Objective To investigate the mechanism of lobetyolin's intervention in HepG2 cells abnormal cholesterol metabolism.Methods This study used oleic acid(OA)stimulation of HepG2 cells as a model.MTT assay,oil red O staining,biochemical kit assay,qRT-PCR assay,Western blot assay and NBD labeled cholesterol effection assay were used to study the effect of lobetyolin on cholesterol metabolism in HepG2 cells.Results The results showed that lobetyolin could reduce the content of lipid drops,the levels of triglyceride(TG)and total cholesterol(TC)in HepG2 cells stimulated by OA,increase cholesterol effection rate,and up-regulate cytochrome 7A1(CYP7A1),liver x receptor α(LXRα),ATP-binding cassette transporter A1(ABCA1),peroxisome proliferator-activated receptor(PPARγ)and other mRNA or protein expression levels.However,combined intervention with PPARγ antagonist Mifobate(SR-202)can significantly inhibit the promoting effect of lobetyolin on cholesterol metabolism in HepG2 cells.Conclusion This study revealed that lobetyolin can improve the cholesterol effection rate of HepG2 cells stimulated by OA and promote cholesterol catabolism,and the mechanism of action may be related to the regulation of PPARγ/CYP7A1 pathway.

Objective To investigate the mechanism of lobetyolin's intervention in HepG2 cells abnormal cholesterol metabolism.Methods This study used oleic acid(OA)stimulation of HepG2 cells as a model.MTT assay,oil red O staining,biochemical kit assay,qRT-PCR assay,Western blot assay and NBD labeled cholesterol effection assay were used to study the effect of lobetyolin on cholesterol metabolism in HepG2 cells.Results The results showed that lobetyolin could reduce the content of lipid drops,the levels of triglyceride(TG)and total cholesterol(TC)in HepG2 cells stimulated by OA,increase cholesterol effection rate,and up-regulate cytochrome 7A1(CYP7A1),liver x receptor α(LXRα),ATP-binding cassette transporter A1(ABCA1),peroxisome proliferator-activated receptor(PPARγ)and other mRNA or protein expression levels.However,combined intervention with PPARγ antagonist Mifobate(SR-202)can significantly inhibit the promoting effect of lobetyolin on cholesterol metabolism in HepG2 cells.Conclusion This study revealed that lobetyolin can improve the cholesterol effection rate of HepG2 cells stimulated by OA and promote cholesterol catabolism,and the mechanism of action may be related to the regulation of PPARγ/CYP7A1 pathway.

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver

Osteoporosis (OP) is a common systemic bone disease which has become a serious public health problem in China. In clinical practice, we found that some primary osteoporosis may be due to parathyroid hyperfunction (subclinical hyperparathyroidism) or hyperparathyroidism which is the result of negative calcium balance and hypocalcemia caused by insufficient calcium intake and/or vitamin D deficiency/insufficiency, which is preventable and controllable. Therefore, we call this kind of osteoporosis parathyroid hyperfunction or hyperparathyroidism associated osteoporosis. The daily calcium intake of Chinese people is generally insufficient, and vitamin D deficiency/insufficiency is also a worldwide public health problem. Parathyroid hyperfunction or hyperparathyroidism associated osteopenia and osteoporosis which are results of hypocalcemia and negative calcium balance caused by long-term insufficient calcium intake and/or vitamin D deficiency/insufficiency exist extensively in clinical practice. Its prevention and treatment can effectively prevent and treat osteopenia and osteoporosis, so as to effectively prevent and treat diseases such as short stature, rachiokyphosis, backache, fatigue, bone pain, fracture, metastatic vascular calcification and systemic calcinosis, improve people’s health and help achieve the goal of "Healthy China 2030" .

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.

Male infertility is an important issue affecting reproductive health, and its etiology and mechanism are complex or not clear. For patients with azoospermia, specific clinical treatments are limited. Therefore, to generate patients' own functional sperms is absolutely necessary. With the development of techniques, the scientists start to think about how to attain functional sperms deriving from human induced pluripotent stem cells (iPSCs) in vitro. Mainly, sperm induction with iPSCs includes two steps, first, the formation of diploid primordial germ cell, then the differentiation of haploid mature sperms. Technically, the difficulties lie in the generation of meiosis from a diploid cell into haploid sperm, and unfortunately, the problem is not solved yet. In order to understand this kind of knowledge well, we try to review the technical progress and principle of male gamete induction from iPSCs. Hopefully, it can help us to understand the mechanism of spermatogenesis in vitro well, and to provide a reference for the clinical application of in vitro fertilization.

Male infertility is an important issue affecting reproductive health, and its etiology and mechanism are complex or not clear. For patients with azoospermia, specific clinical treatments are limited. Therefore, to generate patients' own functional sperms is absolutely necessary. With the development of techniques, the scientists start to think about how to attain functional sperms deriving from human induced pluripotent stem cells (iPSCs) in vitro. Mainly, sperm induction with iPSCs includes two steps, first, the formation of diploid primordial germ cell, then the differentiation of haploid mature sperms. Technically, the difficulties lie in the generation of meiosis from a diploid cell into haploid sperm, and unfortunately, the problem is not solved yet. In order to understand this kind of knowledge well, we try to review the technical progress and principle of male gamete induction from iPSCs. Hopefully, it can help us to understand the mechanism of spermatogenesis in vitro well, and to provide a reference for the clinical application of in vitro fertilization.

