Given the unlimited proliferation and aerobic glycolysis in tumor cells, these cells require more glucose, glutamine, and other nutrients compared with normal cells. Tumor cells are often affected by insufficient nutrient supply. However, by sensing changes in the nutrient supply in tumor microenvironment and by regulating signal-transduction pathways, some specific proteins can help tumor cells in blocking the cell cycle, reprogramming metabolism, and regulating autophagy to progress and survive against nutri-ent stress. Exciting innovations have been made to elucidate the mechanisms relevant to this process. This review aims to highlight re-cent studies on the mechanisms of sensing the low nutrient supply in microenvironments, as well as the downstream effect factors in cancer cells.

BACKGROUND: The upward attack of drug-heat is a special type of syndromes of coexistence of cold and heat, it influence the treatment and conversion of the primary disease.OBJECTIVE: To investigate the pathophysiological basis of upward attack of drug-heat.DESIGN: A randomized and controlled observation. SETTING: Department of Traditional Chinese Medicine (TCM) of the People' s Central Hospital of Huizhou City.PARTICIPANTS: Totally 427 patients with cold syndrome, visiting on Department of TCM of the People's Central Hospital of Huizhou City from January 1996 to December 2001, were given warm-heat remedy. Among them 66 cases, 30 males and 36 females, got upward attack of drug-heat during the process of treatment were enrolled. All these subjects, according to their visiting order, at a ratio of 2:1, were chosen as treatment group (44 cases) and control group (22 cases).METHODS: For the patients in treatment group: Rhubarb 6 g was added boiling water 100 mL and soaked for 8 minutes, then the soaking solution was given to the patients, once a day, for 3 days successively. For patients in control group: Table salt 6 g was added boiling water 100 mL for soaking for 8 minutes, after the salt was completely dissolved, the solution was given to the patients, once a day for 3 days successively. The patients of the two groups were at the same time given remedy to treat cold syndrome. The changes of free triiodothyronine (FT3), free thyronine (FT4), high sensitizing thyroid-stimulating hormone (HS-TSH) and cortisol of the patients were detected before and after administration of warm-heat remedy, before and after medication with rhubarb. MAIN OUTCOME MEASURES: ① The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of warm-heat remedy. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of rhubarb. ③ Comparison of the therapeutic effects in the two groups.RESULTS: All 66 patients involved entered the final result analysis. ①The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of warm-heat remedy: FT3 and FT4 were decreased as compared with those before treatment [(2.51±1.20),(6.50±2.30); (10.01±3.21), (15.50±6.31) pmol/L], but HS-TSH and cortisol were increased as compared with those before treatment [(8.25 ±3.75),(4.11±1.75) mU/L; (0.56±0.17), (0.43±0.10) μmol/L]. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of rhubarb: FT3 and FT4 ywere increased as compared with those before treatment[(4.71 ±1.56), (2.45±1.25); (14.21 ±4.61),(10.21±3.52) pmol/L], but HS-TSH and cortisol were decreased as compared with those before treatment [(6.24±2.25), (8.35±3.51) mU/L; (0.48±0.10),(0.60±0.17) μmol/L]. ③ Comparison of the therapeutic effects in the two groups: The rate of excellenly effect in treatment group was obviously higher than that in control group (33%, 5%).CONCLUSION: The pathophysiological basis of upward attack of drug heat is stress state of the body, the secretions of the pituitary-thyroid axis play a role of physiological protection, the adrenocortical function is hyperactive, and rhubarb can control this stress state through inhibiting the metabolism of the body.

OBJECTIVE: To observe the effects of ginkgolide (GL) on the cerebral blood flow in dogs. METHODS: Dogs anesthetized with sodium pentobarbital were randomly divided into 5 groups, with 4 dogs in each group. Ginkgolide of 4.86, 14.6 and 43.7 mg/kg and Xingling Granule of 0.22 g/kg were administered by gavage to the dogs in each of 4 groups. The dogs in the other group were administered with edible oil (1 ml/kg) as control group. The cerebral blood flow, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and electro-cardiogram of the dogs were measured at different times after the administration. RESULTS: Ginkgolide of 4.86, 14.6 and 43.7 mg/kg had no obvious effects on the blood pressure and the heart rate. Ginkgolide of 14.6 and 43.7 mg/kg increased the cerebral blood flow 90 minutes after administration, and ginkgolide of 43.7 mg/kg obviously decreased the cerebral vascular resistance 150 minutes after administration. CONCLUSION: Ginkgolide can increase the cerebral blood flow and decrease the cerebral vascular resistance, and it has no obvious effects on blood pressure and heart rate in dogs.

