The microRNA let-7 family,functioning as a tumor suppressor,has emerged as a regulator of stem cell differentiation and tumor repression.The RNA-binding protein lin28 is a stem cell pluripotency factor,which contributes to the maintenance of stem cell characteristics and promoting cell malignant transformation.lin28 can block the maturity of let-7 by combining with the precursors of let-7 family miRNAs,which is itself able to repress lin28 by binding to the 3'-UTR of lin28 transcripts,thus forming a feedback loop.The double-negative feedback loop comprising lin28 and let-7 is involved in several biological processes such as differentiation of stem cell,tumorigenesis,invasion and metastasis,drug resistance and relapse,which couldbe a potential target for cancer therapy.

OBJECTIVE:To study the bioequivalence of Alendronate Sodium Tablets in healthy volunteers. METHODS:According to a paired and cross-over design,a bioequivalence test was performed on two different alendronate sodium tablets,10 mg (Group 1) and 70 mg (Group 2). Then each group was subdivided into two groups,i.e. test preparation and reference preparation. The urine concentrations of alendronate at different time point within 48 h were determined by HPLC and the urine excretion rate -time curve was drawn,and the DAS software was used to compute the pharmacokinetic parameters and the relative bioavailability of the tested formulation. RESULTS:The 90% confidence intervals of urine excretion rate of the tested formulations were 82.4% ～122.6% (Group 1) and 85.4% ～124.6% (Group 2),respectively and the maximum excretory rates were 80.3% ～131.5% (Group 1) and 82.3～136.5% (Group 2),respectively,compared with the reference formulations. CONCLUSION:The two different Alendronate Sodium Tablets and their respective reference formulations were proved to be bioequivalent in healthy volunteers.

Objective To examine the impact of diabetic foot patients′ negative emotion on the caregiver′quality of life. Methods Totally 100 pairs of diabetic foot patients and their caregivers were investigated using convenience sampling method. Results The incidence of anxiety, depression of hospitalized patients with diabetic foot was 41.5% (23/200), 44.0% (88/200) respectively. Pearson correlation analysis showed that anxiety score were negatively correlated with caregivers′ quality of life except for mental health dimension, physical pain dimension and the total score of physical health, mental health and the MOS item Short from Health Survey (SF-36) (r=-0.471--0.117, P<0.05), and depression score were negatively correlated with caregivers′ quality of life except for physical pain dimension and the total score of physical health, mental health and SF-36(r=-0.519--0.220, P<0.05). Multiple regression analysis indicated that caregivers educational level, provided support, social support , relationship with patients, self-evaluation of health, live together time with patient, patient care burden, caregivers gender, depression score, patient age, diabetic foot Wagner grade were the influence factors of the caregiver′ quality of life. Conclusions Diabetic foot patients′ negative emotion has an important impact on caregiver′quality of life, we can improve the quality of life of patients and their caregivers by reducing the negative mood of patients with diabetic foot.

Retinopathy of prematurity (ROP) is a proliferative vascular retinal disease. Cryotherapy, laser photocoagulation, intravitreal injection of anti-vascular endothelial growth factor, scleral buckling surgery and vitrectomy are the main treatments. Treated with cryotherapy or laser photocoagulation or intravitreal injection of anti-vascular endothelial growth factor, patients with a history of ROP have thicker foveas, and the morphology of the fovea and the development of the retinal vessels in the macular area are affected, resulting in abnormal vision development. However, the specific mechanisms by which different treatments of ROP affecting the development of the macula are not yet clear. It still need further study with large samples to verify and explore, whether changes in the levels of intraocular vascular endothelial growth factor changing the process of normal macular development and how the abnormal development of the macula affects visual function.

Objective To construct a fusion protein that used for treatment of resistance and palindromia in leukemia and studied its biological activity. Methods IL-3 and LP gene fragments were amplified by PCR. After enzymatic digestion and T4 ligation, the fusion gene was cloned into expression vector pAYZ. The product was purified by exchange chromatography and anti-Etag affinity chromatography. IL3-G4SLP fusion protein was analyzed by SDS-PAGE and Western blot. Protein biological activity was detected by FACS. Results The fusion protein was expressed as soluble protein by E.Coli 16C9. The protein expression level was about 1 mg/L, its purity was over 95 %, and the expression level was about 1 mg/L. The fusion protein can combined specificely with CD123 on leukemia stem cells. Conclusion Fusion protein IL-3-G4S-LP can target on leukemia stem cells and maybe as a potential drug used for treatment of resistance and palindromia in leukemia.

