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Purpose To assess the efficacy and safety between broad spectrum penicillins with or without beta-lactamase inhibitors versus 1st and 2nd generation cephalosporins in prevention of post-caesarean infections.Methods Randomized controlled trials (RCTs) comparing broad spectrum penicillins with or without beta-lactamase inhibitors to 1st and 2nd generation cephalosporins were searched in foreign databases, such as the Cochrane Library, PubMed and EMBASE, and chinese databases, including the China National Knowledge Infrastructure (CNKI) WanFang Data and China Science and Technology Journal Database(CSTJ). The included RCTs were analyzed by the software Rev Man 5.4.Results A total of nine RCTs, 1998 patients were involved. Six trials compared broad spectrum penicillins plus beta-lactamase inhibitors versus 1st and 2nd generation cephalosporins, we found there were no differences between interventions for endometritis(RR 0.85, 95% CI 0.57–1.26, I2 = 0.0%), wound infection(RR 1.28, 95% CI 0.53–3.12, I2 = 0.0%), urinary tract infection(RR 1.70, 95% CI 0.06–47.34, I2 = 79%), febrile morbidity(RR 0.95, 95% CI 0.32–2.84, 1 study), maternal rashes(RR 1.20, 95% CI 0.26–5.58, I2 = 0.0%). Four trials compared broad spectrum penicillins versus 1st and 2nd generation cephalosporins, we found there were no differences between interventions for endometritis(RR 3.22, 95% CI 0.45–22.89, I2 = 64%), febrile morbidity(RR 1.93, 95% CI 0.48–7.83, I2 = 84%), wound infection(RR 1.19, 95% CI 0.20–6.97, I2 = 70%), urinary tract infection(RR 9.00, 95% CI 0.49–163.90, 1 study). The postoperative length of stay was longer for women in the broad spectrum penicillins group than 1st generation cephalosporins group(MD 1.50, 95% CI 0.54–2.46, 1 study). Conclusion Based on the results of this study, broad spectrum penicillins with or without beta-lactamase inhibitors and 1st and 2nd generation cephalosporins may have similar efficacy at caesarean section regarding postoperative infections. PROSPERO Registration Number: CRD42022345721.

Mongolians have a long history of using prescriptions, which can be classified into four stages as follows: the germination and experience accumulation stage before the 13 th century, the theoretical formation stage from the 13 th to 16 th century, the rapid development stage from the 17 th to 20 th century, and the leaping development stage from the mid-20 th century to the present. The prescriptions from the ancient classical or representative medical books have always been used by Mongolian physicians for generations, and they are still in use due to the definite curative effects. In 2008, the Notice on Issuing the Supplementary Provisions to the Registration and Management of Traditional Chinese Medicine(TCM) described that China has attached more importance to the excavation and development of classical prescriptions. As stipulated in the Law of the People's Republic of China on Traditional Chinese Medicine, the classical prescriptions should be those available in ancient TCM classics and still in wide use, with exact curative effects, distinct features, and obvious advantages. This paper expounded the historical formation and development of classical prescriptions in Mongo-lian medicine, introduced the five most influential ancient medical books revealing the formation and development of these classic prescriptions, and traced the origin of such classical prescriptions as Wenguanmu Siwei Decoction, Shouzhangshen Bawei Decoction, Jianghuang Siwei Decoction and summarized the origin, development history and characteristics of classical prescriptions in Mongolian medicine, aiming to provide a reference for their further research and development.

Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARα (P/R) and APL cell differentiation. Recent evidence has suggested that P/R fusion protein degradation by arsenic occurs through two steps, namely, rapid solubility change/shift of the P/R fusion protein following arsenic treatment (i.e., transfer of P/R protein from the soluble fraction to the insoluble pellet fraction), and subsequent degradation of these insoluble proteins. However, there is little information regarding the reversibility of arsenic induced P/R fusion protein solubility change as well as protein degradation in the insoluble fraction after removing arsenic. In this study, we used APL cell line NB4 or P/R and PML over-expressed 293T cells as well as HeLa cells to reveal the solubility change of P/R and PML by arsenic exposure, and further determined the fate of these insoluble proteins after the removal of arsenic. Here, for the first time, we found that arsenic induced P/R or PML protein solubility change is an irreversible process. Once arsenic induces a P/R or PML protein solubility change, these insoluble proteins could be degraded by the proteasomal pathway even without continuous arsenic treatment. However, PML and P/R proteins can be newly synthesized after the removal of arsenic, suggesting that great caution should be taken in the clinical therapy of APL patients before ending arsenic treatment.

