IL23R as an indicator of immune infiltration and poor prognosis in intrahepatic cholangiocarcinoma: a bioinformatics analysis.

Background: Although the incidence of intrahepatic cholangiocarcinoma (CHOL) is low, the prognosis is very poor. The expression level of interleukin 23 receptor (IL23R) is linked to the occurrence and development of cancers. This study aimed to identify the role of IL23R in CHOL using bioinformatics tools and experimental validation. Methods: Circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database, and R software was used for data analysis and visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional enrichment analysis, which was verified with gene set enrichment analysis software. Clinical data were obtained from The Cancer Genome Atlas (TCGA), and survival analyses were performed using the DriverDBv3 database and the Gene Expression Profiling Interactive Analysis website. The TIMER2.0 database provided us for immune cell infiltration analysis results of IL23R. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for IL23R expression verification. Results: Differentially expressed (DE) mRNAs were enriched in phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, immune-related tumor microenvironment (TME), and amino acid metabolism, etc. In addition, expression of IL23R was associated with immune infiltration-related cells. Furthermore, a circRNA-miRNA-IL23R network and a IL23R protein-protein interaction network were established. Most importantly, IL23R, as a prognostic gene, was found to have a low expression in CHOL. Conclusions: A circRNA-miRNA-IL23R network was identified, and it was found that IL23R may be a prognostic and immune-related biomarker in CHOL, which is worthy of further exploration.

The effect of prolonged neoadjuvant endocrine therapy on the efficacy of treatment with breast cancer.

BACKGROUND: At present, there is no consensus on the required duration of neoadjuvant endocrine therapy (NET), yet there is no consistent conclusion on the factors influencing the efficacy of treatment with breast cancer after prolonged treatment. OBJECTIVE: To explore the effect of prolonged NET on the efficacy of patients with breast cancer and analyze the factors influencing the efficacy of treatment with breast cancer after the treatment duration is prolonged. METHODS: The case histories of 51 patients who were diagnosed with breast cancer and received NET in our hospital from September 2017 to December 2021 were retrospectively analyzed. All patients received NET for over 12 months. The clinical efficacy and tumor size changes after treatment for six months and 12 months were compared, and the factors influencing the efficacy of treatment with breast cancer after patients' treatment duration was prolonged were analyzed. RESULTS: (1) Among the 51 patients, the objective remission rate (ORR) of NET, at T = 6 months was 21.6%, and the average tumor size was 15.52 ± 7.30 mm. The ORR of the NET at T = 12 months was 52.9%, and the average tumor size was 13.79 ± 7.43 mm. (2) After the treatment duration was prolonged, the clinical ORRs of patients with estrogen receptor (ER) (+) and progesterone receptor (PR) (+) were significantly higher than that of patients with ER (+) and PR (-) and patients with ER (-) and PR (+), which was (P < 0.05). (3) There was no significant difference between the patients' axillary lymph node status and the Ki67 expression before treatment and the clinical ORR after prolonged treatment, which was (P> 0.05). CONCLUSIONS: (1) Prolonging the NET duration for patients with breast cancer can improve their clinical ORR and further reduce the tumor size, but patients' conditions should be closely monitored during the treatment process to prevent the progression of disease due to drug resistance. (2) The expression state of ER or PR may be used as a factor influencing the efficacy of treatment with breast cancer after prolonged treatment. (3) There was no significant effect on the patients' axillary lymph node status and the Ki67 expression before treatment on the clinical efficacy after prolonged treatment.

Application of triple evaluation method in predicting the efficacy of neoadjuvant therapy for breast cancer.

OBJECTIVE: To analyze the factors related to the efficacy of neoadjuvant therapy for breast cancer and find appropriate evaluation methods for evaluating the efficacy of neoadjuvant therapy METHODS: A total of 143 patients with breast cancer treated by neoadjuvant chemotherapy at Baotou Cancer Hospital were retrospectively analyzed. The chemotherapy regimen was mainly paclitaxel combined with carboplatin for 1 week, docetaxel combined with carboplatin for 3 weeks, and was replaced with epirubicin combined with cyclophosphamide after evaluation of disease progression. All HER2-positive patients were treated with simultaneous targeted therapy, including trastuzumab single-target therapy and trastuzumab combined with pertuzumab double-target therapy. Combined with physical examination, color Doppler ultrasound, and magnetic resonance imaging (MRI), a systematic evaluation system was initially established-the "triple evaluation method." A baseline evaluation was conducted before treatment. The efficacy was evaluated by physical examination and color Doppler every cycle, and the efficacy was evaluated by physical examination, color Doppler, and MRI every two cycles. RESULTS: The increase in ultrasonic blood flow after treatment could affect the efficacy of monitoring. The presence of two preoperative time-signal intensity curves is a therapeutically effective protective factor for inflow. The triple evaluation determined by physical examination, color Doppler ultrasound, and MRI in determining clinical efficacy is consistent with the effectiveness of the pathological gold standard. CONCLUSION: The therapeutic effect of neoadjuvant therapy can be better evaluated by combining clinical physical examination, color ultrasound, and nuclear magnetic resonance evaluation. The three methods complement each other to avoid the insufficient evaluation of a single method, which is convenient for most prefecty-level hospitals. Additionally, this method is simple, feasible, and suitable for promotion.

