ObjectiveTo investigate the effects of different therapeutic methods on borderline hypertension with metabolic syndrome patients. MethodsNinety borderline hypertension with metabolic syndrome patients were divided into three groups by random digits table with 30 cases: control group,conventional therapy group and intensive therapy group. The control group was given regular observation, the conventional therapy group took drug according to the disease situation; and the intensive therapy group not only formulated the aim of therapy, but also received diet control, sport therapy, healthy education and drug therapy. After 1 year's follow-up, the patients' changes were compared. ResultsAfter 1 year's follow-up,the levels of FPG, 2 h PG, 24 h mAlb and IMT were significantly increased(P ＜ 0.05 ), and the levels of other index had no significant changes (P＞ 0.05) in control group. The levels of FPG,2 h PG,TC and TG were significantly decreased and IMT was significantly increased(P ＜0.05), the levels of other index had no significant changes(P ＞ 0.05 ) in conventional therapy group. The levels of SBP, DBP, PP, FPG, 2 h PG, TC,TG,hs-CRP,24 h mAlb and HOMA-IR were significantly decreased and HDL-C, ABI were significantly increased (P ＜ 0.01 or ＜ 0.05 ) in intensive therapy group. After treatment, the levels of ABI and H DL-C were significantly higher and SBP, DBP, PP,TG, hs-CRP, 24 h mAlb, HOMA-IR, IMT were significantly lower in intensive therapy group than those in conventional therapy group (P ＜ 0.01 or ＜ 0.05 ). ConclusionsDrug therapy is efficient in borderline hypertension with metabolic syndrome patients, and intensive therapy can obviously improve the insulin resistance, to control the developing of hypertension can delay the vascular

Backcground:Ankyrin repeat and SOCS box protein 3 (ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain.Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses.However,its effects on oncogenesis are unclear.This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer (CRC).Methods:We used next-generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines,and used real-time quantitative polymerase chain reaction,Western blotting,and immunohistochemical or immunofluorescence assay to determine gene expression.We evaluated cell proliferation by MTT and colony formation assays,tested cell cycle distribution by flow cytometry,and assessed cell migration and invasion by transwell and wound healing assays.We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results:We found that ASB3 gene was frequently mutated (5.3％) and down-regulated (70.4％) in CRC cases.Knockdown of endogenous ASB3 expression promoted CRC cell proliferation,migration,and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo.Conversely,the ectopic overexpression of wild-type ASB3,but not that of ASB3 mutants that occurred in clinical CRC tissues,inhibited tumor growth and metastasis.Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial-mesenchymal transition,which was characterized by the up-regulation of β-catenin and E-cadherin and the down-regulation of transcription factor 8,N-cadherin,and vimentin.Conclusion:ASB3 dysfunction resulted from gene mutations or down-regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

OBJECTIVETo explore the effects of bisphenol A (BPA) exposure on toxicity characteristic and OCT4 and SOX2 gene expression of mouse embryonic stem cells (mESC).

METHODSmESC were cultured, and treated with the doses of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L respectively of BPA and DMSO (the solvent control group)for 24 hours, and three groups of cells were treated with the same method. The morphological changes of mESC in the control and exposure groups were observed through an inverted microscope. Cell counting kit 8 (CCK8) was used to detect the effects of BPA on proliferation of mESC, and based on the results, the half inhibitory concentration (IC50) was calculated. Real-time fluorescent quantitative polymerase chain reaction (RT-QPCR) and western blotting were used to detect the expression of OCT4 and SOX2.

RESULTSBPA had certain toxicity on mESC, the treatment of BPA significantly increased cell toxicity in a concentration-dependent manner, and the IC50 was 4.3×10(-4) mol/L, combined with the BPA exposure concentration of the environment and the related literature, eventually taking the five concentrations of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L as the experimental groups. The mESC morphology were effected after the treatment of BPA for 24 h, compared with the control group, the number of cells decreased, appearing some floating cells, and the cell cloning became irregular and differentiation in the higher concentration groups. The OCT4 mRNA expression level in the 10(-7) mol/L (1.146 ± 0.087), 10(-6) mol/L (1.156 ± 0.030), 10(-5) mol/L (1.158 ± 0.103) and the 10(-4) mol/L (1.374 ± 0.053) dose group were all significantly higher than the control group (1.000 ± 0.000) (t values were -2.384, -2.953, -3.203, -4.021 respectively, P value all < 0.05). Meanwhile, the SOX2 mRNA expression level in the 10(-4) mol/L (1.113 ± 0.052) were higher than the control group (1.000 ± 0.000) (t value was -2.765, P value < 0.05). Moreover, the OCT4 protein expression level in the 10(-5) mol/L (1.360 ± 0.168) and 10(-4) mol/L (1.602 ± 0.151) were all significantly higher than the control group (1.000 ± 0.000) (t values were -3.538, -4.002 respectively, P value all < 0.05), while no obvious change of the SOX2 protein expression level was detected in all treated groups.

CONCLUSIONBPA in a certain dose range could upregulate the expression of OCT4 gene in mouse embryonic stem cells while had no significant effect on the expression of SOX2 gene.