The cytochrome P450 superfamily (CYPs) is a group of metabolic enzymes involved in drug biotransformation/metabolism. It is the most important drug metabolic enzyme; however, its mechanism of action remains unclear.We investigated the expression of CYP2B6 in HeLa cells induced by interleukin-6 (IL-6) and explored the relationship between differentially expressed chondrocytes 1 (DEC1) and CYP2B6 via luciferase reporter, chromatin immunoprecipitation (ChIP) and ELISA assays.We observed the expression of CYP2B6 in HeLa cells exhibited a time-dependent decrease under the effect of IL-6, and the expression of CYP2B6 down-regulated by IL-6was negatively correlated with DEC1. After overexpression or knockdown of DEC1 in HeLa cells, the expression of CYP2B6 decreased or increased. The luciferase reporter assay and ChIP assay confirmed that DEC1 inhibited the expression of CYP2B6 by binding to the CYP2B6 promoter. ELISA results showed that high expression of DEC1 or low expression of CYP2B6 can promote the secretion of IL-6 in HeLa cells, and the secreted IL-6 can continually downregulate the expression of CYP2B6 in HeLa cells.Our results indicate that DEC1/CYP2B6 pathway in the inflammatory environment of tumours, and this provides a small amount of theoretical basis for the study of genes encoding drug-metabolising enzymes. The cytochrome P450 superfamily (CYPs) is a group of metabolic enzymes involved in drug biotransformation/metabolism. It is the most important drug metabolic enzyme; however, its mechanism of action remains unclear. We investigated the expression of CYP2B6 in HeLa cells induced by interleukin-6 (IL-6) and explored the relationship between differentially expressed chondrocytes 1 (DEC1) and CYP2B6 via luciferase reporter, chromatin immunoprecipitation (ChIP) and ELISA assays. We observed the expression of CYP2B6 in HeLa cells exhibited a time-dependent decrease under the effect of IL-6, and the expression of CYP2B6 down-regulated by IL-6was negatively correlated with DEC1. After overexpression or knockdown of DEC1 in HeLa cells, the expression of CYP2B6 decreased or increased. The luciferase reporter assay and ChIP assay confirmed that DEC1 inhibited the expression of CYP2B6 by binding to the CYP2B6 promoter. ELISA results showed that high expression of DEC1 or low expression of CYP2B6 can promote the secretion of IL-6 in HeLa cells, and the secreted IL-6 can continually downregulate the expression of CYP2B6 in HeLa cells. Our results indicate that DEC1/CYP2B6 pathway in the inflammatory environment of tumours, and this provides a small amount of theoretical basis for the study of genes encoding drug-metabolising enzymes.

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein–associated cancers by hyperthermia. Significance: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers. See related commentary by Wu et al., p. 300.

Pure-phase ERI-structure AlPO-17 and SAPO-17 crystals were prepared using isomorphous (AlPO-17) and heterogeneous (zeolite T, SSZ-13 and SAPO-34) seeds. These heterogeneous seeds acts as the sole silica source for SAPO-17 preparation in most of cases. Crystallization mechanism of SAPO-17 and phase transformation process were demonstrated. On contract, SAPO-17 with impurity phases were obtained by in-situ synthesis. Seeded growth using the two kinds of seeds enhanced the crystallization rates by factors of 10–30 compared with in-situ synthesis. Physicochemical properties and Si, Al and P chemical environments of the products were characterized using X-ray diffraction, scanning electron microscopy, N 2 adsorption-desorption, thermogravimetric analysis, inductively coupled plasma elementary analysis, magic-angle-spinning solid-state NMR spectroscopy and temperature-programmed NH 3 desorption. Synthesis of SAPO-17 with all Si in isolated state demonstrated that SAPO-17 crystallization proceeded by a dissolution-construction mechanism. It included twice phase conventions: dissolved silica-rich zeolites inducing the formation of AFI-structure SAPO-5 and AFI structure converting to ERI framework.