Objective To analyze clinical characteristics of bloodstream infections caused by coagulase-negative Staphylococci (CNS) and antibiotic resistance of the bacteria,so that to provide basis for the clinical diagnosis and treatment.Methods A retrospective analysis of CNS in blood cultures collected from 108 hospitalized patients in Puai Hospital of Tongji Medical College from January 2016 to December 2017 was performed.The antimicrobial susceptibilities were tested by Kirby-Bauer method and E test method.For measurement variables,normally distributed variables were compared using t test,and non-normal distributed data were compared using Mann-Whitney U test.Categorical variables were compared using x2 test.Results Of the 108 patients,66 were male and 42 were female;the age range was 26 to 98 years and the average was 49 years.According to the criteria for bacteremia,36 of 108 (33.3％) patients with CNS-positive blood cultures were diagnosed with bacteremia and 72 (66.7％) cases were contaminated.CNS bacteremia mainly occurred in the intensive care unit and nephropathy ward.Among them,23 (62.2％) patients were catheter-related blood stream infections,and 11 (29.7 ％) patients were dialysis catheter-related bloodstream infections.Fifteen of 36 (41.7％) strains were isolated within 48 hours of admission.The level of serum procalcitonin (PCT) for bacteremia patients was 2.56 (1.44,7.60) μg/L,and that was 0.13 (0.05,0.23) μg/L in contaminated patients.The difference was statistically significant (Z=8.097,P＜0.05).The white blood cell count of patients with bacteremia was (11.50±4.54) × 109/L,and that was (10.61 ±5.00) × 109/L for contaminated patients.There was no statistical significance (t=0.895,P＞0.05).After antibiotic treatment,26 of 36 bacteremia patients were survived.The PCT levels before antibiotic treatment were 2.05 (1.42,4.32) μg/L,and 0.24 (0.07,0.61) μg/L after antibiotic treatment.Serum PCT was decreased significantly after antibiotic treatment (Z=4.457,P＜0.05).The PCT levels of 10 deaths within 28 days before antibiotic treatment were 4.78 (1.51,19.75) μg/L,whereas 22 (6.40,55.75) μg/L,after antibiotic treatment.The PCT was increased significantly after antibiotic treatment (Z=2.497,P＜0.05).No significant difference was found in PCT between survivors and deaths within 28 days (Z=0.300,P＞0.05).No significant difference was found in white blood cell count between survivors and deaths at 28 days (t=0.771,P＞0.05).There was no statistical difference of the anti-bacterial drug susceptibility between pathogens and contaminants (P＞0.05).All strains were sensitive to vancomycin,teicoplanin and linezolid.Conclusions The incidence of CNS contamination in blood culture is relatively high.It is important to distinguish true bacteraemia from contamination by a review of the clinical and laboratory indicators.PCT is of clinical value to indicate CNS infection and to monitor therapeutic effect.

Objective To compare the toxicity of outer membrane vesicles ( OMVs) secreted by Acinetobacter baumannii strains with different drug-resistance spectrums.Methods Four Acinetobacter baumannii strains with different drug-resistance spectrums were collected (strain 33, 3237, B29 and 10), and OMVs produced by these strains were extracted and purified.BCA assay was used to determine the protein concentrations, and RAW264.7 cells were incubated with different concentrations of OMVs for 24 h. Cell viability was measured with CCK-8 assay, and gene expression of tumor necrosis factor-alpha ( TNF-α) , interleukin-6 ( IL-6) , interleukin-1 beta ( IL-1β) , keratinocyte-derived chemokine ( KC) and macrophage inflammatory protein 2 (MIP-2) was assessed by quantitative real-time PCR.One-way ANOVA was used for data analysis.Results According to the result of drug susceptibility test, strain 10 was extensively drug-resistant Acinetobacter baumannii ( XDRAB ) strain, strain B29 was multi-drug resistance Acinetobacter baumannii (MDRAB) strain, while strain 33 and 3237 were non-MDRAB strains.After incubated with different concentrations of OMVs for 24 h, cell viability of RAW264.7 declined with the increase of OMVs concentrations.OMVs released from strain10, B29 and 3237 significantly lowered the cell viability at the concentration of 5 μg/mL, while the cytotoxicity of OMVs released from strain 33 was much weaker, and no remarkable decrease in cell viability was observed even at the concentration of 25 μg/mL.OMVs of all strains induced the release of TNF-α, IL-6, IL-1β, KC and MIP-2 in RAW264.7 cells, and the levels of theses cytokines were increased with the concentration of OMVs.Inflammatory response in cells incubated with OMVs from strain 33 was the weakest, while OMVs from strain 10 induced strongest inflammatory response.KC and MIP-2 levels were significantly higher in RAW264.7 cells incubated with OMVs from strain 10 with a concentration of 5 μg/mL than that incubated with OMVs from other strains ( F=19.094 and 19.032,P<0.05 or <0.01).Conclusions OMVs from Acinetobacter baumannii strains with different drug-resistance spectrums are of different toxicity.OMVs from XDRAB and MDRAB strains have higher toxicities and may induce stronger inflammatory response.