The onset of stroke is related to the deficiency of kidney water, internal stirring of liver wind, disorder of brain marrow, and blood. They are in evolutionary relationship. The disorder of kidney-liver-brain axis is the core pathogenesis of stroke. In the aspect of meridian and function, the Du meridian is closely related to the kidney, liver and brain. Acupuncture on the Du meridian to regulate the kidney-liver-brain axis is an effective method in the treatment of stroke. The clinical practice and research have proved that DU20-Baihui and DU14-Dazhu are im-portant acupoints in the treatment of stroke.

Tis study discusses the applicable relationship between Buyang-huanwu decoction and hemodynamic cerebral infarction from pathogenesis of Qi asthenia causing blood stasis.pathological features of hemodynamic cerebral infarction and the function and mechanism of Buyang-huanwu decoction and so on.It also investigates the methods of applying Buyang-huanwu decoction to treat hemodynamic cerebral infarction from such aspects as dose,occasion,contraindication and attentions.

Antiviral Agents ; therapeutic use ; Follow-Up Studies ; Hepatitis B, Chronic ; therapy ; Humans ; Interferon-alpha ; therapeutic use ; Lamivudine ; therapeutic use ; Recombinant Proteins ; Secondary Prevention

OBJECTIVETo explore the changes of the sensitivity of cetuximab-resistant human nasopharyngeal carcinoma (hNPC) cells 5-8F/Erbitux to cetuximab by silencing H-ras gene with RNA interference (RNAi).

METHODSThe 5-8F/Erbitux cells were induced by stepwise exposure to increasing doses of cetuximab. Western blot was conducted to detect the protein levels of H-ras and K-ras. Real-time PCR was employed to detect the expression of H-ras and K-ras. H-ras-shRNA plasmids (shRNA vector carrying the H-ras gene) were constructed and transferred into 5-8F/Erbitux cells. The gene and protein expression levels of H-ras and the changes of the sensitivity of 5-8F/Erbitux cells to cetuximab after transfection were measured, respectively.

RESULTSAfter treatment with cetuximab for 3 and 5 days, the resistance index (RI) of the 5-8F/Erbitux cells was 1.2 and 1.1, and the protein levels of H-ras and K-ras in 5-8F/Erbitux cells were 0.798 +/- 0.019 and 0.190 +/- 0.011, respectively, significantly higher than that in the 5-8F cells (P<0.001). The gene expressions of H-ras and K-ras in 5-8F/Erbitux cells were 1.260 +/- 0.114 and 0.850 +/- 0.006, respectively. Compared with 5-8F cells, the former was higher (P = 0.016) and the latter was lower (P = 0.000). After transfection with H-ras-shRNA plasmid, the 5-8F/Erbitux cells showed reduced levels of H-ras gene and protein, and the cell apoptosis and inhibition rates increased significantly (P<0.001).

CONCLUSIONSH-ras siRNA can reverse cetuximab-resistance of 5-8F/Erbitux cells through down-regulation of H-ras gene expression, indicating that the generation of cetuximab-resistance in 5-8F/Erbitux cells is associated with amplification and overexpression of the H-ras gene.

Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation ; Cetuximab ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Genes, ras ; Humans ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Plasmids ; Proto-Oncogene Proteins p21(ras) ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVETo establish a cetuximab-resistant human nasopharyngeal carcinoma 5-8F/Erbitux cell line and preliminarily study the relationship between the insulin-like growth factor 1 receptor (IGF-1R) signaling pathway and the resistance of nasopharyngeal carcinoma to cetuximab.

METHODSA nasopharyngeal cancer cell line, 5-8F, with high epidermal growth factor receptor (EGFR) expression and cetuximab sensitivity, was selected as study object. The cetuximab-resistant 5-8F/Erbitux cell line was induced by stepwise selection after exposure to increasing doses of cetuximab. The IC(50) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the resistance index (RI) was calculated. The growth curves of 5-8F and 5-8F/Erbitux cells were plotted and the doubling times were calculated by cell counting assay. The cell cycle was detected by flow cytometry. Cross-resistance profiles of 5-8F/Erbitux cells to 5-Fu, Taxol and DDP were tested by MTT assay. Expression levels of P-gP, IGF-1R and P-IGF-1R of 5-8F and 5-8F/Erbitux cells were determined by Western blot analysis and MDR1 gene by real-time fluorescent quantitative PCR.

