocardiograph (ECG)-gating of CT cardiac angiography in congenital heart diseases of Chinese population through a Meta-analysis.Methods The articles were searched to study CT prospective ECG-gating in diagnosis of congenital heart disease from January 1995 to February 2016 in domestic and foreign publications.The study quality was assessed by the Quality Assessment for Diagnostic Accuracy Studies and the data extraction was performed.The software of Meta-disc1.4 was used for heterogeneity test.Different effect models were choosen according to the results of heterogeneity analysis.Meanwhile,this soft was used to calculate the sensitivity,specificity,likelihood ratio and its 95％ confidence interval (CI),respectively.The forest maps and summary receiver operator characteristic (SROC) curve were drawn.In addition,the area under curve (AUC) was calculated.Results Twelve articles were included in the Meta-analysis.The study included 1 431 congenital heart malformations confirmed by surgery or cardiac catheterization angiography.CT prospective ECG-gating technique had no heterogeneity in sensitivity and specificity of congenital heart disease.The total sensitivity,the total specificity,positive likelihood ratios,negative likelihood ratios and its 95％ CI of CT cardiac angiography were 96％ (95％ CI 94％ to 97％),100％ (95％ CI 100％ to 100％),365.94(95％ CI 231.18 to 579.26),0.04(95％ CI 0.03 to 0.05) with fixed effect model,respectively.The AUC of the SROC was 99.86％,Q =0.987 9.Conclusions Prospectively ECG-gating of CT cardiac angiography has high sensitivity and specificity in the diagnosis of congenital heart diseases.Its AUC of the SROC is large.It has high diagnostic value in congenital heart diseases.

Objective To explore the relationship between blood glucose and lipid levels and cognitive function in elderly patients with comorbidity of depression and type 2 diabetes mellitus (T2DM). Methods The clinical data from elderly participants (60 to 79 years old) receiving physical examination between Nov. 1 and Dec. 30, 2017 were collected. According to inclusion and exclusion criteria, 59 cases with comorbidity of depression and T2DM were assigned to comorbid group, 106 depression cases were in depression group, 84 T2DM cases were in diabetes group and 248 were in control group (with no diabetes or depression). The general physiological indicators (height, body mass, waist circumference, hip circumference and blood pressure) were collected, the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and blood glucose and lipid levels were determined. The Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of the elderly in each group. The differences in BMI, WHR, blood pressure, blood glucose level and blood lipid level among the groups were compared, and the relationships between these indicators and the adjusted total score and scores in each cognitive domain of MoCA scale were analyzed. Results (1) There were no significant differences in height, body mass, BMI, WHR or diastolic blood pressure (DBP) among four groups (all P>0.05), while the differences in systolic blood pressure (SBP) and pulse pressure (PP) were significant (both P<0.01), with the increase in the diabetes group being most obvious. (2) Compared with the control group, the fasting blood glucose (FBG) level, oral glucose tolerance test (OGTT) 2 h and glycosylated hemoglobin (HbA1c) level were significantly higher in the comorbid group and the diabetes group (all P<0.01); while there was no significant difference between the control and the depression groups (P>0.05). The triglyceride (TG) level in the comorbid group was significantly higher than that in the control group (P<0.05), and the high-density lipoprotein (HDL) levels in the comorbidity and the diabetes groups were lower than that in the control group (P<0.05, P<0.01). (3) There was no significant difference in the adjusted total score of MoCA scale among the four groups (P>0.05). Compared with the control group, the attention scores of the other three groups were significantly lower (all P<0.01). The elderly in the comorbid group had significantly lower fluency and orientation scores compared with the elderly in the control group (P<0.05, P<0.01), and had significantly lower orientation score compared with the elderly in the diabetes group (P<0.05). (4) Simple linear regression analysis showed that the adjusted total score of MoCA scale was negatively correlated with FBG and HbA1c levels (b=-0.339, P=0.006; b=-0.482, P=0.023), and the attention score was negatively correlated with FBG, OGTT 2h and HbA1c levels (b=-0.119, P<0.001; b=-0.040, P=0.002; b=-0.161, P=0.006). (5) Multiple linear regression analysis revealed that FBG level was negatively correlated with the adjusted total score of MoCA scale (B=-0.349, P=0.004). Conclusion Hyperglycemia may be a risk factor of cognitive dysfunction of elderly patients with comorbid of depression and T2DM.