A new modification strategy using precursors of silanized imidazolium-based room temperature ionic liquids (RTILs) has been developed for surface modification of zeolite membranes by the gentle liquid-phase silanization reaction. The advantage of RTILs in selective adsorption of CO 2 could enhance the CO 2 -selective separation for the RTILs-modified membranes. The parameters, such as the precursor and the anion type of RTILs were optimized. Characterizations including Fourier transform infrared spectroscopy, field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy, showed that silanized imidazolium-based RTILs were grafted on the surface of SSZ-13 crystals and membrane. Carbon dioxide/methane selectivity of the modified membranes was strongly depended on the type of the balanced anion of RTILs. Single-gas permeation for H 2 , CO 2 , N 2 , CH 4 , C 2 H 6 and i -C 4 H 10 and mixture CO 2 /CH 4 separation through the fresh and modified membranes were investigated. When [TESPMIM][BF 4 ] precursor was used, the average CO 2 permeance of three modified membranes decreased by only 44% (average CO 2 permeance of 1.0×10 −7 mol m −2 s −1 Pa −1 ) and CO 2 /CH 4 selectivity increased by a factor of 7 (average CO 2 /CH 4 selectivity of 87) for an equilmolar CO 2 /CH 4 mixture at room temperature compared with those of the fresh membranes.

Antimony (Sb) belongs to the same group as arsenic (As) in the periodic table, and both share similar characteristics. However, Sb2O3 (SbIII) has no methylation capacity, unlike arsenic trioxide (As2O3). In the present study, we determined the effect of SbIII on NB4 cells and found that antimony could induce PML-RARα fusion protein degradation, reorganization of PML-NBs, and NB4 cell differentiation with low cytotoxicity. On the other hand, zinc finger motifs in PML protein are considered to be a key target binding site for arsenic-induced PML-RARα protein degradation. Interestingly, antimony and arsenic lost their ability to degrade PML-RARα fusion protein in NB4 cells following pretreatment with phenanthroline (i.e., chelator of zinc ions), indicating that the integrity of zinc finger motifs in PML-RARα fusion protein is a fundamental condition for inducing the protein's degradation by antimony and arsenic. Moreover, we found that SbIII could not induce mutant PML (e.g., A126V and L218P) solubility change and degradation, similar to As2O3. In contrast, we found that the organic antimony compound phenylstibine oxide (PSO) could induce mutant PML protein degradation. In conclusion, our results indicate that SbIII might also be a promising agent to treat acute promyelocytic leukemia, in the same manner as As2O3.

Background Primary neonatal hypocholinesterase is rare; its genetic pattern and mutation still need to be further studied. Methods The patient and his parents are studied using next-generation sequencing technology. Results A boy one day after birth is admitted to the Neonatal Intensive Care Unit at our hospital after experiencing intermittent vomiting for 12 hours. The patient's serum cholinesterase level (113 - 283 U/L) is lower than normal value (4,000 - 12,600 U/L). Many factors of low serum cholinesterase are excluded. We highly suspect that it may be related to congenital factors. Molecular genetic test results show that the patient carried the BCHE gene (NM_000055.2) and has homozygous frameshift mutations at exon 2 c.401dupA (p.Asn134fs) of chromosome 3q26. It is a pathogenicity mutation. This locus mutation belongs to a novel pathogenic mutation. As a result of this mutation, the 134th amino acid Asn began to frameshift and the translation is terminated early. It can cause the Encoding of protein to truncate and lose its normal function. His parents' serum cholinesterase levels (father: 5,135 U/L; mother: 4,367 U/L) are in the normal value range, but his parents carried a heterozygous BCHE gene. Conclusions This study suggests that gene sequence detection should be carried out early in hypocholinesterase of nknown cause in neonates. This study can not only improve understanding of the etiology and pathological mechanism of hypocholinesterase, but also it can enlarge the hypocholinesterase gene mutation spectrum.

Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (As

Aluminophosphate (AlPO)-17 and silicoaluminophosphate (SAPO)-17, for the first time, were made into selective membranes for CO 2 separations. Pure and submicron SAPO-17 seeds were synthesized using nano zeolite T crystals as silica precursor. Membrane microstructure (thickness and crystal size) and separation performance were strongly affected by the support chemistry and seeds. The selective membranes were prepared by a single hydrothermal synthesis step using the low-cost symmetric macroporous ceramic tubes as substrates. Single-gas and CO 2 /CH 4 mixed-gas permeations through SAPO-17 membranes were investigated as functions of pressure and temperature. Carbon dioxide permeance and CO 2 /CH 4 selectivity were decreased with the increase of pressure and temperature. The best membrane showed the smaller-component permeances of 1.1×10 −6 and 8.0×10 −7 mol/(m 2 s Pa), and mixture selectivities of 53 and 14 for equimolar CO 2 /CH 4 and CO 2 /N 2 mixtures, respectively, at 298 K and 0.2 MPa pressure drop.

High-quality SSZ-13 membranes were synthesized using the combinative structure-directing agents of N,N,N, trimethtyl-1-adamantammonium hydroxide and tetraethylammonium hydroxide by one hydrothermal treatment step. The two organics took a “cooperative structural-directing” role on SSZ-13 crystallization. The best membrane had a CO2 permeance of 2.0×10−7 mol/(m2 s Pa) with a CO2/CH4 selectivity of 300 and a C2H4 permeance of 2.9×10−9 mol/(m2 s Pa) with a C2H4/C2H6 selectivity of 11, at 303 K and 0.2 MPa feed pressure for these equimolar binary mixtures, respectively. SSZ-13 membranes also displayed high performances for CO2/CH4 and C2H4/C2H6 separations at higher feed pressures of 0.8–1 MPa. These SSZ-13 membranes were hydrothermally stable at steam for at least 4 days at 378 K and acid-resistance at pH=1.

Improved NaY zeolite membranes were prepared in the presence of ammonium fluoride. The crystallization and separation performance of fluoride-derived NaY zeolite membranes were studied in comparison with fluoride-free membranes. The addition of ammonium fluoride in gel influenced the crystallization and the morphologies of NaY zeolite and zeolite layers, and effectively suppressed the formation of the impurity phase of P-type zeolite in NaY zeolite layers. The fluoride-derived NaY zeolite membranes had thinner zeolite layers and displayed both higher fluxes and separation factors for the dehydration of bio-alcohols (ethanol and butanol) than the fluoride-free membranes. The separation factors increased with the increasing kinetic diameters of alcohols for the methanol, ethanol, i -propanol and n -butanol aqueous solutions. Synthesis reproducibility of fluoride-derived membranes and membrane stability during the dehydration process were also investigated. 29 Si and 19 F MAS NMR results confirmed that fluorine anions were not included in FAU crystals.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17), resulting in the expression of PML-RARα fusion protein, which disrupts the normal PML nuclear bodies (PML-NBs) to micro-speckled pattern, leading to loss of their original functions. Moreover, reformation of PML-NBs in APL by arsenic is considered as one of the important step for APL treatment. Leptomycin B (LMB), a nuclear export inhibitor, is commonly used to inhibit the proteins exporting from the nucleus to the cytoplasm. In the present study, we found that LMB could induce the reformation of PML-NBs in leukemia NB4 cells as well as in APL blast cells from the patients, implying that nuclear shuttle proteins might be involved in the reformation of PML-NBs. Herein, we further found that LMB totally lost the ability to induce PML-NBs reformation when the endogenous PML gene was knocked out, indicating that endogenous PML protein is probably involved in the reformation of PML-NBs. More interestingly, among all PML isoforms (i.e., seven isoforms), reformation of PML-NBs was only observed when co-transfection of PML-RARα with PML-I after LMB treatment. Similarly, deletion of nuclear export signal (NES) of PML-I could also reform PML-NBs, suggesting that the protein level of endogenous PML-I in nucleus is important for the reformation of PML-NBs that interfered by PML-RARα fusion protein. Additionally, LMB has synergistic effect with iAsIII on enhancing PML-RARα fusion protein degradation, and it might provide new insight into APL treatment at clinical level in the near future.

