Autophagy often occurs after cells are attacked by oxidative stress, where damaged structures are phagocytic and degraded into nutrients, thereby reducing oxidative damage, promoting the survival of cancer cells and reducing the therapeutic effect of photodynamic therapy (PDT). However, excessive activation of autophagy can promote cell apoptosis. In this paper, the photosensitizer pyropheophorbide-a (Ppa) was used to produce a large amount of reactive oxygen species (ROS) to achieve the effect of killing cancer cells. At the same time, icaritin (Ica), an autophagy inducer, was used to over-activate autophagy, which transformed the protection of cancer cells into the promotion of cancer cell apoptosis, so as to improve the effect of photodynamic therapy. In this study, the interaction force between Ica and Ppa was exploited to successfully construct a self-assembled nanomedicine IP with good stability and high drug load. The synthesis method is simple, through using the drug itself as a carrier, and the loading capacity (LA) of Ica and Ppa can be increased to 83.53% and 16.45% without introducing potential biosafety risks of nanocarriers. Compared with free Ppa, self-assembled nanomedicine IP showed superior performance in cellular uptake and reactive oxygen species production. In addition, the self-assembled nanomedicine IP can reverse the protective autophagy induced by PDT by activating the autophagy of tumor cells, and facilitate apoptosis and antitumor coordination, which significantly improves the antitumor activity of PDT.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.
Angiogenesis Inhibitors/therapeutic use* ; Diabetes Mellitus ; Diabetic Retinopathy/drug therapy* ; Humans ; Intravitreal Injections ; Macular Edema/drug therapy* ; Pharmaceutical Preparations ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors/therapeutic use*

【Objective】 To investigate the expressions of ubiquitin-conjugating enzyme(UBE2) family and ubiquitin-conjugating enzyme E2T(UBE2T) gene and their relationships with the clinicopathology in lung adenocarcinoma. 【Methods】 Based on Linkedomics database, the expression levels of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA and their associations with the clinical characteristics of lung adenocarcinoma were collected and detected. Kruskal-Wallis H test was applied to compare the differences of pathologic stage, T stage and N stage, Wilcoxon rank sum test for M stage and Cox regression test for overall survival(OS). The expression profiles of UBE2T gene in lung adenocarcinoma and paracancerous tissues were obtained from the Cancer Genome Atlas(TCGA) database and then analyzed with independent samples t test. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway and the enrichment were examined by using Gene Set Enrichment Analysis(GSEA) software. 【Results】 The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA correlated with the clinicopathological features of lung adenocarcinoma. Compared with low UBE2T expression, high UBE2T expression predicted shorter OS time and advanced TNM stage. Their differences were statistically significant(P < 0.05). The UBE2T mRNA expression level was significantly upregulated in lung adenocarcinoma(P < 0.01). The gene enrichment analysis showed that the overexpression of UBE2T was closely related to 36 signal pathways(FDR < 0.05), including cell cycle(FDR = 0), spliceosome(FDR = 0), DNA repair(FDR = 0) and the glucose metabolism. The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA in UBE2 family correlated with the clinicopathological features of lung adenocarcinoma. UBE2T was further identified as a factor most closely related with pathological grade, prognosis in lung adenocarcinoma and glycolysis process of tumor cells. 【Conclusion】 UBE2 family correlates with clinicopathological features of lung adenocarcinoma. UBE2T mRNA could be a new biomarker for lung adenocarcinoma.

Objective:To optimize the decoction process of Digda-4 decoction(DGD-4D), and provide reference for the standardization study of decoction of Mongolian medicine decoction. Method:Taking DGD-4D as model drug, different decoction methods of Mongolian medicine were compared, HPLC was used to determine contents of aesculetin, geniposide, picroside Ⅰ and picroside Ⅱ.On the basis of single factor tests, central composite design-response surface methodology was adopted to optimize the decoction process of DGD-4D with transfer rates of 4 components and dry extract rate as indexes, regression model fitting was carried out by Design-Expert 8.0.6 software, prediction model of process parameters was established, and the optimal process was verified. Result:The optimal decoction condition of DGD-4D was determined to be adding 40 times the amount of water and decocting for 17 min, decocting once.Transfer rates of aesculetin, geniposide, picroside Ⅰ, picroside Ⅱ and dry extract rate were 70.01%, 94.11%, 61.23%, 92.32%, 32.89%, respectively. Conclusion:The optimum decoction process of DGD-4D is established, it has important reference significance for excavating, sorting, improving the level of Mongolian medicine preparations and ensuring the consistency of their clinical efficacy.

Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.
Antibodies ; Complement System Proteins ; Cytokines ; Humans ; Myasthenia Gravis ; diagnosis ; pathology ; therapy ; Oculomotor Muscles ; pathology

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-β,polyunsaturated fatty acids,and β-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.
Child ; Humans ; Infant, Newborn ; Infant, Premature ; Neovascularization, Pathologic ; therapy ; Retinopathy of Prematurity ; drug therapy ; surgery ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors

Objective To investigate the distribution and antimicrobial resistance of pathogens isolated from blood specimen,and provide laboratory basis for clinical treatment of bloodstream infection. Methods Pathogens isolated from blood specimen in a hospital laboratory from January 1,2015 to December 31,2016 were identified and per-formed antimicrobial susceptibility testing.Results A total of 1 061 pathogenic strains were isolated from blood speci-men,of which gram-negative bacillus,gram-positive coccus,and fungus accounted for 53.35%(n= 566),36.10%(n=383),and 10.55%(n= 112)respectively,the major gram-negative bacillus,gram-positive coccus,and fungus were Escherichia coli(E.coli)and Klebsiella pneumoniae(K.pneumoniae),coagulase-negative Staphylococcus,and Candida parapsilosis respectively. Strains were mainly isolated from intensive care unit(ICU,n= 308,29.03%),followed by hematology department and pediatric internal medicine department. Resistance rates of E.coli and K. pneumoniae to imipenem were 2.65% and 40.12% respectively.Extended-spectrum beta-lactamase(ESBL)-produ-cing E.coli and K.pneumoniae accounted for 62.96% and 33.14% respectively. Linezolid- and vancomycmin-re-sistant Staphylococcusspp. Were not found,isolation rates of methicillin-resistant coagulase-negative Staphylococ-cus and methicillin-resistant Staphylococcus aureus were 83.61% and 45.45% respectively,one vancomycin-resis-tant Enterococcus faeciu m and one linezolid-resistant Enterococcus faecium were isolated respectively.Conclusion There are multiple species of pathogens isolated from blood specimen,distribution and antimicrobial resistance of pathogens casing bloodstream infection should be monitored regularly to guide the empiric antimicrobial therapy.

To establish the high performance liquid chromatography (HPLC) fingerprint for Digeda-4 decoction (DGD-4D), determine the contents of aesculetin, geniposide, picroside Ⅰ, picroside Ⅱ and ellagicacid in DGD-4D, and provide the scientific foundation for quality control of DGD-4D. The analysis was performed on Diamonsil(2) C₁₈ (4.6 mm×250 mm,5 μm) column, with methanol-0.1% phosphoric acid aqueous solution as mobile phase for gradient elution. The flow rate was 1.0 mL·min⁻¹; injection size was 10 μL; temperature was maintained at 30 °C, and the detection wavelength was set at 254 nm. The common mode of DGD-4D HPLC fingerprint was established, and the hidden information was analyzed by Chemometrics. Chromatographic peaks for DGD-4D were identified by HPLC and quantitative analysis was conducted for characteristic peaks. There were 17 common peaks in the fingerprints and the similarity of the fingerprints was over 0.9 in all 15 batches. The samples were broadly divided into four kinds by principal component analysis and clustering analysis. Four marker compounds were verified by partial least squares discriminant analysis, and No. 9, 12 and 14 peaks were identified as geniposide, picroside Ⅱ, and picroside Ⅰ respectively. The average recoveries were in the range of 95.91%-97.31%. The HPLC fingerprint method for content determination is reliable, accurate, rapid, simple, and reproducible, and can be used as one of the effective methods to control the quality of DGD-4D.
Chromatography, High Pressure Liquid ; Cinnamates ; Drugs, Chinese Herbal ; analysis ; standards ; Iridoid Glucosides ; Iridoids ; Methanol ; Principal Component Analysis ; Quality Control

The purpose of this article is to identify Daphne genkwa and its adulterants, Wikstroemia chamaedaphne, according to the morphological and microstructure characteristics of their stem and foliage. The root of D.genkwa was studied simultaneously. The results indicated that the crude drug and processed pieces of Genkwa Ramulus were mainly composed of stems and branches where obvious opposite petiole scars and branch marks were able to be seen on their nodes. Otherwise, foliage or peduncles generally couldn't be found. Moreover, the fine silver flocculent fibers could be observed in the bark of fracture surface. The adulterants were the plant segments which were composed of stems, foliage and peduncles with spikelet-pedicel scars. There existed microstructures differences between Genkwa Ramulus and its adulterants. In the former, single thick lignified phloem fibers were interspersed in the stem phloem of the transverse section with very thick wall and unicellular non-glandular hairs could be observed on the lower epidermis of foliage. Nevertheless, in the latter, there was no thick lignified phloem fibers in cross section of stem phloem, the outer wall of epidermal cells of foliage hadthick cuticles and no non-glandular hairs in lower epidermis of foliage. The results can be used for the identification and the quality standard of the crude drug and processed pieces of D.genkwa.The characteristics of the microstructures and the transverse section can be used to identify the radix D.genkwa.