Design and exploration of 5-nitro-3-trinitromethyl-1H-1,2,4-triazole and its derivatives as energetic materials.

According to the fact that 5-nitro-3-trinitromethyl-1H-1,2,4 triazole (NTNMT) is a successful, good explosive, energetic groups such as -CH3, -NH2, -NHNO2, -NO2, -ONO2, -NF2, -CN, -NC, -N3 groups were introduced into NTNMT and their oxygen balance was at about zero. The energetic properties, detonation performance, and sensitivity were studied at the B3LYP/6-31G** level of density functional theory to seek for possible high energy density compounds. The effects of substituent groups on heat of formation (HOF), density ρ, detonation velocity D, detonation pressure P, detonation energy Q, and sensitivity (evaluated using oxygen balance OB, the nitro group charges -QNO2, and bond dissociation energies BDE were studied and discussed. The order of contribution of the substituent groups to ρ, D, and P was -NF2 > -ONO2 > -NO2 > -NHNO2 > -N3 > -NH2 > -NC > -CN > -CH3; while to HOF is -N3 > -NC > -CN > -NO2 > -NF2 > -ONO2 > -NH2 > -NHNO2 > -CH3. The trigger bonds in the pyrolysis process for NTNMT derivatives may be N-NO2, N-NH2, N-NHNO2, C-NO2, or O-NO2 varying with the attachment of different substituents. Results show that NTNMT-NHNO2, -NH2, -CN, and -NC derivatives have high detonation performance and good stability. In a word, the oxygen balance at about zero strategy in this work offers new routes for the improvement in properties and stabilities of energetic materials. In the present paper, several 5-nitro-3-trinitromethyl-1H-1,2,4 triazole (NTNMT) derivatives were designed. Their energetic properties, detonation performance, and sensitivity were studied at the B3LYP/6-31G** level of density functional theory (DFT) to seek for possible high energy density compounds (HEDCs). The different substituents have some changes in the influence on heat of formation (HOF), density ρ, detonation velocity D, detonation pressure P, detonation energy Q, and sensitivity. In a word, the oxygen balance at about zero strategy in this work offers new routes for the improvement in properties and stabilities of energetic materials.

Chemistry, manufacturing and controls regulatory considerations for marketing authorization application of therapeutic antibody in China / 药学学报

The marketing authorization application is a milestone of drug life cycle, which indicates a candidate has potential to become a commercial drug. As of now, there are only 12 domestic therapeutic antibodies approved in China. The chemistry, manufacturing and controls (CMC) development and evaluation of monoclonal antibody were more challenging for both industry and authority agency. As the result of domestic biopharmaceutical industry development and implement of priority review system, the marketing authorization application of domestic antibody biosimilar and imported antibodies had dramatic increased in recent years. Thus, the CMC evaluation of monoclonal antibody become the important task of biological product's marketing authorization registration management. In the article, the CMC regulatory considerations for marketing authorization application based on author's review experience was proposed, in order to accelerate development and registration of commercial antibody in China.

Nickel sulfide/graphitic carbon nitride/strontium titanate (NiS/g-C3N4/SrTiO3) composites with significantly enhanced photocatalytic hydrogen production activity.

NiS/g-C3N4/SrTiO3 (NS/CN/STO) composites were prepared using a facile hydrothermal method. The synergistic effect of g-C3N4/SrTiO3 (CN/STO) heterojunction and NiS cocatalyst enhanced the photocatalytic hydrogen evolution activity of NS/CN/STO. A hydrogen production rate of 1722.7 µmol h-1 g-1 was obtained when the 2%NiS/20%g-C3N4/SrTiO3 (2NS/20CN/STO) was used for the photocatalytic hydrogen evolution in the presence of methanol used as a sacrificial agent under UV-vis light irradiation; the photocatalytic hydrogen production rate of 2NS/20CN/STO is 32.8, 8.9 and 4.2 times the value of that obtained with pure g-C3N4, SrTiO3 and 20%g-C3N4/SrTiO3 (20CN/STO), respectively. Moreover, in photoelectrochemical investigations when compared with 20CN/STO, SrTiO3 and g-C3N4, 2NS/20CN/STO exhibited significant photocurrent enhancement. The heterojunction and cocatalyst in NS/CN/STO improved the charge separation efficiency and the lifetime of the charge carriers, leading to the enhanced generation of electrons for photocatalytic hydrogen production.

