A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susc...A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.展开更多
The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic ...The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure. The influences of reaction time, reaction temperature, and stirring speed on the catalytic performance were also investigated. Optimal reaction conditions comprised the reaction time of 1 h, the reaction temperature of 40 °C, and the stirring speed of 1500 r·min-1. Under optimal condition, the n-C5 conversion,research octane number(RON) increment, total liquids yield, and isoparaffin yield in isomerized oil were56.80%, 13.51, 89.90 wt%, and 44.32 wt%, respectively. A new mathematical model was constructed to predict the relationships among RON increment, RON increment/n-C5 conversion ratio, and n-C5 conversion. The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%. Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3. The n-C5 conversion increased from 56.80% to 67.32%. The RON increment, total liquids yield, and isoparaffin yield reached 17.83, 97.36 wt%,and 63.74 wt%, respectively.展开更多
BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent prog...BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog(NA)therapy.AIM The study aim was to clarify risk factors and the diagnostic value of alphafetoprotein(AFP)for HCC progression in NA-treated hepatitis B virus(HBV)-related cirrhosis patients.METHODS In this retrospective cross-sectional study,we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital.The patients were divided into two groups,145 who did not progress to HCC(No-HCC group),and 121 who progressed to HCC during NA treatment(HCC group).The logistic regression analysis was used to analyze the risk factors of HCC progression.The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed that age≥60 years(P=0.001),hepatitis B and alcoholic etiology(P=0.007),smoking history(P<0.001),family history of HBV-related HCC(P=0.002),lamivudine resistance(P=0.011),HBV DNA negative(P=0.023),aspartate aminotransferase>80 U/L(P=0.002),gamma-glutamyl transpeptidase>120 U/L(P=0.001),alkaline phosphatase>250 U/L(P=0.001),fasting blood glucose(FBG)≥6.16(mmol/L)(P=0.001)and Child-Pugh class C(P=0.005)were correlated with HCC progression.In multivariate analysis,age≥60 years[hazard ratio(HR)=3.089,95%confidence interval(CI):1.437-6.631,P=0.004],smoking history(HR=4.001,95%CI:1.836-8.716,P<0.01),family history of HBV-related HCC(HR=6.763,95%CI:1.253-36.499,P<0.05),lamivudine resistance(HR=2.949,95%CI:1.207-7.208,P=0.018),HBV DNA negative(HR=0.026,95%CI:0.007-0.139,P<0.01),FBG≥6.16 mmol/L(HR=7.219,95%CI:3.716-14.024,P<0.01)were independent risk factors of HCC progression.ROC of AFP for diagnosis of HCC was 0.746(95%CI:0.674-0.818).A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609,and specificity of 0.818 for diagnosing HCC.CONCLUSION Age≥60 years,smoking history,family history of HCC,lamivudine resistance,HBV DNA negative,FBG≥6.16 mmol/L were risk factors of HCC progression.Serum AFP had limited diagnostic value for HCC.展开更多
objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral...objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral acid. Results Six chiral analogs of Baogongteng A were prepared. In mydriatic tests inrabbits, (+) - 32 - benzoyloxy - 6β - acetoxytropane and (+) - 32 - parachloro benzoyloxy- 6β- acetoxytropanepossess anticholinergic activities. Conclusion The configuration of enantiomers has significant influence on thebioactivity of analogs of Baogongteng A.展开更多
BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconver...BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.展开更多
The fluorescence spectra of the interaction between four new distamycin analogs and DNA from herring sperm have been studied in detail. The fluorescence quenching of the DNA by the analogs was observed, and the fluore...The fluorescence spectra of the interaction between four new distamycin analogs and DNA from herring sperm have been studied in detail. The fluorescence quenching of the DNA by the analogs was observed, and the fluorescence intensity of the DNA was attenuated exponentially with the increasing of the analogs concentration.展开更多
In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR ...In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR and MS methods. The results indicated that the reactivity of phosphoryl biological small molecules was depended on the configuration, function groups and positions.展开更多
