Pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration / 中国中药杂志

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.

Taxane-induced scleroderma: report of two cases / Esclerodermia inducida por taxanos: informe de dos casos

ABSTRACT Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia and onycholysis. Taxane-induced scleroderma is rare. Few cases with skin findings resembling systemic sclerosis, have been reported after the administration of these agents. We report two cases with stage IV breast cancer, aged 66 and 71 years, who developed sclerodermic skin lesions in their extremities after starting treatment with placlitaxel and nabplaclitaxel respectively.

Los taxanos son agentes quimioterapéuticos cuyo uso se asocia a problemas dermatológicos tales como hiperpigmentación, síndrome manos-pies, paroniquia y onicolisis. La esclerodermia inducida por taxanos es rara, con pocos casos informados en la literatura. Informamos los casos de dos pacientes con cáncer de mama en estado IV, de 66 y 71 años, que desarrollaron lesiones esclerodérmicas en las extremidades después de ser tratadas con placlitaxel y nabplaclitaxel, respectivamente.

Optimization of a cucurbit6uril-based real-time label-free method for analyzing the activity of ornithine decarboxylase / 生物工程学报

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthetic pathway of polyamines and catalyzes the decarboxylation of ornithine to produce putrescine. Inhibition of ODC activity is a potential approach for the prevention and treatment of many diseases including cancer, as the expression levels and the activities of ODC in many abnormal cells and tumor cells are generally higher than those of normal cells. The discovery and evaluation of ODC inhibitors rely on the monitoring of the reaction processes catalyzed by ODC. There are several commonly used methods for analyzing the activity of ODC, such as measuring the yield of putrescine by high performance liquid chromatography, or quantifying the yield of isotope labelled carbon dioxide. However, the cumbersome operation and cost of these assays, as well as the difficulty to achieve high-throughput and real-time detection, hampered their applications. In this work, we optimized a real-time label-free method for analyzing the activity of ODC based on the macromolecule cucurbit[6]uril (CB6) and a fluorescent dye, DSMI (trans-4-[4-(dimethylamino) styryl]-1-methylpyridinium iodide). Finally, the optimized method was used to determine the activities of different ODC inhibitors with different inhibition mechanisms.

Assessing taxane-associated adverse events using the FDA adverse event reporting system database / 中华医学杂志(英文版)

BACKGROUND@#Taxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.@*METHODS@#Taxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).@*RESULTS@#A total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).@*CONCLUSIONS@#The results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.

Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy / 癌症

BACKGROUND@#Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy.@*METHODS@#We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.@*RESULTS@#Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027).@*CONCLUSION@#ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

Caracterização do perfil auditivo de frentistas de postos de combustível / Characterization of hearing profile of gas station attendants

RESUMO Introdução Pesquisas voltadas para as populações com baixas exposições a solventes, ou exposições dentro dos níveis de tolerância permitidos em âmbito ocupacional ainda são restritas. Objetivo Caracterizar o perfil auditivo de frentistas de postos de combustíveis. Métodos Estudo transversal, constituído por dois grupos, pareados por gênero e idade: Grupo Controle - 23 indivíduos sem exposição a ruído ou agentes químicos; Grupo Experimental - 21 frentistas de postos de combustíveis. Foi realizada avaliação audiológica, composta por audiometria tonal liminar, logoaudiometria e medidas de imitância acústica. A análise estatística utilizou cálculo de média, desvio padrão, valor mínimo e máximo, teste Qui-quadrado e coeficiente de correlação de Pearson. O nível de significância adotado foi de 5%. Resultados Foram verificadas alterações auditivas nos frentistas, caracterizadas por comprometimento no sistema auditivo periférico, sugerindo ação tóxica da exposição a combustíveis. Houve correlação entre idade e tempo de exposição a solvente. Na comparação entre os grupos, o reflexo acústico demonstrou maior número de alterações no grupo experimental, com diferença para os reflexos acústicos ipsilaterais da orelha direita e contralaterais da orelha esquerda. Conclusão Não houve diferença entre os grupos para os limiares auditivos, porém, a diferença verificada nos reflexos acústicos ipsilaterais e contralaterais no grupo experimental sugere comprometimento retrococlear. Diante das evidências observadas neste estudo, considera-se relevante incluir a pesquisa do reflexo acústico na avaliação auditiva dos frentistas, bem como a integração desta categoria profissional aos programas de prevenção de perda auditiva.