To systematically review the clinical efficacy and safety of Yinzhihuang oral liquid in the treatment of intrahepatic cholestasis of pregnancy(ICP). Literatures published by June 2016 were searched in databases, such as Medline, Pubmed, Cochrane Library, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Full-text Database(VIP), Chinese biomedical literature database(CBM), and Wanfang Database. Randomized controlled trials(RCT) of Yinzhihuang oral liquid were collected according to the inclusion criteria, and the methodological quality of selected literatures was evaluated. The Meta-analysis was conducted by using RevMan 5.3 software. A total of 7 RCTs involving 711 patients were included. The results of Meta-analysis showed that, compared with control group, Yinzhihuang oral liquid significantly alleviated pruritus symptoms[MD=－0.68, 95%CI(－0.95,－041), P

Excessive generation of reactive oxygen species (ROS) is considered to play an important role in arsenic-induced carcinogenicity in the liver, lungs, and urinary bladder. However, little is known about the mechanism of ROS-based carcinogenicity, including where the ROS are generated, and which arsenic species are the most effective ROS inducers. In order to better understand the mechanism of arsenic toxicity, rat liver RLC-16 cells were exposed to arsenite (iAs(III)) and its intermediate metabolites [i.e., monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III))]. MMA(III) (IC(50) = 1 μM) was found to be the most toxic form, followed by DMA(III) (IC(50) = 2 μM) and iAs(III) (IC(50) = 18 μM). Following exposure to MMA(III), ROS were found to be generated primarily in the mitochondria. DMA(III) exposure resulted in ROS generation in other organelles, while no ROS generation was seen following exposures to low levels of iAs(III). This suggests the mechanisms of induction of ROS are different among the three arsenicals. The effects of iAs(III), MMA(III), and DMA(III) on activities of complexes I-IV in the electron transport chain (ETC) of rat liver submitochondrial particles and on the stimulation of ROS production in intact mitochondria were also studied. Activities of complexes II and IV were significantly inhibited by MMA(III), but only the activity of complexes II was inhibited by DMA(III). Incubation with iAs(III) had no inhibitory effects on any of the four complexes. Generation of ROS in intact mitochondria was significantly increased following incubation with MMA(III), while low levels of ROS generation were observed following incubation with DMA(III). ROS was not produced in mitochondria following exposure to iAs(III). The mechanism underlying cell death is different among As(III), MMA(III), and DMA(III), with mitochondria being one of the primary target organelles for MMA(III)-induced cytotoxicity.

Currently, serum biomarkers might usually be thought not to be used for early detection of lung cancer by some researchers. In this study, we used a highly optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight mass spectrometer (MALDI-TOF-MS) to screen non-small cell lung carcinoma (NSCLC) markers in serum. A training set of spectra derived from 45 NSCLC patients, 24 patients with benign lung diseases (BLDs) and 21 healthy individuals, was used to develop a proteomic pattern that discriminated cancer from non-cancer effectively. A test set, including 74 cases (29 NSCLC patients and 45 controls), was used to validate this pattern. After cross-validation, the classifier showed sensitivity and specificity, 86.20% and 80.00%, respectively. Remarkably, 100% of early stage serum samples could be correctly classified as lung cancer. Furthermore, the differential peptides of 1865Da and 4209Da were identified as element of component 3 and eukaryotic peptide chain release factor GTP-binding subunit ERF, respectively. The patterns we described and peptides we identified may have clinical utility as surrogate markers for detection and classification of NSCLC.

// Qian Qian Wang 1, 2, * , Xin Yi Zhou 1, 2, * , Yan Fang Zhang 1, 2 , Na Bu 2 , Jin Zhou 3 , Feng Lin Cao 3 , Hua Naranmandura 1, 2 1 Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China 3 Department of Hematology and Oncology, The First Clinical College of Harbin Medical University, Harbin 150086, China * These authors have contributed equally to this work Correspondence to: Hua Naranmandura, e-mail: narenman@zju.edu.cn Keywords: acute promyelocytic leukemia, arsenic trioxide, trivalent arsenicals, arsenic binding proteins, monomethylarsonous acid Received: June 02, 2015 Accepted: July 06, 2015 Published: July 15, 2015 ABSTRACT Arsenic trioxide (As 2 O 3 ) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As 2 O 3 -induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As 2 O 3 , which results in initiation of PML-RARα degradation. However, after injection, As 2 O 3 is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA III ) and dimethylarsinous acid (DMA III ), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As 2 O 3 (as iAs III ) and its intermediate metabolites (i.e., MMA III /DMA III ) in NB4 cells. Inorganic iAs III predominantly showed induction of cell differentiation, while MMA III and DMA III specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs III , MMA III showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARα fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation.