Two peptide analogs H-Tyr-Thr-Pro-Arg-Lys-OH (1) and H-Tyr-Thr-Pro-Phe-Lys-OH (2) were prepared successfully by the technique of simultaneous multiple peptides synthesis(SMPS) on a single resin support. The profiles o...Two peptide analogs H-Tyr-Thr-Pro-Arg-Lys-OH (1) and H-Tyr-Thr-Pro-Phe-Lys-OH (2) were prepared successfully by the technique of simultaneous multiple peptides synthesis(SMPS) on a single resin support. The profiles of HPLC and amino acid analysis indicated that the purity of 1 and 2 was satisfactory. The average yield(74.9％) of each peptide was reasonable. This new technique of SMPS offered significant savings not only in time but in many expensive reagents as well.展开更多
Peptide analogs of salmon calcitonin (sCT) were synthesized by using Fmoc-based chemistry on MBHA resins Salmon calcitonin was modified by 1) cysteines at p0sitions 1 and 7 were replaced by valine and alanine respecti...Peptide analogs of salmon calcitonin (sCT) were synthesized by using Fmoc-based chemistry on MBHA resins Salmon calcitonin was modified by 1) cysteines at p0sitions 1 and 7 were replaced by valine and alanine respectively to result in open chain analogs. 2) the glycine at position 30 was replaced by alanine, D-alanine and sarcosine respectively, and 3) some residues were deleted besides the above two modifications. A modified two-step deprotection / cleavage procedure, in which a solvent of TFA / TMSBr / thioanisole / EDT / m-cresol combines with HF cleavage,was adopted in SPPS.展开更多
AIM: To draw a Meta-analysis over the comparison of the intraocular pressure(IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin ...AIM: To draw a Meta-analysis over the comparison of the intraocular pressure(IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs(PGAs) monotherapy.·METHODS: After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials(RCTs) comparing the fixed combination of PGAs/timolol therapy(FCs) and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal IOP, percentage of participants whose IOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects,hyperemia and eye irritation. The analysis was carried out in Rev Man version 5.3 software.·RESULTS: After six-month medical intervention, the mean diurnal IOP of FCs was lower than PGAs(MD-1.14,95% CI-1.82 to-0.46, P =0.001); the percentage of target IOP achieving between FCs and PGAs showed no significant difference(RR 1.18, 95% CI 0.97 to 1.43, P =0.10).No statistically significant differences of the incidence of hyperemia(RR 0.67, 95% CI 0.45 to 1.01, P =0.06) and eye irritation(RR 1.20, 95% CI 0.95 to 1.51, P =0.12)between the FCs and PGAs monotherapy were detected.Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects(central endothelial cell density, MD-0.20, 95% CI-0.72 to 0.32, P =0.45; central corneal thickness, MD-0.01, 95% CI-0.02 to 0.00, P =0.23).The evaluation of visual field change was not performeddue to the limited duration of the trials included in this Meta-analysis.·CONCLUSION: The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant.More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.展开更多
Triple negative breast cancer (TNBC) is characterized by a high sensitivity to antiblastic drugs and a high pathological complete remission rate after neoadjuvant therapy. In patients showing complete remission, the p...Triple negative breast cancer (TNBC) is characterized by a high sensitivity to antiblastic drugs and a high pathological complete remission rate after neoadjuvant therapy. In patients showing complete remission, the probability of developing metastatic disease would seem to be reduced. Nonetheless, this cancer has a high percentage of relapse. Anthracyclines, taxanes and platinum compounds are the most effective drugs for the treatment of TNBC. There is substantial evidence to support the efficacy of platinum-based chemotherapy, probably attributable to the mechanism of action of such drugs, which react with the DNA repair system. PARP inhibitors would also seem to be very interesting. Despite promising results, TNBC remains a disease with a poor prognosis due to the lack of targeted therapy. The discovery of new targets and new agents is thus a high priority issue for this type of breast cancer. In this respect, lipoplatin has been identified as a potentially interesting treatment option to evaluate in both neoadjuvant and advanced settings.展开更多
