This paper proposes a mixed game with finitely many leaders and follower populations.In such a game,two types of equilibria are defined.First,a Nash equilibrium is introduced for the scenario in which leaders and foll...This paper proposes a mixed game with finitely many leaders and follower populations.In such a game,two types of equilibria are defined.First,a Nash equilibrium is introduced for the scenario in which leaders and follower populations are in perfect competition,each maximizing its own payoff.Second,a cooperative equilibrium is proposed for the case where leaders and follower populations,respectively,form coalitions and cooperate.Moreover,the existence of both Nash and cooperative equilibria is proved under the condition that the payoff functions are continuous and quasi-concave.Finally,we demonstrate the generic stability of cooperative equilibria in mixed games.More concretely,in the sense of Baire category,the cooperative equilibria in most mixed games are stable under perturbations of the payoff functions.In short,this paper presents two main contributions.On the one hand,we provide a novel mixed-game framework,which differs from both classical leader-follower games and leader-follower population games.On the other hand,the Nash and cooperative equilibria in our mixed games are distinct from those in existing leader-follower population games.The results are further illustrated with examples.展开更多
BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the saf...BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.展开更多
Advancements in animal behavior quantification methods have driven the development of computational ethology,enabling fully automated behavior analysis.Existing multianimal pose estimation workflows rely on tracking-b...Advancements in animal behavior quantification methods have driven the development of computational ethology,enabling fully automated behavior analysis.Existing multianimal pose estimation workflows rely on tracking-bydetection frameworks for either bottom-up or top-down approaches,requiring retraining to accommodate diverse animal appearances.This study introduces InteBOMB,an integrated workflow that enhances top-down approaches by incorporating generic object tracking,eliminating the need for prior knowledge of target animals while maintaining broad generalizability.InteBOMB includes two key strategies for tracking and segmentation in laboratory environments and two techniques for pose estimation in natural settings.The“background enhancement”strategy optimizesforeground-backgroundcontrastiveloss,generating more discriminative correlation maps.The“online proofreading”strategy stores human-in-the-loop long-term memory and dynamic short-term memory,enabling adaptive updates to object visual features.The“automated labeling suggestion”technique reuses the visual features saved during tracking to identify representative frames for training set labeling.Additionally,the“joint behavior analysis”technique integrates these features with multimodal data,expanding the latent space for behavior classification and clustering.To evaluate the framework,six datasets of mice and six datasets of nonhuman primates were compiled,covering laboratory and natural scenes.Benchmarking results demonstrated a24%improvement in zero-shot generic tracking and a 21%enhancement in joint latent space performance across datasets,highlighting the effectiveness of this approach in robust,generalizable behavior analysis.展开更多
In the present study, we aimed to compare the efficacy and adherence of Runzhong;(generic drug, Chiatai Tianqing,Nanjing) and Baraclude;(branded drug, Bristol-Myers Squibb) in patients with chronic hepatitis B. We col...In the present study, we aimed to compare the efficacy and adherence of Runzhong;(generic drug, Chiatai Tianqing,Nanjing) and Baraclude;(branded drug, Bristol-Myers Squibb) in patients with chronic hepatitis B. We collected patient data from three hospitals within 48 weeks and compared the two groups by using the propensity-score matching method. A total of 4889 patients were enrolled in this study;503 initiated a brand-name drug, and 4386 received a generic drug. There was no significant difference in the rates of CVR(complete virologic response) and VB(virologic breakthrough) between the Runzhong;group and Baraclude;group at 24 and 48 weeks. Similar results for HBeAg loss, medication possession ratio(MPR), and biological response were obtained. Age, gender(HR 0.909(0.842–0.981)), normal baseline ALT rate(HR 0.789(0.731–0.851)), HBeAg-positive rate, and baseline undetectable HBV DNA rate(HR 0.306(0.234–0.399)) were independent factors for achieving CVR.展开更多
Attribute-based encryption is drawing more attention with its inherent attractive properties which are potential to be widely used in the newly developing cloud computing. However, one of the main obstacles for its ap...Attribute-based encryption is drawing more attention with its inherent attractive properties which are potential to be widely used in the newly developing cloud computing. However, one of the main obstacles for its application is how to revoke the attributes of the users, though some ABE schemes have realized revocation, they mostly focused on the user revocation that revokes the user＇s whole attributes, or attribute revocation under the indirect revocation model such that all the users＇ private keys will be affected by the revocation. In this paper, we define the model of CP-ABE supporting the attribute revocation under the direct revocation model, in which the revocation list is embed in the ciphertext and none of the users＇ private keys will be affected by the revocation process. Then we propose a generic construction, and prove its security with the decision q-BDHE assumption.展开更多