Background: The study was to examine Perceived Health Status, Climacteric Symptoms, and Health-Promoting Lifestyle among Middle-Aged Women residing in Jeju Island, and to identify the relationship among variables, ultimately to provide the basic data in developing health-promoting program for them in future.Methods: The data were collected from Sep. 1st to Sep. 20th, 2004, and the subjects consisted of 112 women aged between 40 years old and 60 years old, residing at Jejudo. Data analyses were conducted by using Pearson correlation coefficients, t-test, and ANOVA.Results: In Health-promoting lifestyle, the more educated subjects and those who have experienced diseases were found doing more health-promoting lifestyle. In perceived health status, the subjects educated over college, the subjects satisfied with marriage, and the subjects who have not experienced diseases were indicating higher. In climacteric symptoms, subjects aged 50 to 59 years old, subjects educated less than primary school, subjects not satisfied with marriage, and subjects with monthly family income over 2 million Won were higher. Subjects with experience of diseases were also higher than subjects with no experience of diseases. Health-promoting lifestyle was positively correlated with perceived health status and showed no correlation with climacteric symptoms.Conclusion: It was suggested that similar studies should be carried out for more subjects from various provinces, as the study was limited to only 112 middle-aged women residing at Jejudo, and thereby the development of health-promoting program for middle-aged women should be conducted.

Three minor sulfur-containing arsenic metabolites: monomethylmonothioarsonic acid (MMMTA(V)), dimethylmonothioarsinic acid (DMMTA(V)), and dimethyldithioarsinic acid (DMDTA(V)) were recently found in human and animal urine after exposure to inorganic arsenic. However, it remains unclear how the thioarsenicals are formed in the body and then excreted into the urine. It is hypothesized that the generation of thioarsenicals occurs during enterohepatic circulation. To address this hypothesis, male Sprague Dawley (SD) rats and Eisai hyperbilirubinuric (EHB) rats (with deficiency of multidrug resistance-associated protein 2) were orally administered a single dose of inorganic arsenite (iAs(III)) at 3.0 mg kg(-1) of body weight. Five hours after dosing, less than 1.0% of the dose was recovered in the bile of EHB rats, while more than 27% of the dose was recovered in the bile of SD rats, with the majority being monomethylarsinodiglutathione [MMA(SG)(2)] with a small amount of arsenic triglutathione [iAs(SG)(3)]. During the early time periods (3 h and 6 h) the arsenic levels in the liver, red blood cells (RBCs) and plasma of EHB rats were higher than those of SD rats, and approximately 76% and 87% of the dose was recovered in the RBCs of SD and EHB rats, respectively, at day 5 after dosing. However, there were no significant differences in arsenic concentration in urine between the two types of animal. Regarding the arsenic species in the urine of both types of rat, significant levels of thiolated arsenicals MMMTA(V) and DMMTA(V) were detected in SD rat urine, however in EHB rat urine only low levels of DMMTA(V) were detected. The present result of the metabolic balance and speciation study suggests that the formation of MMMTA(V) and DMMTA(V) in rats is dependent on enterohepatic circulation. In addition, in vitro experiments indicated that arsenicals excreted from bile may be transformed by gastrointestinal microbiota into MMMTA(V) and DMMTA(V), which are then absorbed into the bloodstream and finally excreted into the urine.

In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA.We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm.About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%.Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.

Quite a few new thioarsenicals have recently been found in urine of arsenic-exposed humans and animals, and some of them have been shown to be highly toxic to cells. However, little is known about their toxic effects and metabolism in the body. In order to elucidate the toxic mechanism of thioarsenicals, we further focused on the distribution and metabolism of monomethylmonothioarsonic acid (MMMTA(V)) in rats. MMMTA(V) was synthesized chemically and injected intravenously into rats at the dose of 0.5mg As/kg, followed by speciation analysis of selected organs and body fluids at 10 min and 12h after the injection. MMMTA(V) was excreted into urine in its intact form, and approximately 35% of the dose was recovered in urine at 12h after the injection, suggesting that MMMTA(V) was taken up more effectively by organs/tissues than non-thiolated, monomethylarsonous acid (MMA(V)) previously studied. On the other hand, the liver and kidneys contained arsenic that was in a protein-binding form with free forms of DMA(V) or DMDTA(V) at 10 min, and disappeared at 12h after the injection. Moreover, these bound arsenic species in kidneys were converted back to MMA(V) after oxidation with H(2)O(2), suggesting that the arsenic bound to proteins had been reduced within the body and was in a trivalent oxidation state. In red blood cells (RBCs), most of the arsenic was in the form of DMA(III) bound to hemoglobin (Hb), and approximately 40% of the dose was recovered in RBCs at 12h after injection. These results indicate that arsenic accumulated preferentially in RBCs after being transformed to DMA(III). In addition, we have also discussed the effect of MMMTA(V) on viability of human bladder cancer T24 cells in comparison with MMA(V). Consequently, MMMTA(V) was assumed to be a more toxic arsenic metabolite than non-thiolated MMA(V).

