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.

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" .

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

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.

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.

OBJECTIVETo observe the morphological changes of photoreceptor cells in rats with retinitis pigmentosa (RP) induced by N-methyl-N-Nitrosourea (MNU) and the effects of acupuncture against it.

METHODSA total of 16 SD rats were treated with one-time intraperitoneal injection of MNU (50 mg/kg) to induce RP, and randomly divided into an acupuncture group and a model group, 8 rats in each one. In addition, 4 rats were selected as a control group. After model establishment, rats in the acupuncture group were treated with acupuncture at "Xinming-1" (Extra) and "Jingming" (BL 1) for 30 min, once a day for 7 days; rats in the model group and control group received no treatment, and the feeding conditions and fixation were identical as the acupuncture group. 2 h after the end of intervention, rats were sacrificed by cervical dislocation to observe the morphological changes of rhodopsin, rod terminals and rod bipolar cells.

RESULTSDue to the loss of retina photoreceptor cells induced by MNU in rats, in the model group the rhodopsin was stained in residual cell bodies, and there were sporadic rod terminals and little rod bipolar cells; outer segments, inter segments, cell bodies and cell terminals were all affected at different levels. The distribution of rhodopsin was also changed in the acupuncture group, showing more bodies of photoreceptor cells, and the residual rod terminals and rod bipolar cells were more than those in the model group; the injury of retina was less than that in the model group.

CONCLUSIONMNU could lead to a comprehensive injury to the morphology of photoreceptor cells, however, acupuncture is capable of inhibiting morphological changes of photoreceptor cells induced by MNU.

Acupuncture Therapy ; Animals ; Humans ; Male ; Photoreceptor Cells ; cytology ; Rats ; Rats, Sprague-Dawley ; Retinitis Pigmentosa ; physiopathology ; therapy

Objective To screen for clopidogrel metabolism related gene CYP2C19 in patients with coronary artery disease in Wuhan.Methods 316 patients,from Jan to Dec 2014,after cardiology percutaneous coronary interventional therapy (PCI) for the treatment of coronary artery disease were selected as research object.Clopidogrel metabolism related CYP2C19 geno-types (* 1,* 2,* 3)were detected by the gene chip,and for different types of metabolism of patients according to CYP2C19 gene type:strong metabolize type (*1/*1),intermediate metabolizer types (*1/*2,*1/*3),poor metaboli-zer types (*2/*2,*3/*3,*2/*3).Results According to the CYP2C19 gene polymorphism of metabolic function type, strong metabolic type carrying CYP2C19*1 (*1/*1)accounted was 43.4%,intermediate metabolizers carrying CYP2C19*2 or *3 (* 1/* 2 and * 1/* 3)and poor metabolizers (* 2/* 2,* 2/* 3 and * 3/* 3)accounted was 42.4% and 14.2%,respectively.Different gender had no statistical significance in CYP2C19 genotype differences.Conclusion Clopi-dogrel metabolism functional of CYP2C19 gene in patients with interventional coronary heart disease in Wuhan area had more deletion gene.

OBJECTIVE:To investigate the characteristics of cecum and colon-specific drug delivery system of 4-aminosalicyl-ic acid-maltoside (4-ASA-Mal) in vitro. METHODS:With the cumulative release rate of 4-ASA as the index,HPLC was em-ployed to observe the delivery of 4-ASA-Mal (equivalent to 250 μg/ml 4-ASA) in the buffer solutions of different pH (1.2,6.8 and 7.4)and in the aqueous contents in different parts(stomach,small intestine,cecum and colon)of normal rats and the rat mod-els of ulcerative colitis. RESULTS:4-ASA-Mal was hardly released in the buffer solutions of different pH. 12 h cumulative release rates were less than 8% in the aqueous contents in the stomachs and small intestines of normal rats and rat models,and were 55%and 81% in the aqueous contents in the cecum and colons of normal rats,and 55% and 74% in the aqueous contents in the cecum and colons of model rats with ulcerative colitis. CONCLUSIONS:4-ASA-Mal can release a lot of 4-ASA in aqueous contents in ce-cum and colon,targeting cecum and colon in vitro.

CDISC standard has become a set of global data standards that can be used in clinical study, covering the full life cycle of clinical researches. After nearly 20 years of development and continuous version upgrades, CDISC standard can improve the quality and efficiency of clinical research and drug review, and to facilitate all stakeholders involved in researches to exchange the study data and communicate the outcomes. CDISC standard has been or is to be adopted as standard format in data submission by multiple regulatory authorities, and more widely implemented by the global pharmaceutical community. CDISC standard is gradually adopted in China. The feasibility and roadmap of CDISC standard as the Chinese data submission format requirements are undergoing exploration and piloting further.