BACKGROUND: Genistein is the main component of phytoestrogen soy isoflavone and its structure is similar to estrogen,which suggests that it might prevent or delay osteoporosis. Research on the effects of genistein on bone mineralization and calcium(Ca), phosphor(P), zinc(Zn) and magnesium (Mg) in ovariectomized rats are rare.OBJECTIVE: To investigate the effects of genistein on bone mineralization and Ca,P,Zn and Mg in ovariectomized rats to provide a theoretical gist for the prevention of osteoporosis by genistein.DESIGN: A controlled experiment based on experimental animals.SETTING: Department of Nutrition,General Hospital of Chinese PLA.MATERIALS: The study was conducted in the Institute of Hygiene and Environmental Medicine,Academy of Military Medical Sciences of PLA between February and June 2003. Ten-week old female Wistar rats [certification number: (military medical animal): D98014] with a body mass of(170±20) g were selected.INTERVENTIONS: Experimental animals were fed with normal feeding for 6 weeks and then the feeding was changed to AIN-93 compound. Animals were then randomly divided into ovariectomized group (n=40) and sham-operation group(n=7) based on bodyweight after 5 days. Ovariectomized group received ovariectomy and sham-operation group only received abdominal incision. After 5 days of recovery,the ovariectomized group was further randomly divided into 5 subgroups with 8 rats each including ovariectomized control subgroup,estrogen subgroup [diethylstilbestrol 20 μg/(kg · d)],genistein Ⅰ,Ⅱ,or Ⅲ subgroup[dose of 25,50 or 100 mg/(kg · d)]. After 3months of feeding,6 rats were randomly selected from each group for the detection of bone density and corresponding bone hismorphometric indicators.MAIN OUTCOME MEASURES: Bone density,corresponding parameters of bone mineralization,Ca,P,Zn and Mg contents in bone of mice in each group RESULTS: After ovariectomy,femoral bone density decreased [(0. 247± 0.007) g/cm2],mean osteoid width increased[(7. 04 ±0. 32)μm],bone mineralization delayed [(4.96±0.99) days],osteoid maturity prolonged [(26.99±7.70) days],and Ca[ (251.11± 5.31) mg/g],P[(115.08± 3.78) mg/g],Zn[ (299.69±37.1)μg/g] and Mg[(4. 32±0. 12) μg/g]were all significantly different from that of sham-operation group(P<0.05).After the application of genistein,femoral bone density had a tendency of improvement[ (0. 250±0. 007) g/cm2],mean osteoid width narrowed[ (4. 97±0.77) μm],bone mineralization delayed time[ (3.18±0.69) days] and osteoid maturity time[(14.53 ±3.84) days] shortened, contents of Ca [(270.00±5.65) mg/g],P[(124.25±2.37) mg/g] andMg[(4.61±0. 08) μg/g]elevated while Zn content had no significant changes.CONCLUSION: Genistein promotes osteoid mineralization,reduces the loss of Ca, P and Mg in the bone and prevent the generation of osteoporosis in unsexed rats

Objectives To study the radiation-protective effects produced by the estrogenic activities of genistein(Gen) .Method After blocking estrogen receptor activities by Tamoxifen and Faslodex,the effects of Gen on 30d survival rate and average life span of the mice were monitored after exposure to lethal dose ? radiation(7.5Gy),and the effects of Gen on innate(nonspecific) immune response as well as humoral(B-cell mediated)immune response of the mice were examined after exposure to 4.0Gy ? radiation.Results Gen can enhance the survival rate,average life span,and immune response of the ?-radiation exposed mice.While Tamoxifen had no significant effects on survival rate and immune response of the exposed mice,Faslodex caused a decrease in survival rate and average life span and also inhibited the immune response in those exposed mice.Conclusion Genistein can enhance the radiation tolerance in mice through activation of estrogen receptor ? pathway.

