Intracerebral delivery of drugs for the treatment of central nervous system disorders is usually limited by the blood-brain barrier (BBB). Transdermal drug delivery systems (TDDS) have the advantage of improving patient compliance and avoiding first-pass effects compared to intravenous, oral and intranasal drug delivery, and are an emerging non-invasive drug delivery route that facilitates long-term drug delivery to patients. The discovery of direct subcutaneous targeting of lymphatic pathways to brain tissue has made TDDS a new brain-targeted drug delivery strategy. At the same time, the development of nano-delivery technology has further facilitated the application of TDDS for targeted drug delivery to the brain. This review summarizes the mechanism of transdermal drug delivery into the brain and the application of TDDS in the treatment of brain diseases, providing new ideas and methods for the treatment of central nervous system diseases.

Background:Fanconi anemia( FA ),an autosomal or x-linked recessive inherited disease,is caused by gene mutation related to FA pathway of DNA damage and with the clinical features of congenital malformation,bone marrow failure and susceptibility to cancer. Aims:To investigate the expression of Fanconi anemia complementation group D2 (FANCD2)in colorectal cancer and its correlation with prognosis. Methods:Fifty-six surgical resected specimens of colorectal cancer tissue and para-cancer noncancerous tissue from May 2012 to September 2013 at Guangzhou First People’s Hospital were obtained. Ninety-three patients with colorectal cancer from January 2008 to April 2009 at Guangzhou First People ’s Hospital were enrolled and the specimens of colorectal cancer tissue were obtained. The expression of FANCD2 mRNA in 56 specimens of colorectal cancer tissue and para-cancer noncancerous tissue was determined by qPCR. The expression of FANCD2 protein in 49 of 56 specimens of colorectal cancer tissue and para-cancer noncancerous tissue and 93 specimens of colorectal cancer tissue was determined by immunohistochemistry. Follow up was conducted in 93 patients and the correlation between the expression of FANCD2 and prognosis was analyzed. Results:Expression of FANCD2 mRNA was significantly higher in colorectal cancer tissue than that in para-cancer noncancerous tissue [0.102(0.047,0. 163)vs. 0. 051(0. 025,0. 095)](P =0. 007). Expression of FANCD2 mRNA was significantly correlated with lymph node metastasis and Dukes stage( P <0. 05 ). Positivity rates of FANCD2 protein expression in colorectal cancer tissue and para-cancer noncancerous tissue were 77. 6%(38/49)and 22. 4%(11/49),respectively. Expression of FANCD2 protein was significantly correlated with lymph node metastasis and Dukes stage(P<0. 05). The overall 5-year survival rate was significantly lower in patients with positive expression of FANCD2 protein than that in patients with negative expression of FANCD2 protein(35. 5% vs. 71. 0%)(P<0. 01). Conclusions:FANCD2 is associated with malignant potential of colorectal cancer and could be a potential marker for prognosis.

Objective To establish and compare HPLC fingerprint chromatograms of Dipsaci Radix decoction pieces, aqueous decoction and formula granules.Methods The HPLC analysis was carried out in Wondasil C18 column (4.6 mm × 250 mm, 5 μm) with a mobile phase of acetonitrile-0.1% phosphoric acid by gradient elution. The flow rate was 1.0 mL/min; the detection wavelength was set at 212 nm; the column temperature was kept at 30℃. Results The fingerprint chromatograms from 12 batches of Dipsaci Radix decoction pieces, aqueous decoction and formula granules were established respectively. 14 common peaks in the fingerprint chromatogram in the formula granules could be tracked in the aqueous decoction, and 13 common peaks in the fingerprint chromatogram could be tracked in the decoction pieces. 2 chemical compounds were identified, such as asperosaponinⅥ and chlorogenic acid.ConclusionThe method of HPLC fingerprint chromatograms is stable and with good repeatability. Dipsaci Radix decoction pieces, aqueous decoction and formula granules are basically the same chemical composition.