Objective To observe the sequence of fat deposit and its relationship with insulin resistance in SD rats fed by high fat diet.Methods Normal 8-week-old male SD rats were randomly divided into normal chow (NC,n=40)and high fat diet(HF,n=40)groups.Triglyceride(TG)in serum,liver and muscle were measured;glucose infusion rate(GIR)and the mRNA level of genes related to lipid metabolism in liver and muscle were determined in different stages.GIR was detected by eugiyeemic-hyperinsulinemic clamp for evaluating the insulin sensitivity.Gene expression was determined by real-time PCR.Results(1)As compared with NC group,serum TG was not increased after high fat feeding for4 and 8 weeks,it began to increase after 12 weeks [0.52(0.15-1.00) mmol/L vs O.31(0.09-0.53)retool/L, P0.05)in skeletal muscle.After 8 weeks,the expression of ACC1 in liver in HF group was increased by 20.6%,CPT-1 was decreased by 27.1%(P

OBJECTIVETo establish strategies for preventing graft versus host disease (GVHD) and reducing treatment associated morbidity while preserving graft versus leukemia (GVL) effect in nonmyeloablative allogeneic bone marrow transplantation (allo-BMT), with or without donor lymphocyte infusion (DLI) after BMT.

METHODS3 x 10(7) bone marrow cells mixed with 1 x 10(7) spleen cells from the same BALB/c mouse were transplanted into the nonablative irradiated inbred 615 mouse which received a single subcutaneous injection of 1 x 10(6) L615 leukemia cells three days before. The experiments were designed as follows (ten mice in each group): myeloablative BMT control group (group A), nonmyeloablative conditioning without BMT group (group B), nonmyeloablative BMT group (group C), and nonmyeloablative BMT + DLI group (group D). GVL effects were assessed by survival time, white blood cell count and L615 cells in peripheral blood and histologic changes. GVHD was assessed by signs of weight loss, ruffled fur, diarrhea and histologic changes of skin, liver and small intestines. Chimerism was detected by cytogenetic analysis and PCR technique.

RESULTSThe survival time of group A, B, C and D was (20.3 +/- 13.4), (15.9 +/- 1.1), (21.6 +/- 1.7) and (37.8 +/- 2.0) days, respectively, being no significant difference between group A and group C (P > 0.05). The survival time of group C was longer than that of group B (P < 0.01). And among group B, C and D, group D had the longest survival time (P < 0.01). GVHD signs and histologic changes were observed in 60% of control group mice at + 14 day, but none of group C and group D. 40% of mice in group A died of treatment associated morbidity within two weeks, but none in group C and group D. Allogeneic chimerism was kept in group A, but excluded gradually in group C.

CONCLUSIONGVL effect seems preserved in nonmyeloablative BMT mice, but weaker than that in myeloablative BMT mice. GVL effect seems to be enhanced by DLI after nonmyeloablative BMT. GVHD and transplantation associated morbidity seems to be reduced in nonmyeloablative BMT.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Combined Modality Therapy ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; Leukemia, Experimental ; therapy ; Leukemia, Lymphoid ; therapy ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Transplantation Conditioning ; methods ; Transplantation, Heterologous

OBJECTIVETo investigate the age, gender and region specified milk consumption and its changing trends of Chinese 18 - 44 years old adults in 9 provinces (autonomous region) from 1991 to 2006.

METHODSThe data of 18 - 44 aged old adults investigated in Chinese Health and Nutrition Survey from 1991 to 2006 in 9 provinces (autonomous region) were utilized. The numbers of the subjects selected in 1991, 1993, 1997, 2000, 2004 and 2006 were 5593, 5491, 5334, 4188 and 3908, respectively. Changes of the percentage of milk consumption, average intake of daily milk and dietary calcium intake were analyzed across different groups of gender, income levels, and areas.

