15 scores were randomly divided into therapeutic group (30 cases)and control group(30 cases).The two groups were treated with the same conventional therapy. From the 1st day of admission,Xuebijing injection 80 ml was given by intravenous drip once for every 12 hours for 7 days to the therapeutic group.The level of tumor necrosis factor-?(TNF-?),interleukin-1?(IL-1?),IL-6,IL-10,and APACHEⅡscore were tested on 1,3,5 and 7 days after admission.The case fatality and incidences rates of sepsis and MODS in both groups were recorded.Results Compared with the control group,APACHEⅡscore,TNF-?,IL-1?,IL-6 and IL-10 of the therapeutic group were lower significantly on the 3rd day after admission,especially on the 5th day(all P

OBJECTIVETo evaluate the efficacy of Bufei Yishen Granule BFYSG) combined with Shufei Tie acupoint sticking therapy on quality of life of patients with stable chronic obstructive pulmonary disease (COPD).

METHODSA multi-center, double-blinded, double-dummy and randomized controlled method was adopted in this trial. A total of 244 patients were randomly assigned to a trial group and a control group according to the random number, each with 122 patients; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent form. In the trial group, patients were treated with BFYSG combined with "Shufei Tie" acupoint sticking therapy and sustained-release theophylline dummy, and in the control group patients were treated with oral sustained-release theophylline and BFYSG dummy combined with "Shufei Tie" acupoint sticking therapy dummy. The therapeutic course for two groups was 4 months and the follow-up was 6 months. The frequency and duration of acute exacerbation calculated by adding up each frequency and duration of acute exacerbation in treatment and follow-up time respectively, the quality of life measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and adult COPD quality of life (COPD-QOL) scale were observed.

RESULTSAmong the 244 enrolled patients, 234 were screened for full analysis set (FAS); 221 were screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month follow-up there were differences between the trial group and the control group in frequency of acute exacerbation (FAS: P=0.013; PPS: P=0.046); duration of acute exacerbation (FAS: P=0.005; PPS: P=0.006); scores of physiological, psychological and environment aspects of the WHOQOL-BREF questionnaire (FAS: P=0.002, P=0.006, P=0.000; PPS: P=0.00, P=0.001, P=0.000); scores of daily living ability, social activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS: P=0.000, P=0.000, P=0.006; PPS: P=0.002, P=0.001, P=0.001).

CONCLUSIONBFYSG combined with acupoint sticking therapy could improve the quality of life of patients with stable COPD.

Acupuncture Points ; Adult ; Aged ; Anxiety ; complications ; psychology ; Combined Modality Therapy ; Depression ; complications ; psychology ; Disease Progression ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Pulmonary Disease, Chronic Obstructive ; complications ; drug therapy ; psychology ; Quality of Life ; Surveys and Questionnaires ; Treatment Outcome

To observe the expression of cyclin D1, hTERT, and telomerase activity in MNC, HL-60, HL-60A and to explore their effects on leukemogenesis and drug-resistance, normal human peripheral blood mononuclear cells, HL-60 cells sensitive to adriamycin and HL-60A cells resistant to adriamycin were investigated. The cell cycle was analyzed by flow cytometry, and the apoptosis was analyzed by Annexin V-FITC(+) PI staining. Expressions of cyclin D1 and hTERT were determined by real-time PCR and Western blot. Telomerase activity was detected by TRAP-ELISA. The results indicated that the percentage of MNC, HL-60 and HL-60A in S phase was (10.21 + 2.11)%, (44.93 + 3.00)%, and (51.38 + 1.10)% respectively; the percentage of apoptosis cells was (16.14 + 2.13)%, (7.53 + 0.92)%, (4.15 + 0.96)% respectively; the expression of mRNA and protein for cyclin D1 and hTERT increased; the telomerase activities of HL-60 and HL-60A were higher (p = 0.000), whereas the difference between HL-60 and HL-60A was no statistically significant (p = 0.232); positive correlation between cyclin D1, hTERT and telomerase activity had been found (p < 0.01). It is concluded that the cells of S phase increased while the apoptotic cells decreased in HL-60 and HL-60A, especially in HL-60A, which may be due to the up-regulation of cyclin D1, hTERT and telomerase activity.
Cell Cycle ; Cyclin D1 ; metabolism ; HL-60 Cells ; Humans ; Leukemia ; metabolism ; Telomerase ; metabolism