Grape Seed Procyanidin Extract Reduces Arsenic-Induced Renal Inflammatory Injury in Male Mice.

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Application of elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy / 实用医学杂志

Objective To investigate the effect of elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy under general anesthesia. Methods Sixty ASAⅠ~Ⅲgrade patients with tongue body hypertrophy undergoing surgery in general anesthesia were randomly divided into two groups:30 cases in each group. After anesthesia induction ,laryngeal mask airway was inserted in the observation group with assistance of elevating the root of tongue bared-handed ,while inserted in the control group by standard method.Insertion time ,success rate of the first and secondary and total insertion ,pharyngolaryneal complications at 24 hours after removal were recorded ,as well as the success rate of gastric tube intubation was recorded. Results Compared with the control group ,insertion time was significantly shortened (P < 0.05). Success rate of the first and total insertion were increased (P < 0.05).Success rate of gastric tube intubation was increased(P < 0.05),and pharyngolaryneal complications were decreased (P < 0.05) in the observation group. Conclusions Elevating the root of tongue bare-handed to assist ProSeal laryngeal mask airway insertion in patients with tongue body hypertrophy is a simple and fast method with high success rate ,good apposition and less complications. Its efficacy is better than that of the standard method.

Grape Seed Procyanidin Extract Reduces Arsenic-Induced Renal Inflammatory Injury in Male Mice / 生物医学与环境科学（英文）

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

Development of a robust reporter-based assay for the bioactivity determination of anti-VEGF therapeutic antibodies.

Development of anti-VEGF based biologic agents has been a focus in cancer treatment for the past decades, and several anti-VEGF pharmaceuticals have been already approved for treatment of various medical indications especially in cancer. The first anti-angiogenic agent approved by FDA was bevacizumab (BVZ, trade name Avastin, Genentech/Roche), a humanized anti-VEGF monoclonal antibody. Accurate determination of bioactivity is crucial for the safety and efficacy of therapeutic antibodies. The current method widely used in the lot release and stability test for clinical trial batches of BVZ is anti-proliferation assay using primary human umbilical vein endothelial cells (HUVEC), which is tedious with high assay variations. We describe here the development and preliminary validation of a reporter gene assay (RGA) that is based on an HEK293 cell line stably expressing vascular endothelial growth factor receptor 2 (VEGFR-2), and a luciferase reporter under the control of nuclear factor activated T cell (NFAT) response elements. Our study shows this assay not only to be superior on precision, sensitivity and assay simplicity compared with HUVEC assay, but also applicable to other VEGF-targeted biotherapeutics. These results show for the first time that this new reporter assay, based on the VEGF-VEGFR-NFAT pathway, can be a viable supplement to the HUVEC assay and employed in potency determination of BVZ and other kinds of anti-VEGF antibody-based biotherapeutics.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice.

OBJECTIVE: To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. METHODS: Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. RESULTS: ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. CONCLUSION: GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

[Detection of gingipain K in the gingival crevicular fluid of orthodontic patients].

PURPOSE: To explore the correlation between gingipain K (Kgp) and inflammatory reaction of gum in the process of orthodontic treatment, and analyse the role of Kgp in the development of gingivitis during orthodontic treatment. METHODS: Totally 45 orthodontic healthy teenagers were randomly chosen for the study. The subgingival plaques were collected simultaneously before orthodontic treatment and 3 months after treatment. 16S rDNA PCR technique was used to detect Porphyromonas gingivalis (P.g) and Kgp. SPSS17.0 software package was used for statistical analysis. RESULTS: The detection rate of Kgp was 35.71% before orthodontic treatment and 67.86% after treatment. Positive correlation (P<0.05) was observed between Kgp and gingival inflammation. CONCLUSIONS: Fixed orthodontic appliances cause plaque accumulation, accordingly slight gingiva inflammation and the increament of P.gingivalis in the early stage.

Paeoniflorin inhibits macrophage-mediated lung cancer metastasis.

Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 µmol·L(-1), P < 0.01 or P < 0.05 vs control group). Paeoniflorin could decrease the cell populations at S phases (paeoniflorin 10, 30, 100 µmol·L(-1), P < 0.05 vs control group) and increase the cell populations at G0-G1 phases of Lewis lung cancer cells (paeoniflorin 100 µmol·L(-1), P < 0.05 vs control group) and reduce the numbers of M2 macrophages in peritoneal macrophages induced by IL-4 (paeoniflorin 1, 3, 10, 30, 100 µmol·L(-1), P < 0.01 vs Control group). Paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P < 0.01 vs control group). These results suggest that paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

Paeoniflorin inhibits macrophage-mediated lung cancer metastasis / 中国天然药物

Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 or P < 0.05 vs control group). Paeoniflorin could decrease the cell populations at S phases (paeoniflorin 10, 30, 100 μmol·L(-1), P < 0.05 vs control group) and increase the cell populations at G0-G1 phases of Lewis lung cancer cells (paeoniflorin 100 μmol·L(-1), P < 0.05 vs control group) and reduce the numbers of M2 macrophages in peritoneal macrophages induced by IL-4 (paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 vs Control group). Paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P < 0.01 vs control group). These results suggest that paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity.</p><p><b>METHODS</b>Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed.</p><p><b>RESULTS</b>ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST.</p><p><b>CONCLUSION</b>GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.</p>

Analysis of Therapeutic Effect of Ilex hainanensis Merr. Extract on Nonalcoholic Fatty Liver Disease through Urine Metabolite Profiling by Ultraperformance Liquid Chromatography/Quadrupole Time of Flight Mass Spectrometry.

Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is increased worldwide in parallel with the obesity epidemic. Our previous studies have showed that the extract of I. hainanensis (EIH) can prevent NAFLD in rat fed with high-fat diet. In this work, we aimed to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. NAFLD model was induced in male Sprague-Dawley rats by high-fat diet. The NAFLD rats were administered EIH orally (250 mg/kg) for two weeks. After the experimental period, samples of 24 h urine were collected and analyzed by ultraperformance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). Orthogonal partial least squares analysis (OPLSs) models were built to find biomarkers of NAFLD and investigate the therapeutic effects of EIH. 22 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of NAFLD. Taking these biomarkers as screening indexes, EIH could reverse the pathological process of NAFLD through regulating the disturbed pathway of metabolism. The metabolomic results not only supply a systematic view of the development and progression of NAFLD but also provide a theoretical basis for the prevention or treatment of NAFLD.

Evaluation of the cytotoxicity of cigarette smoke condensate by a cellular impedance biosensor.

In this study, a cytotoxicity assay was developed for profiling the cytotoxicity of cigarette smoke condensates (CSCs) base on a cellular impedance biosensor (CIB). Compared with the traditional in vitro cytotoxicity assays, this CIB-based method offered distinct advantages in real-time kinetic measurement which provided a comprehensive understanding of cellular responses for the entire duration of the experiment and prediction of the potential mechanism of action of a given treatment. The time-dependent cell response profiles provided valid evidences for optimization of cell number per well, cell quality control, and identification of the optimal time points for compound treatment and endpoint assays. According to the time dependent IC50 values, the CIB could provide dynamic information that can be used to identify maximum toxicity of cigarette smoke and reversibility of the toxic effects which are difficult to achieve by the endpoint assays. The comparative IC50 values indicated that the as-developed biosensor offered analytical results in good consistency with the commonly used NRU method. The features of the CIB-based cytotoxicity assay, such as no cell labeling, automatic detection, and easy operation, give this assay potential to become routine setting for evaluating the cytotoxicity of CSCs.

Expressions of HIF-1α and VEGF in rhabdomyosarcoma and their clinical significance / 肿瘤