Recently, due to the rapid development of proteomic techniques, great advance has been made in many scientific fields. We aimed to use magnetic beads (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles.Using weak cation exchange magnetic beads (MB-WCX) to isolate and purify low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip-MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic algorithm (GA).In the working mass range of 800 - 10 000 Da, 99 distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were resolved in lung adCA versus healthy persons. The profile gained by GA that could distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with sensitivity of 80%, specificity of 93%, while that could separate adCA from healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of 94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen (CEA) in this experiment was significantly lower than our discriminatory profiles (P0.005). We further identified a eukaryotic peptide chain release factor GTP-binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve as candidate biomarkers for lung adCA.Magnetic beads based MALDI-TOF-MS technology can rapidly and effectively screen distinctive proteins/polypeptides from sera of lung adCA patients and controls, which has potential value for establishing a new diagnostic method for lung adCA.

Using Meta analysis to evaluate the value of (18)F-FDG PET/CT ((18)fluorine-fluorodeoxyglucose Positron emission tomography/computed tomography) in differentiating between benign and malignant pulmonary lesions.Relevant documentations from PubMed and other 5 databases from 1980 to 2008 were searched, and the eligible literatures according to the inclusive criteria were selected. The statistical information and quality of science were assessed and classified. The data were analyzed using Meta-Disc1.4 software. The diagnostic value of PET/CT in distinguishing benign from malignant pulmonary lesions was evaluated by the pooled sensitivity, specificity, the likelihood ratio (LR) and summary receiver operating characteristic curve (SROC curve) statistical indicators.Seven literatures were collected including 5 in English and 2 in Chinese, and 795 cases were included in the study. Heterogeneity test showed that the homogeneity of the study was good. By using deterministic models to analyze the data, the value of the weighted sensitivity was 95% (93% - 97%), the specificity was 77% (71% - 82%), the positive likelihood ratio was 4.12, negative likelihood ratio was 0.08, and the SROC area under the curve (area under curve, AUC) was 94%.PET/CT is of high diagnostic value in differentiation between benign and malignant lung lesions, but large sized, multicenter, prospective studies are needed to assess its clinical value more accurately.

To screen the serum biomarker proteins of lung squamous cell carcinoma (SCCs) by liquid chip-mass spectrometry technology.All serum samples, including 34 SCCs, 46 benign lung diseases (BLDs) and 44 healthy individuals, were analyzed by CLINPROT system in order to study the serum protein expression profiles. Then the discriminatory proteins were detected by FlexAnalysis 3.0 software. Biomarkers were identified by liquid chromatography-tandem mass spectrometry (LCMS/MS).Comparing the differential serum expression proteins between SCCs and healthy individuals, and SCCs and BLDs respectively. Ninety-six differential protein peaks [mass-to-charge ration (M/Z) between 800 and 10 000] were found between SCCs and healthy individuals. In these protein peaks, the expression of protein peaks at 4054.13 M/Z and 4267.46 M/Z had the largest difference between them. The two protein peaks could accurately separate SCCs from healthy individuals by the frame of axes. Similarly, 99 differential protein peaks were automatically detected between SCCs and BLDs. In these protein peaks, the expression of protein peaks at 5065.27 M/Z and 4054.02 M/Z had the largest difference between them. The two protein peaks could accurately separate SCCs from BLDs by the frame of axes. Identified by LC-MS/MS, 1778 M/Z and 1865 M/Z might be assayed jointly and corresponded to complements C3 fragment or C3f precursor.Differential protein expressions existed between SCCs versus healthy individuals and SCCs versus BLD patients. It is feasible to screen the diagnostic serum biomarkers of SCC with a high sensitivity and specificity by using CLINPROT system.