The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

ObjectiveTo investigate the effects of spleen-Yin deficiency on gastrointestinal absorption， water metabolism and intestinal flora in rats with spleen-Yin deficiency syndrome. MethodA rat model of spleen-Yin deficiency syndrome was established by using the composite factors， including irregular meat and vegetable diet， weight-bearing fatigue swimming and gavage with warm-heat injury-Yin drugs. The changes of body weight， food intake， water intake and duration of swimming in the blank and model groups were observed. Hematoxylin-eosin（HE） staining was used to observe the histopathological damage of the stomach and colon. Urinary excretion rate of D-xylose was determined by phloroglucinol method. The content of gastrin（GAS） in serum was determined by enzyme-linked immunosorbent assay（ELISA）. The relative expression levels of vasoactive intestinal peptide（VIP）， aquaporin 3（AQP3） and AQP4 in gastric tissues were detected by Western blot. The relative mRNA expression levels of VIP， AQP3 and AQP4 in gastric tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the changes of intestinal flora were analyzed by 16S rDNA sequencing. ResultCompared with the blank group， the results of general physical signs showed that the body weight and food intake of rats in the model group were significantly decreased， the water intake was significantly increased（P<0.05， P<0.01）， and the duration of swimming was significantly decreased（P<0.01）. Pathological examination results showed that in the mucosa of gastric tissues of rats in the model group appeared to be misaligned， the mucosa of colonic tissues could be seen to be obviously thinned or mutilated， and the epithelial cells appeared to be necrotic or even exfoliated. Compared with the blank group， the urinary D-xylose excretion rate of rats in the model group was significantly decreased（P<0.01）， and the serum GAS content was significantly decreased（P<0.05）. Compared with the blank group， Western blot results showed that the relative expression level of VIP protein in gastric tissues of rats in the model group was significantly decreased， while the relative expression levels of AQP4 and AQP3 proteins were significantly increased（P<0.01）. Compared with the blank group， Real-time PCR results showed that the relative expression level of VIP mRNA in gastric tissues of rats in the model group was significantly decreased（P<0.01）， and the relative mRNA expression levels of AQP3 and AQP4 were significantly increased（P<0.05， P<0.01）. Compared with the blank group， the results of intestinal flora analysis showed that the number of operational taxonomic units（OTUs） and α-diversity increased and β-diversity decreased significantly in the model group， the abundance of Porphyromonadaceae was increased significantly， and the abundance of Oscillibacter_ruminantium was decreased significantly（P<0.05）. Spearman correlation analysis showed that Porphyromonadaceae was significantly positively correlated with AQP4 protein level， while Oscillibacter_ruminantium was significantly positively correlated with VIP protein level， and negatively correlated with AQP3 and AQP4 protein levels（P<0.05）. Linear discriminant analysis effect size（LEfSe） analysis results showed that there were significant differences in a variety of intestinal bacteria between groups， and the intestinal bacteria of the model group were significantly enriched in the phylum/order/family/genus of Elusimicrobia， Betaproteobacteria， Burkholderiales， Sutterellaceae and Parasutterella（P<0.05）. ConclusionSpleen-Yin deficiency syndrome can weaken the digestion and absorption capacity of gastrointestinal tract， and cause the disturbance of water metabolism and intestinal flora. AQP4， AQP3 and VIP protein levels of gastric mucosa are closely related to Porphyromonadaceae and Oscillibacter_ruminantium. And AQP4， AQP3 and VIP may be involved in the regulation of intestinal flora in order to affect the physiological function of spleen governing transportation and transformation.