Objective: To investigate the effects of genistein (Gen) on bone turnover in ovariectomized rats. Methods: Forty-seven Wistar rats were randomly allocated into six groups: sham-operated (sham), ovarietomized (ovx), ovarietomized plus diethyl stilbestrol [E, 20?g/(kg bw?d)] or Gen [25、50、100 mg/(kg bw?d)] administration. After the rats had been fed for 3 mo,bone mineral density (BMD), histomorphometric parameters, the serum concentration of osteocalcin (BGP) and urinary contents of pyridine and hydroxyproline (HYPRO) were analysed. Results: BMD, trabecular bone volume (TBV) and mean trabecular plate density (MTPD) of ovariectomized rats were significantly decreased, but serum concentrations of BGP,urinary contents of deoxypyridinoline and HYPRO and mean trabecular plate space (MTPS) increased compared with the sham. After 3 mo of Gen supplementation, TBV,MTPD and urinary deoxypyridinoline were improved significantly in ovariectomized rats. Conclusion: Genistein reduced bone loss in ovariecromized rats by suppressing bone metabolism and osteoclast activity.

OBJECTIVETo investigate the association between catecholamine-beta-adrenoceptor (beta-AR)-adenosine 3', 5'-monophosphate (cAMP) system and long-term prognosis in patients with chronic heart failure (CHF).

METHODSThe study population comprised 73 patients with CHF (EF: 23% +/- 10%) with a mean follow-up of 3.8 +/- 1.9 years. Plasma levels of norepinephrine (NE) were measured using high performance lipid chromatography, beta-adrenergic receptor density (Bmax) and the content of cAMP in peripheral lymphocytes were calculated using 3H-dihydroalpneolo as ligand and competitive immunoassay, respectively. Deaths due to cardiovascular events within the follow-up period were registered.

RESULTSThe total mortality was 64.7%, 57.4% of which was for cardiogenic (worsening heart failure: 32.4%; sudden death: 25.0%). In the cardiogenic death group, plasma levels of NE and epinephrine (E) (3.74 nmol/L +/- 0.09 nmol/L and 3.17 nmol/L +/- 1.0 nmol/L) and the contents of peripheral lymphocyte cAMP (3.64 pmol/mg protein +/- 1.4 pmol/mg protein) were significantly increased as compared with the survival group (2.68 nmol/L +/- 0.07 nmol/L, 2.41 nmol/L +/- 0.24 nmol/L and 2.73 pmol/mg protein +/- 0.9 pmol/mg protein, respectively, all P < 0.01). In the sudden death group, plasma levels of NE and E (5.01 nmol/L +/- 0.06 nmol/L and 4.13 nmol/L +/- 0.08 nmol/L) were significantly increased as compared with the worsening heart failure group (2.49 nmol/L +/- 0.07 nmol/L and 2.33 nmol/L +/- 0.8 nmol/L, all P < 0.001) and to the survival group (2.68 nmol/L +/- 0.07 nmol/L and 2.41 nmol/L +/- 0.14 nmol/L, all P < 0.01). The incidences of sudden death were 0%, 75%, and 100% (chi(2) = 16.018, P < 0.01) in patients with plasma NE < 2.5 nmol/L, NE 2.5 nmol/L - 4.5 nmol/L, and NE > 4.5 nmol/L, respectively. In the worsening heart failure group, the content of peripheral lymphocyte cAMP (4.46 pmol/mg protein +/- 0.18 pmol/mg protein) was significantly increased compared with the sudden death group (2.39 pmol/mg protein +/- 0.9 pmol/mg protein, P < 0.001) and to the survival group (2.73 pmol/mg protein +/- 1.1 pmol/mg protein, P < 0.001). The worsening heart failure death occurences were 5.0%, 72.2%, and 100% (chi(2) = 14.26, P < 0.01) in patients with a content of peripheral lymphocyte cAMP < 2.5 nmol/L, cAMP 2.5 nmol/L - 4.5 nmol/L, and cAMP > 4.5 nmol/L, respectively. Bmax in peripheral lymphocyte was not significantly different (P > 0.05) among the sudden death, worsening heart failure, and survival groups in CHF patients.