OBJECTIVE:To evaluate the rationality and validity of chemical medicine tablet production equipment cleaning pro-cedure. METHODS:Among several chemical medicines prepared by similar production technology as Metoprolol succinate sus-tained-release tablets,Captopril tablets,Isosorbide mononitrate tablet and Metformin hydrochloride tablet,Metoprolol succinate sus-tained-release tablets had strongest toxicity and were included in validation test. The production equipment was cleaned and disinfect-ed according to cleaning procedure. The point which was most difficult to clean could be wiped and sampled by using the cotton swab method. The detection limit and the limit of quantitation of the residue limits were verified as well as the recovery rate of wip-ing,in order to evaluate whether the results meet the requirements. RESULTS:The cotton swab method is adopted to wipe sample and detect the point which is most difficult to clean. The visible foreign body has not been found in each sampling point. The amount of residual drug is <29.75 μg/cotton bud,and microbial limits are <50 CFU/cotton bud,indicating test items are in line with the standard. CONCLUSIONS:The cleaning method can effectively clean the production equipment,and can effectively pre-vent product contamination and cross contamination to ensure the quality,efficacy and safety of the next batch of products.

Atrial Fibrillation ; therapy ; Coronary Vessels ; Humans ; Percutaneous Coronary Intervention

Objective To investigate the influence of fear of hypoglycemia on the compliance of diabetes patients.Methods A total of 201 diabetes inpatients with hypoglycemia in four first-class hospital of grade three in Ji'nan were selected by convenience sampling method and investigated by General Information Questionnaire,Chinese version of Hypoglycemia Fear Survey Ⅱ-Worry Scale and Diabetes Treatment Compliance Scale.And carrid on the correlation analysis and the multiple linear regression analysis.Results The scores of fear of hypoglycemia was 3-33 points,the median score was 12 points(interquartile range,10-15 points).The score of treatment compliance was 23-55(35.90±5.84)points.Spearman correlation analysis showed that fear of hypoglycemia score were negative correlated with treatment compliance score,drug,diet,exercise dimensions(r=-0.467-0.288),and it was positively correlated with self monitoring dimension(r=0.259),the difference was statistically significant(P＜0.01),it was not associated with periodic inspection dimension.Multiple linear regression analysis showed that the economic income,occupation,whether to participate in health education of diabetes mellitus,glycosylated hemoglobin,fear of hypoglycemia were the influence factors of treatment compliance.Conclusions Diabetes patients'fear of hypoglycemia can influence treatment compliance.medical staff should pay attention to and take effective measures to reduce their fear of hypoglycemia and improve treatment compliance.

Objective To investigate the distribution of circadian typology of patients with type 2 diabetes mellitus (T2DM) and to analyze its consequent impact on glycemic control. Methods From January 2016 to June 2016, a total of 283 T2DM patients were interviewed in this study. Self designed questionnaire, Morningness-Eveningness Questionnaire (MEQ), Pittsburg Sleep Quality Index (PSQI) and Center for Epidemiological Survey-Depression Scale (CES-D) were used to collect information on diabetes history, circadian typology, sleep quality and depression. HbA1c and other biochemical indicators were determined. The glycemic control target was<7%. The 283 T2DM patients were divided into three groups:morning type group, evening type group and neither type group according to MEQ score. Results Of the 283 subjects, 97 (34.3%) were classified as morning type, 42 (14.8%) as evening type, and 144 (50.9%) as neither. Participants with evening type were younger, shorter diabetes duration, more depressive symptoms, higher perceived sleep debt, higher FBG and higher HbA1c than those with morning type. The binary Logistic regression analysis showed that HbAlc≥7%was associated with higher FBG, higher PSQI score, higher sleep debt, lower HDL-C, and lower MEQ scores (OR=0.189-2.904, all P<0.05). Conclusions Evening type was associated with higher HbA1c and poorer glycemic control in T2DM patients compared with morning type and may be one of the risk factors affecting glycemic control.

OBJECTIVETo establish a fast and sensitive method for the detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in precision-cut rat liver slices by HPLC-MS/MS and to investigate isoniazid (INH) -induced oxidative DNA damage.

METHODSPrecision-cut liver slices (300 microm) were prepared from male rats, and incubated with INH (0.018 mol/L) for 2 h after 1 h preincubation. DNA in the slices was extracted and digested into free nucleosides at 37 degrees C. The samples were injected into HPLC-MS/MS after the proteins were removed. The level of oxidative DNA damage was estimated using the ratio of 8-OHdG to deoxyguanosine (dG).

RESULTSThe limit of detection of 8-OHdG was 1 ng/mL (S/N=3) and the intra-assay relative standard variation was 3.38% when one transition 284.3/168.4 was used as a quantifier and another two transitions 284.3/140.2, 306.1/190.2 as qualifiers. 8-OHdG and dG were well separated, as indicated by elution at 10.02 and 7.37 min, respectively. INH significantly increased the ratio of 8-OHdG to dG in rat liver slices (P<0.05).

CONCLUSION8-OHdG in precision-cut liver slices could be sensitively determined by HPLC-MS/MS. HPLC-MS/MS coupled with precision-cut tissue slices is a fast and reliable analytical technique to evaluate oxidative DNA damage of target tissues caused by procarcinogens and cytotoxins.

Animals ; Chromatography, Liquid ; DNA Damage ; drug effects ; Deoxyguanosine ; analogs & derivatives ; analysis ; Humans ; Isoniazid ; pharmacology ; Liver ; drug effects ; metabolism ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Wistar ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Time Factors