The elements of the teaching system driven by the "Internet +" era are undergoing fundamental changes . Intelligent teaching platform is gradually becoming an important guarantee of the reform of teaching system elements for educators while they are teaching. With the support of intelligent teaching platform, the elements of teaching system break through the limitation of classroom teaching, the traditional structure of teacher-centered is disintegrating, the individual roles of teachers and students are being reconstructed , the teaching content is greatly enriched , and the function of teaching media is becoming more and more intelligent. This thesis, which will take the learning support function of the WeChat Public Platform of "Medical History" as an example by drawing lessons from the reversed classroom teaching mode, carries out the mixed teaching model of Chinese Medical History course by three stages: pre-class autonomous learning, in-class knowledge perfection and after-class knowledge transfer. It will elaborate its overall influence on the elements of the teaching system of Chinese Medical History and its important technical support for the reform of classroom teaching structure.

Objective To explore the effects of high-frequency electromagnetic radiation exposure on the mood-cognitive behaviors of mice, and to provide an experimental basis for the study on radiation damage mechanism and protection. Methods The electromagnetic reverberation chamber can produce continuous and uniform high-frequency electromagnetic waves. Different groups of ICR mice were exposed to high-frequency electromagnetic radiation in this chamber for 1 d, 3 d and 7 d, and then series of behavioral tests were conducted to observe the changes in locomotor activities,depressive-like and anxiety-like behaviors, and cognitive function of the mice. Results After exposed to the high-frequency electromagnetic radiation(3 GHz,SAR 4 W/kg)4 h/d for 7 d,there was no obvious change in locomotor activity(times of grid crossing and standing up in the open field test)of the mice,while the times of entering the central region(P< 0.05)and the time duration(P< 0.05)were significantly decreased. Compared with the unexposed group, the percentage of the times of entering the open arm in the elevated-plus maze(P< 0.05)and the time duration in the open arm(P< 0.01)of the mice in the radiation group were significantly decreased. Meanwhile, the immobility time in the forced-swimming test(P< 0.01)and the tail suspension test(P < 0.05)of the mice exposed to electromagnetic radiation was significantly increased, and the discrimination index of new objects in the new object recognition test was significantly reduced(P < 0.001). Conclusions Continual exposure to high-frequency electromagnetic radiation(3 GHz,SAR 4 W/kg)can lead to anxious-depression behaviors and cognitive impairment of mice in a time-dependent manner,which provides an experimental basis for the relevant study of prevention and therapy techniques.

OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.

OBJECTIVE To investigate the relationship between the anti-post-traumatic stress disorder(PTSD)effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline(15 mg · kg-1) intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and 7th day after the extinction training in rats. The NO contents were detected by Griess method and the nNOS and iNOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group ,the freezing time was significantly increased in extinction control group and extinction training group(P<0.01),indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline(15 mg·kg-1)group was decreased compared with extinction training group (P<0.05). At the 7th day,the freezing time was significantly decreased(P<0.01),indicating that ser?traline reversed the fear response. At the same time,the contents of NO,nNOS and iNOS on amygdala of rats in sertraline group were lower than that in extinction training group(P<0.01). CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has anti-PTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.

Objective To explore the mediating effects of college students＇ online social support on the relationship between online self-disclosure and internet altruistic behavior.Methods Using cluster random sampling,the self-disclosure questionnaire for Chinese undergraduates with their internet friend,the online social support scale of adolescence and the internet altruistic behavior scale of undergraduates were applied to 351 college students.Results The score of college students＇ online self-disclosure,online social support and internet altruistic behavior were respectively(2.22±0.45),(2.93±0.59) and (2.04±0.46).The college students＇ online self-disclosure,online social support and internet altruistic behavior were positively correlated with each other (P＜0.01).College students＇ online self-disclosure not only predicted internet altruistic behavior directly,but also predicted internet altruistic behavior indirectly through online social support.The direct effects and indirect effects were 0.200 and 0.265.The ratio of the mediating effect on the total effect was 57％.The fit index of mediation model was x2/df=2.87,RMSEA =0.07,CFI =0.94,TLI =0.93,GFI=0.92,IFI=0.94,NFI=0.91.Conclusion The college students＇ online self-disclosure not only affects the interuet altruistic behavior directly,but also can take the same effect on online social support indirectly.