RESULTSThere was an increasing trend in the percentage of milk consumption and daily intake of milk from 1991 to 2006. The average percentage of Chinese adult milk consumption went up from 2.2% (123/5593) in 1991 to 7.6% (297/3908) in 2006 (Z = -22.16, P < 0.01). Specifically, urban adult and rural adult showed significant increase in the percentages from 9.7% (80/823) to 23.7% (112/472) (Z = -12.81, P < 0.01) and 0.1% (2/2937) to 1.8% (36/1987) (Z = -9.21, P < 0.01) respectively. Percentages of adult who ever drank milk at top income level and bottom income level increased from 4.7% (95/2006) to 14.6% (200/1373) (Z = -17.36, P < 0.01) and from 0.1% (2/1748) to 2.4% (28/1171) (Z = -9.58, P < 0.01), respectively. Meanwhile, the average daily intake of milk increased from (3.6 ± 24.6) g/d in 1991 to (11.8 ± 51.4) g/d in 2006 (F = 67.07, P < 0.01). The daily milk consumption among top income level adults and bottom income level adults increased from (8.5 ± 50.9) g/d to (23.1 ± 71.5) g/d and from (0.2 ± 6.5) g/d to (3.3 ± 23.5) g/d (F = 13.90, P < 0.01), respectively. From 1991 to 2006, milk consumers significantly promoted their percentage of achieving the Chinese dietary reference intake on calcium (800 mg/d) from 6.5% (8/123) to 12.8% (38/297) (Z = -1.67, P < 0.05), whereas this percentage increased from 1.6% (38/5470) to 3.6% (130/3611) among milk non-consumers (Z = -5.66, P < 0.01).

CONCLUSIONChinese adult milk intake still remains in quite low level, and the situation of milk consumption among rural adults requires further promotion.

Adolescent ; Adult ; Animals ; Asian Continental Ancestry Group ; Calcium, Dietary ; analysis ; China ; Feeding Behavior ; Female ; Humans ; Male ; Milk ; Nutrition Surveys ; Rural Population ; Suburban Population ; Urban Population ; Young Adult

OBJECTIVETo determine the O/W partition coefficient of panax pseudo-ginseng saponin (PNS) and investigate the absortion kinetics of it in whole small intestine and different intestinal segments of rats.

METHODThe shake-flask method was employed to determine the O/W partition co-efficient of geniposide, and an in situ intestinal perfusion model was employed to investigate the absorptive kinetics of geniposide.

RESULTThe partition coefficient (P) of R1, Rg1 and Rb, of PNS were 1.0814, 6.3104 and 0.2743, respectively, and their logP were 0.0340, 0.8001, -0.5618, the absorptive rate constants (Ka) of R1, Rg1 and Rb1 of PNS at the concentration of 0.2, 0.5, 1.0 g x L(-1) were (0.135 +/- 0.006), (0.110 +/- 0.002), (0.095 +/- 0.016), (0.144 +/- 0.015), (0.110 +/- 0.006), (0.099 +/- 0.011), (0.238 +/- 0.013), (0.140 +/- 0.008), (0.137 +/- 0.012)h(-1), respectively. The Kb of R1, Rg1 and Rb1 of PNS were (0.030 +/- 0.006), (0.033 +/- 0.004), (0.033 +/- 0.007), (0.032 +/- 0.006), (0.044 +/- 0.012), (0.044 +/- 0.011), (0.042 +/- 0.007), (0.065 +/- 0.007), (0.044 +/- 0.014)h(-1) at duodenum, jejunum, ileum, respectively. The absorption rate of Rb1 was higher than R1 and Rg1.

CONCLUSIONAccording to the P and the logP, it can be conjectured that the absorption of R1 and Rg1 are better than Rb1. The absorption rate is decreased with the increase of the PNS concentration. Their absorption is the passive diffusion mechanism and other transport may also take part in the transport process. PNS is absorbed at all small-intestinal segments of rats, there are no significant differences between the three sections.

