Multicenter real world study on the efficacy and safety of eribulin for the treatment of advanced breast cancer / 中华肿瘤杂志

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model / 中华医学杂志(英文版)

BACKGROUND@#Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model.@*METHODS@#A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.@*RESULTS@#The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10vs. 1.00 ± 0.43, t = 3.98, P < 0.05).@*CONCLUSIONS@#Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model / 中华医学杂志(英文版)

Background@#Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those without such facilities or 2019-novel coronavirus (2019-nCoV). This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV related coronavirus model.@*Methods@#A 2019-nCoV related pangolin coronavirus GX_P2V/pangolin/2017/ Guangxi was described. Whether GX_P2X uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2X infection. The antiviral activities and antiviral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.@*Results@#The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs-cepharanthine (CEP), selamectin and mefloquine hydrochloride exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48±0.02]×10-4 vs. 1.00±0.12, t=150.38, P<0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP has potent antiviral activities against both viral entry (1.00±0.37 vs. 0.46±0.12, t=2.42, P<0.05) and viral replication (1.00±0.43 vs. [6.18±0.95]×10-4, t=3.98, P<0.05).@*Conclusions@#Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and clinical trial of CEP for treatment of 2019-nCoV infection is warranted.

Study on in vitro release and percutaneous absorption of Huoxue Zhitong gel / 中国中药杂志

To evaluate in vitro release and transdermal behaviors of Huoxue Zhitong gel, modified Franz diffusion cell methods was applied to investigate in vitro transdermal absorption of Huoxue Zhitong gel and the content of paeonolan in receptor fluid composed of PEG400%-95% ethanol-water (l:3:6)were determined by HPLC. The results were processed and different equations were fitted. The release law were in accordance with Weibull equation and the fitting equation was In[-1/(1 - Q)] = -0.790 51nt - 1.7012 (r = 0.9809). In 8 hours, cumulative release of paeonol was 85. 18% and the release rate was 2.827 µg . cm-2 h-1. Transdermal actions were consistent with zero-level model fit and the fitting equation was Q(t) = 1.7579t + 0. 7213 (r = 0.9991). In 8 hours, cumulative transdermal rate and transmission rate of paeonol was 54. 85%, 1. 820 µg . cm-2 h-1. So the Huoxue Zhitong gel had a good release and transdermal properties.

Comparison of two quantitation methods of circulating tumor cells in patients with small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a quantitative method to detect circulating tumor cells (CTC) in patients with small cell lung cancer, and analyze its sensitivity and stability.</p><p><b>METHODS</b>A specific primer and probe for prepro-gastrin-releasing peptide (preproGRP) was designed and a quantitative RT-PCR method was established to detect preproGRP mRNA. Cell incorporation method was used to evaluate the sensitivity. Magnetic cell sorting (MACS) was used to isolate and purify CTC from peripheral blood, and the MACS in combination with morphological diagnosis were used for cell counting.</p><p><b>RESULTS</b>The isolation rate of CTC by MACS was 30% and the lower detection limit was 5 cells per ml blood. The sensitivity of quantitative RT-PCR in detection of preproGRP mRNA in CTC was 0.64 cells per reaction, and the lower detection limit was 50 cells per ml blood, which was lower than that of MACS. However, the cell numbers calculated by Ct value was in greater accordance (about 80%) with actual cell numbers than that obtained by MACS.</p><p><b>CONCLUSIONS</b>PreproGRP quantitative RT-PCR and MACS have both advantages and disadvantages in detecting CTC of SCLC patients. MACS has a higher sensitivity, and is more favorable when CTC count is below 50 per ml blood. Meanwhile, preproGRP mRNA quantitative RT-PCR is more reliable in calculating actual cell numbers.</p>

Study on in vitro release and percutaneous absorption for Zhitong cataplasm / 中国中药杂志

To evaluate in vitro release and transdermal behaviors of Zhitong cataplasm, modified Franz diffusion cell method was applied to investigate in vitro transdermal absorption of Zhitong cataplasm and the content of tetrahydropalmatine was determined by HPLC. In 24 hours, accumulative release rate of tetrahydropalmatine was 81. 9%, transmission rate was 2.26 microg x cm(-2) x h(-1). In 48 hours, accumulative transdermal rate and transmission rate of tetrahydropalmatine were 20.31%, 0.22 pg x cm(-2) x h(-1). So Zhitong cataplasm had a good release and transdermal properties and transdermal actions were consistent with zero-order kinetics process.

