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Objective To investigete a new synthetic route for carbapenem skeleton(1)for industrial production. Methods (3S,4R)-4-acetoxy-3-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one(4-AA)was used as raw material,and 1 was obtained from it through a homemade chiral auxiliary zinc powder catalyzed Reformatsky reaction,hydrolysis,the introduction of β-carboxyl es?ter structure,deprotection,cyclization,and activation by diphenyl chlorophosphate. The each key process was optimized,and the structures of intermediate and target compounds were confirmed by MS,GC-MS and 1H NMR.Results and Conclusion The total yield was 19.9%.The improved process conditions are mild,easy to operate,and suitable for industrial production.
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Objective To research and optimize the synthesis process of(7-methoxy-1-naphthyl)acetonitrile for industrial production.Methods(7-Methoxy-1-naphthyl)acetonitrile was synthesized from industrial grade 1-amino-7-naphthol,by diazotiza?tion,Sandmeyer reaction and coupled reaction.Factors such as the reaction temperature,the reaction time and the ratio of the raw ma?terial were optimized to make the reaction conditions mild.The total yield was 53.9%.Results and Conclusion The structures of in?termediate and target compounds were confirmed by MS and 1H NMR.The new method is suitable for industrial production.
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<p><b>OBJECTIVE</b>To investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males.</p><p><b>METHODS</b>Using the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations.</p><p><b>RESULTS</b>Among the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS.</p><p><b>CONCLUSION</b>The concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.</p>
Subject(s)
Adult , Aged , Humans , Male , Middle Aged , Blood Pressure , Body Mass Index , Homocysteine , Blood , Luteinizing Hormone , Blood , Metabolic Syndrome , Blood , Diagnosis , Reproduction , Rural Population , Sex Hormone-Binding Globulin , Metabolism , Surveys and Questionnaires , Testosterone , Blood , Thyroxine , Blood , Waist Circumference , Waist-Hip RatioABSTRACT
A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further examined the relationship between ouabain and asthenozoospermia. In this study, the rat was intraperitoneally injected with ouabain at different concentrations (low-dose ouabain group: 12.5 μg/kg body weight per day, and high-dose ouabain group: 25 μg/kg body weight per day) for 30 days to establish the asthenozoospermia model. The sperms from 60 males with normal fertility were incubated with ouabain of gradient concentrations (10(-7)-10(-2) mol/L) for 4 h. The sperm motility was evaluated under a microscope. Moreover, the endogenous ouabain (EO) level was determined in seminal plasma of mild or severe asthenozoospermia patients and males with normal fertility by competitive inhibition ELISA. The results showed that the sperm motility was significantly diminished in the rats treated with different concentrations of ouabain. The number of motile sperms (grades a and b) was decreased greatly in a time- and dose-dependent manner in 10(-5)-10(-2) mol/L ouabain groups (P0.05). Furthermore, the EO level was significantly increased in asthenozoospermia patients as compared with that in males with normal fertility (25.27±1.71 μg/L in mild asthenozoospermia patients, 26.52±1.82 μg/L in severe asthenozoospermia patients, 19.31±1.45 μg/L in normal fertility men) (P<0.01). In conclusion, rat asthenozoospermia was successfully established by intraperitoneal injection of ouabain, and 10(-5) mol/L ouabain was sufficient enough to inhibit sperm motility in vitro. Moreover, EO, a normal constituent of seminal plasma, was highly expressed in asthenozoospermia males as compared with normal fertility ones.
ABSTRACT
A growing number of researches have shown that ouabain can regulate mammalian sperm function and male reproduction by modulating the sperm motility, capacitation and acrosome reaction in vitro. This study further examined the relationship between ouabain and asthenozoospermia. In this study, the rat was intraperitoneally injected with ouabain at different concentrations (low-dose ouabain group: 12.5 μg/kg body weight per day, and high-dose ouabain group: 25 μg/kg body weight per day) for 30 days to establish the asthenozoospermia model. The sperms from 60 males with normal fertility were incubated with ouabain of gradient concentrations (10(-7)-10(-2) mol/L) for 4 h. The sperm motility was evaluated under a microscope. Moreover, the endogenous ouabain (EO) level was determined in seminal plasma of mild or severe asthenozoospermia patients and males with normal fertility by competitive inhibition ELISA. The results showed that the sperm motility was significantly diminished in the rats treated with different concentrations of ouabain. The number of motile sperms (grades a and b) was decreased greatly in a time- and dose-dependent manner in 10(-5)-10(-2) mol/L ouabain groups (P<0.01), while no obvious change in sperm motility was observed in 10(-7)-10(-6)mol/L groups even for 4-h incubation (P>0.05). Furthermore, the EO level was significantly increased in asthenozoospermia patients as compared with that in males with normal fertility (25.27±1.71 μg/L in mild asthenozoospermia patients, 26.52±1.82 μg/L in severe asthenozoospermia patients, 19.31±1.45 μg/L in normal fertility men) (P<0.01). In conclusion, rat asthenozoospermia was successfully established by intraperitoneal injection of ouabain, and 10(-5) mol/L ouabain was sufficient enough to inhibit sperm motility in vitro. Moreover, EO, a normal constituent of seminal plasma, was highly expressed in asthenozoospermia males as compared with normal fertility ones.