Natural product jacaranone, 1, and three analog derivatives were synthesized and their apoptotic and necrotic activity against four cancer cell lines was tested. One of these derivatives 7, was more active than the na...Natural product jacaranone, 1, and three analog derivatives were synthesized and their apoptotic and necrotic activity against four cancer cell lines was tested. One of these derivatives 7, was more active than the natural product, and exhibited an important necrotic effect against three of the cell lines tested (ovarian carcinoma, liver cancer and breast cancer cells). Derivative 6 was more active than the natural product, and showed a significant apoptotic activity against breast cancer and ovarian carcinoma cells. Some derivatives analyzed in this study showed promising anti-tumor results, nevertheless, further studies have to be done in order to determine their in vivo activity, their mechanism as well as their safety and stability.展开更多
A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives...A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives and amines can produce yields ranging from 50% to 85% of the resulting amide.展开更多
A series of N-carbonyl-functionalized ureas, carbamates and thiocarbamates derivatives (or N-Chloro sulfonyl isocyanate “N-CSI”) were involved in linear and nonlinear physicochemical quantitative structure-activity ...A series of N-carbonyl-functionalized ureas, carbamates and thiocarbamates derivatives (or N-Chloro sulfonyl isocyanate “N-CSI”) were involved in linear and nonlinear physicochemical quantitative structure-activity relationship “QSAR” analysis to find out the structural keys to control the inhibition against Sterol O-Acyl-Transferase-1 “SOAT-1”. The results indicate the important effects of geometrical and chemical descriptors on the inhibitory activity of SOAT-1. The molecules were also screened for three-dimensional molecular docking on the crystal structure of ACAT-1 (1WL5 for ACAT-1, PDB). A comparison between 2D-QSAR and 3D molecular docking studies shows that the latter confirm the first results and represent a good prediction of the chemical and physical nature of interactions between our drug molecules and enzyme SOAT-1.展开更多
AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar...AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.展开更多
6—O—Mcthylgossypol (3) was obtained with the methods of synthesis for the first time.For the purpose ofe一iminating some prob一ems assoeiatedwith the eliniea一use orgossypol such as irreversibility and hypokalemia,w...6—O—Mcthylgossypol (3) was obtained with the methods of synthesis for the first time.For the purpose ofe一iminating some prob一ems assoeiatedwith the eliniea一use orgossypol such as irreversibility and hypokalemia,while retaining its pl飞armacologieally desirableantifertility effeets,numerous derivatives and展开更多
基金supported by Major R&D Program of New Drugs-National S&T Key Special Subject of China (No.2009ZX09103-115)National Natural Science Foundation of China(No.20872081)Natural Science Foundation of Shandong(No.Y2006C31)
文摘A series of novel 4'-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.
基金Supported by the National Natural Science Foundation of China(21802047)the Scientific Research Funds of Huaqiao University(600005-Z17Y0073).
文摘The isomerization of n-pentane to generate high-quality blending components for clean gasoline was catalyzed by several amide-AlCl3-based ionic liquid(IL) analogs with various amides as donor molecules. The catalytic performance of these IL analogs was evaluated in a magnetic agitated autoclave operated in batch mode.IL analog based n-methylacetamide(NMA)-AlCl3 with the amide/AlCl3 molar ratio of 0.65 showed excellent performance toward n-pentane isomerization because 0.65 NMA-1.0 AlCl3 had a low viscosity and bidentate coordination structure. The influences of reaction time, reaction temperature, and stirring speed on the catalytic performance were also investigated. Optimal reaction conditions comprised the reaction time of 1 h, the reaction temperature of 40 °C, and the stirring speed of 1500 r·min-1. Under optimal condition, the n-C5 conversion,research octane number(RON) increment, total liquids yield, and isoparaffin yield in isomerized oil were56.80%, 13.51, 89.90 wt%, and 44.32 wt%, respectively. A new mathematical model was constructed to predict the relationships among RON increment, RON increment/n-C5 conversion ratio, and n-C5 conversion. The new model indicated that an appropriate conversion per pass of n-C5 did not exceed 50%–55%. Various cycloparaffin additives were used to improve the catalytic performance of 0.65 NMA-1.0 AlCl3. The n-C5 conversion increased from 56.80% to 67.32%. The RON increment, total liquids yield, and isoparaffin yield reached 17.83, 97.36 wt%,and 63.74 wt%, respectively.