Clinical value of CEA and CYFRA21-1 as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of carcinoembryonic antigen (CEA) or cytokeratin 19 fragment (CYFRA21-1) as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients.</p><p><b>METHODS</b>228 cases of advanced NSCLC with chemotherapy were enrolled into this retrospective study. The serum CEA or CYFRA21-1 levels of all patients were above the cut-off limit before treatment. The relationship between changes of tumor markers (TMs) and imaging therapeutic efficacy or progression-free survival (PFS) was analyzed, and the value of TMs in therapeutic efficacy assessment was evaluated.</p><p><b>RESULTS</b>According to RECIST criteria, partial response (PR) occurred in 40 cases, stable disease (SD) in 151 and PD (progressive disease) in 37. The cut-off values of the changes of TMs between pre- and post-treatment were determined according to the above mentioned criteria. The CEA down (D), stable (S), above (A) groups were 90, 49 and 66 cases, respectively. CYFRA21-1 down (D), stable (S), above (A) groups were 84, 26 and 37 cases, respectively. PR groups were 68.4% and 88.9% in CEA and cyfra21-1 down groups, respectively, 7.9% and 5.6% in the above groups, respectively. PD groups were 59.4% and 76.2% in CEA and CYFRA21-1 above groups, respectively. No PD cases were in the down groups. The changes of TMs in SD group were between them. Statistically significant correlations were observed between changes of TMs and imaging therapeutic efficacy (r(CEA) = 0.45, P = 0.00; r(CYFRA21-1) = 0.44, P = 0.00). PFS among different TMs groups were significantly different (all P < 0.05), which can be used to further distinguish the prognosis among SD subgroups.</p><p><b>CONCLUSION</b>Changes of TMs can be used to predict the imaging therapeutic effect and PFS of the patients, and if the SD group is divided into subgroups according to different therapeutic efficacy and prognosis, it may help the patients to receive individualized treatment.</p>

An overview of epidemics in Liberia and its revelation for epidemic prevention during peacekeeping operations / 军事医学科学院院刊

Communicable diseases are the major threats to the health and security of all the people living in Liberia, including UN peacekeepers from China. The most prevalent communicable diseases in Liberia include malaria, HIV/AIDS, acute respiratory infection, sexual transmitted disease, schistosomiasis, onchocerciasis, tuberculosis, cholera, pertussis, hepatitis, meningococcal disease, typhoid fever, Lassa fever and yellow fever. An insight into the profiles and epidemiology of the above epidemics in Liberia would greatly help peacekeepers with disease diagnosis and epidemic prevention. According to the profiles of epidemics in Liberia and the authors' experience in epidemic prevention in Liberia, the authors recommend that peacekeepers strengthen their epidemic prevention as follows. Firstly, a combined vector control strategy is suggested for the prevention and control of vector-borne diseases. Secondly, water safety should be highlighted by water disinfection and regular water quality testing. Thirdly, vaccines, diagnostic reagents and medications should be accordingly outfitted. Then, the awareness of epidemic prevention and individual hygiene should be improved by education and strict management. Finally, the daily life management for peacekeepers is also very important. The epidemic overviews and strategies for epidemic prevention described in this paper are also useful for all the other peacekeepers deployed in Africa.

