BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not bee...BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.展开更多
The flotation separation of chalcopyrite and talc is challenging due to their similar natural floatability characteristics.Besides,it is usually difficult to effectively inhibit talc by adding sodium carboxymethyl cel...The flotation separation of chalcopyrite and talc is challenging due to their similar natural floatability characteristics.Besides,it is usually difficult to effectively inhibit talc by adding sodium carboxymethyl cellulose(CMC)alone during chalcopyrite flotation.Here,a combined inhibitor comprising acidified sodium silicate(ASS)and CMC was employed to realize effective flotation separation of chalcopyrite and talc,and the combined inhibition mechanism was further investigated.Microflotation results showed that adding ASS strengthened the inhibitory effect of CMC on talc and improved the separation of chalcopyrite and talc.The zeta potential,Fourier transform infrared,and X-ray photoelectron spectroscopy analysis indicated that CMC was mainly adsorbed on the talc surface via hydroxyl and carboxyl groups.Moreover,the addition of ASS improved the adsorption of carboxyl groups.Furthermore,the adsorption experiments and apparent viscosity measurements revealed that adding ASS dispersed the pulp well,which reduced the apparent viscosity,improved the adsorption amount of CMC on the talc surface,and enhanced the inhibition of talc in chalcopyrite flotation.展开更多
The effects of bleomycin A5 (BLM A5) alone and combined with calmodulin inhibitor N-(4-aminobutyl)-5-chloro-2-naphthalene sulfonamide (W-13) on the proliferation on S-180 cells in vitro were studied. IC50 of BLM used ...The effects of bleomycin A5 (BLM A5) alone and combined with calmodulin inhibitor N-(4-aminobutyl)-5-chloro-2-naphthalene sulfonamide (W-13) on the proliferation on S-180 cells in vitro were studied. IC50 of BLM used alone for the cells was about 2.63 μg/ml, but it was reduced to 1/3.8 and 1/9.5 of 2.63 μg/ml when plus W-13 1, 5 μg/ml respectively. The results indicated that nontoxic doses of W-13 enhanced the hinibition of cell proliferation under the condition of BLM 0.5 - 2.5 μg/ ml. In colony forming test, the survival fraction of S-180 cells treated with BLM plus W-13 was decreased to 1/87 - 240 of that of the cells treated with BLM alone. The results suggest that W-13 can enhance antitumor activity of BLM in vitro and may be used as an synergist of BLM A5 in vivo.展开更多
In oil and gas field, the application of kinetic hydrate inhibitors (KHIs) independently has remained problematic in high subcooling and high water-cut situation. One feasible method to resolve this problem is the c...In oil and gas field, the application of kinetic hydrate inhibitors (KHIs) independently has remained problematic in high subcooling and high water-cut situation. One feasible method to resolve this problem is the combined use of KHIs and some synergists, which would enhance KHIs’ inhibitory effect on both hydrate nucleation and hydrate crystal growth. In this study, a novel kind of KHI copolymer poly(N-vinyl-2-pyrrolidone-co-2-vinyl pyridine)s (HGs) is used in conjunction with TBAB to show its high performance on hydrate inhibition. The performance of HGs with different monomer ratios in structure II tetrahydrofuran (THF) hydrate is investigated using kinetic hydrate inhibitor evaluation apparatus by step-cooling method and isothermal cooling method. With the combined gas hydrate inhibitor at the concentration of 1.0 wt%, the induction time of 19 wt% THF solution could be prolonged to 8.5 h at a high subcooling of 6℃. Finally, the mechanism of HGs inhibiting the formation of gas hydrate is proposed.展开更多
For patients with chronic myeloid leukemia(CML) failing imatinib therapy,second-generation tyrosine kinase inhibitors(TKIs) are recommended.Here,we describe two patients with advanced CML who failed imatinib thera...For patients with chronic myeloid leukemia(CML) failing imatinib therapy,second-generation tyrosine kinase inhibitors(TKIs) are recommended.Here,we describe two patients with advanced CML who failed imatinib therapy and did not tolerate the recommended dose of dasatinib,but then achieved a major molecular response with the combination of imatinib and dasatinib with no significant extramedullar/ toxicity.Our observations suggest that combination of TKIs may provide an additive/synergistic antileukemic effect.展开更多
Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 ...Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.展开更多
基金supported by the China Cardiovascular Health Alliance-Advanced Fund (2019CCA-ACCESS-054)the Beijing Lisheng Cardiovascular Health Foundation Pilot Fund Key Projects。
文摘BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.
