OBJECTIVETo study the effect of aqueous extract of Taxus chinensis var. mairei (AETC) combined Erlotnib on the growth of A549 xenograft in nude mice and its mechanism.

METHODSThe xenograft model in nude mice was established by inoculating A549 cells subcutaneously. BALB/c nude mice bearing A549 xenograft were randomly divided into six groups, i.e., the low dose Erlotinib group (A) , the standard dose Erlotnib group (B) , the low dose Erlotinib combined AETC group (C), the standard dose Erlotnib combined AETC group (D), the AETC group (E), the control group (F), 12 in each group. Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken. The tumor inhibition rate was calculated. The combined effect was analyzed by Jin's Formula [Q = Ea + b/(Ea + Eb-Ea x Eb) ]. mRNA and protein expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), and B cell lymphoma-2 (Bcl-2) in xenografts were detected using real-time RT-PCR and ELISA.

RESULTSCompared with Group F, the xenograft weight was obviously lowered in Group B-E (P < 0.05, P < 0.01). The q value was 0.92 in Group C and 0.96 in Group D, which was obtained by simple adding of the two drugs. Compared with Group F, EG- FR mRNA expression in Group D and E, COX-2 mRNA expression in Group A-E; Bcl-2 mRNA expression in Group B-D; COX-2 protein expression in Group B-E; Bcl-2 protein expression in Group C and D were obviously lowered with statistical difference (P < 0.05, P < 0.01).

CONCLUSIONSAETC combined low dose and standard dose Erlotinib had synergistic effect on tumor inhibition. Its mechanism might be associated with down-regulating mRNA and protein expression levels of COX-2 and Bcl-2.

Animals ; Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Erlotinib Hydrochloride ; pharmacology ; Heterografts ; Lung Neoplasms ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Receptor, Epidermal Growth Factor ; metabolism ; Taxus ; Transplantation, Heterologous

Objective:To investigate the efficiency of carbon nanotube(CNT)-PAMAM mediated entrance of anti-survivin oligonucleotide into HepG2 cells,and its effects on the proliferation of HepG2 cells.Methods:CNT-PAMAM-anti-survivin oligonucleotide compounds were prepared and characterized by AFM and 1% agarose gel electrophoresis analysis.TEM was used to observe the distribution of CNT-PAMAM-ASODN compounds in HepG2 cells.CNT-PAMAM-ASODN compounds were added into the medium and co-cultured with HepG2 cells for 24 h,48 h,72 h,and 96 h at 37℃,5% CO_2.MTT method was used to detect the effects of ASODN and CNT-PAMAM-ASODN on the proliferation of HepG2 cells.Results:CNT-PAMAM-ASODN compounds were successfully synthesized via AFM and agarose gel electrophoresis.TEM showed that the compounds were located in the cytoplasm.When CNT-PAMAM-ASODN(1.0 ?mol/L)and ASODN(1.0 ?mol/L)were used for a 48 h culture,the inhibitory rates of HepG2 cells were(45.97?4.28)% for CNT-PAMAM-ASODN compounds group,(9.33?0.85)% for ASODN group,and(6.37?0.69)% for CNT-PAMAM group.CNT-PAMAM-ASODN compounds at 1.5 ?mol/L inhibited HepG2 cells by(70.22?7.25)%,and the inhibitory effects were in a time-and concentration-dependent manner.There was statistical difference between experiment group and control group(P