Aim To explore the effects of chrysin on endothelial dysfunction induced by acute high glucose.Methods ① The effects of chrysin on normal isolated aortic at contraction induced by PE and on endothelial dysfunction induced by high glucose were tested in the following medium: normal group,chrysin group;normal-glucose group: glucose 11mmol·L-1 in Krebs' solution;high-glucose group: glucose 44 mmol·L-1 in Krebs' solution;mannitol group: mannitol 33 mmol·L-1 in Krebs' solution and chrysin group: 44 mmol·L-1 Glu+chrysin 1.0 μmol·L-1 in Krebs' solution.② The effects of chrysin on HUVEC cell viability after incubated in high glucose were observed in the following groups: normal-glucose group: glucose 5.5 mmol·L-1 in culture solution;high-glucose group: glucose 33.3 mmol·L-1 in culture solution;mannitol group: mannitol 27.8 mmol·L-1 in culture solution and chrysin group: chrysin(25,50 μmol·L-1)in culture solution.And the NO release was also testd in these groups.Results ① Chrysin could induce vaso-dilation in a dose-dependent manner at normal glucose.The Emax was(58.94±9.61)％,and the EC50 value was 51.9 μmol·L-1.After incubating the aortic rings with high glucose(44 mmol·L-1)for 4 h,there were significant differences in ACh-induced vascular relaxation between the normal glucose group and the high glucose group.The Emax was(32.12±3.92)％and the EC50 value was 78.0 μmol·L-1 of high glucose group(P<0.01).The endothelium-independent relaxation induced by SNP was not significantly different between the two groups.And chrysin(1.0 μmol·L-1)could reverse the decline of ACh-induced vasorelaxation response induced by high glucose(44 mmol·L-1).The Emax was(70.7±3.87)％and the EC50 value was 0.852 μmol·L-1.② The cell viability of HUVEC was depressed after incubated in high glucose,and chrysin could reverse the decline in a concentration-dependent way.And chrysin in defferent concentrations could increase the cell NO release.Conclusion Chrysin could prevent the acute high glucose-induced vascular endothelial dysfunction and could increase the NO release.

Objective To analyze the efficacy of vertebroplasty using the patient data in our hospital so as to better serve those clinical patients.Methods A retrospectively review was performed on 1 080 with data integrity out of 1 084 cases undergone vertebroplasty from January 2003 to March 2012.Basic information measured was age,gender,entity,number of operated vertebral bodies,distribution of operated vertebral bodies,postoperative X-ray films,bone cement volume,bone cement leakage into the vertebral canal,cases with balloon kyphoplasty,cases with bilateral or bilateral vertebroplasty,and intraoperative vital signs.Clinical manifestations and quality of life were observed after operation.Results In all,306 cases occupying 28.33％ presented bone cement leaks based on postoperative X-ray films.Volume of bone cement infused in each vertebral body varied from 1.5 ml to 7.5 ml.No bone cement leaked into the vertebral canal during operation.There were 706 cases occupying 65.37％ managed by balloon kyphoplasty and 984 cases occupying 91.11％ by unilateral vertebroplasty.Within 3-5 days after surgery,associated symptoms were found in 23 cases,among which 3 had neurologic symptoms and 20 composing 5 men and 15 women had symptoms related to pulmonary embolism including one severely affected was transferred to the department of pneumology.Among the 23 cases,8 were managed by unilateral vertebroplasty and 15 by bilateral vertebroplasty,including 17 involving thoracic surgery.Conclusion Although various complications relate to the procedure,vertebroplasty may be widely used on condition that techniques and indications iu surgery are correctly mastered.

OBJECTIVETo explore the change in the distensibility of large arteries and its influencing factors in elderly patients with essential hypertension.

METHODSAutomatic measuring system for pulse wave velocity (PWV) was applied to examine carotid-femoral PWV as an index reflecting distensibility of large arteries. 118 hypertensive patients aged 64 - 83 (mean age 67.12 +/- 10.26) years were included in the study. Of them, 87 were males and 31 were females.

RESULTSPWV of 118 hypertensive patients increased with increasing age (P < 0.001). Multivariate regressive analysis demonstrated that age and systolic blood pressure had the close relationship with PWV (P < 0.001).