基金financially supported by the National Natural Science Foundation of China (Nos.52104266 and 52074206)Open Foundation of State Key Laboratory of Mineral Processing (No.BGRIMM-KJSKL-2021-19)+2 种基金the Natural Science Basic Research Program of Shaanxi Province (No.2021JQ-507)the Natural Science Project of Shaanxi Education Department (No.21JK0731)Key Research and Development Projects of Anhui Province (No.202104a07020012)。
文摘The flotation separation of chalcopyrite and talc is challenging due to their similar natural floatability characteristics.Besides,it is usually difficult to effectively inhibit talc by adding sodium carboxymethyl cellulose(CMC)alone during chalcopyrite flotation.Here,a combined inhibitor comprising acidified sodium silicate(ASS)and CMC was employed to realize effective flotation separation of chalcopyrite and talc,and the combined inhibition mechanism was further investigated.Microflotation results showed that adding ASS strengthened the inhibitory effect of CMC on talc and improved the separation of chalcopyrite and talc.The zeta potential,Fourier transform infrared,and X-ray photoelectron spectroscopy analysis indicated that CMC was mainly adsorbed on the talc surface via hydroxyl and carboxyl groups.Moreover,the addition of ASS improved the adsorption of carboxyl groups.Furthermore,the adsorption experiments and apparent viscosity measurements revealed that adding ASS dispersed the pulp well,which reduced the apparent viscosity,improved the adsorption amount of CMC on the talc surface,and enhanced the inhibition of talc in chalcopyrite flotation.
文摘The effects of bleomycin A5 (BLM A5) alone and combined with calmodulin inhibitor N-(4-aminobutyl)-5-chloro-2-naphthalene sulfonamide (W-13) on the proliferation on S-180 cells in vitro were studied. IC50 of BLM used alone for the cells was about 2.63 μg/ml, but it was reduced to 1/3.8 and 1/9.5 of 2.63 μg/ml when plus W-13 1, 5 μg/ml respectively. The results indicated that nontoxic doses of W-13 enhanced the hinibition of cell proliferation under the condition of BLM 0.5 - 2.5 μg/ ml. In colony forming test, the survival fraction of S-180 cells treated with BLM plus W-13 was decreased to 1/87 - 240 of that of the cells treated with BLM alone. The results suggest that W-13 can enhance antitumor activity of BLM in vitro and may be used as an synergist of BLM A5 in vivo.
基金supported by the National Basic Research Program of China ("973" Program) (Grant No. 2009CB219504-03)the National Natural Science Foundation of China (Grant No 51106054)the Colleges and Universities High-level Talents Program of Guangdong
文摘In oil and gas field, the application of kinetic hydrate inhibitors (KHIs) independently has remained problematic in high subcooling and high water-cut situation. One feasible method to resolve this problem is the combined use of KHIs and some synergists, which would enhance KHIs’ inhibitory effect on both hydrate nucleation and hydrate crystal growth. In this study, a novel kind of KHI copolymer poly(N-vinyl-2-pyrrolidone-co-2-vinyl pyridine)s (HGs) is used in conjunction with TBAB to show its high performance on hydrate inhibition. The performance of HGs with different monomer ratios in structure II tetrahydrofuran (THF) hydrate is investigated using kinetic hydrate inhibitor evaluation apparatus by step-cooling method and isothermal cooling method. With the combined gas hydrate inhibitor at the concentration of 1.0 wt%, the induction time of 19 wt% THF solution could be prolonged to 8.5 h at a high subcooling of 6℃. Finally, the mechanism of HGs inhibiting the formation of gas hydrate is proposed.
基金supported by the National Natural Science Foundation of the People's Republic of China(No.81070437,81270614 and 81300379)the National Science & Technology Pillar Program of China(No.2008BAI61B01)
文摘For patients with chronic myeloid leukemia(CML) failing imatinib therapy,second-generation tyrosine kinase inhibitors(TKIs) are recommended.Here,we describe two patients with advanced CML who failed imatinib therapy and did not tolerate the recommended dose of dasatinib,but then achieved a major molecular response with the combination of imatinib and dasatinib with no significant extramedullar/ toxicity.Our observations suggest that combination of TKIs may provide an additive/synergistic antileukemic effect.
基金This research was supported by the National Natural Science Foundation of China(81430083,81903462 and 82073703)the China Postdoctoral Science Foundation(2018M641694)the Fundamental Research Funds for the Central Universities(DUT20LK28 and DUT20YG133).
文摘Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.