Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Effect of low dose laser cycloplasty on deepening anterior chamber in chronic angle-closure glaucoma

AIM:To describe the outcome of using low-dose laser cycloplasty(LCP)in chronic angle-closure glaucoma(CACG).METHODS:A retrospective case series.Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed.The main outcomes included intraocular pressure(IOP),the number of glaucoma medication,anterior segment parameters and surgery-related complications.RESULTS:A total of 7 eyes of 7 CACG patients(age 38.9±11.0y)underwent LCP with a mean follow-up of 27.1±13.7mo(range 16-48mo).Following LCP,mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg(P=0.027)with 0.4±1.1 glaucoma medications(P=0.001)at final follow-up.The anterior chamber depth(ACD),angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm,0.05 mm(range 0-0.30 mm)and 5.1°(range,0-31.97°)at baseline to 1.98±0.43 mm(P=0.073),0.53 mm(range 0.42-0.91 mm,P=0.015),45.9°(range,40.2°-59.4°),(P=0.015)in the long-term follow-up,respectively.The deepening of ACD and reopening of anterior chamber angle(ACA)was observed in 6 eyes(85.7%).CONCLUSION:LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications.In addition,LCP can bring a significant deepening in ACD and reopening of ACA.

Variant Wasserstein Generative Adversarial Network Applied on Low Dose CT Image Denoising

Computed Tomography(CT)images have been extensively employed in disease diagnosis and treatment,causing a huge concern over the dose of radiation to which patients are exposed.Increasing the radiation dose to get a better image may lead to the development of genetic disorders and cancer in the patients;on the other hand,decreasing it by using a Low-Dose CT(LDCT)image may cause more noise and increased artifacts,which can compromise the diagnosis.So,image reconstruction from LDCT image data is necessary to improve radiologists’judgment and confidence.This study proposed three novel models for denoising LDCT images based on Wasserstein Generative Adversarial Network(WGAN).They were incorporated with different loss functions,including Visual Geometry Group(VGG),Structural Similarity Loss(SSIM),and Structurally Sensitive Loss(SSL),to reduce noise and preserve important information on LDCT images and investigate the effect of different types of loss functions.Furthermore,experiments have been conducted on the Graphical Processing Unit(GPU)and Central Processing Unit(CPU)to compare the performance of the proposed models.The results demonstrated that images from the proposed WGAN-SSIM,WGAN-VGG-SSIM,and WGAN-VGG-SSL were denoised better than those from state-of-the-art models(WGAN,WGAN-VGG,and SMGAN)and converged to a stable equilibrium compared with WGAN and WGAN-VGG.The proposed models are effective in reducing noise,suppressing artifacts,and maintaining informative structure and texture details,especially WGAN-VGG-SSL which achieved a high peak-signalto-noise ratio(PNSR)on both GPU(26.1336)and CPU(25.8270).The average accuracy of WGAN-VGG-SSL outperformed that of the state-ofthe-art methods by 1 percent.Experiments prove that theWGAN-VGG-SSL is more stable than the other models on both GPU and CPU.

Efficacy of Low Dose Naltrexone on Pain Reduction in Chronic Pain Syndromes: A Meta Analysis

Chronic pain is a multifaceted debilitating experience often associated with significant physical and emotional burden. Low dose naltrexone (LDN) has gained attention in recent years for its potential utility in the management of fibromyalgia, irritable bowel syndrome, multiple sclerosis, and painful diabetic neuropathy. LDN’s analgesic effects have been associated with its ability to increase the production of endorphins while reducing the production of tumor necrosis factor-alpha, interleukin-6, reactive oxygen species and nitric oxide. This meta-analysis aims to systematically review and synthesize the available evidence on efficacy of LDN as an analgesic in pain syndromes, with a focus on chronic (neuro) inflammatory diseases. The goal is to provide clinicians with a more comprehensive estimate of the effectiveness of LDN as a non-opioid option for managing chronic pain and guide future research in the area. Thirteen randomized control trials, published from 1990 to 2022, were selected for the analysis that satisfied inclusion criteria. The overall effects in these studies were calculated using the standardized mean difference (SMD) between the LDN and placebo groups. We found an overall SMD of -10.77 (95% CI: -13.96 to -7.58) with a p-value of 0.002. This indicated that the LDN group experienced a statistically significant reduction in pain compared to placebo. This meta-analysis provides evidence for the potential efficacy of low dose naltrexone in reducing pain and enhancing analgesia in various pain syndromes. LDN may be a useful treatment option for patients suffering from chronic pain, particularly with fibromyalgia, multiple sclerosis, or diabetic neuropathy. However, further research is needed to confirm the efficacy and safety of low dose naltrexone for chronic pain conditions, especially with larger sample sizes, standardized dosing regimens and treatment durations.