CONCLUSIONHypertension of the elderly could cause reduction of distensibility of large arteries. Age and systolic blood pressure had the close relationship with distensibility of large arteries in elderly patients with essential hypertension.

Age Factors ; Aged ; Aged, 80 and over ; Blood Flow Velocity ; Carotid Arteries ; physiopathology ; Elasticity ; Female ; Femoral Artery ; physiopathology ; Hemodynamics ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Pulse

Objective To evaluate the clinical efficacy and safety of edaravone combined with butylphthalide in treatment of acute cerebral ischemic stroke.Methods Eighty-three patients with acute cerebral ischemic stroke in the department of neurology of the Leqing People′s Hospital. And the included 83 cases were randomly divided into treatment group ( n =40 ) and control group ( n =43 ) . All of the included patients were underwent treatment of anti -platelet and depressurization.Patients in the control group were also treated with edaravone 30 mg+0.9%sodium chloride 100 mL intravenous transfusion bid ×14 d. And patients in the treatment group were administered butylphthalide 200 mg po, tid ×14 d. After treatment, the clinical efficacy and neurological function between the two groups were evaluated. Results The total clinical efficacy was not statistical significant (82.50% vs 76.74%) between the two groups ( P>0.05) , but the treatment group had the trend of higher compared to control group.The neurological score of the two groups were all improved significantly (P<0.05).And the treatment group was superior to control group (P<0.05).The adverse incidence rate were 10.00% and 4.65% in the treatment and control group respectively with no statistical different (P>0.05).ConclusionEdaravonecombinedwithbutylphthalideintreatmentofacutecerebralischemicwas effective and safe.

OBJECTIVETo study erythrocyte oxidative stress status and its association with left to right shunt congenital heart disease (CHD) in children.

METHODSA total of 31 children with left to right shunt CHD were enrolled, including 7 cases of atrial septal defect (ASD), 12 ventricular septal defect (VSD), 4 patent ductus arteriosus (PDA), 6 patent foramen ovale (PFO), and 2 complete endocardial cushion defect. Twenty healthy age-matched (1 month to 3 years old) children severed as the control group. The contents of superoxide dismutase (SOD) and malonaldehyde (MDA) in erythrocytes were determined using ELISA. ESR was measured by Westergen. PaO(2) and PaCO(2) were measured by Blood Gas Analyzer (GEM Premier 3000).

RESULTSThe MDA content in erythrocytes in the CHD group was significantly higher, in contrast, SOD content was significantly lower than that in the control group (P<0.05). The CHD children with heart failure had more decreased SOD and more increased MDA contents compared with the control group (P<0.01). The SOD level was the highest in the PFO group and was the lowest in the complete endocardial cushion defect group. The SOD level in the PFO group was significantly higher than that in the ASD, VSD and complete endocardial cushion defect groups (P<0.05). The MDA level was the highest in the VSD group and was the lowest in the complete endocardial cushion defect group. There were significant differences in the MDA level among CHD subgroups (P<0.05). The ESR was negatively correlated to the SOD level (r=-0.191, P<0.05), while positively correlated to PaO(2) level in CHD children (r=0.216, P<0.05). There was a negative correlation between SOD and MDA levels (r=-0.312, P<0.05).

CONCLUSIONSOxidative stress exists in children with left to right shunt CHD. The SOD and MDA contents in erythrocytes can be used as markers for the assessment of severity of the disease.

Blood Gas Analysis ; Blood Sedimentation ; Child, Preschool ; Erythrocytes ; metabolism ; Female ; Heart Defects, Congenital ; metabolism ; Humans ; Infant ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; Superoxide Dismutase ; blood

BACKGROUNDCortical spreading depression can cause migraine attack, and up-regulate matrix metalloproteinase-9 (MMP-9) expression in animal. This study aimed to determine the impact on the structure and function of the blood-brain barrier by measuring plasma MMP-9 levels in patients at the acute and late stages of migraine attacks in order to elucidate the pathological mechanisms involved.

METHODSWe recruited a case-control cohort of 38 adult migraine patients and 20 age- and gender-matched healthy control subjects. Five milliliter blood samples were collected at the acute and late stages of migraine (days 1 - 7), and also from the control subjects. Solid phase double antibody sandwich enzyme-linked immunosorbent assay was used to determine plasma MMP-9 levels. Statistical analysis was performed using the SAS version 9.1.