ABSTRACT Introduction Researches into populations with low solvent exposures, or exposures within tolerance levels allowed in the occupational field are still restricted. Purpose To characterize the hearing profile of gas station attendants. Methods Cross-sectional study, constituted of two groups, matched by gender and age: Control Group - 23 subjects without exposure to noise or chemicals; Experimental Group - 21 gas station attendants. An audiological evaluation was performed, composed by pure tone audiometry, speech audiometry and acoustic impedance tests. The statistical analysis used average calculation, standard deviation, minimum and maximum value; Chi-square Test and Pearson’s correlation coefficient. The significance level was 5%. Results Hearing loss was verified in gas station attendants characterized by impairment of the peripheral auditory system, suggesting toxic effects of exposure to fuels. There was a correlation between age and solvent exposure time. Comparing the groups, the acoustic reflex showed more alterations in the experimental group, with a difference for the ipsilateral acoustic reflexes of the right ear and contralateral ones of the left ear. Conclusion There was no difference between the groups for the hearing thresholds; however, the difference observed in the ipsilateral and contralateral acoustic reflexes in the experimental group suggests retrocochlear impairment. Due to the evidence observed in this study, it is considered relevant to include the acoustic reflex research in the auditory evaluation of the gas station attendants, as well as the integration of this professional category into hearing loss prevention programs.

Protective effects of paeoniflorin and albiflorin on chemotherapy-induced myelosuppression in mice / 中国天然药物

Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in traditional Chinese medicines (TCM). Two isomers, paeoniflorin (PF) and albiflorin (AF), are isolated from P. lactiflora. The present study aimed to investigate the protective effects of PF and AF on myelosuppression induced by chemotherapy in mice and to explore the underlying mechanisms. The mouse myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CP, 200 mg·kg(-1)). The blood cell counts were performed. The thymus index and spleen index were also determined and bone morrow histological examination was performed. The levels of tumor necrosis factor-α (TNF-α) in serum and colony-stimulating factor (G-CSF) in plasma were measured by Enzyme-Linked Immunosorbent Assays (ELISA) and the serum levels of interleukin-3 (IL-3), granulocyte-macrophagecolony-stimulatingfactor (GM-CSF), and interleukin-6 (IL-6) were measured by radioimmunoassay (RIA). The levels of mRNA expression protein of IL-3, GM-CSF and G-CSF in spleen and bone marrow cells were determined respectively. PF and AF significantly increased the white blood cell (WBC) counts and reversed the atrophy of thymus. They also increased the serum levels of GM-CSF and IL-3 and the plasma level of G-CSF and reduced the level of TNF-α in serum. PF enhanced the mRNA level of IL-3 and AF enhanced the mRNA levels of GM-CSF and G-CSF in the spleen. PF and AF both increased the protein levels of GM-CSF and G-CSF in bone marrow cells. In conclusion, our results demonstrated that PF and AF promoted the recovery of bone marrow hemopoietic function in the mouse myelosuppression model.

Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer.@*METHOD@#Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis.@*RESULT@#A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group.@*CONCLUSION@#The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