RESULTSA cetuximab-resistant human nasopharyngeal carcinoma cell line 5-8F/Erbitux was successfully established and their resistance index (RI) were 1.2 and 1.1, respectively, at 3 d and 5 d of the cetuximab treatment. The doubling times of 5-8F and 5-8F/Erbitux cells were 26.63 h and 142.30 h, respectively. Flow cytometry demonstrated that 5-8F/Erbitux cells showed an increased population at G(0)/G(1) phase (P < 0.001) and reduced population at S phase (P < 0.001), compared with 5-8F cells. The 5-8F/Erbitux cells showed cross-resistance to 5-Fu (RI = 3.95, P < 0.01) and some resistance to Taxol as well as enhanced sensitivity to DDP (P > 0.05 for all). The 5-8F/Erbitux cells also had increased levels of P-gP, IGF-1R and P-IGF-1R compared with 5-8F cells (P < 0.001 for all). Expression of MDR1 gene was not detected in 5-8F cells and only very weak expression in 5-8F/Erbitux cells.

CONCLUSIONCetuximab-resistant 5-8F/Erbitux cells have no common multidrug resistance like that induced by traditional chemotherapeutic drugs. The excessive activation of the IGF-1R signaling pathway is probably one of the mechanisms that caused resistance of 5-8F/Erbitux cells to cetuximab.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cetuximab ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Phosphorylation ; Receptor, IGF Type 1 ; metabolism ; Signal Transduction

ObjectiveTo investigate the risk factors and morbidity of carotid atherosclerosis (CA) and unstable plague in patients with sleep apnea-related hypertension (SA-RH).MethodsA total of 603 SA-RH subjects screened by polysomnography according to apnea hypopnea index (AHI) were recruited and divided into 3 groups:mild (AHI 5-15 ),moderate (AHI 15-30) and severe (AHI ≥ 30) group,with hypertensive patients with AHI less than 5 served as control.CA was determined by doppler ultrasound as formation of plaque and/or intima-media thickness more than 0.9 mm.Unstable atheroma plaque (UAP) was defined as low echo plaque and/or admixing echo plaque.Results Gender,age,BMI and blood pressure were not matched among groups.The prevalence of CA increased in moderate and severe SA-RH than that in control ( P ＜ 0.01 ) with no significant difference for UAP among groups.Factor analysis was performed to extracted common factors that may influence CA and UAP,such as factor 1-6,represent obstructive sleep apnea (OSA),dyslipidemia (TC,LDL),BMI,blood pressure,age and duration of disease and dyslipidemia (TG,HDL) respectively.Logistic analysis show that OSA and dyslipidemia (TC,LDL) increased the risk of CA,with OR 1.36(95％ CI 1.15-1.59),1.31 (95％ CI 1.12-1.54)respectively,and dyslipidemia (TC,LDL) increased the risk of UAP,with OR 1.30 (95％ CI 1.06-1.58).ConclusionsIn SA-RH populations,higher prevalence of CA may be associated with severity of OSA independently,meanwhile the formation of UAP may be mainly associated with dyslipidemia.