The purified oil of Anguilla japonica (139. 6-1116. 8 mg/kg) was administrated ig for 20 days in mice. Positive cell number of macrophage with Fc receptor, phago-cytic percentage and index were increased significantly. T lymphocyte transformation and activity of NK cell were enhanced merkedly. The amount of antibody forming cells was risen dramatically.

AIM: To study the therapeutical effects of salvianolic acid B (Sal B) on myocardial infarction(MI) in dogs. METHODS : The models of myocardial infarction were produced by ligation of the left anterior descending (LAD) coronary artery in the anaesthetized dogs. The extent of myocardial ischemia was detected by epicardial-electrocardiogram and the extent of infarction was determhled by N-BT staining method. The parameter of lactate dehydrogenase was determined in the serums of dogs. RESULTS : It was indicated that the adminstration of Sal B(1、3 and 10mg/kg) by the way of intravenous injection reduced the extent of myocardial infarction (N-ST) ( P

Objective: To ascertain the process condition of extraction Mashi Granules(Herba Ephedrae, Gypsum Fibrosum, Radix Puerariae, Herba Methal, Semen Armeniacae Amerum, etc.) Methods: In combination with area under the curve of hypothermy in rabbits, process water, macerating time and boiling times were used as parameters in uniformidy design. And then appropriate excipients were selected on the basis of hygroscopicity and granulation. Results: 20 times amount of water as much as herbs was added, macerating time reached as far as 40 min, and extracted 3 times, 2h a time. Excipient formula consisted of lactose and mannitol(4∶1, w/w). Conclusion: The experimental results provide the basis for the ascertainment of extracting process and formulation of Mashi Granules.

AIM: To study the effects of the composite lactogenic decoction (CLD) on milk secretion of hypoprolactinemia induced by L dopa in rats. METHODS: The models of hypoprolactinemia were established with L dopa in rats. The weight of young rats was recorded during 15 days. Levels of serum prolactin were detected by ELISA and the mammary gland histology was observed by electron microscop. RESULTS: The administration of CLD (3, 6 and 20 g?kg -1 ) by the way of ig increased serum prolactin (PRL) level significantly (P

Objective:To investigate the inhibitory effect of Dickkopf-1 (Dkk1) on vasculogenic mimicry (VM) formation and the relevant mechanism. Methods:CD34-PAS dual staining and immunohistochemical staining were used to detect and analyze the re-lationship between VM existence and Dkk1 expression in 217 human colon cancer tissue samples;three dimensional (3D) culture was used to detect the influence of Dkk1 on tube structure formation and on VE-cadherin expression;a subcutaneous mouse xenograft mod-el was made to further validate the inhibitory role of Dkk1 on VM formation in vivo. Results:VM-positive samples indicated a lower expression of Dkk1(P<0.05);colon cancer cells with Dkk1 overexpression exhibited a decreased ability to form tube-like structure and a decreased expression of VE-cadherin;Dkk1 inhibited the VM-formation abilities of human colorectal carcinoma cell line xenograft tu-mor tissue. Conclusion:Dkk1 inhibits the VM formation of colon cancer.

