A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer / 亚洲男科学杂志(英文版)

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

Association between microRNA-137 Gene Polymorphisms and Ischemic Post-stroke Depression / 中国康复理论与实践

Objective:To analyze the relationship between microRNA-137 gene polymorphisms and ischemic post-stroke depression (PSD). Methods:January, 2017 to January, 2019, the single nucleotide polymorphism (SNP) of rs1625579 in microRNA-137 was genotyped in 250 ischemic PSD patients and 250 healthy controls with SNaPshot. The expression of microRNA-137 was measured with quantitative real-time polymerase chain reaction in the mononuclear cells, and the association of the SNP rs1625579 with microRNA-137 expression was analyzed. Results:The allele T was more in the patients than in the controls (OR = 2.033, 95%CI 1.255 to 3.294, P = 0.003), as well as the genotype TT (OR = 2.139, 95%CI 1.272~3.595, P = 0.004). The microRNA-137 expression was less in the patients than in the controls (t = 28.23, P < 0.001). For the controls, the microRNA-137 expression was also less in those with genotype of TT than with GT and GG (t = 3.764, P < 0.001). Conclusion:The genotype TT of SNP rs1625579 in microRNA-137 is a risk factor of susceptibility to ischemic PSD, which may associate with the decrease of expression of microRNA-137.

Nucleophosmin modulates the alleviation of atopic dermatitis caused by the marine-derived compound dihydroaustrasulfone alcohol

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

Effects of Tcd A on Rho GTPases and the Cytoskeleton of Leukemia Cell Line K562 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of clostridium difficile toxin A(TcdA) on the Rho GTPases and the cytoskeleton in K562 cells.</p><p><b>METHODS</b>K562 cells were cultured in vitro with different concentration of TcdA.The effect of TcdA proliferation of cells was detected by MTT method after the K562 cells were stimulated with TcdA for 24,48 and 72h; the expression of cdc42, RhoA, Rac1 mRNA was assessed by RT-PCR; the changes of the microtubule, the microfilament were observed by confocal laser scanning microscopy.</p><p><b>RESULTS</b>The proliferation of K562 cells was inhibited after exposure to TcdA for 24, 48 and 72h, and the inhibitory rate was 47.67% in the treatment for 48 h. the cdc42，RhoA and Rac1 mRNA expressions in the experimental groups decreased after treated with TcdA(P<0.05), which positively correlated with concentration of TcdA. Also, the microfilament decreased ,which was observed by confocal laser scanning microscopy.</p><p><b>CONCLUSION</b>TcdA inhibites K562 cell proliferation and induces apoptosis, TcdA can change the cytoskeleton structure through the cytoskeletal protein genes cdc42 and RhoA, Rac1 mRNA expression,. It is related with cell microfilament content decreasing.</p>

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties / 癌症

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

Inhibitory effect of apatinib on HL-60 cell proliferation and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of apatinib, a small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, on the proliferation of human acute myeloid leukemia HL-60 cells and explore the possible mechanism.</p><p><b>METHODS</b>MTT assay was used to assess the cytotoxicity of apatinib in HL-60 cells. The apoptosis and cell cycle changes of the cells in response to apatinib treatment were analyzed by flow cytometry, and Western blotting was used to assay P-Akt and P-Erk1/2 expressions in the cells.</p><p><b>RESULTS</b>Apatinib significantly inhibited the proliferation of HL-60 cells in vitro with an IC(50) of 4.96∓0.32 µmol/L. Apatinib treatment significantly increased the apoptotic rate of the cells in a dose-dependent manner, but produced no significant effect on the cell cycle (P>0.05). Western blotting showed that the expressions of P-Akt and P-Erk1/2 decreased in HL-60 cells after a 48-h apatinib treatment.</p><p><b>CONCLUSION</b>Apatinib inhibits the proliferation of HL-60 cells by inducing cell apoptosis probably through the mechanism of inhibiting the expressions of the Akt/Erk1/2 signal transduction pathway.</p>

Multidrug resistance-associated proteins and their roles in multidrug resistance / 药学学报

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Multidrug resistance-associated proteins (MRPs) play an important role in the process of MDR. As an ATP-binding cassette (ABC) transporter superfamily, MRPs are selective and specific drug efflux pumps. In this paper, physiological characteristics, structural characteristics and resistance profile of MRPs and the associated reversal studies are reviewed.