Objective To study the epidemiological status of reproductive health related behaviors of out of school adolescents in Kunming and Shenzhen City,and to explore the social-psychological influencing factors of the behaviors.Methods A cross-sectional study was conducted in 410 out of school adolescents aged 15-24 years who were recruited with accidental sampling.All the subjects were required to complete a self-administrated questionnaire.Single factor Chi-square analysis and multi-factor Logistic method were used for data analysis.Results The correct respondent rate of the questions on reproductive health knowledge among the adolescents was low.The sexual intercourse rate was 42.9％ (176/410).Nearly 44.9％ (79/176) of the adolescents who had sexual experience did not use condom in the latest sexual intercourse,and those who had no less than one sexual partner accounted for 48.9％ (86/176).The prevalence of genital discomfort and sexual transmitted disease was 48.8％ (200/410) and 2.9％ (12/ 410),respectively.Chi-square test showed that marriage,living statue,behaviors of holding hands,kiss,caress the body,sexual intercourse and having no less than one sexual partner influenced the prevalence of genital discomfort(x2 values were 4.667,10.862,10.032,15.619,17.423,28.239,17.817 and 21.369,respectively ; all P ＜ 0.05).In binary Logistic analysis,living in a dormitory or with other people,behaviors of caress the body,sexual intercourse and having no less than one sexual partner influenced the prevalence of genital discomfort (odds ratio (OR) was 0.449 (95％ CI:0.216-0.933),0.377 (95％ CI:0.147-0.967),4.364 (95％ CI:1.594-11.949),0.312 (95％ CI:0.111-0.877) and2.646 (95％ CI:1.417-4.941),respectively ; all P ＜ 0.05).Conclusions The status of reproductive health was poor among out of school girls in kunming and Shenzhen,and living status,behaviors of caress the body,sexual intercourse and having no less than one sexual partner could influence the prevalence of genital discomfort.Comprehensive measures should be taken to strengthen the reproductive health management in this population.

Aim To explore the inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and the mechanism.Methods Mouse model of subcutaneous liver cancer was used.Single agent of lenvatinib, single agent of fluvastatin, a combination of lenvatinib and fluvastatin and control solvent were given to four groups of mice.Tumor volume was measured.Immunohistochemistry was used to examine proliferation of tumor cells.Tunel was employed to detect the cell apoptosis.qRT-PCR and immunohistochemistry were used to measure the expression of TLR4.Western blot was employed to determine β-catenin expression.Rescue experiment was done using human hepatoma cells cultured in vitro.Results Treatment with both lenvatinib and fluvastatin significantly suppressed tumor growth in nude mice.Combined treatment significantly decreased the expressions of PNCA and increased apoptosis in tumor cells.Mechanically combined treatment synergistically suppressed the mRNA and protein expression of TLR4 which further inhibited the expression of β-catenin in hepatoma cells.Conclusions A combination of lenvatinib and fluvastatin synergistically inhibits tumor growth and promotes tumor cell apoptosis.The combination treatment significantly inhibits TLR4/β-catenin signaling pathway.

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.

OBJECTIVETo investigate the expression of beta-catenin in the intestinal mucosa of rats with severe abdominal infection.

METHODSForty healthy adult Wistar rats were randomly divided into a control group (n=10, with celiotomy only) and 3 abdominal infection groups (n=10) sacrificed at 12, 24, 48 h after cecal ligation plus puncture for inducing severe abdominal infection, respectively. Immunohistochemistry and RT-PCR were performed to detect beta-catenin expression in the crypt of the small intestine during severe abdominal infection and in normal conditions.

RESULTSRats with severe abdominal infection showed stronger beta-catenin expression in the crypt of the small intestine than normal rats, and the transcription level of beta-catenin was associated with the stages of severe abdominal infection. RT-PCR showed that beta-catenin mRNA increased rapidly 12 h after the infection (0.74-/+0.10 vs 0.52-/+0.06, P<0.01), reaching the peak level at 24 h (0.90-/+0.09, P<0.01), followed then by gradual decrease but remained still obviously higher than the control level at 24 h (0.80-/+0.09, P<0.01).

CONCLUSIONSSevere abdominal infection may induce beta-catenin expression which might be related with the proliferation and differentiation of intestinal stem cells in such condition and play an important role in intestinal mucosa damage and repair.

Animals ; Immunohistochemistry ; Intestinal Mucosa ; metabolism ; pathology ; Intestine, Small ; metabolism ; pathology ; Peritonitis ; metabolism ; pathology ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; beta Catenin ; biosynthesis ; genetics