Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

【Objective】 To develop a new approach for the preparation of 0.7~0.8 hematocrit concentrated washed red blood cells(RBCs) for fetal anemia in utero transfusion and apply it in clinical. 【Methods】 The erythrocyte suspension and frozen stored erythrocytes within expiry date in Guangzhou Blood Center from March 2020 to February 2021 were taken to prepare concentrated washed RBCs. According to the derivation formula, corresponding weight of RBC preservation solution was added to obtain 0.7~0.8 hematocrit concentrated washed RBCs. Routine blood test data were statistically analyzed by single-sample t test, and P<0.05 was considered statistically significant. Qualified Rh-negative/ O-type 0.7~0.8 hematocrit concentrated RBCs within expiry date were used in clinical intrauterine blood transfusion. 【Results】 The hematocrit of concentrated washing RBCs prepared by the new approach could reach 0.7~0.8. The RBCs count (8.389 ±0.808)×1 0¹²/ L and hemoglobin content(233.730±15.498)g/L were higher while the erythrocyte count (0.732±0.469)×10⁹ /L and platelets count(26.000±26.276)×10⁹/L were lower than the normal values of adults. The mean erythrocyte volume(fL), hemoglobin content(pg) and concentration(g/L )were 88.123±6.359, 30.004±2.809 and 339.980±11.865, respectively, which were normal values of adults. Fetal anemia was significantly improved and the prognosis was good after intrauterine blood transfusion. 【Conclusion】 The 0.7~0.8 hematocrit concentrated washed RBCs prepared by the new approach is consistent with the special blood requirements during fetal anaemia transfusion, meets the clinical treatment standards, and can be applied in clinical.

Objective To investigate the number and distribution of dendritic cells in normal endometrium of reproductive age during the normal menstrual cycle .Methods Normal endometrial samples were collected from 40 women of reproductive age . 20 endometrium samples at the proliferative phase (day 6th to 10th) and 20 endometrium samples at the window of implantation(day 20th to 24th) were obtained .These patients underwent intrauterine exploration before IVF and ET resulting from tubal resec-tion or male factor infertility .Endometrial tissue was collected with a pipelle aspirator .Sections were stained with hematoxylin-eosin (HE) to identify the morphological characteristics of endometrial tissues .The Envision two-step immunohistochemical staining technique was used to detect the expression of CD1a and CD83 in the endometrium .Normal human skin and tonsil were used as pos-itive control tissues for CD1a and CD83 ,respectively .The serum levels of ovarian steroid hormones were measured to analyze their relationship with the expression of CD1a and CD83 .Results CD1a + DCs were found in all samples of window of implantationand most samples of the proliferative phase (18/20 ,90% ) .DCs showed irregular shape with different processes and were buffy in cell membrane ,mainly in stroma around grand and blood vessels .The density of CD1a + DCs at the window of implantation were (18 .2 ± 5 .76)cells/mm2 ,significantly higher than that at the proliferative phase [(6 .5 ± 4 .05)cells/mm2 ,P < 0 .05] .CD83 was considered as the marker for mature DCs .However ,immunohistochemistry with specific antibody revealed no CD83 + DCs were found in human emdometrium in the present study .During the menstrual cycle ,the expression of CD1a+ DCs in endometrium (the density of CD1a + DCs) correlated with serum progesterone level(r= 0 .630 ,P< 0 .01) .Serum estradiol showed no correlation with the density of CD1a + DCs(P> 0 .05) .Conclusion Increased CD1a+ immature DCs at the window of implantation in endometri-um may play an important role in the establishment of maternal-fetal tolerance .

Aiming at evidence-based medicine course of graduate students, foreign medical colleges and universities usually took in the teaching philosophy that emphasized stages (focusing on knowledge ac-cumulation) and practicality (focusing on ability training). And they put forward a lot of teaching methods which implemented the conception, such as problem-based learning, journal club, blended learning approach, online learning platform, concept mapping etc. In order to provide a useful reference for the domestic teaching reform and development, this paper introduced the teaching philosophy and related teaching meth-ods mentioned above.

