Objective:To explore the mechanism of Eucommiae Cortex- Epimedii Folium herbal pair in the treatment of osteoporosis through network pharmacology, molecular docking, and molecular dynamics methods. Methods:Search the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and relevant literature to screen the active compounds of Eucommiae Cortex- Epimedii Folium herbal pair. Using TargetNet, SwissTargetPrediction, and STITCH databases to predict the target of active compounds. GeneCards, OMIM, TTD and DisGeNET databases were used to screen the related targets of osteoporosis, and the intersection targets were obtained by Venny 2.1.0 online tool. Using STRING database for protein-protein interaction (PPI) network analysis. Construct a network diagram using Cytoscape 3.8.2 software and perform network feature analysis to determine key targets and core compounds. Using R 3.6.3 software for gene ontology (GO) functional annotation and Kyoto Encyclopedia of genes and genomes (KEGG) signaling pathway analysis. Apply SYBYL-X 2.1.1 software to perform molecular docking between core compounds and key targets, and use GROMACS 2021.6 software for molecular dynamics simulation. Results:Totally 47 active compounds, 329 targets related to compounds, 4 604 targets related to osteoporosis, and 210 intersecting targets of Eucommiae Cortex- Epimedii Folium herbal pair were selected. Network feature analysis showed that luteolin, quercetin, kaempferol, caffeic acid, chryseriol, and pinoresinol were core compounds, while protein kinase B1(Akt1), interleukin-6 (IL-6), steroid receptor coactivator (Src), cysteinyl aspartate specific proteinase-3 (CASP3), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 8 (MAPK8), and JUN were key targets. GO analysis showed that biological process (BP) mainly involve cellular hormone metabolism, intracellular receptor signaling pathways, oxidative stress responses, hormone metabolism processes, etc. Cell component (CC) mainly involved membrane rafts, membrane microregions, membrane regions, transcription factor complexes, etc. Molecular function (MF) mainly involved nuclear receptor activity, transcription factor activity, steroid hormone receptors, hormone binding, etc. KEGG analysis showed that the signaling pathways of Eucommiae Cortex- Epimedii Folium herbal pair in the treatment of osteoporosis mainly included osteoclast differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking showed that the core compounds could accurately bind to the active sites of key target proteins, and molecular dynamics analysis further verified the binding stability between the core compounds and key target proteins. Conclusions:The combination of Eucommiae Cortex- Epimedii Folium herbal pair has the characteristics of multiple components, targets, and pathways in the treatment of osteoporosis, laying a theoretical foundation for its clinical use.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To develope and analyze and optimize the performance of some kinds of environmentally friendly flexible X-ray protective materials in attempt to tackle the various environmental and high energy consumption problems in the development of traditional medical X-ray protective clothing.Methods:The Monte Carlo program was used to establish a simplified model of medical X-ray tube. The aim was to carry out numerical simulation and prediction of the shielding materials′ performance against X-ray, prepare the flexible X-ray shielding materials through experiments and test and verify the their shielding performances The development and optimization path was also obtained by comparing the result between simulation and experiment.Results:Bi was the preferred alternative to toxic Pb elements, while W was able to compensate for weak X-ray absorption zone of Bi. The shielding efficiency of the composite material doped with 25% Bi+ 25% W was able to reach 77.8% and 66.3% at 80 and 120 kV p tube voltages, respectively. Conclusions:With both the selection of elements and the optimization of functional particles, the combination of W and Bi is an economical, environmentally friendly, and efficient shielding way within the energy range of medical diagnostic X-rays. The numerical simulation helps reduce experimental costs, shorten the research period, and improve the design efficiency of X-ray shielding materials.

Organophosphorus flame retardants (OPFRs) pollution and its impacts on human health are of global concern. The review briefly reviewed the current state-of-knowledge on exposure assessment and epidemiological evidence of OPFRs-related health effects. Specifically, this paper provided an overview and comparison of the levels of respiratory and gastrointestinal exposure to OPFRs and their body burden in different populations worldwide; summarized potential adverse effects of long-term low-level OPFRs exposure on children's neurodevelopment, adults' reproductive system, and thyroid function. Available epidemiological studies have revealed that the OPFRs exposure level of Chinese population is low, and rice consumption may be a potential source of exposure to OPFRs; OPFRs such as tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl) phosphate (TCEP) have both neurotoxicity and reproductive toxicity, and possibly affect the thyroid function in adults and increase the risk of wheezing and eczema in children. Finally, the future research focus on population exposure and health effects of OPFRs was prospected.

Objective:To explore the mediating effect of meaning in life between family care and subjective well-being of family caregivers of community disabled elderly, and provide reference for improving caregivers' mental health.Methods:From August 2019 to August 2020, A total of 526 family caregivers of disabled elderly from several communities in Guangzhou were household surveyed by general information questionnaire, family APGRA index, Chinese meaning in life questionnaire and general well-being schedule.SPSS 22.0 software was used for descriptive analysis, correlation analysis and mediating effect analysis.AMOS 22.0 software was used for structural equation model construction, and Bootstrap method was used for mediation effect test.Results:The score of subjective well-being, family care, meaning in life of family caregivers of disabled elderly were (69.41±19.17), (6.42±2.56), (42.96±7.61), respectively.The family care was positively correlated with meaning in life and subjective well-being ( r=0.275, 0.289, both P<0.01) and a positive correlation was found between meaning in life and subjective well-being ( r=0.345, P<0.01). Meaning in life had a partial mediating effect between family care and subjective well-being.The mediating effect value was 4.304, accounting for 30.6% of the total effect value. Conclusion:The family care can directly or indirectly affect caregivers' subjective well-being through meaning in life.