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved b...Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.展开更多
In this paper, we report the results of quality control based in pbysicochemical characteriza- tion and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were ...In this paper, we report the results of quality control based in pbysicochemical characteriza- tion and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were supplied by different pharmaceuticals companies. The sample A, as the discovered product, was supplied by Pfizer, while samples B and C （generics）, were manufactured by two different Indian industries. Solid-state characterization of the three samples was realized with different physicochemical methods as： X-ray powder diffraction, Fourier-transformation infrared spectroscopy, differential scanning calorimetry. High performance liquid chromatography was used to quantify the impurities in the different samples. The results from the physicochemical methods cited above, showed difference in polymorph structure of the three drug substances. Sample A consisted in pure polymorph II1, sample B consisted in pure polymorph I1, sample C consisted in a mixture of fluconazole Form Ili, form II and the monohydrate. This result was confirmed by differential scanning calorimetry. Also it was demonstrated that solvents used during the re-crystallization step were among the origins of these differences in the structure form. On the other hand, the result of the stability study under humidity and temperature showed that fluconazole polymorphic transformation could be owed to the no compliance with the conditions of storage. The HPLC analysis of these compounds showed the presence of specific展开更多
Perceptions of Chinese pharmacists towards generic drugs were evaluated by a cross-sectional study from Aug.2018 to Dec.2018.Online survey tool Sojump was adopted to release the questionnaires using convenience sampli...Perceptions of Chinese pharmacists towards generic drugs were evaluated by a cross-sectional study from Aug.2018 to Dec.2018.Online survey tool Sojump was adopted to release the questionnaires using convenience sampling.A total of 577 questionnaires by pharmacists were analyzed.A meaningful proportion of pharmacists expressed negative perceptions of generic drugs,such as perceiving generics as less effective,less safe and more likely to cause side effects compared to their branded equivalents.Educational campaigns that focus on misperceptions of generic drugs may be necessary.展开更多
Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and...Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and perception can promote the quality use of generic drugs.The objective of this study was to investigate the knowledge,attitudes,and perception of pharmacists from tertiary hospitals in China regarding generic drugs.Methods:A cross-sectional survey using a postal questionnaire was conducted,which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province.A total of 125 questionnaires out of 200 were received.Of the respondents,80 were female and 45 were male.Results:The majority of respondents(87.2%)could clearly distinguish between original and generic drugs.Pharmacists agreed that generic drugs were less effective(52.8%)and produced more side effects(52%).Forty-nine respondents thought that generic drug products were not adequately tested.Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases,respectively.Most of them supported the recommendation of generic drugs based on professional judgment.Conclusion:Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs.Interventions to improve pharmacists'knowledge of generic drugs are needed.展开更多
In the present study, the subcritical flow past a generic side mirror on a base plane is investigated at the Reynolds number of 5.2 × 10~5 using delayed detached eddy simulation(DDES) turbulence model. Asides fro...In the present study, the subcritical flow past a generic side mirror on a base plane is investigated at the Reynolds number of 5.2 × 10~5 using delayed detached eddy simulation(DDES) turbulence model. Asides from the capability of capturing main features of the large recirculation vortex in the wake of the side mirror and the front horseshoe vortex, the accuracy of DDES estimation of recirculation length is significantly increased by over20%, compared to the detached eddy simulation(DES) estimation using the same grid. And DDES prediction of pressure coefficient at the trailing edge of the mirror is in good agreement with the experiments, which is more accurate than both DES and large eddy simulation(LES) results. The results verify the capacity of DDES turbulence model to solve the turbulent flow around the side mirror. This is a key foundation for possible future study of full simulation of external flow field of vehicle.展开更多