Subject(s)
Animals , Humans , Male , Rats , Asthenozoospermia , Metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Ouabain , Metabolism , Pharmacology , Toxicity , Rats, Sprague-Dawley , Semen , Metabolism , Sperm Motility , Physiology , Spermatozoa , Physiology , Time FactorsABSTRACT
Asoprisnil, a member of the selective progesterone receptor modulators, exerts high progesterone receptor selectivity, endometrial targeted advantages and significant anti-implantation effect in rats. The purpose of this study was to confirm the anti-implantation effect of asoprisil, investigate the ultrastructural changes of the peri-implantation endometrium in mice and explore the effect of asoprisnil on endometrial receptivity and its targeted contraceptive proficiency. Post-coitus mice were administered with different dosages (0.2, 0.1, 0.05 mg·g(-1)·day(-1)) of asoprisnil from day 1 of pregnancy to day 3. Then 3 animals in each group were killed on day 5 of pregnancy, and uteri were collected to examine the ultrastructural changes of endometria under a transmission electron microscope (TEM). A total of 80 animals were sacrificed on day 8 of pregnancy, and the uterine horns were examined for the presence or absence of nidation sites and the number of implantation embryos. The results showed that the implantation rate and the average number of implantation embryos in asoprisnil groups were statistically significantly decreased as compared with the vehicle control group (P<0.05). The TEM results revealed that, in vehicle control group, the tight junction between the luminal epithelia cells was short and straight, the gap was wide; the luminal epithelia cells were covered with plenty of short, clavate and neatly arranged microvilli; the endometril stromal cells were large with plenty of cytoplasm, and showed significant decidual change; there was more than one nucleus in stromal cells, and the karyotheca was integrity. In low dosage and high dosage asoprisnil groups, the tight junction was longer and more curve than in the vehicle control group; microvilli were uneven and asymmetrically distributed in luminal epithelia; the stromal cells were small and the decidual change was not significant; there were karyopyknosis and karyolysis in stromal cells; there were abnormal thick-wall vessels in the endometrium. It was suggested that asoprisnil changed the ultrastructure of the endometrium in implantation window, disturbed the endometrial receptivity and finally resulted in embryo implantation failure.
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Asoprisnil, a member of the selective progesterone receptor modulators, exerts high progesterone receptor selectivity, endometrial targeted advantages and significant anti-implantation effect in rats. The purpose of this study was to confirm the anti-implantation effect of asoprisil, investigate the ultrastructural changes of the peri-implantation endometrium in mice and explore the effect of asoprisnil on endometrial receptivity and its targeted contraceptive proficiency. Post-coitus mice were administered with different dosages (0.2, 0.1, 0.05 mg·g(-1)·day(-1)) of asoprisnil from day 1 of pregnancy to day 3. Then 3 animals in each group were killed on day 5 of pregnancy, and uteri were collected to examine the ultrastructural changes of endometria under a transmission electron microscope (TEM). A total of 80 animals were sacrificed on day 8 of pregnancy, and the uterine horns were examined for the presence or absence of nidation sites and the number of implantation embryos. The results showed that the implantation rate and the average number of implantation embryos in asoprisnil groups were statistically significantly decreased as compared with the vehicle control group (P<0.05). The TEM results revealed that, in vehicle control group, the tight junction between the luminal epithelia cells was short and straight, the gap was wide; the luminal epithelia cells were covered with plenty of short, clavate and neatly arranged microvilli; the endometril stromal cells were large with plenty of cytoplasm, and showed significant decidual change; there was more than one nucleus in stromal cells, and the karyotheca was integrity. In low dosage and high dosage asoprisnil groups, the tight junction was longer and more curve than in the vehicle control group; microvilli were uneven and asymmetrically distributed in luminal epithelia; the stromal cells were small and the decidual change was not significant; there were karyopyknosis and karyolysis in stromal cells; there were abnormal thick-wall vessels in the endometrium. It was suggested that asoprisnil changed the ultrastructure of the endometrium in implantation window, disturbed the endometrial receptivity and finally resulted in embryo implantation failure.