Effects of Low Dose Radiation on Tumor Apoptosis, Cell Cycle and Apoptosis-Related Protein Bcl-2 in Tumor-Bearing Mice

To study the effects of low dose radiation (LDR) on tumor apoptosis, cellcycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods:Male mice of Kunming strain were implanted subcutaneously with S180 sarcoma cells in the left inguenas an in situ experimental animal model. Seven days later, the mice were subjected to 75 mGywhole-body γ-irradiation. At 24 and 48 h after the irradiation, all mice were sacrificed. The tumorsizes were measured, and tumor cell apoptosis and cell cycle progression were analyzed by flowcytometry. The expression of apoptosis-related protein Bcl-2 and the apoptotic rate of tumor cellswere observed by immunohistochemistry and electron microscopy. Results: Tumors grew significantlyslower after LDR (P 【 0.05). The tumor cells were arrested in G1 phrase and the expression of Bcl-2protein decreased at 24 h. Apoptotic rate of tumor cells was increased significantly at 48 h afterLDR (P 【 0.01). Conclusion: LDR could cause a G1-phase arrest and increase the apoptosis of tumorcells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. Theorganized immune function and anti-tumor ability are markedly increased after LDR. Our studyprovides practical evidence of clinical application to cancer treatment.

Increased Levels of p53 and PARP-1 in EL-4 Cells Probably Related with the Immune Adaptive Response Induced by Low Dose Ionizing Radiation in vitro

Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.

Modifications produced by selective inhibitors of cyclooxygenase and ultra low dose aspirin on platelet activity in portal hypertension

AIM: To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo. METHODS: Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1α, TXB2, PGE2 and LTB4 were also performed. RESULTS: The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1α was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged. CONCLUSION: These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats, could act through a COX 2 pathway more than the COX 1, predominant for aspirin at higher doses.

A retrospective analysis of the safety and efficacy of low dose tacrolimus (FK506) for living donor liver transplant recipients

We sought to evaluate the efficacy and effects of low-dose tacrolimus （FK506） to recipients with living donor liver transplantation （LDLT）. A total of 66 patients who underwent LDLT between 2001 and 2007 were enrolled in this study. According to different doses of tacrolimus, the recipients were randomly divided into two groups： the low-dose tacrolimus group （group A） and the normal-dose tacrolimus group （group B）. The blood concentration of tacrolimus and its side effects including infection, hyperglycemia, hypertension, high blood creatinine and jaundice were monitored once a week at the perioperative period, and once a month thereafter. Besides, the survival rates of the recipients were analyzed at the 1and 3-year time point after operation. Among these patients, no significant acute rejection was detected after LDLT. The incidences of infection, hyperglycemia, liver dysfunction and renal impairment in group A were markedly lower than those in group B. However, no significant differences were detected in the incidence of hypertension between the two groups. Moreover, the recipients in each group had a similar survival rate according to the results of 1and 3-year follow-up. The incidence of side effects that associated with tacrolimus positively correlated with tacrolimus blood concentration. In conclusion, long-term and low-dose administration of tacrolimus is a safe and effective treatment for LDLT recipients.

Effect of Cycloheximide on the Adaptive Response Induced by Low Dose Radiation

Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.

Low Dose Hyper-radiosensitivity in Human Lung Cancer Cell Line A549 and Its Possible Mechanisms

The low dose hyper-radiosensitivity （HRS） in human lung cancer cell line A549 was investigated, the changes of ATM kinase, cell cycle and apoptosis of cells at different doses of radiation were observed, and the possible mechanisms were discussed. A549 cells in logarithmic growth phase were irradiated with ^60Co y-rays at doses of 0-2 Gy. Together with flow cytometry for precise cell sorting, cell survival fraction was measured by means of conventional colony-formation assay. The expression of ATM1981 Ser-P protein was examined by Western blot 1 h after radiation. Apoptosis was detected by Hoechst 33258 fluorescent staining, and Annexin V-FITC/PI staining flow cytometry 24 h after radiation. Cell cycle distribution was observed by flow cytometry 6, 12 and 24 h after radiation. The results showed that the expression of ATM1981Ser-P protein was observed at 0.2 Gy, followed by an increase at 〉0.2 Gy, and reached the peak at 0.5 Gy, with little further increase as the dose exceeded 0.5 Gy. Twenty-four h after radiation, partial cells presented the characteristic morphological changes of apoptosis, and the cell apoptosis curve was coincident with the survival curve. As compared with control group, the cell cycle almost had no changes after exposure to 0.1 and 0.2 Gy radiation （P〉0.05）. After exposure to 0.3, 0.4 and 0.5 Gy radiation, G2/M phase arrest occurred 6 and 12 h after radiation （P〈0.05）, and the ratio of G2/M phase cells was decreased 24 h after radiation （P〈0.05）. It was concluded that A549 cells displayed the phenomenon of HRS/IRR. The mode of cell death was mainly apoptosis. The activity of ATM and cell cycle change may take an important role in HRS/IRR.