Objective To observe the changes of the totle nitric oxide synthase (NOS) activity in brain tissue,the metabolism of arsenic speciations in urine and the totle contents in blood,brain after rats drinking water containing different doses of arsenic.Methods Forty SD rats were divided into 4 groups according to random number table,10 rats in each group:control group,5 mg/L NaAsO2 group,10 mg/L NaAsO2 group and 50 mg/L NaAsO2 group.The animals were allowed free access to water and food.Body mass was weighted once a week.Expose to arsenic was continued for three months,then the animals were put to death and their blood,urine and brain tissues were collected.Determination of four kinds of speciations of arsenic (3 valence inorganic arsenic,iAs3+;5 valence inorganic arsenic,iAs5+;monomethylated arsenic,MMA;dimethylated arsenic,DMA) in urine was carried out by high performance liquid chromatography-hydride atomic fluorescence spectrometry.Total arsenic concentration in blood and brain tissue was detected by Atomic Fluorescence Spectrometry.The activity of total NOS in blood and brain tissue was detected using the spectrophotometer method.Results ①Weight:at the 5th-12th week after arsenic exposure,compared with the weight of control group [(420.93 ± 21.13),(441.52 ± 28.85),(462.45 ± 30.57),(470.16 ± 31.17),(484.92 ± 32.93),(483.79 ± 29.63),(482.02 ± 29.14),(483.89 ± 29.31) g],weight of rats in 50 mg/L NaAsO2 group [(391.66 ± 32.88),(410.17 ± 33.47),(426.96 ± 33.49),(427.15 ± 32.20),(441.78 ± 33.69),(438.27 ± 33.05),(440.98 ± 33.33),(441.46 ± 32.45) g] was significantly lighter (all P ＜ 0.05).② Urine arsenic:the medians of iAs3+ content (0.00,57.30,236.33,857.80 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =31.982,P ＜ 0.01);the medians of iAs5+ content (0.00,0.00,80.75,162.90 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =24.206,P ＜ 0.01);the medians of DMA content (12.83,1 711.13,l0 386.20,37 038.90 μg/L) were compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (x2 =34.338,P ＜ 0.01).③Blood arsenic:total arsenic content in serum of rats [(5.04 ± 1.57),(25.40 ± 7.33),(32.28 ± 7.75),(56.11 ± 19.87) mg/L] was compared between control group,5,10 and 50 mg/L NaAsO2 groups,the differences were statistically significant (F =27.78,P ＜ 0.05).④Brain arsenic:total arsenic content in brain tissue of 5,10 and 50 mg/L NaAsO2 groups [(0.57 ± 0.20),(1.56 ± 0.52),(3.63 ± 0.48) μg/g] was respectively compared with that of control group [(0.11 ± 0.06) μg/g],the differences were statistically significant (all P ＜ 0.05).⑤NOS activity:compared with control group [(27.69 ± 5.56) kU/L],total NOS activity [(33.63 ± 2.26),(34.19 ± 2.55) kU/L] in serum of rats in 10 mg/L NaAsO2 group and 50 mg/L NaAsO2 group increased significantly (all P ＜ 0.05);compared with control group [(1.79 ± 0.79) U/(mg·prot)],total NOS activity [(2.63 ± 0.60)U/(mg ·prot)] in brain tissue of 50 mg/L NaAsO2 group increased significantly (P ＜ 0.05).Conclusions A high dose of arsenic exposure can increase totle contents of arsenic in blood,brain and the activity of total NOS in rat brain tissue.

Objective To analyze the CT pulmonary angiography(CTPA) image quality and radiation dose of obesity patients with high and low tube voltage iterative reconstruction(IR) and the filtered back projection(FBP) reconstruct algorithm,and to explore the feasibility of low tube voltage IR algorithms in CTPA of obese patients.Methods Obese patients with suspected pulmonary embolism were randomly assigned into 80 kV or 120 kV group, and the images were treated with IR and FBP reconstructions.CT value of the basal segment of the right pulmonary artery, right upper lobe and main pulmonary artery were measured, and the average CT value of the pulmonary artery was further calculated, and the independent sample t test analysis was used.Results Comparing the CT value of the IR and FBP subgroup of two tube voltage groups, the differences were not significant (P>0.05), the differences of noise, signal noise ratio(SNR) and contrast noise ratio (CNR) were statistically significant (P<0.05), respectively.The CT value,noise,SNR and CNR of 80 kV group were significantly higher than those of the 120 kV group, and the differences were statistically significant (P<0.05), while the radiation dose were significantly lower than those of 120 kV group (P=0.000).Conclusion The CTPA image quality of 80 kV IR algorithm is significantly improved compared with the 120 kV FBP algorithm, and the radiation dose is significantly reduced, which could be used for CT pulmonary angiography in obese patients.