Hedgehog signaling pathway is excessive activated in breast cancer.LKBl is currently accepted as a tumor-suppressor gene,which can inhibit the proliferation of breast cancer.The overexpression of LKB1 can regulate the expression of CyclinDl series gene which is a target gene of Hedgehog signaling pathway.Meanwhile,the study found that PKA gene play an important role in Hedgehog signaling pathway,its activation is related with the cAMP state,and LKB1 genes can influence the cAMP state.Therefore,LKB1 gene and the Hedgehog signaling pathway may exist some inevitable connection.

Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application.
Gout ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pharmacology ; methods ; Tablets ; Technology, Pharmaceutical ; methods

OBJECTIVETo assess the effects of ambient air pollutants on hospital outpatient visits for allergic disease and pollinosis.

METHODSThe monitoring data of daily air pollution (SO(2), NO(2) and PM(10)) in 8 national monitoring and controlling sites of Beijing air quality, airborne pollen in 4 monitoring sites of Beijing, and daily meteorological data, along with the daily numbers of outpatients visits for allergic disease and pollinosis at the Allergy Department of Beijing Shijitan Hospital from April to September in 2004 were collected. Associations between the levels of air pollutants and outpatient visits for allergic disease and pollinosis were estimated by time serial analysis using a generalized addictive model (GAM), considering lag effect and the influence of multipollutants.

RESULTSDuring the study period, the average daily ambient concentrations of SO(2), NO(2) and PM(10) were (20.9 ± 12.9), (58.6 ± 13.6) and (126.8 ± 64.1) µg/m(3), respectively. The mean daily pollen count was (163.8 ± 209.0) grains/1000 mm(2), while the average daily numbers of doctor visits for allergic disease and pollinosis were (16.3 ± 5.3) and (3.5 ± 5.0), respectively. Time serial analysis showed that significant positive associations were found between levels of airborne pollen and doctor visits, with an excess risk (ER) of 2.44% (95%CI: 0.75% - 4.13%)for allergic disease and 6.58% (95%CI: 3.82% - 9.34%) for pollinosis per 100 grains/1000 mm(2) increase in pollen, in single-pollutant models. There were associations between ambient air pollutants (SO(2), NO(2), PM(10)) and doctor visits with lag effects. A 10 µg/m(3) increase in NO(2) was associated with a 3.14% (95%CI: 0.42% - 5.85%) increase in doctor visits for allergic disease at lag 6 d. For pollinosis, the highest ER was observed for 10 µg/m(3) increases in SO(2) at lag 1 d, NO(2) at lag 6 d, PM(10) at lag 3 d. However, this association was not statistically significant (RR (95%CI) were 1.0460 (0.9640 - 1.1280), 1.0325 (0.9633 - 1.1017), 1.0079 (0.9942 - 1.0217), respectively). The associations enhanced slightly in multi-pollutant models with an ER of 2.56% (95%CI: 0.80% - 4.31%) for allergic disease and 6.81% (95%CI: 3.91% - 9.71%) for pollinosis per 100 grains/1000 mm(2) of pollen.

CONCLUSIONSOur results suggest that level of airborne pollen may have a stronger effect than ambient air pollutants on allergic disease and pollinosis.

Air Pollutants ; analysis ; Air Pollution ; analysis ; Environmental Illness ; prevention & control ; Environmental Monitoring ; Humans ; Outpatient Clinics, Hospital ; statistics & numerical data ; Rhinitis, Allergic, Seasonal ; prevention & control

OBJECTIVETo investigate the correlation between expression of A-kinase anchoring protein 95 (AKAP95) and protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.

METHODSFifty-one cases of lung cancer were included in the study. The protein expression of AKAP95, cyclin E1, and cyclin D1 were measured by immunohistochemistry.