Effect of Low Dose Radiation on Intracellular Calcium and Protein Kinase C in Lymphocytes

It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming micc With 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+], mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBl with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic（LC） method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature（40 1C） using a mobile phase of acetonitrile：methanol：0.03 M ammonium acetate（p H 3.8）（30：15：55, v/v/v）, run at a flow rate of 1.5 m L/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2（paddle） at 100 rpm and 900 m L of phosphate buffer at p H 6.8 as the dissolution medium.Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

EVALUATION OF NEUROPROTECTIVE EFFECTS OF LONG-TERM LOW DOSE HORMONE REPLACEMENT THERAPY ON POSTMENOPAUSAL WO-MEN BRAIN HIPPOCAMPUS USING MAGNETIC RESONANCE SCANNER

To investigate the effects of long-term low dose hormone replacement therapy （HRT） on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy （MRS） parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol （E2 ） 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay （ELISA）. The gene types of apolipoprotein E （ApoE） were measured by polymerase chain reaction, and the subjects with susceptible genes （ ApoE ε3/ε4） of Alzheimer＇s disease （AD） were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging （MRI）, and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher （P 〈0. 05） except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 （HRT group 14 cases, control group 11 cases） showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group （0. 406 ± 0.028） was signiticantlyhigher than control gronp （0.369±0.031, P〈0.05）. Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 （ HRT group 12 cases, control group 11 cases） showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group （ 1.54±0. 08 ） were significantly higher than control group （ 1.45±0. 13, P 〈 0. 05）. Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.

Estimation of enhanced low dose rate sensitivity mechanisms using temperature switching irradiation on gate-controlled lateral PNP transistor

The mechanisms occurring when the switched temperature technique is applied,as an accelerated enhanced low dose rate sensitivity(ELDRS)test technique,are investigated in terms of a specially designed gate-controlled lateral PNP transistor(GLPNP)that used to extract the interface traps(Nit)and oxide trapped charges(Not).Electrical characteristics in GLPNP transistors induced by ^(60)Co gamma irradiation are measured in situ as a function of total dose,showing that generation of Nit in the oxide is the primary cause of base current variations for the GLPNP.Based on the analysis of the variations of Nit and Not,with switching the temperature,the properties of accelerated protons release and suppressed protons loss play critical roles in determining the increased Nit formation leading to the base current degradation with dose accumulation.Simultaneously the hydrogen cracking mechanisms responsible for additional protons release are related to the neutralization of Not extending enhanced Nit buildup.In this study the switched temperature irradiation has been employed to conservatively estimate the ELDRS of GLPNP,which provides us with a new insight into the test technique for ELDRS.

Modulation of MMP-2 and TIMP-2 by low dose radiation in mice bearing S180 sarcoma

Objective To investigate the inhibition of low dose radiation （LDR） on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into two groups： control （N） and low dose radiation （LDR） groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 （LDR-12 h）, 24 （LDR-24 h）, 48 （LDR-48 h）, and 72 （LDR-72 h） h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression. Results Compared with the control group, the tumor growth was significantly inhibited in the LDR groups （P 〈 0.05）. MMP-2 expression was considerably reduced in LDR-24h （P 〈 0.05） and LDR-48h （P 〈 0.05）, whereas the change of TIMP-2 was not obvious in the LDR groups （P 〉 0.05） in contrast to that of the control group. Conclusion LDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.

Time and Dose-related Effects of the Pyrethroid Fluvalinate on Haemolymph Carbohydrates and Gut Lipids of Honeybees,Following in vivo Injection of very Low Doses

The injection to emerging adult workerbees with fluvalinate doses ranging from 1 femtomol to 1 nanomol per individual resulted in a reduction of haemolymph carbohydrate concentrations, particularly at the lowest dose 1 hour after injections. At the same time, a large increase was observed for triacylglycerols and to a much lesser extent for steroids and phospholipids with 0.1 picomol per bee. By contrast, fatty acids, steroids and triacylglycerols exhibited a depress at the higher dose. Most responses were thus biphasic, showing that much attention should be paid to the effects of very low doses of pesticide.