[Objective]Examine the expression of microsomal prostaglandin E synthase-1(mPGES-1)and nuclear transcription factor kappa B p65(NF-κB p65)in diffuse large B cell lymphoma(DLBCL),assessing their correlation with clinical variables,prognosis and potential clinical valve.[Methods]The immunohistochemistry was uesd to investigate the expression of mPGES-1 and NF-κB p65 in 83 DLBCL patiens'tissues.The relationship between these two proteins and the clinical variables and prognosis of these patients was evaluated.[Results]The high expression of mPGES-1 and NF-κB p65 were observed in 65.1%(54/83)and 73.5%(61/83)cases of DLBCL,respectively.The expression level of NF-κB p65 was positively correlated with mPGES-1 expression(P<0.05).The expression of these two proteins was found to be significantly associated with B cell lymphoma/leukemia-2 protein(BCL-2),higher expression of Ki67,higher lactate dehydrogenase (LDH),more extranodal lesions,advanced Ann Arbor stage and higher international prognostic index(IPI)score(P<0.05). In addition,NF-κB p65 was related with multiple myeloma oncogene 1(MUM1),pathological type(P<0.05). Both mPGES-1 and NF-κB p65 overexpression was correlated with worse overall survival(OS)while NF-κB p65 was an in-dependent prognostic factor for OS of DLBCL(P<0.05).[Conclusions]mPGES-1 and NF-κB p65 were highly expressed in DLBCL and closely linked with each other. The overexpression of mPGES-1 and NF-κB p65 was correlated with tumor progression and unfavorable prognosis in patients with DLBCL.

OBJECTIVETo explore the effect of serum restriction on the invasiveness and expressions of insulin-like growth factor-1 (IGF-1) and matrix metalloproteinase-2 (MMP-2) in human trophoblast HTR-8/SVneo cells in vitro.

METHODSHTR-8/SVneo cells were cultured in the presence of 1%, 5%, or 10% fetal bovine serum (FBS) for 48 h. Fluorescence quantitative PCR and immunofluorescence staining were employed to examine the changes in IGF-1 and MMP-2 expressions at both the mRNA and protein levels in HTR-8/SVneo cells; MTT assay and Transwell invasion assay were used to assess the changes of the cell proliferation and the cell invasion ability, respectively. MMP-2 expression, cell proliferation and invasiveness were also assessed in the cells treated with recombinant human IGF-1.

RESULTSHTR-8/SVneo cells exhibited significantly lowered cell proliferation in cultures containing low concentrations of FBS (P<0.05). The expressions of IGF-1 and MMP-2 at both mRNA and protein levels were significantly down-regulated and the invasiveness was significantly lowered in cells cultured in the medium containing 1% FBS as compared with those of cells cultured in the presence of 5% and 10% FBS (P<0.05). Treatment of the cells with recombinant human IGF-1 significantly up-regulated MMP-2 expression (P<0.05) and increased the cell invasiveness (P<0.05).

CONCLUSIONSFBS restriction down-regulates IGF-1 expression in human trophoblast HTR-8/SVneo cells and suppress the cell invasiveness possibly by suppressing MMP-2 expression. Treatment with recombinant human IGF-1 can up-regulate MMP-2 expression and promote the invasiveness of HTR-8/SVneo cells.