CONCLUSIONSPlasma levels of catecholamine increase significantly, and Bmax and the contents of cAMP in peripheral lymphocytes decrease significantly in patients with CHF. High plasma catecholamine levels may be associated with sudden death, and high intralymphocyte cAMP content may be associated with worsening heart failure in CHF patients.

Adult ; Aged ; Catecholamines ; blood ; Cyclic AMP ; blood ; Death, Sudden, Cardiac ; Female ; Heart Failure ; blood ; mortality ; Humans ; Lymphocytes ; chemistry ; Male ; Middle Aged ; Receptors, Adrenergic, beta ; blood

OBJECTIVE: To verify the therapeutic effect and adverse reactions of ?-receptor blocker, domestic urapidil, on severe hypertension. METHODS: Observation was carried out in a multi-center, random sampling and controlled pattern. Drug was iv injected first and then infused. At the same time, the patients' systolic pressure, diastolic pressure, heart rate, EKG, blood & urine routine, serum GPT and urea nitrogen were measured and examined.RESULTS: Of 41 cases in this series. 16 satis- factory(39.0%), 23 improved (56.1%), 2 unsatisfactory(4.9%) .The total effective rate was 95.1%. After drug administra- tion, systolic pressure was lowered by 43 .97mmHg(P

Objective To investigate the changes of sex hormone and androgen receptor levels and evaluate the relationship of the sex hormones and androgen receptor with coronary heart disease (CHD) in elderly men. Methods A cross-sectional study was performed in 539 elderly men, including 400 healthy people aged 62-92 years and 139 CHD patients aged 60-88 years. The plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) level was tested by flow cytometry. Results The fluorescence intensity of DHEAS, TT, SHBG, FT and AR were significantly lower in CHD group than in healthy group (P<0.01);however, FSH and E2 in CHD group were higher(P(0.01). Age was negatively correlated with TT(r=-0.28,P<0.01) and FT (r=-0.17,P<0.05), and positively correlated with SHBG(r=0.14,P<0.05) and E2 (r=0.33, P<0.01). AR fluorescence intensity was negatively correlated with systolic blood pressure (r=-0.12,P<0.01). Logistic regression analysis indicated that TT (OR=1.065,9% CI: 1.012～1.121,P<0.05), SHBG(OR=0.994,95% CI:0.990～0.998,P<0.01) and AR (OR=0.971,95%CI:0.956～0.986, P<0.01)were significantly associated with CHD in elderly male patients. Conclusions The levels of DHEAS, TT, SHBG, FT and AR are lower in elderly men with CHD than in elderly healthy men;however, the FSH and E2 concentrations are higher. Low levels of TT, SHBG and AR may be the independent risk factors for CHD in elderly men.

Objective:To explore the application effect of the blended learning based on Rain Classroom in normal human morphology course.Methods:A total of 118 undergraduates majoring in medical laboratory technology of Batch 2017 and Batch 2018 from Xinjiang Medical University were included in this study, and they were divided into the observation group (Batch 2018) and the control group (Batch 2017), with 59 students in each group, adopting the traditional teaching method and blended learning method based on Rain Classroom respectively. The mid-term, final and comprehensive scores of the two groups were compared by t test and chi-square test through SPSS 23.0. And the evaluation of teaching satisfaction of the observation group was obtained by the questionnaire survey. Results:The mid-term results [(74.02±8.71) vs. (62.00±8.97), t=-6.073, P<0.001], the final results [(83.21±7.73) vs. (70.44±11.43), t=-6.250, P<0.001], and the comprehensive results [(82.26±9.53) vs. (70.52±11.09), t=-6.012, P<0.001] of the observation group were significantly superior than those of the control group ( P<0.05). The excellence rate of the final results (23.72% vs. 3.45%, χ2=10.412, P=0.001) and comprehensive results (18.64% vs. 5.08%, χ2=5.187, P=0.023) in the observation group were significantly higher than those in the control group ( P<0.05). The results of the questionnaire survey showed that the observation group generally had a good satisfaction with the blended learning. Conclusion:The blended learning could make up for the deficiency of the traditional teaching methods, have preferable teaching effects, and get wide recognition from students.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.