A panel study of associations between phenolic compound exposure and blood lipid levels / 环境与职业医学

Background Phenolic compounds, which are widely used as plasticizers, antibacterial agents, and preservatives in industrial production, have endocrine disrupting effects on humans. Previous epidemiological studies on the associations between phenolic compound exposure and blood lipids are mainly based on single measurement of spot urine samples, neglecting potential lag effects of phenolic compounds, and the conclusions are inconsistent. Objective To investigate the effects of short-term exposure to phenolic compounds at different lag days on blood lipid levels in adults. Methods We recruited 143 adults (43 males and 100 females) in Wuhan for three consecutive seasonal rounds of repeated visits: summer and autumn rounds of 2017 and winter of 2018. Morning urine samples were collected for four consecutive days during each round. A set of questionnaires were also distributed on the first day. Physical examinations and fasting venous blood sample collection were conducted on the fourth day. A total of 126 adults were included for analysis (340 person-time, 1251 urine samples). The concentrations of six urinary phenolic compounds [bisphenol A (BPA), bisphenol S (BPS), triclosan (TCS), methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP)] were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. Linear mixed-effect models (LMEs), multiple informant models, and generalized linear models were utilized to estimate the associations of urinary phenolic compounds at different lag days with total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and the ratio of TG to HDL-C (TG/HDL-C). Stratified analyses were conducted by selected characteristics. Results After covariate and multiple adjustments, the LMEs indicated that a change in urinary BPA at lag 0 day from the low concentration group (<LOD) to the high concentration group (≥LOD) was associated with a 16.48% (95%CI: 4.41%, 29.94%) increase in TG/HDL-C (P FDR<0.05), and this association was more pronounced in men (P interaction=0.028) and smokers (P interaction=0.040). In addition, a change in urinary TCS at lag 2 day from the low concentration group (<LOD) to the high concentration group (≥LOD) was associated with a 13.22% (95%CI: 3.73%, 23.56%) increase in TG (P FDR<0.05). The positive association of TCS with TG was more evident in subjects aged < 50 years (P interaction=0.037). No significant associations were found between urinary phenolic compounds at other lag days and blood lipids. Conclusion Short-term exposures to BPA and TCS are positively correlated with unfavorable changes in blood lipids in adults, and the association seem to be more pronounced in men, smokers, or individuals aged < 50 years.

Effect of Wumeisan on Gut Lactase Activity and Microflora Diversity of Mice with Dysbacteriosis Diarrhea / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wumeisan on gut lactase activity and microflora diversity of mice with dysbacteriosis diarrhea. MethodThe mice were randomly divided into 4 groups， namely， the normal group， the model group， and the low-dose and high-dose Wumeisan groups， with 8 mice in each group. The mouse model was made by gavage of mixed antibiotics for 7 d， and the low-dose and high-dose Wumeisan groups （5.98， 11.96 g·kg-1） were given gavage for 7 d continuously. The normal group and the model group were given the same volume of sterile water. The changes in the body weight， food intake， and diarrhea of mice were recorded. Feces were collected after the last administration， and the lactase activity was detected by the colorimetric method. The gut microbiota changes were detected by the 16S rRNA high-throughput sequencing technology. ResultCompared with those in the normal group， the mice in the model group had dilute and soft stools， reduced body mass， reduced food intake， reduced lactase activity， significantly reduced intestinal flora diversity， and significant changes in the relative abundance phylum and genus levels of flora. Compared with the model group， Wumeisan reduced the diarrhea rate of mice， promoted the rapid recovery of body weight and food intake， increased the lactase activity decreased by antibiotic， improved the community abundance and diversity of mice with dysbacteriosis， and made the species composition closer to that in the normal group. The abundance of three phyla （Bacteroidota， Proteobacteria， Verrucomicrobiota） and nine genera （Odoribacter， Enterococcus， Clostridium innocuum group， etc.） of mice with diarrhea were regulated by Wumeisan. Among them， norank f Muribaculaceae， norank f norank o Clostridia UCG-014， Lachnospiraceae NK4A136 group， and Odoribacter showed significant positive correlation with the body weight and lactase activity， and Escherichia-Shigella， Enterobacter， Enterococcus， and Clostridium innocuum group showed significant positive correlation with the diarrhea rate. Function prediction showed that the high-dose Wumeisan significantly reseted 6 functional levels of metabolism， genetic information processing， and human diseases， and had positive effects on endocrine and metabolic diseases， immune diseases， infectious disease， and parasitic infectious diseases. ConclusionWumeisan can relieve the symptoms of dysbacteriological diarrhea by increasing the lactase activity and regulating the gut microbiota composition.

Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

Study about target-network of anti-cerebral infarction neuropathy based on theory of neurovascular unit and network pharmacology / 中国中药杂志

<p><b>OBJECTIVE</b>Potention drug-targets on anti-neuropathy of stroke were summarized, and it will provide materials for developing innovation components traditional Chinese medicine on anti-cerebral infarction neuropathy.</p><p><b>METHOD</b>This article had done a series of researching work about neurovascular unit which includes three kinds of cells: neuron, gliacyte,brain microvascular endothelial cell, then signal mechanism of cell death or apoptosis of each section of stroke neuropathy was analysised by the historical documents.</p><p><b>RESULT</b>There are five important pathways: inflammatory factor-MMPs pathway- Caspases, Ca2+ -mitochondrial pathway-Caspases, Ca2+ -Phospholipase-PI-3K/AK pathway, Ca2+ -radical-MAPK pathway, Ca2+ -NO-protease pathway, among all the nodes, Caspases, Ca2+, NO were the most important ones.</p><p><b>CONCLUSION</b>Developing the multi-mechanism and multilevel of traditional chinese medicine under the guidance of the theories of network pharmacology and neurovascular unit will play an important role in studying the key links of signal-network of stroke neuropathy.</p>

Application of network pharmacology and high through-put technology on active compounds screening from traditional Chinese medicine / 中国中药杂志

<p><b>OBJECTIVE</b>To solve the difficult in the active compounds screening from traditional Chinese medicines (TCM).</p><p><b>METHOD</b>According to preliminary lab results and related literature, systematic analysis of the high-throughput technology was made.</p><p><b>RESULT</b>Technologies of rapid preparation, high-throughput screening and biochip, together with the thought of drug target network, will contribute to TCM research on active ingredients screening, toxic components exclusion and molecular mechanisms. They are key technologies and ideas for modernization of TCM and research of TCM network pharmacology.</p><p><b>CONCLUSION</b>High throughput technology and network pharmacology-related technologies will provide new ideas and key methods for active compounds screening from TCM.</p>

Research of Teaching Acupuncture and Massage Elective Course in College of Western Medicine / 中华医学教育探索杂志

At present,there are some problems about teaching acupuncture and massage elective course in colleges of western medicine,which are caused by student's specialty,thinking mode and the teaching material of elective course.To improve the quality of the teaching in acupuncture and massage,it is necessary to reorientate the teaching intention,adjust the course plan.