文摘BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma(HCC).Furthermore,there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog(NA)therapy.AIM The study aim was to clarify risk factors and the diagnostic value of alphafetoprotein(AFP)for HCC progression in NA-treated hepatitis B virus(HBV)-related cirrhosis patients.METHODS In this retrospective cross-sectional study,we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital.The patients were divided into two groups,145 who did not progress to HCC(No-HCC group),and 121 who progressed to HCC during NA treatment(HCC group).The logistic regression analysis was used to analyze the risk factors of HCC progression.The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed that age≥60 years(P=0.001),hepatitis B and alcoholic etiology(P=0.007),smoking history(P<0.001),family history of HBV-related HCC(P=0.002),lamivudine resistance(P=0.011),HBV DNA negative(P=0.023),aspartate aminotransferase>80 U/L(P=0.002),gamma-glutamyl transpeptidase>120 U/L(P=0.001),alkaline phosphatase>250 U/L(P=0.001),fasting blood glucose(FBG)≥6.16(mmol/L)(P=0.001)and Child-Pugh class C(P=0.005)were correlated with HCC progression.In multivariate analysis,age≥60 years[hazard ratio(HR)=3.089,95%confidence interval(CI):1.437-6.631,P=0.004],smoking history(HR=4.001,95%CI:1.836-8.716,P<0.01),family history of HBV-related HCC(HR=6.763,95%CI:1.253-36.499,P<0.05),lamivudine resistance(HR=2.949,95%CI:1.207-7.208,P=0.018),HBV DNA negative(HR=0.026,95%CI:0.007-0.139,P<0.01),FBG≥6.16 mmol/L(HR=7.219,95%CI:3.716-14.024,P<0.01)were independent risk factors of HCC progression.ROC of AFP for diagnosis of HCC was 0.746(95%CI:0.674-0.818).A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609,and specificity of 0.818 for diagnosing HCC.CONCLUSION Age≥60 years,smoking history,family history of HCC,lamivudine resistance,HBV DNA negative,FBG≥6.16 mmol/L were risk factors of HCC progression.Serum AFP had limited diagnostic value for HCC.
文摘objective We prepared optical analogs of Baogongteng A and investigated their bioactivities soas to find new effective hypotoxic drugs at M- receptors. Methods Racemic analogs of Baogongteng A wereresolved with chiral acid. Results Six chiral analogs of Baogongteng A were prepared. In mydriatic tests inrabbits, (+) - 32 - benzoyloxy - 6β - acetoxytropane and (+) - 32 - parachloro benzoyloxy- 6β- acetoxytropanepossess anticholinergic activities. Conclusion The configuration of enantiomers has significant influence on thebioactivity of analogs of Baogongteng A.
基金The Shandong Province Natural Science Foundation,No.ZR2019PH052the National Key Research and Development Program of China,No.2017YFC0908104.
文摘BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.
基金The project was supported by the National Natural Science Foundation of China (No.39970169,29872001).
文摘The fluorescence spectra of the interaction between four new distamycin analogs and DNA from herring sperm have been studied in detail. The fluorescence quenching of the DNA by the analogs was observed, and the fluorescence intensity of the DNA was attenuated exponentially with the increasing of the analogs concentration.
文摘In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR and MS methods. The results indicated that the reactivity of phosphoryl biological small molecules was depended on the configuration, function groups and positions.
文摘Two peptide analogs H-Tyr-Thr-Pro-Arg-Lys-OH (1) and H-Tyr-Thr-Pro-Phe-Lys-OH (2) were prepared successfully by the technique of simultaneous multiple peptides synthesis(SMPS) on a single resin support. The profiles of HPLC and amino acid analysis indicated that the purity of 1 and 2 was satisfactory. The average yield(74.9％) of each peptide was reasonable. This new technique of SMPS offered significant savings not only in time but in many expensive reagents as well.
文摘Peptide analogs of salmon calcitonin (sCT) were synthesized by using Fmoc-based chemistry on MBHA resins Salmon calcitonin was modified by 1) cysteines at p0sitions 1 and 7 were replaced by valine and alanine respectively to result in open chain analogs. 2) the glycine at position 30 was replaced by alanine, D-alanine and sarcosine respectively, and 3) some residues were deleted besides the above two modifications. A modified two-step deprotection / cleavage procedure, in which a solvent of TFA / TMSBr / thioanisole / EDT / m-cresol combines with HF cleavage,was adopted in SPPS.
