Objective To construct an active targeting drug delivery system‐polymer vesicles(PVs), and examined the cellular uptake. Methods Maleimide‐ polyethylene glycol‐poly(lactic‐co‐glycolic acid)(MAL‐PEG‐PLGA)was used as carrier materials to prepare PVs by self‐assembling. And then PVs was modified by Tf and Tet‐1(Tf/Tet‐1‐PVs). To evaluate its ac‐tive targeting, coumarin‐6 was used as a fluorescent probe to analyze cellular uptake of PVs for both BCEC and Neuro‐2a cells. Results PVs was about 80 nm with rounded shape and had obvious film structure. Tf/Tet‐1‐PVs exhibited a significant role in promoting cellular uptake for both BCEC and Neuro‐2a cells compared with control and single ligand‐modified group. Conclusion PVs modified with dual ligands could promote the cell uptake for both brain capillary cells and nerve cells.

Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar.Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively;co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release.Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm;transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1∶1;the nanoparticles released slowly in vitro.Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.

Objective To investigate the subtle changes of the brain function at olfactory region of MD patients with olfactory dysfunction at resting state, through the application of fMRI-BOLD. Methods This study enrolled 28 MD patients with olfactory dysfunction(Case group) who had been treated from February 2016 to March 2017, and 23 healthy volunteers (Control group) with matching gender, age and education background to the Case group.All subjects were examined by Symptoms Checklists-90(SCL-90), Hamilton Depression Rating Scale-24 (HAMD-24), 70% isopropyl alcohol inhalation test, and fMRI at resting state. The two independent samples t test was used to compare the two groups' educational years, psychological scales and olfactory test scores.Regional homogeneity(ReHo)analysis was conducted for the whole brain of subjects.The ReHo values at some brain regions of both groups were compared through two independent sample t-test.The ReHo values,extracted from the case group's brain regions with differences, were run through by Pearson correlation analysis.Results There was a negative correlation between the HAMD-24 score(r=-0.413,P=0.029)and the severity of olfactory decline in the MD patients with olfactory dysfunction.In addition,it was found by fMRI that Case group,as compared to Control group,demonstrate declined ReHo values at left orbital frontal gyrus(cluster=80,t=3.27),bilateral cingulate gyrus(right cluster=204,t=4.34,left cluster=204,t=3.63),bilateral middle frontal gyrus(right cluster=56,t=3.67,left cluster=28, t=3.50),rightinsular(cluster=40,t=3.53),bilateral amygdala(right cluster=76,t=3.66,left cluster=86,t=2.93),but increased ReHo values at bilateral inferior frontal gyrus(right cluster=44,t=3.62,left cluster=33,t=3.25), right thalamus(cluster=34, t=3.21)and bilateral gyri rectus(right cluster=45,t=3.78,left cluster=24,t=3.01)(AlphaSim correction,P<0.001).Moreover,there was a positive correlation between the ReHo value at left orbital frontal gyrus and the olfactory test distance(r=0.628,P<0.05).But the ReHo value at left orbital frontal gyruswas negatively correlated with HAMD-24 (r=-0.414,P=0.029). There was no correlation with other clinical data.Conclusion The abnormal brain functional activities of left orbital frontal gyrus at resting state might be related to the olfactory dysfunction of patients with depression.

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

Objective To investigate the characteristics of the adverse drug reaction (ADR) in the traditional Chinese medicine (TCM) treatment followed the "COVID-19 Diagnosis and Treatment Program (trial version 7)" during the medical observation period, and to provide a guideline for rational clinical drug use. Methods 9 TCM induced ADR were collected from CNKI, Wanfang database and PubMed. Statistical analysis was conducted on gender, age, occurrence time, involved system/organ, treatment, outcome and relevance evaluation. Results 61 literatures were collected according to the inclusion and exclusion criteria with 70 cases and 5 TCM prescriptions. There was no significant bias in gender. The age span was large. Most ADR occurred within 1 day after administration. The involved systems/organs are extensive, mainly on the skin and its accessories. The most common therapeutic drugs were antihistamines and steroids, and other medications are mainly for symptom treatment. The turnaround time was 1 h in most cases (47%). Conclusions During the observation period, the incident population was widely distributed and there was no obvious characteristics. Medication monitoring should be reinforced to reduce the ADR incidence.

Based on the data from the -, the bibliometric analysis was applied to analyze and evaluate the literature regarding clinical research of acupuncture for ophthalmopathy published between 1954 to 2016, hoping to objectively reflect the disease spectrum and indication of acupuncture for ophthalmopathy. The results showed that the disease spectrum of acupuncture for ophthalmopathy involved 47 specific diseases in 13 types of diseases. The total number of cases was 176 469, and the number of effective cases was 160 662, and the effective rate was 91.0%. The indication of acupuncture for ophthalmopathy included myopia, blepharoptosis and conjunctivitis. The commonly used indications were strabismus, dry eye and ophthalmoplegia, and the secondary indications were optic atrophy, blepharoptosis, oculomotor paralysis, blepharospasm, amblyopia. The most commonly used acupuncture points for ophthalmopathy were Cuanzhu (BL 2), Jingming (BL 1), Taiyang (EX-HN 5), and the most commonly used auricular points were yan (LO), gan (CO) and shen (CO). As for the methods of acupoint combination, local acupoints were mainly selected, combined with distal acupoint to assist treatment.

Objective To explore the anti-inflammatory and hepatoprotective mechanism of Shuganning injection through establishing the active ingredients-targets network and protein interactions network. Methods The main active ingredients of Artemisiae scopariae, Fructus gardenia, Radix scutellariae, Radix isatidis and Ganoderma in Shuganning injection were obtained by TCMSP; GeneCards and OMIM were used to screen the hepatitis-related targets among the corresponding targets of the active ingredient of Shuganning injection; The Cytoscape software was used to construct the active ingredient-targets network of Shuganning injection. The protein interactions network was constructed using the String database and Cytoscape software. The GO and KEGG pathways involved in the targets were analyzed by DAVID database. Results The results showed that 20 active ingredients and 83 targets of Shuganning injection were involved. GO analysis showed that Shuganning injection mainly affected the regulation of cellular processes and biological processes, as well as the response to chemical stimulation and stress. KEGG pathway analysis showed that the targets of the anti-inflammatory and hepatoprotective effect of Shuganning injection mainly involved in signaling pathways such as TNF, IL-17, and MAPK. Conclusion The anti-inflammatory and hepatoprotective effect of Shuganning injection have the characteristics of multiple components, multiple targets and multiple pathways, which may play a role by regulating pathways such as TNF、IL-17 and MAPK .

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.