RESULTSThe protein expression of cyclin E1 in lung cancer tissues was significantly higher than that in para-cancerous tissues (positive rate: 75.56%vs 20%, P < 0.01); its expression showed no relationship with histopathological type, lymph node metastasis, and cellular differentiation (P > 0.05). The protein expression of cyclin D1 in lung cancer tissues was higher than that in para-cancerous tissues (positive rate: 69.39% vs 14.29%); its expression showed a significant relationship with histopathological type (P < 0.05). The expression of AKAP95 was correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissues (P < 0.01).

CONCLUSIONCyclin E1 and cyclin D1 are highly expressed in lung cancer tissue, suggesting that they play an important role in the development and progression of lung cancer. The protein expression of cyclin E1 has no relationship with cellular differentiation, lymph node metastasis, and histopathological type of lung cancer, and the protein expression of cyclin D1 has a significant relationship with histopathological type. The expression of AKAP95 is correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.

A Kinase Anchor Proteins ; metabolism ; Adult ; Aged ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Middle Aged ; Oncogene Proteins ; metabolism

OBJECTIVESTo explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma.

METHODSFrom January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations, treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis.

RESULTSAll cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases, pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free. The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63.8% and 49.9% at the same periods, and there is no difference in the survival rate of five years (P > 0.05) but significant difference in that of ten years (P < 0.01).

CONCLUSIONSChromophobe renal cell carcinoma is a morphologically uncommon subtype of renal cell carcinoma with the good prognosis. Definite diagnosis depends on its typical pathological feature. Radical nephrectomy is the first choice for the treatment of chromophobe renal cell carcinoma.

Adult ; Aged ; Carcinoma, Renal Cell ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Nephrectomy ; methods ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the effects of mangiferin on proliferation, apoptosis and cycle of FLT3-ITD mutation-positive acute myeloid leukemia cells and its mechanism. METHODS: The effects of different concentration of mangiferin on proliferation of MV4-11 cells were detected by CCK8 method. Apoptosis, cell cycle and FLT3 transmembrane protein expression were detected by flow cytometry. FLT3 mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR) . RESULTS: Mangiferin obviously inhibited MV4-11 proliferation in a concentration and time dependent manner (48 h，r=0.922；72 h，r=0.959；96 h，r=0.973). The ratio of G0/G1 phase in cell cycle increased with the enhancement of concentration of mangiferin in MV4-11 cells for 48 h, and the ratio of S phase decreased with enhasment of concentration. The increase of apoptosis was more obvious. The expression of FLT3 transmembrane protein significantly decreased after the actior of IC50 concentration of mangiferin in MV4-11 cells for 48 h. The results of qRT-PCR showed that the expression of FLT3 mRNA significantly decreased after treatment of MN4-11 cells with mangiferin (P＜0.05). CONCLUSION Mangiferin inhibits MV4-11 cell proliferation, arrests cell cycle progression and promotes apoptosis, which may be related with the inhibition of FLT3 activity by mangiferin and the subsequent signaling pathways involved in apoptosis and proliferation of cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Xanthones ; fms-Like Tyrosine Kinase 3

In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.
Drugs, Chinese Herbal ; therapeutic use ; Dysmenorrhea ; drug therapy ; genetics ; metabolism ; Female ; Gene Regulatory Networks ; drug effects ; Humans ; Leiomyoma ; drug therapy ; genetics ; metabolism ; Pelvic Inflammatory Disease ; drug therapy ; genetics ; metabolism

BACKGROUNDSinonasal inverted papilloma (IP) is a rare benign tumor of the nasal cavities and paranasal sinuses. It is destructive or bone-remodeling, tends to recur after surgical resection, and has a significant malignant potential. The present study aimed to perform a retrospective analysis of patients with squamous cell carcinoma (SCC) arising from IP, including characteristics, survival outcome, and predictors of associated malignancy.

METHODSThe medical records of 213 patients diagnosed with IP from January 1970 to January 2014 were retrospectively reviewed. Eighty-seven patients were diagnosed with SCC/IP; their clinical characteristics, treatments, and survival outcomes were analyzed.