In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic...In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation. Adult male Zucker diabetes fatty rats received Glucophage~? or the generic metformin through gastric gavage at a dose of 180 mg/kg(n = 6 per condition). Both pharmacokinetic parameters(AUC0–t, AUC0–∞, Cmax) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage~? or the generic metformin at doses of 180 and 300 mg·kg–1·d–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein(GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05. In single dosing experiments, pharmacokinetic parameters(t1/2, AUC0–t and Cmax) did not differ between Glucophage~? and the generic metformin(P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h(P = 0.03) and 4 h(P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage~? were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin(P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage~? group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage~?. However, Glucophage~? was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.展开更多
This paper presents a generalization of the authors＇ earlier work. In this paper, the two concepts, generic regular decomposition （GRD） and regular-decomposition-unstable （RDU） variety introduced in the authors＇...This paper presents a generalization of the authors＇ earlier work. In this paper, the two concepts, generic regular decomposition （GRD） and regular-decomposition-unstable （RDU） variety introduced in the authors＇ previous work for generic zero-dimensional systems, are extended to the case where the parametric systems are not necessarily zero-dimensional. An algorithm is provided to compute GRDs and the associated RDU varieties of parametric systems simultaneously on the basis of the algorithm for generic zero-dimensional systems proposed in the authors＇ previous work. Then the solutions of any parametric system can be represented by the solutions of finitely many regular systems and the decomposition is stable at any parameter value in the complement of the associated RDU variety of the parameter space. The related definitions and the results presented in the authors＇ previous work are also generalized and a further discussion on RDU varieties is given from an experimental point of view. The new algorithm has been implemented on the basis of DISCOVERER with Maple 16 and experimented with a number of benchmarks from the literature.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.11271098)the Guizhou Provincial Basic Research Program(Grant No.MS[2025]676)。
文摘This paper proposes a mixed game with finitely many leaders and follower populations.In such a game,two types of equilibria are defined.First,a Nash equilibrium is introduced for the scenario in which leaders and follower populations are in perfect competition,each maximizing its own payoff.Second,a cooperative equilibrium is proposed for the case where leaders and follower populations,respectively,form coalitions and cooperate.Moreover,the existence of both Nash and cooperative equilibria is proved under the condition that the payoff functions are continuous and quasi-concave.Finally,we demonstrate the generic stability of cooperative equilibria in mixed games.More concretely,in the sense of Baire category,the cooperative equilibria in most mixed games are stable under perturbations of the payoff functions.In short,this paper presents two main contributions.On the one hand,we provide a novel mixed-game framework,which differs from both classical leader-follower games and leader-follower population games.On the other hand,the Nash and cooperative equilibria in our mixed games are distinct from those in existing leader-follower population games.The results are further illustrated with examples.
文摘BACKGROUND Direct acting antivirals have revolutionized hepatitis C virus(HCV)treatment.However,the high price of the brand forms is a barrier for their use in resource limited countries as Egypt.AIM To assess the safety and efficacy of the generic sofosbuvir(SOF)/ledipasvir(LED)in Egyptian HCV-infected children and to compare the results with the brand form.METHODS This analytical retrospective study included HCV infected children and adolescents aged 12-18 years or weighing>35 kg.Collected data included:Age,sex,risk factors of HCV acquisition,comorbidities,liver functions,HCV viral load,degree of hepatic fibrosis,sustained virologic response(SVR)and frequency of treatment adverse effects.Patients who received the generic form of SOF/LED(Ledisbuvir)were compared to patients who received the brand form(Harvoni®)regarding SVR and frequency of adverse events.RESULTS The study included 43 patients who received Ledisbuvir and 73 who received Harvoni®.All patients achieved SVR.Treatment side effects were mild,transient and comparable in both groups.CONCLUSION The use of generic SOF/LED in HCV infected children is safe and effective.It is comparable to the brand form at a reduced price and represents an affordable and effective alternative.