A cell-based screen for anticancer activity of 13 pyrazolone derivatives / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed.</p><p><b>METHODS</b>To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells.</p><p><b>RESULTS</b>Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively.</p><p><b>CONCLUSION</b>Compound 9 was the most promising antitumor agent in this study.</p>

Study of dental caries and correlated factors of 12-year-old children in Dongxiang, Baoan and Yugu races / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the epidemiology of dental caries and its correlated factors of 12-year-old children in Dongxiang, Baoan and Yugu races.</p><p><b>METHODS</b>According to the method of third national oral health epidemiologic investigation, 448 12-year-old children in Dongxiang, Baoan and Yugu races were randomly collected and the epidemiological investigation of dental caries, oral bacteriological detection and oral hygiene behavior were carried out.</p><p><b>RESULTS</b>1) The caries prevalence rate of Dongxiang, Baoan and Yugu races were 40.52%, 44.29%, 46.45%, respectively. The average caries of Dongxiang, Baoan and Yugu races were 0.92, 0.90, 1.13, respectively. 2) The main ranks of Streptococcus mutans in saliva were class 2 and class 3 in Dongxiang and Baoan races. However, it was class 0 or class 1 in Yugu race. The level of Streptococcus mutans in dental plaque was higher in Dongxiang and Baoan races than in Yugu race. 3) The children's everyday brushing rate was higher in Yugu race than in Dongxiang and Baoan races (P<0.01). But there were no difference between Dongxiang and Baoan races.</p><p><b>CONCLUSION</b>The caries prevalence rates of 12-year-old children in Dongxiang, Baoan and Yugu races are high. The main factors of high caries prevalence rate were low brushing rate and dental plaque couldn't be removed effectively. Oral health education should be strengthened in the three race areas.</p>

Progress of individualized chemotherapy guided by chemosensitivity test / 药学学报

In spite of receiving chemotherapy, the response of patients with cancer can be extremely variable. Chemosensitivity testing is being applied in institutes and some hospitals to improve the effects of chemotherapy. It would be useful for choosing the most effective drug and strategy for individual chemotherapy and to exclude the resistance of the tumor cells. In this way, the individualized chemotherapy can be established. Up to today, there are more than 10 approaches established for chemosensitivity testing assays, such as single cell culture assay (including MTT, MTS, ATP), nude mouse model sensitivity examination, collagen gel droplet embedded culture drug sensitivity test and histoculture drug response assay etc. This paper reviews some current methods, and their possibility for directing clinical chemotherapy.

An overview of type E botulism in China / 生物医学与环境科学（英文）

The geographical distribution of C. botulinum type E and its associated disease, type E botulism in China, is different from that in other areas of the world. Cases of type E botulism generally arise in costal regions. In China, however, type E botulism is found primarily in the Qinghai-Tibet plateau of northwest China far from the ocean, at an altitude of approximately 4-5 km. The foods most commonly associated with the disease are fermented grain and beans as well as raw meat. A suspected outbreak of type E botulism poisoning in the central costal region of China in the 1990s prompted the collection and analysis of samples of mud, sand, and fish from the region. The toxin produced by type E botulinum was found in these samples. Surprisingly, though, upon further analysis, the strain isolated from the samples was identified not as type E C. botulinum, but as the neurotoxigenic bacterium Clostridium butyricum.

Advance of several types of important marine antitumor drugs / 药学学报

Marine antitumor drugs have been the research focus in the world. Recently, advancement has been made in the investigation of six types of compounds including bryostatin-1, ecteinascidin-743, dolastatin, didemnin B, psammaplin and halichondrin B. In this review, we summarized the recent research progress of the above mentioned marine antitumor drugs and their derivatives. Also, the development tendency of marine antitumor drugs was discussed.

Advances in the study of expression and regulation of P-glycoprotein / 药学学报

Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to the establishment of curative chemotherapy regimens for cancer. Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene is the major molecular mechanism enhancing efflux pump for various anticancer agents, hence caused MDR. Transcription factor, DNA methylation, histone acetylation/deacetylation, phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role in regulation of P-glycoprotein, and may become new therapeutic targets. This paper summarized the advances of studies on expression and regulation of P-glycoprotein.