Relationship of HepG2 cell sensitivity to continuous low dose-rate irradiation with ATM phosphorylation

Objective: To investigate the change of ATM phosphorylation in HepG2 cells and its effect on HepG2 cell survival under a continuous low dose-rate irradiation. Methods: HepG2 cells were exposed to equivalent doses of irradiation deliv- ered at either a continuous low dose-rate (7.76 cGy/h) or a high dose-rate (4500 cGy/h). The ATM phosphorylated proteins and surviving fraction of HepG2 cell after low dose-rate irradiation were compared with that after equivalent doses of high dose-rate irradiation. Results: The phosphorylation of ATM protein was maximal at 0.5 Gy irradiation delivered at either a high dose-rate or a continuous low dose-rate. As the radiation dose increased, the phosphorylation of ATM protein decreased under continuous low dose-rate irradiation. However, the phosphorylation of ATM protein was remained stable under high dose-rate irradiation. When the phosphorylation of ATM protein under continuous low dose-rate irradiation was equal to that under high dose-rate irradiation, there was no significant difference in the surviving fraction of HepG2 cells between two ir- radiation methods (P > 0.05). When the phosphorylation of ATM protein significantly decreased after continuous low dose-rate irradiation compared with that after high dose-rate irradiation, increased amounts of cell killing was found in low dose-rate irradiation (P < 0.01). Conclusion: Continuous low dose-rate irradiation increases HepG2 cells radiosensitivity compared with high dose-rate irradiation. The increased amounts of cell killing following continuous low dose-rate exposures are associated with reduced ATM phosphorylated protein.

The effect of low dose radiation on cytokine correlated to injury of lungs induced by Bleomycin A5

Objective： The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods： Kunming male mice were randomly divided into three groups： blank group, PYM group （P group）, low dose radiation ＋ PYM group （P ＋ L group）. Mice of P ＋ L group were given whole body low dose radiation 75 mGY, dose rate were 12.5 mGY/min. After 6 h, mice in both P ＋ L group and P group were given inbreathe of atomization of PYM, concentration was 2 mg/mL. Mice were sacrificed after the dl, d7, d14, d21 and d28, IL-6 were detected in alveolar irrigating solution. The tissue samples of mice lung were fixed in 10% formalin, TNF-α and TGF-β were analyzed by immuno- histochemistry. Results： Compared with P group, IL-6 in low dose radiation ＋ PYM group were lower, near to blank group, the difference had notable statistical significance on the dl and the d7, while on the d14, d21, d28, the difference had not statisti- cal significance. It suggested that low dose radiation could reduce the resection of IL-6 at the begin of lung injure induced by low dose radiation. The expression of TGF-β and TNF-α in P ＋ L group were lower than that in P group, but the difference in the two groups had statistical significance by gray analysis P 〈 0.05. Conclusion： In the early stage of lung injure caused by PYM in mice, low dose radiation of 75 mGY can reduce the secretion of IL-6, decrease the production of TGF-β and TNF-α.

Changes in Lymphocyte Reactivity to ModulatoryFactors Following Low DoseIonizing Radiation

Catecholamines (CA) and corticosterone (CS) exerted modulatory effect on the proliferative activity of splenic and thymic lymphocytes in response to mitogenic stimulation in vilro. Epinephrine (E) and norepinephrine (NE) potentiated proliferation in concentrations above 1 and 10 nmol/L, respectively, while CS showed a biphasic effect, stimulating proliferation at concentrations below 0.1 nmol/L and suppressing proliferation at concentrations above 10 nmol/L. Combination of CS with E, NE or both in an ineffective concentration of each (0.1 nmol/L ) showed stimulatory effect on the proliferative response of both splenic and thymic lympliocytes to Con A. Whole-body irradiation (WBI) of mice with 75 mGy incIeased the reactivity of splenic and thymic lymphocytes to Con A. It is reported for the first time in the present paper that the proliferative reactivity of splenic and thymic lymphocytes from low dose irradiated mice could be further increased in the presence of suboptimal concentrations of CS and E as well as suboptimal concentrations of phorbol myristate acetate (PMA ) and A23187. These findings may have significance in the mechanism of immunologic stimulation after low dose WBI