Study on the ability of mammalian reovirus BYD1 to induce apoptosis and analysis of the structure of viral major membrane penetration protein involved in proapoptosis induction / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study a newly isolated domestic mammalian reovirus, BYD1, its ability to induce apoptosis analyze the three-dimensional structure of its major membrane penetration protein to predict its function in inducing apoptosis.</p><p><b>METHODS</b>HeLa cells infected with BYD1 reovirus were metered with flow cytometer (FCM) to quantify the ratio of apoptotic cells. The data were analyzed with Student's t-test to judge the ability of BYD1 strain to induce apoptosis. The primary sequence ranged from 582 to 675 per microliter protein of BYD1, T1L, T2J and T3D were aligned and compared. The three-dimensional comparative protein structure model of microliter protein was generated by homology-modeling pipeline SWISS MODEL was applied to annotate its secondary and tertiary structure.</p><p><b>RESULTS</b>BYD1 strain was verified with the ability to induce the apoptosis of HeLa cells. The 643-675 segment composing an alpha-helix showed major difference compared with prototype T2J.</p><p><b>CONCLUSION</b>The newly isolated reovirus BYD1 is an apoptosis inducing strain. The alpha-helix (residues 643 to 675) of microliter protein of BYD1 may play a key role to induce the proapoptotic activity of infected cells.</p>

Hepatic gene expression profile early after 60Co-γ irradiation in mice / 第二军医大学学报

Objective: To study the hepatic gene expression profile early after 60Co-γ irradiaiton in mice with cDNA microarray, in an attempt to understand the molecular mechanism of irradiation damage to liver in mice. Methods: Total RNA was extracted from mice liver 2 days after irradiation with 60Co-γ ray and from normal mice liver. Hepatic gene expression patterns of irradiated and normal mice were compared with cDNA microarray(4 096 genes). RT-PCR was performed to validate the cDNA microarray results. Results: Compared with normal group, 124 genes showed a differential expression in irradiation group, with 46 genes upregulated(maily cell cycle and transcription regulation related proteins) and 78 down-regulated(mainly cytoskeletal genes). Of the 124 genes, 57 had identified functions and could be divided into 6 groups: DNA repair and stress response, cytoskeleton, hydronium channel/transport protein, signaling transduction, intermediary metabolism, and immune related proteins. RT-PCR analysis indicated that the expression of heat shock 70kD protein 5 (Hspa5), RAS p21 protein activator 3 (Rasa3), and NAD(P) H dehydrogenase, quinone 1 (Nqo1) were consistent with cDNA microarray data. Conclusion: Irradiation-induced hepatic injury is of multi-target and multi-pathway.

The Advances and Application in the Expression of Heterologous Gene in Pichia pastoris / 中国生物工程杂志

Pichia pastoris is a new eukaryotic expression system with great potentials, has unexampled advantages in expressing the heterologous proteins and has gotten more and more wide application. The following aspects were described in detail: the advantages of Pichia pastoris in the expression of heterologous genes, the mechanism of the heterologous gene integrations, the glycosylation of the expressed protein and the modification of the post-translated protein.

Effects of soybean isoflavone on liver oxidative stress resulting from 60Co-gamma rays / 第二军医大学学报

To study the effect of soybean isoflavone on liver oxidative stress resulting from 60Co-gamma rays. Methods: Totally 80 normal female Kunming mice were evenly randomized into 5 groups according to body weight: 3 intervention groups, single irradiation group and normal control group. The normal group and single irradiation groups were given 0.5% CMC-Na, and the 3 intervention groups were given different doses of soybean isoflavone (50 mg/kg, 100 mg/kg, 400 mg/kg) respectively for 14 d. The whole body of single irradiation group and intervention groups were subjected to 4.56 Gy 60Co-γ radiation once on the 7th day, and then the mice were killed on the 2nd day and the 7th day after radiation. Results: The CAT activity of liver tissue of 100,400 mg/kg intervention groups and 3 SI groups were significantly increased on the 2nd day and 7th day after irradiation(P<0.05), respectively; the GSH-Px activity of 100 mg/kg SI group was significantly increased(P<0.05) on the 7th day after irradiation; the T-SOD activity of 50 mg/kg SI group was significantly decreased (P<0.05) on the 2nd day after irradiation,while no difference was observed among remaining groups. The MDA content of 100 mg/kg group was significantly decreased on the 7th day after radiation compared with control group, and MDA content of each group subjected to irradiation were increased on the 2nd day after irradiation,but 3 SI groups nearly decreased to normal level on the 7th day after irradiation. Conclusion: The soybean isoflavone can enhance the antioxidant capability of mice, but it does not show a dose-effect relationship.