Objective To evaluate the features of the encapsulated papillary thyroid carcinoma (EPTC) by ultrasound and histopathology.Methods The EPTC were classified into the following two types based on the shape,characteristics of the border,size of the nodule,echogenicity,a hypoechoic halo and microcalcification by ultrasound features:papillary carcinoma (PC) type and follicular tumor (FT) type.Results Of all the 33 cases,21 cases were PC type and 12 cases were FT type.The histopathological result of PC type was papillary carcinoma.PC type had a jagged border,an irregular tumor shape with marked hypoechogenicity by ultrasound.PC type were composed of papillae by histopathology,completely surrounded by a fibrous capsule with tumor cells having the nuclear features of papillary thyroid carcinoma,densely interstitial fibrosis and microcalcification;FT type had a smooth border,a regular shape (spherical to oval),isoechogenicity and a hypoechoic halo by ultrasound.FT type were completely or significantly composed of follicles by histopathology,completely surrounded by a fibrous capsule with tumor cells having the nuclear features of papillary thyroid carcinoma.Hypoechoic halo were more frequently observed in FT type than in PC type.The nodule size of FT type(1.8-7.0 cm)was larger than that of PC type(0.8-5.2 cm).Fine and multiple strong echoes were characteristically present only in PC type.Conclusion The EPTC have characteristic features that are similar to those of the benign follicular thyroid tumor by ultrasound.

Pulmonary infection is a common kind of respiratory disease caused by a wide range of pathogens,which seriously threatens human health.The researches of molecular mechanisms of lung infection have attracted more and more attentions in recent years.It is found that cytokines play an important role on acute and chronic inflammatory reactions caused by lung infection,including interleukins,tumor necrosis factor-α,and so on.In this paper,the correlations between these cytokines with pathogenesis and prognosis of pulmonary infection are reviewed.

Objective To investigate the attitudes of urban and rural community members toward total banning on smoking in public places and to explore the factors associated with these attitudes, in three counties/cities in China. Methods A cross-sectional study was conducted in three counties/cities in 2004, including Xin' an county of Henan province, Anyi county of Jiangxi province, and Mianzhu city of Sichuan province. A total of 5642 residents at age of 18-69 years old were interviewed face-to-face with a uniform questionnaire by locally-trained interviewers, through a random three-stage stratified sampling in each county. Factors were assumed to be associated with attitudes, using chi-square test in univariate analysis and non-conditional logistic regression model in multivariate analysis. Results The prevalence of current smoking among respondents was 44.3%. 80.7% (1379/1709) of the current smokers reported smoking often or sometimes in public places. Only 9.6% (479/4983) of the respondents reported that their indoor workplaces had totally banned on smoking. 43.5% of the respondents supported a total smoking ban strategy in pubic venues. The results of multivariate logistic regression model showed that eight factors were significantly associated with support for the total smoking ban in public places included region, residency, age, gender, education, smoking status, awareness about passive smoking hazards, and hearing of any message on tobacco control through media differences of rates regarding the factors as: residents in urban to rural areas (OR=1.29), elderly to youngsters (30-49 vs. 18-29, OR=1.46; 50-69 vs. 18-29, OR=1.71), female to male(OR=1.27), high-educated to less-educated ones, quitters to current smokers (OR=1.90), nonsmokers to current smokers (OR=2.01). Those who know messages on health hazards of passive smoking (OR=2.26), or heard of message on tobacco control through media (OR= 1.43). Conclusion Results from our study revealed that a thorough smoke-flee policy in public places should be developed and implemented in these three counties/cities.

BACKGROUNDAdoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD). Here, we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice.

METHODSC57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation (TBI), or 7 Gy TBI plus bone marrow transplantation. Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression. B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1, 3, 5, 7, 9, 11, and 13 after irradiation. White blood cell levels were measured and transforming growth factor β1 (TGF-b1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-b1, IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens. B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2), dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment, tumor areas and system GVHD were observed every 3 days. Mice were killed 21 days after the DC-CTLs adoptive transfer; histologic analyses of eyes, skin, liver, lungs, and intestine were then performed.

RESULTSIrradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however, it down-regulated the proportion of Tregs in spleens and the TGF-b1 and IL-10 levels in sera and spleens, suggesting inhibition of autoimmunity and intervention of tumor microenvironment. Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth. GVHD assessment and histology analysis showed no significant difference among the groups.

CONCLUSIONAdoptive transfer of haploidentical tumor-specific T cells in irradiation-pretreated B16-melanoma bearing mice preserved antitumor capacity without causing a GVHD response.