BACKGROUND:Endovascular embolization materials have been produced and used clinicaly, but new problems constantly occur in the clinical application and new demands are also developed for embolic materials. OBJECTIVE:To retrospectively analyze the advantages and disadvantages of various types of embolic materials and to investigate the relationship between application fields and selection of embolic materials, thereby providing a reference for clinical treatment. METHODS:CNKI and PubMed databases were retrieved for relevant literature, and then embolic materials were systemicaly reviewed based on relevant clinical application and basic research literature in the folowing aspects: embolism mechanisms, clinical applications, advantages and disadvantages of various embolic materials. In this review, the existing problems in the current study were pointed out, and the development direction of relevant research and clinical application were also prospected. RESULTS AND CONCLUSION:Embolic materials should have biodegradability and biocompatibility. Current embolic materials include absorbable gelatin sponge, Polyvinylalcohol embolic agent, micro-coils and liquid embolic materials. Gelatin embolic material has no antigenicity and good histocompatibility, as wel as has excelent compressibility and water re-expansibility. Polyvinylalcohol particles are a polymer material that is insoluble in water, has high expansion coefficient, mechanical embolization, non-alergenic reaction, no acute systemic toxicity, no intracutaneous irritation, and can be used safely and effectively. Adhesive liquid embolic material has no vascular toxicity and has been widely used. Endovascular embolization materials have been produced in succession, and meanwhile, new problems in clinical applications have been found and new demands for embolic materials have been put forward continuously. Thus, a variety of embolic materials have their own advantages and disadvantages, and none of embolic materials can be applied to al diseases. To select an appropriate embolic material is very important for safe and effective treatment.

The clinical or experimental study proves that Chinese medicine such as Tripteryglum wilfordii, Lignum Sappan, Caulis Sinomenii, Radix Trichosanthis and Herba Artemisiae Annuae have good immunosuppressive activity. Further researches on the immunosuppressive active components from Chinese medicine have been the main direction in recent years. The recent researches on immunosuppressive effect and possible mechanisms for the monomers such as triperine, triptolide, bazilein, potosappanin A, sinomenine, trichosanthin and artemisinin extracted from those Chinese medicine are introduced in this review.
Animals ; Artemisinins ; pharmacology ; therapeutic use ; Diterpenes ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epoxy Compounds ; pharmacology ; therapeutic use ; Humans ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Morphinans ; pharmacology ; therapeutic use ; Phenanthrenes ; pharmacology ; therapeutic use ; Plants, Medicinal ; chemistry ; Trichosanthin ; pharmacology ; therapeutic use

Objective To explore the expression of N-myc downstream regulated gene 1 (NDRG1) in gastric carcinoma and the relationship with clinicopathological parameters and prognosis. Methods The expression of NDRGI was detected by immunohisto chemistry in formalin-fixed and paraffin-embedded sections with a total of 220 specimens including 110 gastric carcinoma and 110 corresponding paraneoplastic tissue. The correlation between clinicopathological parameters and the expression of NDRG1 in gastric carcinoma were also analyzed. Results Low expression of NDRG1 was detected in most gastric carcinoma sections. Among the gastric cancer tissues, NDRG1 protein expression was significantly lower in tumors with more advanced pathological stage, local tumor invasion and lymphatic metastases. There was no significant difference in sex, age, tumor differentiation and gross types of the tumor. The 1-, 3- and 5 year survival and disease free survival in patients with low NDRG1 protein expression was 84.2%, 53.9%, 21.1%, and 60.5%, 31.6%, 19.7%, respectively, which was signifivantly poorer when compared with patients with high NDRG1 protein expression. Conclusion The expression of NDRG1 is low in the majority of patients with gastric carcinoma, which was in a close relationship with advanced stage, local invasion and lymphatic metastases of gastric carcinoma. NDRG1 may be a candidate metastasis suppressor gene.