The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.
Syringa ; Sesquiterpenes ; Terpenes ; Asthma ; Chromatography, Liquid

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.
Corydalis ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Tibetan Traditional ; Molecular Docking Simulation ; Myocardial Ischemia/drug therapy* ; Vascular Endothelial Growth Factor A

OBJECTIVE: To explore the epidemiologic characteristics of acupuncturists who are sensitive to stimulation of moxa smoke, which could provide further direction for safety protection of exerting moxibustion and to further verify the feasibility of internet survey. METHODS: A self-made questionnaire regarding body response to moxa smoke was established, which was used to conduct a face-to-face survey among acupuncturists who had performed long-term moxibustion. The Logistic regression model was used to analyze the factors affecting the stimulation response of acupuncturists and the epidemiological characteristics of acupuncturists was obtained. RESULTS: A total of 733 valid data was obtained. The multivariate Logistic regression analysis showed that the history of chronic respiratory disease was the main risk factor of stimulus response including cough, phlegm in the throat, asthma, dyspnea, shortness of breath and nasal dryness after exposure to moxa smoke (<0.05, <0.01). The risk of stimulus response such as cough, tearing and nasal dryness was higher in women than in men (<0.05, <0.01). The risk of dry eyes and eyes pain in smokers was higher than those in non-smokers (<0.05). The risk of shortness of breath in those who were exposed to second-hand smoke was higher than those who were not exposed to second-hand smoke (<0.05). The analysis of index trend line showed that the results of internet survey were similar to those of face-to-face survey. CONCLUSION The stimulus response of acupuncturist after long-term exposure to moxa smoke is related to the history of chronic respiratory disease, being female, smoking or exposure of second-hand smoke, therefore more attention should be paid to those populations. In addition, the internet survey can be used for the epidemiological investigation of safety of moxa smoke.
Cough ; Female ; Humans ; Male ; Moxibustion ; Mucus ; Smoke ; Surveys and Questionnaires

Usnic acid and its derivatives, a group of organic molecules with great importance, are characteristic to lichens, possessing pharmacological activities such as anti-virus, anti-bacteria, anti-humor, anti-inflammatory, analgesic, and anaesthetic effects. Many of them have been widely used as medicine, but also bring side effects such as dermatitis and liver damages. In the past decades, great efforts by isolation, organic synthesis, and structure modification methods were put on discovery of UA derivatives with higher biological activities or less side effects. This paper describes herein the most progress on natural sources, isolation and structure elucidation, structural characteristics, synthesis and modification results, pharmacological activities and toxicities of UA and its derivatives, hopefully to provide valuable reference for further research.
Benzofurans ; chemistry ; pharmacology ; Biological Products ; Lichens ; chemistry

OBJECTIVETo investigate the effect of FCGR3A polymorphisms on the antibody-dependent cell-mediated cytotoxicity (ADCC) activity induced by cetuximab against A549 cells.

METHODSA549 cell line was used as target cells and NKTm cells as effector cells. FCGR3A polymorphisms were detected by direct sequencing. The ADCC activity mediated by cetuximab was assessed by CCK-8 assay.

RESULTSThree genotypes of FCGR3A were detected:V/V,V/F,and F/F. The ADCC activity of NKTm cells with these three different genotypes mediated by cetuximab were significantly different (P=0.0015). NKTm cells with FCGR3A-158V/V genotypes had significantly higher ADCC activity than FCGR3A-V/F or F/F genotypes (P<0.01),whereas the ADCC activity between V/F and F/F genotype showed no statistical significance(P>0.05).

CONCLUSIONFCGR3A polymorphisms have an impact on ADCC activity mediated by cetuximab in NKTm cells.

Antibody-Dependent Cell Cytotoxicity ; Cell Line, Tumor ; Cetuximab ; Genotype ; Humans ; Polymorphism, Genetic ; Receptors, IgG

OBJECTIVETo determine the prognostic value of tumor-infiltrating lymphocytes in the recurrence and metastasis of non-small cell lung cancer (NSCLC).

METHODSA PubMed, EMBASE, Cochrane Library databases, NIH databases, and China Biology Medicine disc, China National Knowledge Infrastructure, Chinese Science and Technology Periodical literature search strategy was designed. Studies on the prognostic values of intratumoural CD3⁺,CD4⁺,CD8⁺, and FoxP3+lymphocytes for NSLCL were retrieved. RevMan 5.1 was applied for Meta analysis.

RESULTSTotally 8 studies entered the final analysis. In pooled analysis of 1197 patients,the high expressions of CD3⁺ and CD8⁺ cells were correlated with the increase of overall survival (OS) (OR=0.52,95% CI=0.40- 0.68, P<0.0001; OR=0.52,95% CI=0.34-0.79,P=0.002), and the high expression of CD8⁺ was significantly correlated with the increase of disease-free survival (DFS) (OR=0.68,95% CI=0.51-0.91,P=0.01). The CD4⁺ cell expression level was not significantly correlated with OS or DFS (P=0.14, P=0.73). The high expression of FoxP3⁺ cells did not favor the DFS(OR=1.78,95% CI=1.36-2.31; P<0.0001).

CONCLUSIONThe expression levels of CD3⁺, CD8⁺ and FoxP3⁺ in NSCLC microenviroment are related with the prognosis of NSCLC, while the role of CD4⁺ in the development of NSCLC warrants further investigations.

CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Carcinoma, Non-Small-Cell Lung ; China ; Disease-Free Survival ; Humans ; Lung Neoplasms ; Lymphocytes, Tumor-Infiltrating ; Neoplasm Metastasis ; Prognosis ; Recurrence

OBJECTIVETo investigate the role of epidermal growth factor receptor (EGFR) expression level in cetuximab cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) effect against A549 lung cancer cell line.

METHODSA549 cell line and NKTm cells were used as the target cell and the effector cell, respectively. pEGFR-EGFP plasmids were transfected into A549 cells by nucleofector method. EGFR expression levels were measured by immunohistochemistry. The ADCC activity induced by cetuximab was assessed by cell counting kit-8 assay.

RESULTSA549 cells transfected with pEGFR-EGFP plasmids expressed higher level of EGFR protein on membrane and were more sensitive to ADCC activity mediated by cetuximab (P<0.05). The inhibition rate of A549 cells showed no significant difference between transfection group and wild-type group when treated with cetuximab alone (P> 0.05).

CONCLUSIONEGFR expression level influences the sensitivity of A549 lung cancer cell line to ADCC activity mediated by cetuximab but not to cetuximab alone.

Adenocarcinoma ; pathology ; Antibodies, Monoclonal, Humanized ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cetuximab ; Humans ; Immunohistochemistry ; Lung Neoplasms ; pathology ; Receptor, Epidermal Growth Factor ; metabolism ; Tumor Cells, Cultured

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; surgery ; CD8-Positive T-Lymphocytes ; metabolism ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Outcome Assessment (Health Care) ; methods ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Protein Precursors ; metabolism ; Retrospective Studies ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

METHODSFifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.

RESULTSEighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.

CONCLUSIONSAddition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Aged ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Capecitabine ; China ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Esophageal Neoplasms ; drug therapy ; pathology ; Esophagogastric Junction ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Neutropenia ; chemically induced ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Trastuzumab ; Vomiting ; chemically induced

OBJECTIVETo assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.

METHODSParaffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) .

RESULTSIntraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.

CONCLUSIONSIn the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; diagnosis ; pathology ; therapy ; CD4-Positive T-Lymphocytes ; pathology ; CD8-Positive T-Lymphocytes ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; pathology ; Middle Aged ; Prognosis ; Retrospective Studies