Animals ; Benzhydryl Compounds ; toxicity ; Cells, Cultured ; Embryonic Stem Cells ; drug effects ; metabolism ; Gene Expression ; Mice ; Octamer Transcription Factor-3 ; genetics ; Phenols ; toxicity ; SOXB1 Transcription Factors ; genetics ; Signal Transduction ; drug effects

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.
Child ; Dyskeratosis Congenita ; complications ; therapy ; Female ; Humans ; Mouth Diseases ; etiology ; Mouth Mucosa ; pathology ; Recurrence ; Respiratory Tract Infections ; etiology ; Telomere ; drug effects ; Ulcer ; etiology

Objective: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. Methods: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. Results: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia. Conclusion This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

OBJECTIVEUsing the stable HSPA1A (HSP70-1) promoter-driven luciferase reporter HepG2 cells (HepG2/HSPA1A cells) to assess the overall toxicity of coke oven emissions.

METHODSThe stable HepG2/HSPA1A cells were treated with different concentrations of coke oven emissions (COEs) collected from the top, side, and bottom of a coke oven battery for 24 h. After the treatments, luciferase activity, cell viability, malondialdehyde (MDA) concentration, Olive tail moment, and micronuclei frequency were determined, respectively.

RESULTSThe bottom COEs induced significant increases (P < 0.01) in relative luciferase activity up to 1.4 times the control level at 0.15 µg/L. The low dose of side COEs (0.02 µg/L) led to a significant increase (P < 0.01) in relative luciferase activity that progressively increased to 2.1 times the control level at 65.4 µg/L. The top COEs produced a strong dose-dependent induction of relative luciferase activity up to over 5 times the control level at the highest concentration tested (202 µg/L). In HepG2/HSPA1A cells treated with the bottom COEs, relative luciferase activity was positively correlated with MDA concentration (r = 0.404, P < 0.05). For the three COEs samples, positive correlations were observed between relative luciferase activity and Olive tail moment and micronuclei frequency.

CONCLUSIONThe relative luciferase activity in HepG2/HSPA1A cells can sensitively reflect the overall toxicity of COEs. The stable HepG2/HSPA1A cells can be used for rapid screening of the overall toxicity of complex air pollutants in the workplace.

Coke ; toxicity ; Genes, Reporter ; HSP70 Heat-Shock Proteins ; genetics ; Hep G2 Cells ; Humans ; Luciferases ; genetics ; Malondialdehyde ; analysis ; Micronuclei, Chromosome-Defective ; Occupational Exposure ; Promoter Regions, Genetic ; Toxicity Tests

Objective To dynamically analyze the evolutionary process of cerebral edema absorption and the level of local iron in rats with intra-cerebral hematoma by high-field strength 7 Tesla MRI and explore the characteristics and mechanism of secondary injury after intra-cerebral hematoma.Methods Sixteen adult SD rats (about 150 g) were randomly divided into experimental group (n=10) and control group (n=6).Rat models in the experimental group were established by performing injection of 50 μL their own venous blood into their right caudate nucleus accurately. Rats in the control group were used normal saline,instead.After that,head MRI (T2 and T2-star scans) was performed 1,2,3,7 and 14 d after the injection; their imaging features were compared. Results Nine rats in the experimental group survived and 1 died after the operation; in the early days (within 3 d), the T2 weighing imaging showed that the time of relaxation surrounding the hematoma was longer than that in control group,suggesting that the zone of the edema surrounding the hematoma became more clearly.In the early days (within 3 d),T2-weighted imaging was clear,and the time of relaxation surrounding the hematoma increased rapidly,steadily improved 3 d after the operation and reached its peak level 7 dafter the operation; the damage area absorption decreased steadily but turned widening 3 d later and reached the peak 7 d later.T2-star value reached the peak rapidly 3 d after the operation,and then,moderated the downturn.The rats in the control group showed no obvious signal changes under MRI,except those with needle tract injury. Conclusion Secondary injury after intra-cerebral hemorrhage shows a rapidly injury progress in the short terrn at first,and then,has intensify again after a stable period; the local iron diffusion trend is synchronized to the secondary injury,suggesting that iron may play a key role in the mechanism of secondary brain edema.

Malignant tumors seriously endanger human life and health, and their treatment has always been a research focus of scientists all over the world. Natural flavonoids and their derivatives have a variety of biological activities, especially regarding antitumor growth, with unique biological activities. They can interfere with the growth cycle of tumor cells, change the mitochondrial membrane potential, promote apoptosis, and can reduce the immune escape of tumor cells and prevent tumor metastasis by improving human immunity. In the human body, they regulate the biological signal transduction, leading to the up-regulation of pro-apoptotic protein expression. They inhibit the growth of solid tumors by regulating the growth of vascular epithelial cells and blocking the formation of blood vessels in tumor tissue. Recent studies have shown that these compounds can play an important role in the treatment of various human tumors and are expected to be developed into new antitumor drugs. This review summarizes the recent research results on the antitumor mechanism of flavonoids and their ability to inhibit tumor growth.

Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 μmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.
Animals ; Down-Regulation ; Heart Atria ; Myocytes, Cardiac ; Rats ; Tumor Necrosis Factor-alpha ; src-Family Kinases

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L