Objective:To compare the differences of children’ s health in different area, and to confirm if the prevalence of respiratory diseases and symptoms among children are closely associated with the air pollution. Methods:A cross-sectional study was conducted in an urban area A and a suburban area B with different levels of air pollution in Beijing. Using a cluster sampling method, we recruited 4 564 chil-dren from 3 primary schools in urban A and 4 primary schools in suburban B. Respiratory symptoms were investigated using an international standardized questionnaire including characteristics of children, living conditions, respiratory diseases and symptoms and situation of parents. The concentrations of air pollu-tants for recent five years were obtained from Reports on the Quality of the Beijing Environment. SPSS 16. 0 was used to analyze data. Results: The prevalence of cough, persistent cough, phlegm, persistent phlegm, wheeze and asthma in A area were higher than those in B area[(62. 2% vs. 59. 9%), (6. 3%vs. 3. 1%), (42. 4% vs. 37. 4%),(3. 6% vs. 2. 4%),(13. 3% vs. 9. 9%) and(9. 5% vs. 5. 4%)]. Except for cough, cough with cold, cough without cold, the prevalence of respiratory diseases and symp-toms in A area were significantly higher than those in B area ( P <0 . 05 ) . Logistic regression analysis showed the prevalence of persistent cough, phlegm without cold, asthma in A area were significantly higher than those in B area ( P<0 . 05 ) . Conclusion:Respiratory diseases and symptoms among school-age children were closely associated with the level of air pollution.

Purpose The diagnosis, treatment and prognosis of benign and malignant biliary stricture are significantly different. This study aims to evaluate the quantitative analysis of biliary structures using magnetic resonance cholangiopancreatography (MRCP) combined with dynamic contrast enhanced CT (DCE-CT).Materials and Methods The quantitative parameters of MRCP and DCE-CT imaging data from 27 patients with benign biliary stricture (benign group) and 30 patients with malignant biliary stricture (malignant group) were retrospectively analyzed. The wall thickness, stricture length and diameter, proximal ductal dilatation and degree of enhancement in two groups were compared, and its correlation was analyzed to evaluate the accuracy of MRCP and DCE-CT.Results There were significant differences in wall thickness [(3.2±2.0) mmvs (2.1±0.6) mm], stricture length [(15.8±8.1) mmvs (9.5±6.5) mm] and diameter [0 mmvs (2.0±0.9) mm], proximal ductal dilatation and the degree of enhancement [(12.7±3.6) mmvs (9.3±2.7) mm] between the two groups (t=2.825, 3.270, 4.025,P<0.001;Z=-3.909,P<0.001). Multivariable stepwise regression analysis showed that the wall thickness and diameter, and the CT HU in portal venous and equilibrium phases combined with CT plain scanning were significant predictors of malignant biliary strictures (t=-6.424-2.309,P<0.05). The sensitivity, specificity, inter-modality agreement and Youden index of MRCP and DCE-CT in diagnosing 57 patients with biliary stricture were 96.67%, 100.00%, 98.25% and 0.97, respectively; with statistical significance in predicting benign and malignant biliary stricture (AUC=0.994,P<0.001).Conclusion Using MRCP and DCE-CT, the wall thickness and diameter of the stricture, and the difference in CT HU in portal venous and equilibrium phases combined with CT plain scanning are valuable in differential diagnosis of benign and malignant biliary stricture.

Aim To investigate the expression of CD31 , CD105 , HIF-1αand VEGF in xenografts tumor of HT-29 tumor cells during different stages of growth. Methods HT-29 tumor cells were transplanted into nude mice, the tumor was removed when the tumor volumes reached <100 mm3 , 100 ~300 mm3 and >300 mm3 respectively. Immunochemical method was a-dopted to detect the expression of CD31 , CD105 , HIF-1α and VEGF. Results HT-29 xenografts tumor vol-umes <100 mm3 , 100 ~300 mm3 , and >300 mm3 showed expressions with CD31-MVD at 37.40±4.17 , 18.80±1.72 and 14.20±2.23 respectively; CD105-MVD at 22.80 ±3.54 , 15.60 ±1.35 and 10.20 ±2.48; positive expression rate of VEGF was 26.20%
±0.83%,40.73% ±6.29% and 13.41% ±1.20%respectively; while positive expression rate of HIF-1αwas 3.20% ± 2.97%, 11.89% ± 1.94% and 80.62% ±3.47% respectively. On the other hand, for different volumes group, CD31-MVD, CD105-MVD, VEGF and HIF-1αexpression ratios had signifi-cant differences ( P <0.01 ) . Conclusions The ex-pression of MVD and vascular-related factors within the tumor caused by HT-29 xenografts tumor in nude mice at different growth stages was varied. There was a cer-tain correlation between tumor volume and MVD, VEGF, HIF-1α.