Objective The proto-oncogene c-Met was found to express on human laryngeal carcinoma Hep-2 cell line in previous research. In the present study, the author further examined whether inhibition of c-Met by RNA interference(RNAi) might inhibit biologic activity of Hep-2 cell line in vitro and proliferation using a murine laryngeal carcinoma model. Methods RNAi plasmid that can express small interfering RNA targeting c-Met or siRNA that did not match any known human coding mRNA( control siRNA plasmid) was designed,constructed,and transfected into Hep-2 cell line by using cationic liposome Lipofectamine2000 as transfecting agent. In vitro, the transfection efficacy was tested by RT-PCR and Western Blot method, then elected the most inhibitive c-Met-siRNA sequence. Cell proliferation, movement and invasion were studied using MTT, cell migration assay and cell invasion assay, respectively. The Hep-2 cells were transplanted into nude mice, then the time of tumor formation and growth were observed. After tumor formation, c-Met-siRNA was given as the anti-tumor therapy. Expression of c-Met, MMP-9 and VEGF were detected by Western Blot method. Results After the pSilencer2. 0/c-Met-shRNA recombinant plasmid transfeetion into laryngeal carcinoma Hep-2 cells, the expression of mRNA and proteinum of c-Met decreased significantly in Hep-2 cells. On the 35th day after tumor vaccination, the tumor volume was (138±27)mm~3 in c-Met-siRNA transfection group, Which was diminished significantly in contrast with control group( P<0. 01 ). The expression of c-Met, MMP-9 and VEGF in the tumor of experiment group was decreased significantly, respectively (P<0.05 ). Conclusions The results indicated that c-Met-siRNA can down-regulate the expression of c-Met and markedly inhibit laryngeal carcinoma Hep-2 cell proliferation, movement and invasion and the growth of transplantation tumor of nude mice. The siRNA expressing plasmid mediated gene therapy might be a new strategy in targeting molecular therapy of cancer of larynx.

Objective To investigate the causal relationship between obstructive sleep apnea(OSA)and hypertension using bidirectional Mendelian randomization(MR).Methods Genetic data for OSA were obtained from the Genome-wide association study(GWAS)of FinnGen Biobank,including 16 761 cases and 201 194 controls,from which 5 single-nucleotide polymorphisms(SNPs)were screened as instrumental variables(IVs)for OSA.Genetic data for hypertension were obtained from GWAS of UK Biobank,including 124 227 cases and 337 653 controls from which 214 SNPs were selected as IVs for hypertension.Multiple MR methods,mainly Inverse variance weighted(IVW),were used for analysis.Sensitivity analysis of MR results was performed using MR-Egger regression et al,and IVs were evaluated using F values.Results OSA was associated with an increased risk of hypertension(OR=1.053,95%CI 1.019-1.089,P<0.01),and hypertension was significantly associated with the risk of developing OSA(OR=1.812,95%CI 1.354-2.425,P<0.001).Heterogeneity was observed in both two-way outcomes(OSA→ hypertension,P<0.001;hypertension→ OSA,P<0.001),but no evidence of horizontal pleiotropy was detected(OSA→ hypertension,P=0.666;hypertension→ OSA,P=0.556).The IVs selected in this study were strong instrumental variables for both OSA and hypertension(OSA-IVs F=14.695;hypertension-IVs F=39.624).Conclusions Our findings indicate a bidirectional causal relationship between OSA and hypertension,with a particularly significant effect of hypertension on the development of OSA.

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell-like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.
Adolescent ; Adult ; Aged ; Carcinoma ; Cell Line, Tumor ; China ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Knockdown Techniques ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Neoplasm Staging ; Neoplastic Stem Cells ; pathology ; RNA, Small Interfering ; genetics ; S-Phase Kinase-Associated Proteins ; genetics ; metabolism ; Sex Factors ; Survival Rate ; Tissue Array Analysis ; Transfection ; Young Adult

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.
Rats ; Animals ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal ; Precancerous Conditions ; Triterpenes/pharmacology*