Objective:To explore the status of post-traumatic growth and meaning in life among family caregivers of the disabled elderly in the community, and to analyze the correlation between the two.Methods:From August 2019 to August 2020, convenience sampling was used to select 560 family caregivers of the disabled elderly in the community of Guangzhou as the research object. The General Information Questionnaire, Posttraumatic Growth Inventory (PTGI) and the Chinese Meaning in Life Questionnaire (C-MLQ) were used for the investigation. Pearson correlation and hierarchical regression were used to analyze the correlation between post-traumatic growth and meaning in life in family caregivers of the disabled elderly. A total of 560 questionnaires were distributed, and 526 valid questionnaires were recovered after excluding incomplete questionnaires and answering questionnaires according to a certain rule.Results:The total scores of PTGI and C-MLQ of 526 family caregivers of the disabled elderly were (49.43±20.43) and (42.96±7.61) , respectively. The total score of PTGI and the scores of each dimension were positively correlated with the total score of C-MLQ and the two dimensions of meaning experience and meaning pursuit ( P<0.01) . The hierarchical regression showed that, after controlling for general data, both meaning experience and meaning pursuit could positively predict post-traumatic growth. Conclusions:Post-traumatic growth of family caregivers of disabled elderly is at low level. Family caregivers' meaning in life has a positive effect on post-traumatic growth. Community workers should strengthen the meaning in life education, help caregivers to effectively cope with traumatic events, improve the level of post-traumatic growth, and promote mental health.

OBJECTIVE：To es tablish a method for the content determination of heavy metals [lead （Pb），cadmium（Cd）， copper （Cu）， mercury （Hg）] and harmful elements [arsenic （As）] in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules. METHODS ：The samples were conducted pretreatment by microwave digestion instrument and determined by inductively coupled plasma mass spectrometry （ICP-MS）using elements germanium ，indium，bismuth as internal standard. RESULTS ：The linear ranges of Pb ，As，Cu，Cd and Hg were 1-20，0.5-10，5-100，0.5-10 and 0.2-4 ng/mL， respectively （all r＞0.997）. The limits of detection （LODs） were 0.041 1，0.013 2，0.057 3，0.009 0，0.005 4 ng/mL， respectively. The limits of quantification （LOQs）were 0.137 0，0.044 0，0.191 0，0.030 0，0.018 0 ng/mL，respectively. RSDs of precision and repeatability tests were all less than 6％. RSDs of stability tests （28 h）of Pb ，As，Cu and Cd were all less than 5％， and that of stability test （28 h）of Hg was less than 7％. The average recoveries were 89.44％（RSD＝5.87％，n＝9），99.56％ （RSD＝5.46％ ，n＝9），96.12％（RSD＝4.62％ ，n＝9），105.82％（RSD＝2.80％ ，n＝9）and 90.23％（RSD＝3.59％ ，n＝9）， respectively. Five elements were all detected in 63 batches of samples ，and the contents of them were 0.191 0-1.527 6，0.002 5- 0.047 4，0.034 1-1.549 0，0.001 5-0.078 8 and 0.001 9-0.005 4 mg/kg，respectively. CONCLUSIONS ：The method is simple ， sensitive and accurate. It is suitable for simultaneous determination of 5 elements in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules.

OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.

Objective To retrieve,assess and summarize the best evidence on breast milk expression of premature infants' mothers in maternal separation so as to provide high-quality evidence for medical staff to carry out breast feeding guide. Methods Guidelines,systematic reviews,recommended practices and evidence summaries were retrieved in the UpToDate,WHO,Academy of Breastfeeding Medicine(ABM), Cochrane Library,Joanna Briggs Institute Library,Registered Nurses' Association of Ontario(RNAO), National Guideline Clearinghouse(NGC),PubMed,Embase,Chinese Biological Medicine,Chinese National Knowledge Infrastructure,WanFang data,VIP and the evidence-based nursing database of Fudan University from January 2008 to December 2018. Results A total of 7 literatures were included,two guidelines,one clinical decision,two systematic reviews and two evidence summaries. A total of 19 evidences were gathered in 7 aspects,such as training for medical staff,parents' education,selection of breast pump,preparation before expression,operational skills of breast expression,measures for increasing lactation and expression effects monitor. Conclusions Clinical medical staff should lay down the individualized nursing measures for maternal women to ensure breast milk collected as soon as possible,gain enough breast milk and fill the bill of growth and development of premature infants.

Objective To explore the effect of early supplemental parenteral nutrition on the outcomes of critically ill patients.Methods Totally 302 patients admitted in the intensive care unit (ICU) of Taizhou Hospital of Zhejiang Province from 2015 to March 2017 were enrolled and divided into two groups:the enteral nutrition group and the supplemental parenteral nutrition group.The clinical data of the two groups were retrospectively analyzed and the outcomes was compared between the two groups.Results The time of ICU stay,mechanical ventilation days,nosocomial infections in ICU and the rate of feeding intolerance were significantly lower in the supplemental parenteral nutrition group than in the enteral nutrition group (P＜0.05).There was no statistically significant difference in the mortality rate in 28 days between the two groups.Conclusion Supplemental parenteral nutrition has many advantages like reduce the duration of ventilation,ICU stay and the rate of feeding intolerance,and it does not affect the 28-day mortality rate of critically ill patients with NRS2002 score＞5,or increase the complication of infection.