Subject(s)
Animals , Female , Mice , Pregnancy , Contraception, Postcoital , Methods , Embryo Implantation, Delayed , Physiology , Endometrium , Physiology , Estrenes , Oximes , Oxytocics , Pregnancy, Animal , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>Stem cells transplantation is a promising strategy in cardiology. This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients.</p><p><b>METHODS</b>The following databases were searched, including Cochrane Library (Issue 4, 2011), PubMed (1980 to 2011), Embase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). Search criteria:studies were screened and the quality was evaluated according to predefined inclusion and exclusion criteria. Intervention measures: the treatment group using stem cell transplantation therapy on top of standard drug treatment, while the control group using standard drug treatments.</p><p><b>RESULTS</b>A total of 31 studies involving 2375 patients were included. The results show that the improvement of LVEDV in the stem cell treatment group is greater than in the control group [SMD = -11.8% (95%CI: -0.223 - 0.013), P = 0.027] and the relative-risk of cardiac events is lower in stem cell treatment group [RR = 0.77 (95%CI: 0.66 - 0.90), P < 0.01] than in control group.</p><p><b>CONCLUSION</b>Stem cells therapy is effective in improving cardiac remodeling and reducing the relative-risk of cardiac events in patients with chronic heart failure.</p>
Subject(s)
Humans , Chronic Disease , Heart Failure , General Surgery , Stem Cell Transplantation , Ventricular RemodelingABSTRACT
This study was purposed to investigate the relationship between NQO1C(609T), RAD51(G135C), XRCC3(C241T) single nucleotide polymorphisms and incidence of acute lymphoblastic leukemia (ALL). NQO1C(609T), RAD51(G135C), XRCC3(C241T) genotypes were detected by PCR-RFLP in 170 patients with de novo ALL and 458 normal persons as control. The results indicated that the genotype ratio of NQO1C(609T), RAD51(G135C) and XRCC3(C241T) in single genotype analysis showed no statistical difference between ALL patients and normal controls, which suggested that the single genotype affect onset of ALL without statistical significance. In combined genotype analysis, presence of both variants for NQO1C(609T) and RAD51(G135C) increased onset risk of ALL with myeloid antigen positive and with balanced translocation (OR value 5.553 and 2.618 respectively); the presence of homozygosity variant for NQO1C(609T) increased onset risk of ALL in the country-children (OR = 2.541). In conclusion, the combined effect of NQO1C(609T), RAD51(G135C) and XRCC3(C241T) genotypes may promote occurrence of ALL, which suggests that the combined analysis of 3 genotypes has more predictive significance for ALL than single genotype analysis.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Case-Control Studies , DNA Repair , DNA-Binding Proteins , Genetics , NAD(P)H Dehydrogenase (Quinone) , Genetics , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , Rad51 Recombinase , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate JAK2V617F mutation and its clinical significance in patients with chronic myeloproliferative disorders (cMPD).</p><p><b>METHODS</b>A retrospective study was performed on 523 cMPD patients diagnosed according to the current World Health Organization (WHO) criteria. Allele-specific PCR (ASP) was used to identify JAK2V617F mutation, the mutation status was analyzed by PCR-RFLP, and the results were confirmed by sequence analysis. The mutation burden was calculated by the ratio of T/G. The correlation between the allele burden and the clinical and hematologic features was analysed. For those without JAK2 V617F, MPL W515L mutation was analyzed.</p><p><b>RESULTS</b>JAK2 V617F was detected in 66% of all patients (94% in PV, 80% in ET, 78% in CIMF, 75% in CMPD-U and 14% in HES). The majority of patients carried JAK2 V617F mutation were heterozygous , homozygote was found in only 5 cases (4 in PV and 1 in ET). The mutation burden in most patients (71.5%) was low with PV>ET>CIMF (P =0.003). Hemoglobin level was significantly related to high mutation burden in PV (r = 0. 203, P =0.033). Bone marrow megakaryocyte counts were found to be marked increased in ET with high JAK2 V617F loads (P = 0.024), and hepatomegaly in CIMF was significantly associated with high JAK2 V617F mutation burden (r = 0.315, P = 0.001).</p><p><b>CONCLUSIONS</b>1) Most cMPD patients, especially those with PV, carry JAK2 V617F mutation, except for CML. 2) .98% of JAK2 V617F mutation occurs of heterozygous status. 3) The mutation burden is PV>FT>CIMF. High JAK2 V617F loads are significantly associated with higher hemoglobin level in PV and higher bone marrow megakaryocyte counts in ET. 4) The positive correlation between hepatomegaly and JAK2 V617F mutation burden is found in CIMF.</p>