Asian Continental Ancestry Group ; China ; epidemiology ; Fatty Liver ; epidemiology ; Humans ; Hyperlipidemias ; epidemiology

OBJECTIVETo generate the skeletal muscle-specific transforming growth factor beta receptor II (TbetaR II) gene knockout mice for the research on the function of the TbetaR II gene in skeletal muscles.

METHODSTbetaR II (flox/flox) mice were generated using embryonic stem cell technology. The MCK-Cre mice were engineered containing Cre recombinase under the control of creatine kinase (MCK) muscle-specific promoter. TbetaR II (flox/flox) mice were crossed with MCK-Cre mice generating TbetaR II (flox/flox)/MCK-Cre double Tg mice. And then, TbetaR II (flox/wt) /MCK-Cre(+) double Tg mice were crossed with TbetaR II (flox/flox) mice to generate TbetaR II (flox/flox)/MCK- Cre(+) mice genetically ablating TbetaR II in cre-expressing skeletal muscle cells.

RESULTSAs predicted, mice lacking TbetaR II by gene targeting in skeletal muscles were generated first in the world using Cre/loxP system. TbetaR II null mutant mice were viable, fertile and showed apparently normal development.

Animals ; Mice ; Mice, Knockout ; Mice, Transgenic ; Muscle, Skeletal ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Receptors, Transforming Growth Factor beta ; genetics ; metabolism ; Recombination, Genetic ; Signal Transduction

OBJECTIVE: Observe the changes of small airway function in patients with rhinitis but without asthma and/or lower airway symptoms. METHOD: Between June 2008 and December 2012, we recruited 903 subjects, including 377 with allergic rhinitis (AR), 262 with non-allergic rhinitis (NAR) and 264 healthy subjects. All subjects underwent meticulous history taking, nasal examination, allergen skin prick test, blood routine test, serum total immunoglobin E assay, pulmonary ventilation function test and bronchial challenge test. RESULT: The indices of FEV1/FVC%, MEF25pred% and MMEFpred% were lower in AR group than in the control group (P < 0.05). The indices of FEV1/FVC, MMEFpred%, MEF25pred% and MEF50pred% were also lower in NAR group than in the control group (P < 0.05). According to the FVCpred% and FEV1pred%, there were no differences between rhinitis group and the control group (P > 0.05). The positive rate of airway hyperresponsiveness(AHR) in AR group and in NAR group was 12.2%, 6.1% respectively. Indices of small airway function were all lower in the AHR group than NAHR group in rhinitis. CONCLUSION Compared with healthy controls, small airway function in patients with rhinitis has apparent changes, part of rhinitis patients has AHR, and is associated with small airway function changes.
Asthma ; Case-Control Studies ; Humans ; Respiratory Function Tests ; Respiratory System ; physiopathology ; Rhinitis ; physiopathology ; Rhinitis, Allergic ; physiopathology ; Skin Tests

OBJECTIVESTo evaluate the efficacy and toxicity of the B-NHL-BFM-90 protocol in the treatment of Chinese childhood and adolescent B-cell non-Hodgkin's lymphomas (B-NHL).

METHODSForty-two untreated childhood and adolescent B-NHL were enrolled in the present study. Of them 18 cases were Burkitt's lymphoma, 16 diffuse large B cell lymphoma and 8 anaplastic lymphoma. There were 10 cases in stage II and 32 in stage III/IV. The patients were grouped by risk factors into low, medium and high risk groups. All patients were treated with the B-NHL-BFM 90 (Berlin-Frankfurt- Münster) protocol. The low risk group received A, B courses for 4 cycles, the medium risk group AA, BB courses for 6 cycles, and the high risk group AA, BB, CC courses for 6 cycles.

RESULTSComplete remission (CR) was obtained in 37 patients (88%), and partial remission (PR) in 5 (12%). Of the 5 PR patients, I received autologous hematopoietic stem cell transplantation, 3 received radiotherapy for residual disease and 1 just under watching. Major toxicity was myelosuppression and mucositis, especially in AA, BB and CC cycles, but was tolerant and manageable. Median follow-up was 20 (4 - 89) months. Kaplan-Meier method was used to analyse survival data. Two year event free survival (EFS) for all patients was 86. 24%, being 100% for stage II and 80.95% for stage III/IV.