基金Supported by the National Outstanding Youth Science Fund Project(No.81202726)
文摘AIM: To draw a Meta-analysis over the comparison of the intraocular pressure(IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs(PGAs) monotherapy.·METHODS: After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials(RCTs) comparing the fixed combination of PGAs/timolol therapy(FCs) and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal IOP, percentage of participants whose IOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects,hyperemia and eye irritation. The analysis was carried out in Rev Man version 5.3 software.·RESULTS: After six-month medical intervention, the mean diurnal IOP of FCs was lower than PGAs(MD-1.14,95% CI-1.82 to-0.46, P =0.001); the percentage of target IOP achieving between FCs and PGAs showed no significant difference(RR 1.18, 95% CI 0.97 to 1.43, P =0.10).No statistically significant differences of the incidence of hyperemia(RR 0.67, 95% CI 0.45 to 1.01, P =0.06) and eye irritation(RR 1.20, 95% CI 0.95 to 1.51, P =0.12)between the FCs and PGAs monotherapy were detected.Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects(central endothelial cell density, MD-0.20, 95% CI-0.72 to 0.32, P =0.45; central corneal thickness, MD-0.01, 95% CI-0.02 to 0.00, P =0.23).The evaluation of visual field change was not performeddue to the limited duration of the trials included in this Meta-analysis.·CONCLUSION: The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant.More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted.
文摘Triple negative breast cancer (TNBC) is characterized by a high sensitivity to antiblastic drugs and a high pathological complete remission rate after neoadjuvant therapy. In patients showing complete remission, the probability of developing metastatic disease would seem to be reduced. Nonetheless, this cancer has a high percentage of relapse. Anthracyclines, taxanes and platinum compounds are the most effective drugs for the treatment of TNBC. There is substantial evidence to support the efficacy of platinum-based chemotherapy, probably attributable to the mechanism of action of such drugs, which react with the DNA repair system. PARP inhibitors would also seem to be very interesting. Despite promising results, TNBC remains a disease with a poor prognosis due to the lack of targeted therapy. The discovery of new targets and new agents is thus a high priority issue for this type of breast cancer. In this respect, lipoplatin has been identified as a potentially interesting treatment option to evaluate in both neoadjuvant and advanced settings.
文摘Natural product jacaranone, 1, and three analog derivatives were synthesized and their apoptotic and necrotic activity against four cancer cell lines was tested. One of these derivatives 7, was more active than the natural product, and exhibited an important necrotic effect against three of the cell lines tested (ovarian carcinoma, liver cancer and breast cancer cells). Derivative 6 was more active than the natural product, and showed a significant apoptotic activity against breast cancer and ovarian carcinoma cells. Some derivatives analyzed in this study showed promising anti-tumor results, nevertheless, further studies have to be done in order to determine their in vivo activity, their mechanism as well as their safety and stability.
基金PAPIIT/UNAM Projects No.IN200614 and IT202015 and project PIAPI VC02 for partially supporting this worka part of the Project Catedra:Diseno de Sustancias Bioactivas of FESC-UNAM-2012.
文摘A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives and amines can produce yields ranging from 50% to 85% of the resulting amide.
文摘A series of N-carbonyl-functionalized ureas, carbamates and thiocarbamates derivatives (or N-Chloro sulfonyl isocyanate “N-CSI”) were involved in linear and nonlinear physicochemical quantitative structure-activity relationship “QSAR” analysis to find out the structural keys to control the inhibition against Sterol O-Acyl-Transferase-1 “SOAT-1”. The results indicate the important effects of geometrical and chemical descriptors on the inhibitory activity of SOAT-1. The molecules were also screened for three-dimensional molecular docking on the crystal structure of ACAT-1 (1WL5 for ACAT-1, PDB). A comparison between 2D-QSAR and 3D molecular docking studies shows that the latter confirm the first results and represent a good prediction of the chemical and physical nature of interactions between our drug molecules and enzyme SOAT-1.
基金Supported by Russian Science Foundation,No.17-75-30052
文摘AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.
文摘6—O—Mcthylgossypol (3) was obtained with the methods of synthesis for the first time.For the purpose ofe一iminating some prob一ems assoeiatedwith the eliniea一use orgossypol such as irreversibility and hypokalemia,while retaining its pl飞armacologieally desirableantifertility effeets,numerous derivatives and