Animals ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Graft vs Host Disease ; Immunotherapy, Adoptive ; methods ; Male ; Melanoma, Experimental ; metabolism ; therapy ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes ; immunology ; T-Lymphocytes, Regulatory ; immunology

BACKGROUNDTreatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.

METHODSHuman glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.

RESULTSMild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).

CONCLUSIONVPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.

Apoptosis ; drug effects ; radiation effects ; Blotting, Western ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Dacarbazine ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Glioma ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Valproic Acid ; pharmacology

OBJECTIVETo observe the effects of exogenous adrenomedullin (ADM) on endogenous expression of ADM in the kidney and hypothalamus of rats early after mechanical renal trauma.

METHODSAdult Wistar rats were randomized into 4 groups (n=32), namely the control group, renal impact trauma group, preventive ADM injection group, and therapeutic ADM injection group. In the latter two groups, ADM (0.1 nmol/kg) was administrated by intraperitoneal injection 10 min before and 10 min after renal trauma. The rats were executed at 1, 6, 12, and 24 h after the trauma to examine the expression of ADM in the kidney and hypothalamus.

RESULTSIn preventive ADM injection group, the renal expression of ADM increased significantly at 1 h after the trauma (P<0.05) and tended to further increase with time till 24 h when its expression recovered the normal level. In the therapeutic ADM injection group, strong renal ADM positivity was found at 1 and 6 h after the injury (P<0.05) followed by gradual decrease till recovering the normal level at 24 h. Low renal ADM expression was detected, which was the strongest at 1 and 12 h (P<0.05) and became normal at 24 h. The time course of ADM expression in the hypothalamus was similar to that in the kidney in the therapeutic ADM injection group, and in the preventive injection group, the strongest ADM expression in the hypothalamus occurred at 6 and 24 h, and the lowest expression occurred at 12 h (P<0.05). The trauma group showed significantly decreased ADM expression in the hypothalamus compared with the control group (P<0.05).

CONCLUSIONThe hypothalamic ADM expression can upregulate renal ADM expression. ADM maintains the relative stability of the internal environment and physiological activity by local and systemic positive and negative feedback mechanisms.

Adrenomedullin ; metabolism ; pharmacology ; Animals ; Female ; Hypothalamus ; drug effects ; metabolism ; Kidney ; drug effects ; injuries ; metabolism ; Male ; Rats ; Rats, Wistar ; Wounds and Injuries ; metabolism

Objective:Based on the perspective of supply and demand balance, to analyze the implementation effects of primary-feature medical services measures in medical alliances.Methods:From July to September 2019, two regions with different levels of economic development were chosen, and from each region one leading hospital and two community health service centers/township hospitals were selected from its medical alliance. A total of 213 medical staff and 703 residents were surveyed, to learn their awareness and performance appraisal of these feature services.Frequency and proportion were calculated in a descriptive statistical analysis. The scores of the performance appraisal of both supply and demand sides were tested by independent sample t. Results:In the performance appraisal of such measures, the average scoring by medical staff was 4.39±0.07, and that by residents was 3.85±0.06; the residents were more concerned with service capabilities and contents, while medical staff were more concerned with service content and delivery mode; supply and demand sides were found with consensus in terms of improving the medical service quality of chronic diseases in primary level and service accessibility.Conclusions:The county-level medical alliances should focus on enhancing their capacity of primary medical services, and improving their primary service mode with the help of medical insurance institutions. Meanwhile, it is imperative to optimize the primary medical service policy in view of supply and demand balance.

Building an integrated health care service system is key to the Healthy China strategy. Based on the integrated health care service conceptual framework, the authors took two pilots regions of health-centered medical alliances in Zhejiang province as an example, and analyzed their conception framework, organizational structure, operation elements and effects. The study found initial success of the two alliances in terms of the contents, capabilities, effects and satisfaction of primary health care service. Such alliances feature a health-centered multi-entity participation mechanism, carry out health care and prevention integration leveraging the information platform, hence conducive to the effective governance of the alliances. However, the contents of their health related services are expected to be broadened and deepened; functionalities of health-related institutions need to be clarified and refined, while their performance appraisal needs to be further improved.