CONCLUSIONShort term and intensive chemotherapy can improves the efficacy and survival rate of childhood and adolescent B-NHL, especially for advanced stage patients.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Infant ; Lymphoma, B-Cell ; drug therapy ; Male ; Retrospective Studies ; Treatment Outcome

Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 μmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.
Homocysteine ; Humans ; Hyperhomocysteinemia ; complications ; Kidney Diseases ; complications

Aim To investigate the effects of Bigelovii A on autophagy and its mechanism.Methods Fluorescence microscope,flow cytometry and Western blot were employed to analyze autophagy.Western blot was used to detect the protein expressions of mTOR pathway.MTT colorimetry was used to assay cell viability after treatment with 3-MA and Bigelovii A or Bigelovii A alone.Results Bigelovii A-treated MCF7 cells displayed a dramatic increase in the number of MDC-labeled vesicles and the expressions of LC3-Ⅱ,indicating cell autophagy.Ⅰt was proved that in MCF7 cells,Bigelovii A inhibited mTOR signaling by decreasing Akt and p-ERK.Consistently,Bigelovii A decreased phosphorylation levels of mTOR,p70S6K (Ser371,Thr389) and 4EBP1 proteins.Inhibiting Bigelovii Ainduced autophagy with the autophagy inhibitor 3-methyladenine significantly decreased cell viability,which suggested that Bigelovii A-induced autophagy played a pro-survival role.Conclusion Bigelovii A is likely to induce autophagy through inhibiting mTOR pathway.

OBJECTIVETo analyse the effectiveness and toxicity of combined chemotherapy regimen containing pirarubicin (THP) in the treatment of non-Hodgkin's lymphoma (NHL).

METHODSThree hundred and ninety two patients with NHL were treated by THP containing regimen with or without involved field radiotherapy. The clinical characteristics, response, toxicity and long-term survival rates were analysed.

RESULTSThe median age of the patients was 47 (5 - 87) years and 26.0% aged more than 60 years. 61.0% of the patients were males and 39.0% females. B-cell and T/NK cell NHL accounted for 68.4% and 23.2% respectively with 56.9% of diffuse large B cell lymphoma and 12.5% of peripheral T cell lymphoma. 92.6% of the patients were ECOG < 1, 63.2% in stage I + II, 84.7% with IPI score 0 - 2 and 25% with B symptoms, 93.9% (368/392) of the patients received CTOP (containing THP) regimen chemotherapy and among them 28.5% (112/392) plus involved field radiotherapy. Altogether 1598 courses were administered on 368 patients. The overall response rate was 88.5% (341/385) with a complete remission (CR) rate of 63.6%, major toxicity was myelosuppression with 12.8%, 1.0% and 1.5% of grade III - IV neutropenia, thrombocytopenia and anemia, respectively. G-CSF support was given for 553 courses (34.6%). Alopecia account for 19.8%. The incidence of mild cardiotoxicity was 5.8%. Treatment-related mortality was 1.6% (6/368). Median follow-up was 24 months. The 1, 3 and 5 year actuarial survival rates were 86.4% , 66.5% and 59.2%, respectively. Median survival time has not been achieved.

CONCLUSIONThe efficacy of THP based regimen CTOP for the treatment of aggressive NHL is promising. Further clinical trial is warranted.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Middle Aged ; Survival Rate ; Treatment Outcome

Adipose tissue is the energy storage organ of the body, and excess energy is stored in adipocytes in the form of lipid droplets. The homeostasis of adipose tissue is the basis for the body to maintain normal metabolic activity. Prostaglandin E (PGE) is an important lipid mediator in the body. It is synthesized in almost all tissues and participates in the regulation of many physiological processes such as blood pressure, glucose and lipid metabolism, and inflammation. PGE is abundant in white adipose tissue, where it is involved in the regulation of fat metabolism. PGE plays its biological role through binding to four G protein coupled receptors (prostaglandin E receptors), including EP-1, -2, -3, and -4. The EP4 subtype has been proved to play an important role in adipogenesis and adipose metabolism: it could inhibit adipogenesis while it was activated, whereas its knockout could promote lipolysis. This review summarized the relationship between EP4 and adipose metabolism, hoping to identify new targets of drug development for metabolic disorders.
Adipocytes ; Adipogenesis ; Adipose Tissue ; metabolism ; Humans ; Receptors, Prostaglandin E, EP4 Subtype ; physiology

As a member of the nuclear receptor superfamily, the pregnane X receptor (PXR) is a ligand-activated transcription factor. PXR is highly expressed in liver and intestinal tissues, and also found in other tissues and organs, such as stomach and kidney. After heterodimerization with retinoid X receptor (RXR), PXR recruits numerous co-activating factors, and binds to specific DNA response elements to perform transcriptional regulation of the downstream target genes. As an acknowledged receptor for xenobiotics, PXR was initially considered as a nuclear receptor regulating drug metabolizing enzymes and transporters. However, nowadays, PXR has also been recognized as an important endobiotic receptor. Recent studies have shown that PXR activation can regulate glucose metabolism, lipid metabolism, steroid endocrine homeostasis, detoxification of cholic acid and bilirubin, bone mineral balance, and immune inflammation in vivo. This review focuses on the role of PXR in metabolism of endogenous substances.
Animals ; Gene Expression Regulation ; Humans ; Pregnane X Receptor ; metabolism ; Xenobiotics ; metabolism

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.
Arachidonic Acid/metabolism* ; Diabetes Mellitus, Type 2 ; Glucose/metabolism* ; Homeostasis ; Humans ; Lipid Metabolism ; Liver