Comparative study on effects of blood enriching on mouse model of blood deficiency syndrome induced by cyclophosphamide of albiflorin, paeoniflorin on levels of GM-CSF, IL-3 and TNF-α / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the effects and mechanism of blood enriching on mouse model of blood deficiency syndrome induced by cyclophosphamide of albiflorin and paeoniflorin.</p><p><b>METHOD</b>Albiflorin and paeoniflorin were determined by using animal models of blood deficiency syndrome induced by cyclophosphamide. The amount of WBC, RBC, HGB, index of thymus gland and spleen, and the changes of GM-CSF, IL-3 and TNF-α in serum were detected after the treatment.</p><p><b>RESULT</b>Compared with the model group, the amount of WBC in the group of 30 mg x kg(-1) albiflorin and 30 mg x kg(-1) paeoniflorin were increased obviously (P < 0.01). The amount of RBC in the group of 30 mg x kg(-1) albiflorin and 30 mg x kg(-1) paeoniflorin were increased obviously (P < 0.01, P < 0.001), which did not had a significant difference compared with the same dose. The index of thymus gland in the group of 30 mg x kg(-1) albiflorin was superior to the model group (P < 0.01), the difference was significant compared with the same dose of paeoniflorin (P < 0.05). The GM-CSF in serum in all groups of 30 mg x kg(-1) albiflorin, 15 mg x kg(-1) albiflorin, 30 mg x kg(-1) paeoniflorin and 15 mg x kg(-1) paeoniflorin increased obviously (P < 0.01, P < 0.05, P < 0.01, P < 0.05); The IL-3 in serum in both group of 30 mg x kg(-1) albiflorin and 30 mg x kg(-1) paeoniflorin also increased (P < 0.001). The content of TNF-α in group of 30 mg x kg(-1) albiflorin and 30 mg x kg(-1) paeoniflorin were reduced (P < 0.01), which showed the obvious difference compared with the same dose group (P < 0.01).</p><p><b>CONCLUSION</b>Albiflorin had the effect of blood enriching by regulating the immune function, same with the paeoniflorin. The probable mechanism of nourishing blood and liver of Paeoniae Radix Alba was not only the better effect of adjusting the content of TNF-α, but also might act synergistically with paeoniflorin.</p>

Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.</p><p><b>METHODS</b>Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.</p><p><b>RESULTS</b>With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).</p><p><b>CONCLUSION</b>Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.</p>

An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology / 药学学报

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

Qualitative and quantitative analysis of major constituents of Paeoniae Radix Alba and Paeoniae Radix Rubra by HPLC-DAD-Q-TOF-MS/MS / 中国中药杂志

In order to explore the differences of chemical constituents of Paeoniae Radix Alba and Paeoniae Radix Rubra, a qualitative analytical method of liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) was developed for identification of multi-constituents and an HPLC-DAD analytical method was developed for simultaneously determining 14 major compounds (gallic acid, protocatechuic acid, paeoniflorin sulfonate, protocatechuic aldehyde, methyl gallate, oxypaeoniflorin, catechin, albiflorin, and paeoniflorin, ethyl gallate, benzoic acid, pentagaloylglucose, benzoyl-paeoniflorin, and paeonol) in Paeoniae Radix Alba and Paeoniae Radix Rubra. Q-TOF/MS qualitative analysis was performed under negative ion mode and inferred 38 components of Paeoniae Radix Alba and 30 components of Paeoniae Radix Rubra. HPLC-DAD quantitative method result showed the contents of 8 ingredients were different between Paeoniae Radix Alba and Paeoniae Radix Rubra. The results indicated that the new approach was applicable in qualitative and quantitative quality control of Paeoniae Radix Alba and Paeoniae Radix Rubra.

Comparison of chemical composition between raw and vinegar-baked Paeoniae Radix Alba using NMR based metabolomic approach / 药学学报

To compare the chemical change of Paeoniae Radix Alba (PRA) after vinegar-baking processing, as well as the effect of vinegar types exerted on the processing, 1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to investigate the different metabolites between the raw and two vinegar-baked PRA. More than thirty metabolites were identified in the 1H NMR spectrum of PRA, and the multivariate statistical analysis showed that raw and two vinegar-baked PRA could be separated obviously. After vinegar-baking, the contents of isoleucine, lactate, alanine, arginine, albiflorin, and 5-hydroxymethyl furfural (5-HMF) elevated, while those of sucrose, paeoniflorin and its analogues (calculated by benzoate) decreased. The chemical compositions of two vinegar-baked PRA were also different. Shanxi vinegar- baked PRA showed higher levels of leucine, isoleucine, valine, and albiflorin, while rice vinegar-baked PRA contained more sucrose and paeoniflorin's analogues (calculated by benzoate). And the chemical changes in Shanxi vinegar-baked PRA were greater than those of rice vinegar-baked PRA. The results revealed the chemical differences between raw and vinegar-baked PRA, as well as the influence of vinegar type on processing, in a holistic manner, the results obtained suggested that the correlations between the chemical change and the drug action after processing, as well as the vinegar type used in processing, should be further studied.

Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.</p><p><b>METHODS</b>Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).</p><p><b>RESULTS</b>After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.</p><p><b>CONCLUSIONS</b>NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.</p>

Research progress of chemical composition of taxane in Taxus canadensis and medicine source crisis solution / 中国中药杂志

Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.

Effect of acetamide on histopathology in cerebral cortex of rats with tetramine poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effect of different doses of acetamide on the histopathology in the cerebral cortex of rats with tetramine (TET) poisoning and to provide a basis for the treatment of fluoroacetamide poisoning with acetamide.</p><p><b>METHODS</b>Eighty clean Sprague-Dawley rats were randomly divided into five groups: saline control group,dimethylsulfoxide water solution control group,TET poisoning group, acetamide (2.88 g/kg/d) treatment group, and acetamide (5.68 g/kg/d) treatment group, with 16 rats in each group. Rats in the poisoning group and treatment groups were poisoned with TET by intragastric administration after fasting; then, saline was injected intramuscularly into rats of the poisoning group, and different doses of acetamide were injected intramuscularly into rats of treatment groups; the course of treatment was 5 d. At 3 h, 12 h, 48 h, and 7 d after treatment, the cerebral cortex was harvested from rats in each group, and the histopathological changes in the cerebral cortex were evaluated under light and electron microscopes.</p><p><b>RESULTS</b>The light microscopy showed that the TET poisoning group had hypoxia changes in the cerebral cortex, which worsened over time; the treatment groups had reduced hypoxia changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group. The electron microscopy showed that the apoptosis of neuronal cells were the main pathological changes in the TET poisoning group; the treatment groups had reduced apoptotic changes, and the acetamide (2.88 g/kg/d) treatment group had more reduction than the acetamide (5.68 g/kg/d) treatment group.</p><p><b>CONCLUSION</b>No pathological changes associated with the synergistic toxic effect of acetamide and TET are found in the cerebral cortex. Acetamide (2.88 g/kg/d) could reduce central nervous lesions, but the efficacy is not improved after increasing the dose. For patients who cannot be identified with TET or fluoroacetamide poisoning, acetamide could be considered for treatment.</p>

Effects of acetamide at different doses on expression of amino acids in cerebral cortex of rats with acute tetramine poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of acetamide at different doses on the expression of inhibitory amino acids (gamma-aminobutyric acid, GABA) and excitatory amino acid (glutamate, Glu) in the cerebral cortex of rats with acute tetramine (TET) poisoning.</p><p><b>METHODS</b>Eighty Sprague-Dawley rats (SPF) were randomly divided into five groups, with 16 rats in each group: saline control group, dimethyl sulfoxide (DMSO) control group, TET exposure group, high-dose (2.8 g/kg/d) acetamide treatment group, and super-high-dose (5.6 g/kg/d) acetamide treatment group. Rats in the exposure group and treatment groups were exposed to TET by intragastric administration after fasting, and were then intramuscularly injected with saline or different doses of acetamide in the following 5 days. The cortex of the temporal lobe was collected at 3 h, 12 h, 48 h, or 7 d after treatment. The expression levels of GABA and Glu in the cortex of the temporal lobe were determined by average optical density (OD) values in immunohistochemistry.</p><p><b>RESULTS</b>1) Expression of GABA: The OD value of GABA in TET exposure group started to increase at 12 h after treatment, reached the peak at 48 h, and decreased to the normal level at 7 d. In the high-dose acetamide treatment group, the increase in OD at 12 h was not so significant as that in the TET exposure group, OD value decreased to the normal level at 48 h and was lower than that in the exposure group, and the changes were more like those in the control groups. In the super-high-dose acetamide treatment group, OD value began to increase significantly at 3 h and was significantly higher than that in the TET exposure group (P < 0.01), it reached the peak at 12 h, and was restored to the normal value at 48 h. 2) Expression of Glu: The OD value of Glu in TET exposure group at 3 h after treatment was significantly lower than those in the two control groups, it increased gradually from 12 h to 48 h, and recovered to the normal level at the 7th d. The changes in the high-dose acetamide treatment group were similar to those in the TET exposure group, but became more like those in the control groups after 48 h; the OD value in super-high-dose acetamide treatment group was significantly higher than that in the TET exposure group at 3 h after treatment (P < 0.01), while no significant difference was found at 12 h; it was significantly lower than those of all other groups at 48 h and 7 d (P < 0.01).</p><p><b>CONCLUSIONS</b>Treatment with high dose of acetamide has some curative effect on TET poisoning-induced central nervous lesion, while the effect of super-high-dose acetamide on expression of neurotransmitters is too complex to evaluate.</p>

Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), and Ki-67 expressions in patients with breast cancer.</p><p><b>METHODS</b>Pre- and post-neoadjuvant chemotherapy, paired-tumor specimens from 103 patients with breast cancer administrated with anthracycline or anthracycline combined taxane regimen were collected. Immunohistochemical staining for ER, PR, Her-2, and Ki-67 was performed by the DAKO EnVision method.</p><p><b>RESULTS</b>Among the 103 cases, five patients (4.9%) had a complete response (CR), 82 (79.6%) partial response (PR), 15 (14.6%) stable disease (SD), and one (0.9%) progressive disease (PD), yielding an overall response rate (CR + PR) of 84.5%. Nine patients achieved pathological CR. There was a significant decrease in the average index of Ki-67 postneoadjuvant chemotherapy, compared with that before chemotherapy (24.1% vs. 39.7%, P < 0.001). After neoadjuvant chemotherapy, the changes of Ki-67 in different subtypes of breast cancer were different (P < 0.001), and these changes correlated with response to neoadjuvant chemotherapy (P < 0.001). No significant changes in immunohistochemical expression were observed for ER, PR and Her-2.</p><p><b>CONCLUSIONS</b>Neoadjuvant chemotherapy apparently reduced Ki-67 index in primary breast carcinomas, but profiles for ER, PR and Her-2 were not significantly different before and after neoadjuvant chemotherapy. The change of Ki-67 correlated with molecular subtypes and response to neoadjuvant chemotherapy, suggesting that Ki-67 index was a surrogate marker to predict the treatment response of neoadjuvant chemotherapy.</p>

Study on blood enriching effects of γ-ray radiation of paeoniflorin and albiflorin on mouse model of blood deficiency / 中国中药杂志

<p><b>OBJECTIVE</b>To study the blood enriching effects of Paeoniae Radix Rubra and Paeoniae Radix Alba, paeoniflorin and albiflorin on mouse model of blood deficiency caused by γ-ray radiation.</p><p><b>METHOD</b>Build mouse model of blood deficiency induced by γ-ray radiation. Paeoniae Radix Rubra and Paeoniae Radix Alba were given during modeling. The amount of WBC was detected af- ter the treatment. Based on the result of WBC and paeoniflorin content, albiflorin content in Paeoniae Radix Rubra and Paeoniae Radix Alba, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.</p><p><b>RESULT</b>On the 7th day, the amount of WBC in model mice treated with 2 g x kg(-1) Paeoniae Radix Alba and 2 g x kg(-1) Paeoniae Radix Rubra significantly increased compared with that of model group (P < 0.05). In another experiment with the same model, the amount of WBC in model mice treated with 120 mg x kg(-1) paeoflorin and 120 mg x kg(-1) albiflorin significantly increased (P < 0.05) compared with that of model group on the 7th day. On the 10th day, the amount of WBC in rats treated with 120 mg x kg(-1) paeoflorin increased significantly (P < 0.05) compared with that of model group. Compared with the same dose of paeoniflorin, the amount of WBC in mice treated with albiflorin had no significant difference.</p><p><b>CONCLUSION</b>All Paeoniae Radix Alba, Paeoniae Radix Rubra, paeoniflorin and al- biflorin can raise the amount of WBC and have the effect of enriching blood induced by radiation, while paeoniflorin and albiflorin have a similar result in this model. The result indicated that both paeoniflorin and albiflorin are effective constituents in Paeoniae Radix Alba, and paeoniflorin work as the common effective constituent in both Paeoniae Radix Rubra and Paeoniae Radix Alba.</p>

Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma.

Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1) surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion) or (2) organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes). Results: The mean age of this population was 55 years. Most (83%) of the patients had pyriform sinus (PFS) involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33) and organ preservation protocol was planned after NACT in 73% (19/26) patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%), mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.