Objective: To investigate the expressions of HIF-1α (hypoxia inducible factor-1α) and VEGF (vascular endothelial growth factor) in rhabdomyosarcoma and their clinical significance. Methods: The expressions of HIF-1α and VEGF preteins in 70 cases of rhabdomyosarcoma were detected by immunohistochemistry, and the correlations of the expressions of HIF-1α and VEGF with the clinicopathological characteristics and the prognosis were analyzed. Results: The positive-expression rates of HIF-1α and VEGF in rhabdomyosarcoma tissues were 75.7% (53/70) and 72.9% (51/70), respectively. HIF-1α expression was positively correlated to VEGF expression (r = 0.554, P = 0.000). HIF-1α expression was significantly associated with the factors of gender (P = 0.035), tumor size (P = 0.016) and clinical staging (P = 0.008), but it was not associated with the age (P = 0.555), pathological type (P = 0.625) and lymph node metastasis (P = 0.750). The three-year overall survival rates of HIF-1α-negative patients and HIF-1α-positive patients were 54.5% and 38.0%, respectively (P = 0.045). VEGF expression was significantly associated with clinical stage (P = 0.026), but it was not associated with the age (P = 0.478), gender (P = 0.944), tumor size (P = 0.535), pathological type (P = 0.399) and lymph node metastasis (P = 0.356). The three-year overall survival rates of VEGF-negative patients and VEGF-positive patients were 68.1% and 31.1% (P = 0.011). COX regression model showed that the factors of VEGF expression (P = 0.005), clinical staging (P = 0.004) and tumor size (P = 0.000) were independent predictors of poor prognosis of rhabdomyosarcoma. HIF-1α could not be considered as an independent prognostic factor of rhabdomyosarcoma (P = 0.845). Conclusion: The overexpression of HIF-1α and VEGF in rhabdomyosarcoma is related to clinical staging. HIF-1α expression is associated with VEGF expression, and VEGF is an independent predictor of poor prognosis of rhabdomyosarcoma. Copyright © 2012 by TUMOR.

[Determination of trace elements in cigarette flavours by closed-vessel microwave digestion-inductively coupled plasma mass spectrometry].

Tobacco flavours have great effect on the aroma, taste and quality stabilization of cigarettes. In order to effectively control the quality of cigarette flavours and reduce the content level of toxic elements in cigarette mainstream smoke, a method for the simultaneous determination of Be, V, Cr, Mn, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Tl and Pb in cigarette flavours by inductively coupled plasma mass spectrometry (ICP-MS) with closed-vessel microwave assisted digestion was developed. The linear correlative coefficients for all elements are better than 0.999 4 and the precision of measurement ranges from 1.3% to 9.5% in terms of relative standard deviation (n = 5). The recoveries for the cigarette flavour samples and the limits of detection are in the range of 88.1%-109.3% and 0.003-0.13 microg x L(-1), respectively. The results of experiment show that the method can meet the requirements of trace analysis. Thirty eight cigarette flavours from different cigarette manufacturing enterprises were determined. The results indicate that: (1) the contents of Be, Tl, Mo, Cd, V, Pb and As in cigarette flavours are very lower, the average values of which are all lower than 0.1 microg x g(-1). The content levels of Mn, Zn and Sr in cigarette flavours are higher, and that of other 4 elements are moderate. (2) The content difference of Mn, Cd and Sr in different cigarette flavours is usually bigger, the coefficients of variation of which are 276.4%, 238.7% and 243.8%, respectively.

[Efficacy and survival of 92 cases of Ewing's sarcoma family of tumor initially treated with multidisciplinary therapy].

BACKGROUND AND OBJECTIVE: Ewing's sarcoma family of tumor (ESFT) is aggressive. The optimal therapy modality for ESFT is still to be found. This study was to explore the clinical characteristics and therapy for ESFT. METHODS: Ninety-two cases of ESFT were collected from January 1995 to April 2008 in Sun Yat-sen University Cancer Center and analyzed retrospectively. RESULT: Of 92 cases, 23 were Ewing's sarcoma of bone, 21 extraosseous Ewing's sarcoma, 43 peripheral primitive neuroectodermal tumor, and 5 Askin tumor. Median follow-up time was 31.5 months (range, 10-137 months). Thirty-eight patients received multidisciplinary therapy and 19 single model therapy in non-metastasis group. Three-year overall survival (OS) and event-free survival (EFS) were significantly different between non-metastatic multidisciplinary therapy group and non-metastatic single model group (63% vs. 20%, 46% vs. 18%, respectively, P<0.001). The patients who received surgery plus chemotherapy and plus radiation or not had longer survival than those treated with chemotherapy plus radiation in non-metastatic multidisciplinary therapy group (Chi2=7.591, 9.212; P=0.006, 0.002). CAV/IE alternative regimen was superior to other regimens in event-free survival, but not in overall survival (Chi2=6.950, 3.530; P=0.008, 0.06). Cox regression analysis suggested therapy model and response to treatment were independent prognostic factors for ESFT. CONCLUSIONS: Our studying showed multidisciplinary therapy could significantly improve non-metastatic ESFT patients' survival. Chemotherapy plus surgery and plus radiation or not were superior to chemotherapy plus radiation in local control for the non-metastatic ESFT. Therapy model and response were independent prognostic factors.