Induction of apoptosis of tumor multidrug resistance cell by uvarigrin and its mechanism / 药学学报

<p><b>AIM</b>To study the effect of uvarigrin on mitochondrial dependent pathway during the apoptosis induced by it in MDR KBv200 cells and their parental sensitive KB cells.</p><p><b>METHODS</b>MTT assay was used to detect the cytotoxic effect of uvarigrin on KBv200 and KB cells. Annexin V FITC staining identified uvarigrin-induced apoptosis in KBv200 and KB cells. These cells underwent incubation with DCFH-DA, or DiOC6, followed by flowcytometry for the measurement of reactive oxygen species (ROS) and mitochondrial membrane potential (deltapsim), respectively. The Western blotting analysis was performed on Caspase-9 activation.</p><p><b>RESULTS</b>Uvarigrin inhibited the growth of KBv200 cells and KB cells in vitro. Most of the uvarigrin-induced cells death was found to be due to apoptosis, as determined by Annexin V FITC staining. During the apoptosis, the level of ROS increased while the level of deltapsim decreased in a time-dependent manner. Uvarigrin triggered Caspase-9 activation.</p><p><b>CONCLUSION</b>Uvarigrin induced apoptosis in KBv200 cells and KB cells probably through a mitochondria-dependent pathway.</p>

Apoptosis of human carcinoma of mouth floor KB cells and multidrug resistant KBv200 cells induced by azide methyl anthraquinone derivative / 药学学报

<p><b>AIM</b>To determine the effects of azide methyl anthraquinone derivative (AMAD) on growth inhibition and inducing apoptosis of multidrug resistant (MDR) KBv200 cells and parental drug-sensitive KB cells.</p><p><b>METHODS</b>Cytotoxicity was determined by tetrazolium (MTF) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (deltapsi(m)) in cells were labeled with DCFH-DA and DiOC6 and tested by flow cytometry. Annexin V stain and DNA ladder were used to examine the apoptosis of KB and KBv200 cells induced by AMAD.</p><p><b>RESULTS</b>AMAD was shown to inhibit the growth of KB and KBv200 cells significantly in a concentration-dependent manner, with mean IC50 of 0.36 and 0.45 micromol x L(-1), respectively. The generation of ROS increased obviously after the cells were treated with AMAD for 12 h, up to the peak in 24 h, meanwhile the levels of deltapsi(m) were time-dependently decreased. DNA fragmentation appeared on the agarose gel. Annexin V stain showed AMAD induced apoptosis of KB and KBv200 cells also in a concentration-dependent manner.</p><p><b>CONCLUSION</b>AMAD showed inhibitory effect on both MDR KBv200 cells and parental drug-sensitive KB cells. The mechanism of action was associated with the increase of the cellular ROS level and the decrease of the mitochondrial membrane potential induced by AMAD, which result in cell apoptosis.</p>

Synthesis and antitumour activities of some pteridine derivatives / 药学学报

<p><b>AIM</b>To study the synthesis and antitumour activities of some aryl-substituted pteridines.</p><p><b>METHODS</b>A series of aryl-substituted pteridines were synthesized from 4, 6-diamino-5-nitrosopyrimidines by cyclization with 4-aminophenylacetonitriles. The antitumour activities were tested by MTT method.</p><p><b>RESULTS</b>Nine new compounds (I-III) were synthesized and their structures were characterized by EA, IR, 1HNMR and MS spectra. Compounds I-III showed antitumour activities in vitro.</p><p><b>CONCLUSION</b>Compounds I-III showed remarkable antitumour activities in vitro. No interaction was determined between the title compounds and calf thymus DNA. It indicated that these compounds possibly inhibit dihydrofolate reductase (DHFR) or other enzymes on which folic acid depends.</p>

Apoptosis and hemodynamic changes of the penile tissue in diabetic rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the apoptosis and hemodynamic changes of the penile tissue in diabetic and healthy rats.</p><p><b>METHODS</b>Sixteen chronic diabetic and 10 matched normal control rats were injected with a single dose of streptozotocin (STZ) 65 mg/kg and the diabetic model established. Eight weeks later the rats were killed, their haemoglobin Alc( HbAlc) measured, and their penises harvested. TUNEL assay (in situ nick end-labeling) and flow cytometry were used to analyse the penile cells for apoptosis. The thickness and diameter of the arteries were measured.</p><p><b>RESULTS</b>TUNEL showed apoptosis in the chronic diabetic rats. Flow cytometric analysis showed the apoptotic peak in the penile cells of the chronic diabetic rats when compared with the controls (P < 0.05). There was significant difference between the diabetic and healthy rats. Morphological analysis revealed that the thickness of the artery wall increased while the artery diameter decreased in the diabetes group compared with the controls.</p><p><b>CONCLUSION</b>Diabetes can lead to increasing apoptosis of the penile tissue, cause a decrease in the penile artery diameter and the thickening of the penile artery wall.</p>

Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89-2 / 药学学报

<p><b>AIM</b>Annonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells.</p><p><b>METHODS</b>Cytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay.</p><p><b>RESULTS</b>The compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol.L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P < 0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg.kg-1, q2d x 6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol.L-1 of 89-2.</p><p><b>CONCLUSION</b>Both MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.</p>

An experimental study of the inhibition of tamoxifen on rat model of benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVES</b>To study the inhibitory mechanism of tamoxifen on benign prostatic hyperplasia.</p><p><b>METHODS</b>The Wistar male adult rats were injected into muscle with testosterone propionate 4-6 mg/kg, simultaneously were irrigated into stomach with tamoxifen citrate 0.21 mg/kg. The partly rats of each group were decapitated at 7, 15 and 30 days, then their index numbers of prostate were calculated, and the structural changes of the prostatic histocyte were observed in the light microscopy and scan electronic microscopy.</p><p><b>RESULTS</b>At the 7th, 15th, and 30th day, the index numbers of prostate of those rats which had been injected only with testosterone propionate were higher than that of the control group and the irrigating group(P < 0.05). The hyperplasia of the prostatic epithelial cells and the ground substance of those rats, which had been irrigated with tamoxifen citrate, had not happened in light microscopy and the scan electronic microscopy.</p><p><b>CONCLUSIONS</b>Tamoxifen could block the effect of the estrogen, which could suppress the prostatic hyperplasia. This study could provide the experimental evidences for using Tamoxifen to treat the human benign prostatic hyperplasia.</p>

Minerais pesados provenientes do leito do rio amazonas

ABSTRACT Bed samples of the Amazon River were collected from Iquitos (Peru) to Belém (Brazil). 28 selected samples were analysed and 12 types of heavy minerals were found: tourmaline, zircon, garnet, staurolite, hypersthene, pyroxene (augite), amphibole (hornblende), tremolite, magnetite or ilmenite and leucoxene. Most of the samples presented large amount of idiomorphic unstable minerals such as hypersthene, augite and amphibole pointing towards basic and ultra-basic rocks source. These unstable minerals diminish toward the lower portion of the river. Stable minerals such as zircon and tourmaline have showed both angular and round shapes, which indicate more than one source but in any case originating from acid rocks. A cluster analysis method was applied to the data and two main clusters were determined. The first group, located at the upper Amazon River, is rich in unstable minerals, probably from an Andean source. The second group, which includes samples located below the confluence of the Juruá River, presents a high zircon and tourmaline percentage which indicates a contribution from the Precambrian Shields in adition to the Andean source.

Resumo Com a intenção de verificar a origem do material transportado pelo Rio Amazonas, amostras de calha foram coletadas em 60 locais entre Belém (Brasil) até Iquitos (Peru). Tendo sido escolhidos 28 amostras, as mesmas foram submetidas a um estudo mineralógico, o qual revelou os seguintes minerais pesados presentes: turmalina, zircão, granada, estaurolita, hiperstênio, piroxênio (augita), anfibólio (hornblenda), tremolita, magnetita ou ilmenita e leucoxênio. Em quase todas as amostras ocorre uma grande quantidade de minerais instáveis idiomórficos, como hiperstênio, augita e anfibólio, indicando uma área fonte constituída pelas rochas básicas e ultrabásicas, diminuindo para jusatite. Minerais estáveis, como zircão e turmalina, apresentam-se tanto angulosos como arredondados, indicando mais de uma área fonte, mas de qualquer modo sempre a partir de rochas ácidas. Aplicando aos dados o método classificatório multivariante da análise de agrupamentcs (cluster analysis), dois maiores grupos de amostras foram ressaltados: um constituído por amostras localizadas no alto Rio Amazonas e com maior teor em minerais instáveis, provavelmente com origem andina; o outro formado principalmente por amostras que se localizam, a partir da confluência com o Rio Juruá, até Belém e contendo uma alta porcentagem em zircão e turmalina, indicando além de uma contribuição andina, fontes nos escudos precambrianos a norte e sul do Rio Amazonas.