Effects of soybean isoflavone on liver oxidative stress resulting from 60Co-gamma rays / 第二军医大学学报

To study the effect of soybean isoflavone on liver oxidative stress resulting from 60Co-gamma rays. Methods: Totally 80 normal female Kunming mice were evenly randomized into 5 groups according to body weight: 3 intervention groups, single irradiation group and normal control group. The normal group and single irradiation groups were given 0.5% CMC-Na, and the 3 intervention groups were given different doses of soybean isoflavone (50 mg/kg, 100 mg/kg, 400 mg/kg) respectively for 14 d. The whole body of single irradiation group and intervention groups were subjected to 4.56 Gy 60Co-γ radiation once on the 7th day, and then the mice were killed on the 2nd day and the 7th day after radiation. Results: The CAT activity of liver tissue of 100,400 mg/kg intervention groups and 3 SI groups were significantly increased on the 2nd day and 7th day after irradiation(P<0.05), respectively; the GSH-Px activity of 100 mg/kg SI group was significantly increased(P<0.05) on the 7th day after irradiation; the T-SOD activity of 50 mg/kg SI group was significantly decreased (P<0.05) on the 2nd day after irradiation,while no difference was observed among remaining groups. The MDA content of 100 mg/kg group was significantly decreased on the 7th day after radiation compared with control group, and MDA content of each group subjected to irradiation were increased on the 2nd day after irradiation,but 3 SI groups nearly decreased to normal level on the 7th day after irradiation. Conclusion: The soybean isoflavone can enhance the antioxidant capability of mice, but it does not show a dose-effect relationship.

Prognostic factors in patients with small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors of small cell lung cancer (SCLC) and establish a reliable model of clinical prognostic index.</p><p><b>METHODS</b>Kaplan-Meier and Cox regression were used to analyze the relationship between survival time and prognostic factors in 60 cases of SCLC. The prognostic factors included clinical and laboratory parameters, serum cytokeratin fragment 19 (CYFRA21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R).</p><p><b>RESULTS</b>Kaplan-Meier analysis showed that poor prognosis was in patients with KPS < 80 or extensive disease and unrelated to other clinical parameters such as age, sex and smoking index, and in patients with serum NSE > 30 micro g/L, CEA > 5.0 micro g/L, CA125 > 37 KU/L and sIL-2R > 500 KU/L. Serum IL-2 and CYFRA21-1 were also elevated, but had no significant prognostic value. Multivariate analysis indicated that serum NSE, stage and treatment of disease were independent prognostic factors. The three prognostic factors enabled establishment of a prognostic index (PI) based on a simple algorithm: PI = NSE (0 if < or = 30 micro g/L, 1 if > 30 microg/L) + stage (0 = LD, 1 = ED) + CEA (0 if < or = 5.0 microg/L, 1 if > 5.0 microg/L).</p><p><b>CONCLUSION</b>The stage of disease, systemic treatment and the level of serum NSE are independent prognostic factors. Without considering the influence of treatment-related factors on survival, the levels of serum CEA, NSE and stage of disease before treatment are significant independent prognostic factors. PI calculated on the basis of CEA, NSE and stage is recommended to predict the survival of SCLC.</p>