RESULTSOf the 87 patients with SCC/IP, the 5- and 10-year overall survival outcomes were 39.6% and 31.8%, respectively. Twenty-nine of these patients received surgery and 58 received combined surgery and radiation. Of the patients with stages III-IV, the 5-year survival rate was 30.7% for those treated with surgery only and 39.9% for those given the combination treatment (P = 0.849). Factors associated with significantly poor prognosis were advanced-stage, metachronous tumors, or with cranial base and orbit invasion. Age, synchronous or metachronous tumors, and pathological stage were independent risk factors for mortality, shown by multivariate analysis.

CONCLUSIONPatients with SCC/IP had low overall survival outcomes. Advanced age, stage, and metachronous tumors are the main factors affecting prognosis. Treatment planning should consider high-risk factors to improve survival outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; etiology ; mortality ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Papilloma, Inverted ; complications ; mortality ; Retrospective Studies ; Young Adult

OBJECTIVETo explore a novel non-invasive method in detection of thyroid cancer by Fourier transform infrared (FTIR) spectroscopy.

METHODSSurface FTIR spectra of 15 cases of thyroid cancer and 51 cases of normal subjects were collected. 22 variables of 11 bands including peak positions and relative intensities were measured and all data were statistically analyzed.

RESULTSIn the cancer group: (1) the peak position of 1743 cm(-1) was shifted toward higher wave number (P < 0.05), and that of 1250 cm(-1) to the lower (P < 0.05), when compared to those of normal ones. (2) The relative intensity ratios of I(1546)/I(1460), I(1250)/I(1460), I(1120)/I(1460), I(1080)/I(1460) were significantly increased (P < 0.05). (3) The presence rate of band of 1340 cm(-1) was significantly decreased (P < 0.05).

CONCLUSIONFTIR surface spectra may become a novel powerful non-invasive approach of detecting thyroid cancer in regular routine check-up.

Humans ; Spectroscopy, Fourier Transform Infrared ; methods ; Thyroid Gland ; chemistry ; Thyroid Neoplasms ; chemistry ; diagnosis

Objective:To explore the effects and mechanism of zedoary turmeric oil and its active components on the vascular endothelial growth factor A （VEGFA）， signal transducer and activator of transcription 3 （STAT3）， and mechanistic target of rapamycin （mTOR） in the ovarian cancer （OC）. Method:Network pharmacology technology was employed to analyze the mechanism of Curcumae Rhizoma on OC. Bioinformatics was used to analyze the expression of VEGFA， STAT3， and mTOR in OC and the effect on the prognosis of OC to explore the feasibility of zedoary turmeric oil in regulating VEGFA， STAT3， and mTOR in OC.The xenograft tumor model of nude mice was established， and the effects of zedoary turmeric oil and its active components on VEGFA， STAT3， and mTOR in OC were observed by hematoxylin-eosin （HE） staining， real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry （IHC）. Result:Bioinformatics analysis and literature research showed that VEGFA， STAT3， and mTOR played a special regulatory role in the occurrence and development of OC， and were potential key targets for the proliferation of OC. Network pharmacology analysis revealed that Curcumae Rhizoma could regulate multiple disease targets of OC， and mediate VEGFA， STAT3， and mTOR in OC through these multiple targets. As demonstrated by HE staining， the tumor cells in the model group were densely arranged， with no erosion on the edge and no vesicles inside. Compared with the model group， the cell density in other treatment groups was reduced， and strip-shaped erosion on the edge and small empty vesicles were observed in the tumor tissue， especially in the zedoary turmeric oil group. According to the results of Real-time PCR and IHC， zedoary turmeric oil and its active components could inhibit the mRNA and protein expression of VEGFA， STAT3， and mTOR in the OC tissue （P<0.05）. Conclusion:Zedoary turmeric oil and its active components could reduce the expression of VEGFA， STAT3， and mTOR in tumor tissue of nude mice， and inhibited the proliferation of OC through VEGFA， STAT3， and mTOR.