Acute Disease ; Female ; Humans ; Infant ; Infant, Newborn ; Propionates ; blood ; Pyruvate Carboxylase Deficiency Disease

Objective To review retrospectively the clinical experience in surgical treatment of congenital subaortic stenosis in 21 cases. Methods A total of 21 cases of congenital subaortic stenosis, including 12 cases of diaphragmatic type of stenosis and 9 cases of cast constriction, underwent intracardiac surgery from January 1999 to June 2003. Simple resection of stenosis membrane was performed in 12 cases, simple resection of stenosis membrane plus resection of myocardium of left ventricle outflow tract in 9 cases, simple resection of stenosis membrane plus resection of myocardium of left ventricle outflow tract plus treatment of united cardiac monstrosity in 16 case. Results No operative death and complications were found in all patients. Disappearance of cardiac murmur was found in 15 cases and diminishment of cardiac murmur in the rest of the patients after operation. A follow up time for 6 months to 2 years revealed that there were no obvious clinical symptoms, and the surgical outcomes were satisfactory. The cardiac ultrasound suggested that the left ventricular outflow tract was fluent without recurrent constriction. Conclusion Early treatment of congenital subaortic stenosis should be conducted when the disease was diagnosed. Better knowledge of pathological anatomy, proper operation, and prevention of complications are essential.

Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death ; Humans ; Hypoxia-Inducible Factor 1 ; antagonists & inhibitors ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Neoplasms ; drug therapy ; Oxygen ; metabolism ; Signal Transduction

OBJECTIVETo provide evidence for Chinese medical treatment of children with EB virus infection by exploring its clinical efficacy from multiple angles.

METHODSTotally 81 children patients were randomly assigned to the treatment group (46 cases) and the control group (35 cases). Patients in the treatment group took Chinese medical decoction, while those in the control received intravenous dripping of Ganciclovir and oral administration of pidotimod. The treatment period for the two groups was 2 weeks. Patients were followed-up till the 12th week. Clinical symptoms such as fever, lymphadenopathy and hepatosplenomegaly, as well as lab indices such as abnormal lymphocyte percentage, EB virus antibody, virus DNA load, T cell subsets, immunoglobulin, and so on were observed before and after treatment, at week 4 and 12 of follow-ups.

RESULTS(1) The total effective rate at week 2 was 95.6% in the treatment group, higher than that of the control group (94.3%), but there was no statistical difference between the two groups. (2) The time for defervescence, duration of pharyngeal hyperemia, duration of swollen tonsils was shorter in the treatment group than in the control group (P<0.05). The subsidence of lymphadenopathy, hepatomegaly, and abnormal lymphocytes was better in the treatment group than in the control group (P < 0.05). (3) The positive cases of peripheral blood hetero-lymphocyte was significantly reduced after treatment, at week 4 and 12 of follow-ups both in the treatment group and the control group (P < 0.01). The expression of IgA and IgM decreased after treatment in the two groups when compared with before treatment in the same group (P < 0.05, P < 0.01). IgG in the treatment group also obviously decreased after treatment, at week 4 and 12 of follow-ups (P < 0.05, P < 0.01), while it decreased only after treatment in the control group (P < 0.05). Activities of AST and ALT in the treatment group and the AST activity in the control group were markedly improved when compared with those before treatment (P < 0.05). Compared with the control group, the abnormal lymphocyte positive case number obviously decreased in the treatment group after treatment, at week 4 and 12 of follow-ups (P < 0.05). (4) After treatment, at week 4 and 12 of follow-ups, CD3+ and CD8+ significantly decreased; CD4+, CD4/CD8, and B cells significantly increased in the two groups, when compared with before treatment (P < 0.05). NK cells significantly increased more in the treatment group after treatment, at week 4 and 12 of follow-ups, higher than before treatment as well as the control group (P < 0.05). (5) EB viral DNA and EB viral CA-IgM negative conversion case numbers significantly increased in the two groups after treatment, at week 4 and 12 of follow-ups (P < 0.05). Compared with the control group, EB viral DNA and EB viral CA-IgM negative conversion case numbers significantly increased in the treatment group after treatment and at week 4 of follow-ups (P < 0.05).