RESULTSInitial plasma MMP-9 levels of migraine patients were significantly higher than those of controls ((12.612 ± 0.016) µg/L vs. (6.069 ± 0.023) µg/L, respectively, P < 0.05). High MMP-9 expression was observed during days 1 - 6 of migraine attacks, with highest expression occurring on day 3 ((17.524 ± 0.035) µg/L). During attacks, MMP-9 levels were similar in migraine patients with and without aura (P > 0.05); in addition, levels were not correlated with degree of headache pain (P > 0.05).

CONCLUSIONSWe hypothesize that migraine could lead to increased plasma MMP-9 levels resulting in blood-brain barrier damage. MMP-9 levels increase during days 1 - 6 of migraine attacks, peaking on day 3. Therefore, MMP-9 could be used as a biological marker to guide treatment of migraine attacks.

Adult ; Blood-Brain Barrier ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Migraine Disorders ; physiopathology ; Young Adult

Objective:To investigate the risk factors of lymph node metastasis for patients with colorectal cancer in T 3 and T 4, and to provide a reference for clinical diagnosis and treatment. Methods:The clinicopathological data of 1 112 patients with colorectal cancer in T 3 and T 4 who underwent radical resection of colorectal cancer in Xijing Digestive Disease Hospital from January 2008 to December 2017 were retrospectively analyzed. The correlation between lymph node metastasis status and the clinicopathological factors as well as tumor markers was analyzed. The related risk factors of lymph node metastasis were analyzed by using logistic multivariate regression analysis. Results:Univariate analysis showed that there was no statistically significant difference in the incidence of lymph node metastasis among colorectal cancer patients stratified by gender, age and tumor location (all P > 0.05). The different tumor diameter [<5 cm and ≥5 cm: 37.75% (211/559), 52.26% (289/553), χ2 = 23.666, P < 0.01], general type [infiltration, ulcer, parasol, bulge: 37.04% (20/54), 47.52% (432/909), 34.33% (23/67), 69.51% (57/82), χ2 = 13.787, P = 0.003], degree of differentiation [highly-differentiated, moderately-differentiated, poorly-differentiated: 34.11% (102/299), 49.00% (317/647), 48.80% (81/166), χ2 = 19.771, P < 0.01], mismatch repair deficiency (dMMR) [yes and no: 26.34% (64/243), 50.17% (436/869), χ2 = 43.996, P < 0.01], neurological invasion [yes and no: 48.17% (421/874), 33.20% (79/238), χ2 = 16.954, P < 0.01], vascular invasion [yes and no: 79.16% (338/427), 23.65% (162/685), χ2 = 327.493, P < 0.01] and preoperative carcino-embryonic antigen (CEA) [positive (≥5 mg/ml) and negative (<5 mg/ml): 52.87% (249/471), 39.16% (251/641), χ2 = 20.162, P < 0.01] and CA199 [positive (≥35 U/ml) and negative (<35 U/ml): 59.33% (124/209), 41.64% (376/903), χ2 = 21.465, P < 0.01] had statistically significant differences in the incidence of lymph node metastasis for above stratified patients. Logistic multivariate regression analysis showed that vascular invasion and preoperative CA199-positive were independent risk factors for lymph node metastasis in patients with colorectal cancer in T 3 and T 4 ( OR = 13.006, 95% CI 9.329-17.276, P < 0.01; OR = 2.194, 95% CI 1.513-3.181, P < 0.01), and dMMR-positive was a protective factor for lymph node metastasis ( OR = 0.279, 95% CI 0.190-0.411, P < 0.01). Conclusions:Vascular invasion is the main risk affecting factor for the lymph node metastasis of patients with colorectal cancer in T 3 and T 4. The detection of preoperative tumor marker CA199 can be used as an index to predict the lymph node metastasis of patients with colorectal cancer in T 3 and T 4. To a certain extent, it can provide a reference for the diagnosis and treatment of patients with colorectal cancer in T 3 and T 4.