Prognostic factors in patients with stage III and IV non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors in non-small cell lung cancer (NSCLC) at stage III and IV and establish a reliable model of clinical prognostic index.</p><p><b>METHODS</b>Kaplan-Meier and Cox regression were used to analyze the relationship between the prognostic factors and survival time in 114 cases of NSCLC. The prognostic factors included clinical-pathological features and serum levels of cytokeratin fragment 19 (Cyfra21-1), CEA, neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R).</p><p><b>RESULTS</b>Kaplan-Meier analysis showed that KPS, sex, disease stage, treatment, Cyfra21-1, sIL-2R and CA125 were related to prognosis. Multivariate analysis indicated that Cyfra21-1, stage and treatment were independent prognostic factors. When Cyfra21-1 > 3.5 mg/L, stage IV and chemotherapy < 3 cycles, the relative risk (RR) was 1.691, 2.229 and 3.035, respectively. In patients given 3 or more cycles of chemotherapy, serum Cyfra21-1, sIL-2R and stage at diagnosis were significantly independent prognostic factors. Three of these prognostic factors were used to establish a prognostic index (PI) model based on a simple algorithm: PI = Cyfra21-1 + sIL-2R + stage. The median survival period of patients with 3 or more cycles of chemotherapy were 18 months if PI = 0, 8 months if PI = 1 or 2, and 5 months if PI = 3.</p><p><b>CONCLUSION</b>The serum Cyfra21-1, sIL-2R and disease stage in unresectable NSCLC were independent prognostic factors. PI calculated on the basis of Cyfra21-1, sIL-2R and stage is recommended to predict the survival period of NSCLC.</p>

Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular free Ca2+ in cultured rat hippocampal neurons / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the effects of Pb2+ on N-methyl-D-aspartate (NMDA)-, K(+)- and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration ([Ca2+]i) in cultured fetal rat hippocampal neurons in order to explain the cognitive and learning deficits produced by this heavy metal.</p><p><b>METHODS</b>Laser scanning confocal microscopy was used.</p><p><b>RESULTS</b>The results clearly demonstrated that adding Pb2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca2+]i in a concentration-dependent manner. In contrast, Pb2+ treatment did not markedly affect increases in [Ca2+]i induced by an admixture of QA and KA. The minimal inhibitory effect of Pb2+ occurred at 1 mumol/L, and more than seventy percent abolition of the NMDA-stimulated increase in [Ca2+]i was observed at 100 mumol/L Pb2+. Evaluation of Pb(2+)-induced increase in [Ca2+]i response to elevating extracellular concentrations of NMDA, glycine or calcium revealed that Pb2+ was a noncompetitive antagonist of both NMDA and glycine, and a competitive antagonist of Ca2+ at NMDA receptor channels. In addition, Pb2+ inhibited depolarization-evoked increases in [Ca2+]i mediated by K+ stimulation (30 mumol/L), indicating that Pb2+ also depressed the voltage-dependent calcium channels. Also, the results showed that Pb2+ appeared to be able to elevate the resting levels of [Ca2+]i in cultured neurons, implying a reason for Pb(2+)-enhanced spontaneous release of several neurotransmitters reported in several previous studies.</p><p><b>CONCLUSION</b>Lead can inhibit NMDA-, K(+)-, QA/KA-induced increases in intracellular [Ca2+]i in cultured hippocampal neurons.</p>

Study on Method for Phototoxicity Test / 环境与健康杂志

Objective To explore the influence factors and experimental conditions of phototoxicity test using pure UVA light source.Method The variations of light intensity associated with the exposure duration,the influence of exposure duration to UVA radiation on the temperature of the exposed area were both observed.The phototoxicity of positive control of 8_methoxypsoralen(8_MOP)to skin of healthy adult guinea pigs exposed to UVA radiation at dose of 10 J/cm2 for about 50min was observed also.Results The intensities of UVA light source were stable in the range of 3.3～3.4 mW/cm2 during the period of 100 minute_radiation.After a 100 minute_exposure to UVA radiation at 18 ℃,the temperature of the irridiated area increased 1.5 ℃,8_MOP revealed significant phototoxicity.Conclusion This method for phototoxicity test using pure UVA light source could examine the phototoxicity of a certain chemicals accurately,which was scientific and feasible.