CONCLUSIONSTreatment of EB virus infection by Chinese medical treatment was effective. It could promote the recovery of EB viral infection, and reduce the risk of vicious disease after EB viral infection.

Adolescent ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; therapeutic use ; Epstein-Barr Virus Infections ; drug therapy ; immunology ; Female ; Herpesvirus 4, Human ; Humans ; Infant ; Male ; Phytotherapy ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo investigate the effect of different pressure oxygen pre-breathing in preventing decompression sickness of rats.

METHODSForty male SD rats were randomly divided into 4 groups: decompression sickness (DCS) group and three oxygen pre-breathing groups with 1 ATA, 2 ATA and 3 ATA pressure respectively. The rats of DCS group were placed in the hyperbaric chamber and the chamber was compressed evenly within 3 minutes to depths of 7 absolute atmosphere(ATA) and held at the designated depth for 60 min, then decompressed (3 min) at constant speed to the surface pressure. After that, the rats were taken out for further detection. While the rats of oxygen pretreatment groups pre-breathed different pressure oxygen for 20 min before entering into chamber. The mortality and behavioral of rats were observed with 30 min post decompression. The dry/wet ratio of the lung, protein levels in the bronchoalveolar lavage fluid (BALF), and the inflammatory cytokine tumor necrosis factor (TNF-alpha) expression were also tested.

RESULTSCompared with that of the DCS group, the mortality and morbidity of oxygen pre-breathe groups didn't change obviously. But the total BALF protein level and the inflammatory cytokine TNF-alpha expression of 1 ATA oxygen pre-breathe group were obviously decreased, while the dry/wet ratio of lung as obviously increased instead (P < 0.05).

CONCLUSIONAlthough preoxygenation can' t obviously change the mortality and mobidity of rats, normal pressure oxygen pre-breathing can mitigate the protein infiltration in BALF and the expression of inflammatory cytokine in lung tissue.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Decompression Sickness ; Diving ; Lung ; pathology ; Oxygen ; physiology ; Pressure ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil (5-Fu) as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro. IPM acted as oil phase, AOT as surfactant, Tween 85 as cosurfactant, water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, then 5-Fu powder was added. The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel. The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity. Refer to 5-Fu cream, the irritation of microemulsion and microemulsion-based gel on the rat skin was studied. Based on the water/AOT/Tween 85/IPM microemulsion, only the gelatin can form the microemulsion-based gel. At 25 degrees C, 32 degrees C and 40 degrees C, the amount of gelatin required for the formation of microemulsion-based gel were 7%, 14% and more than 17%, respectively. The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were (876.5 +/- 29.1) microg x cm(-2), 12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5% (w/w) 5-Fu cream, respectively. Microemulsion-based gel exhibited some irritation, but could be subsided after drug withdrawal. Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.

Adhesives ; Anti-Bacterial Agents ; Dental Cements ; Dental Materials ; Humans

Objective:To explore the role of indoleamine-pyrrole 2,3-dioxygenase (IDO),an immunomodulatory enzyme,in renal cell carcinoma (RCC).Methods:A total of 40 patients diagnosed as RCC in the Second Xiangya Hospital were included in this study.All patients received nephrectomy.The histopathological features of samples were assessed semi-quantitatively.IDO mRNA level in RCC and non-RCC renal tissues was determined by real-time quantitative PCR (RT-qPCR).And the expression of IDO protein in endothelial cells was examined by immunohistochemistry; a Kaplan-Meier survival curves was calculated on the basis of IDO mRNA level.Results:Level of IDO mRNA in RCC samples was significantly higher than that in tumor-free samples with P＜0.001.Patients with high IDO expression had an significantly longer survival time than those with low IDO expression (P=0.01).There was a statistically significant inverse correlation between IDO and proliferation marker Ki67.Patients with high IDO level were of low Ki67 level,and vice versa (P＜0.01).Conclusion:IDO might be a prognostic biomarker for patients with RCC.