Animals ; Calibration ; Drug Stability ; Intestinal Absorption ; Intestine, Small ; metabolism ; Kinetics ; Male ; Oils ; chemistry ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Saponins ; chemistry ; metabolism ; Water ; chemistry

OBJECTIVETo explore the prophylaxis effect of pretreatment of allograft with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and anti-OX40L monoclonal antibody (McAb) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice.

METHODSResponder splenocytes from C57BL/6 donor mice (H-2(b)) were co-cultured with stimulator splenocytes from BALB/c recipient mice (H-2(d)) for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA chemical modification. Donor bone marrow cells plus the mixed culture of T-cells were then transplanted into lethally irradiated BALB/c mice. The BALB/c recipient mice were divided into four groups: group A (allo-BMT control group), group B(mPEG-SPA modification group), group C (anti-OX40L McAb pretreated group) and group D (mPEG-SPA and anti-OX40L McAb dual-treated group). Survival time and survival rate of the recipients were observed after allo-BMT. GVHD was assessed by clinical signs and histological changes of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines (IL-4, IL-10 and INF-gamma) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.

RESULTS(1) The mice in group A developed typical clinical signs of aGVHD and all mice died within 17 days after BMT with an average survival time (AST) of (12.1 +/- 5.5) days. The signs of aGVHD were less evident in mice of groups B, C and D, and their AST (36.2 +/- 24.9, 32.0 +/- 24.8 and 44.3 +/- 23.2 days, respectively) were all longer than that in group A (P < 0.05). AST of group D being the longest (P < 0.05). The survival rates at day 60 post-BMT in groups B, C and D were 50%, 41.7% and 66.7%, respectively. (2) Serum IFN-gamma level was increased after BMT in group A, and peaked in day 10 to day 15 post-BMT, while the level was decreased in groups B, C and D, reached the nadir on the day 10 post-BMT, with the lowest in group D (P < 0.01). After BMT, IL-4 and IL-10 levels were slightly decreased in group A, their levels were elevated in groups B and C (P < 0.05) and even more significantly increased in group D (P < 0.01). IL-4 and IL-10 levels peaked between day 10 and 15 post-BMT. (3) The average proportion of H-2(b) positive cells in recipient mice was 95% - 100% on day 60 post-BMT, with complete donor-type implantation.

CONCLUSIONCombination of mPEG-SPA and anti-OX40L McAb can block T-cell activated antigens and co-stimulatory pathway, regulate the T cells differentiation and induce the immune shift of Th0 cells toward Th2 cells. The immune tolerance induced by this method can significantly relieve aGVHD after allo-BMT.

Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

OBJECTIVEPulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left-to-right shunt. However, the mechanism is still not clear. The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow.

METHODSSixteen male SD rats were randomly divided into control group (n = 8) and shunting group (n = 8). Aortocaval shunting was produced for 11 weeks in shunt rats. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] was detected. Pulmonary vascular micro-and ultra-structure was examined by using a light microscope and a transmitted electronic microscope. Meanwhile, the concentration of plasma NO was measured by spectrophotometry. The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively.

RESULTSAfter 11-week aortocaval shunting, mPAP was significantly increased [(22.5 +/- 2.6) mmHg vs. (15.8 +/- 2.8) mmHg, 1 mmHg = 0.133 kPa, t = 4.97, P < 0.01], and RV/(LV + S) was also markedly increased (0.267 +/- 0.022 vs. 0.221 +/- 0.016, t = 4.85, P < 0.01). The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23.2 +/- 2.4)% vs. (13.5 +/- 2.1)%, t = 7.82, P < 0.01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery: (7.76 +/- 0.56)% vs. (4.82 +/- 1.03)%, t = 6.23, P < 0.01; small pulmonary artery: (11.94 +/- 0.66)% vs. (6.91 +/- 0.53)%, t = 14.96, P < 0.01]. Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased [(30.2 +/- 7.9) micromol/L vs (19.7 +/- 5.7) micromol/L, t = 3.05, P < 0.01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group.

CONCLUSIONThe upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling.

Animals ; Blood Flow Velocity ; Hypertension, Pulmonary ; physiopathology ; Immunohistochemistry ; In Situ Hybridization ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; genetics ; Nitric Oxide Synthase Type III ; Pulmonary Artery ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley