At present, brain disease has become a "killer" in the field of general health, and the existence of blood-brain barrier has become one of the challenges in drug delivery into the brain. According to studies, cell membrane coating technique can endow nanoparticles with the characteristics of immune escape, long circulation, targeted delivery, and so on. Therefore, membrane biomimetic nanoparticles have been widely used in the field of disease treatment. Among them, the cell membrane derived from immune cells, tumor cells, and stem cells can cross the blood-brain barrier through the transcellular pathway and cell bypass pathway, which is used to prepare biomimetic membrane nanoparticles to break through the blood-brain barrier to achieve the treatment of brain diseases. What's more, the brain targeted ability of biomimetic nanoparticles would be further enhanced by modifying the cell membrane with peptides. This paper introduces the preparation methods of membrane biomimetic nanoparticles, expounds in detail the way that cell membrane coated nanoparticles break through the blood-brain barrier and achieve efficient intracerebral drug delivery. It also summarizes the prospects and challenges of this novel drug delivery system in the treatment of brain diseases, providing a reference for the research of membrane biomimetic nanoparticles in the treatment of brain diseases.

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7β-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7β-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7β-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).
Cornus/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Iridoids ; Wine

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: Prior pulmonary tuberculosis (PTB) on chest X-ray (CXR) was commonly found in infertile patients receiving examinations before Method: We conducted a retrospective cohort study of 14,254 infertile patients who had received IVF-ET at Peking University Third Hospital in 2017. Prior PTB was defined as the presence of signs suggestive of old or inactive PTB on CXR, with or without a clinical TB history. Patients who had prior PTB on CXR but had not received a clinical diagnosis and anti-TB therapy were included for analysis. Live birth, clinical pregnancy, and miscarriage rates were compared between the untreated PTB and non-PTB groups. Results: The untreated PTB group had significantly lower clinical pregnancy (31.7% Conclusions Untreated PTB was associated with adverse pregnancy outcomes after IVF-ET, especially in patients with unexplained infertility, highlighting the clinical significance of PTB in this specific patient population.
Abortion, Spontaneous/epidemiology* ; Adult ; China/epidemiology* ; Embryo Transfer/statistics & numerical data* ; Female ; Fertilization in Vitro/statistics & numerical data* ; Humans ; Infertility, Female/etiology* ; Live Birth/epidemiology* ; Middle Aged ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology* ; Pregnancy Outcome/epidemiology* ; Radiography, Thoracic ; Retrospective Studies ; Tuberculosis, Pulmonary/epidemiology* ; Young Adult

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.
Analgesics/pharmacology* ; Animals ; Anti-Inflammatory Agents/pharmacology* ; Drugs, Chinese Herbal ; Edema/drug therapy* ; Inflammation/genetics* ; Mice ; Oils, Volatile ; Plant Extracts

OBJECTIVE: To study the expression of B lymphocyte-induced mature protein-1 (BLIMP-1) in regulatory T cells (Tregs) of children with aplastic anemia (AA), and analyze its correlation with the number of Tregs and the levels of inhibitory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β in plasma. METHODS: The peripheral blood samples of 10 newly diagnosed AA children and 10 healthy children were collected for experiment. qPCR was used to detect FOXP3 and PRDM1 mRNA expression levels. Flow cytometry was used to detect the proportion of Tregs, the expression of BLIMP-1 in Tregs, and the levels of cytokines such as IL-2, IL-17A, IL-6, interferon (IFN)-γ, IL-10 and TGF-β in plasma. Pearson correlation model was used to evaluate the relationship between the expression of BLIMP-1 in Treg and the number of Tregs, as well as the levels of IL-10 and TGF-β in plasma. RESULTS: Compared with control group, the proportion of Tregs in peripheral blood of AA children was decreased significantly (P<0.001); The plasma levels of proinflammatory cytokines IL-2, IL-6 and IFN-γ in AA children were increased significantly (P=0.033, P=0.031, P=0.006), and IL-17A also was increased but the difference was not statistically significant (P=0.052), while anti-inflammatory cytokines IL-10 and TGF-β were significantly reduced (P=0.048, P=0.002). The relative expressions level of FOXP3 and PRDM1 mRNA in AA children were significantly lower than those in control group (P=0.037, P=0.016). The expression of BLIMP-1 protein in Tregs of AA children was significantly lower than that in control group (P<0.001). The expression level of BLIMP-1 protein in Tregs was positively correlated with the percentage of Tregs in lymphocytes (r=0.671, P=0.001), and was also positively correlated with the levels of IL-10 and TGF-β in plasma (r=0.500, P=0.029; r=0.486, P=0.030). CONCLUSION The expression of BLIMP-1 in Tregs of AA children is impaired, and the low expression of BLIMP-1 is related to the decrease of the number in Tregs and IL-10 and TGF-β expressions.
Anemia, Aplastic ; Child ; Cytokines ; Flow Cytometry ; Forkhead Transcription Factors ; Humans ; Positive Regulatory Domain I-Binding Factor 1 ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta

Objective:To observe the effect of Dredging Correcting Manipulation on cblC methylmalonic aciduria (MMA). Methods:From October, 2017 to October, 2018, 72 children with cblC MMA combined with growth retardation were divided into control group (n = 36) and experimental group (n = 36) according to the consent of their parents. The control group accepted routine medicine, and the experimental group received Dredging Correcting Manipulation in addition. The Griffiths Development Scale-Chinese version (GDS-C) was used to evaluate the two groups before and after treatment. At the same time, body length, body mass and head circumference were measured. Results:Six cases in the control group and five cases in the experimental group were dropped out. There was no significant difference in the development quotients of GDS-C in gross movement, personal and social, hearing and speech, hand-eye coordination, operation and total quotient between two groups before treatment (P > 0.05). After treatment, all the development quotients increased in both groups (t > 6.110, P < 0.001), and the development quotients of GDS-C in gross movement, personal and social, hand-eye coordination and total quotient were higher in the experimental group than in the control group (t > 2.154, P < 0.05), as well as the body length (t = 2.027, P < 0.05). Conclusion:Dredging Correcting Manipulation can promote the neuropsychological and physical development of children with cblC MMA combined with retardation.

Background: In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism. Methods: The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student’s t test, and comparisons among multiple samples were performed by oneway analysis of variance and a Bonferroni post hoc test. Results: The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286 ± 0.017 vs. 3.211 ± 0.034, t= 11.540, P < 0.0001) and cell lines (P < 0.01 in all BC cell lines). Besides, we also indicated that over-expression of miR-139-5p reduced the proliferation of ECV-304 (P = 0.001) and T24 cells (P = 0.005). Moreover, miR-139-5p over-expression weakened the invasion (P = 0.001) and migration (P = 0.001) of ECV-304 cells. Furthermore, the relative luciferase activity of CX43-wild type construct was distinctly lessened by up-regulation of miR-139-5p (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.916 ± 0.063 vs. 0.356 ± 0.048, t = 7.085, P = 0.002), nevertheless the activity of CX43-mutant type construct was untouched (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.918 ± 0.057 vs. 0.878 ± 0.039, t= 0.577, P = 0.595). Finally, the rescue assay revealed that CX43 deletion enhanced the depressor effect of miR-139-5p on ECV-304 cell proliferation (P < 0.01), invasion (P = 0.028), and migration (P = 0.014). Conclusion MiR-139-5p, as a tumor-suppressor, repressed cell proliferation, invasion, and migration in BC, which might be achieved by regulating CX43.