基金supported by the STI 2030-Major Projects(2022ZD0211900,2022ZD0211902)STI 2030-Major Projects(2021ZD0204500,2021ZD0204503)+1 种基金National Natural Science Foundation of China(32171461)National Key Research and Development Program of China(2023YFC3208303)。
文摘Advancements in animal behavior quantification methods have driven the development of computational ethology,enabling fully automated behavior analysis.Existing multianimal pose estimation workflows rely on tracking-bydetection frameworks for either bottom-up or top-down approaches,requiring retraining to accommodate diverse animal appearances.This study introduces InteBOMB,an integrated workflow that enhances top-down approaches by incorporating generic object tracking,eliminating the need for prior knowledge of target animals while maintaining broad generalizability.InteBOMB includes two key strategies for tracking and segmentation in laboratory environments and two techniques for pose estimation in natural settings.The“background enhancement”strategy optimizesforeground-backgroundcontrastiveloss,generating more discriminative correlation maps.The“online proofreading”strategy stores human-in-the-loop long-term memory and dynamic short-term memory,enabling adaptive updates to object visual features.The“automated labeling suggestion”technique reuses the visual features saved during tracking to identify representative frames for training set labeling.Additionally,the“joint behavior analysis”technique integrates these features with multimodal data,expanding the latent space for behavior classification and clustering.To evaluate the framework,six datasets of mice and six datasets of nonhuman primates were compiled,covering laboratory and natural scenes.Benchmarking results demonstrated a24%improvement in zero-shot generic tracking and a 21%enhancement in joint latent space performance across datasets,highlighting the effectiveness of this approach in robust,generalizable behavior analysis.
基金Beijing Pharmacological Society and Science Foundation of Sichuan Education Department (Grant No. 18ZA0186)。
文摘In the present study, we aimed to compare the efficacy and adherence of Runzhong;(generic drug, Chiatai Tianqing,Nanjing) and Baraclude;(branded drug, Bristol-Myers Squibb) in patients with chronic hepatitis B. We collected patient data from three hospitals within 48 weeks and compared the two groups by using the propensity-score matching method. A total of 4889 patients were enrolled in this study;503 initiated a brand-name drug, and 4386 received a generic drug. There was no significant difference in the rates of CVR(complete virologic response) and VB(virologic breakthrough) between the Runzhong;group and Baraclude;group at 24 and 48 weeks. Similar results for HBeAg loss, medication possession ratio(MPR), and biological response were obtained. Age, gender(HR 0.909(0.842–0.981)), normal baseline ALT rate(HR 0.789(0.731–0.851)), HBeAg-positive rate, and baseline undetectable HBV DNA rate(HR 0.306(0.234–0.399)) were independent factors for achieving CVR.
文摘Attribute-based encryption is drawing more attention with its inherent attractive properties which are potential to be widely used in the newly developing cloud computing. However, one of the main obstacles for its application is how to revoke the attributes of the users, though some ABE schemes have realized revocation, they mostly focused on the user revocation that revokes the user＇s whole attributes, or attribute revocation under the indirect revocation model such that all the users＇ private keys will be affected by the revocation. In this paper, we define the model of CP-ABE supporting the attribute revocation under the direct revocation model, in which the revocation list is embed in the ciphertext and none of the users＇ private keys will be affected by the revocation process. Then we propose a generic construction, and prove its security with the decision q-BDHE assumption.
文摘Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.
文摘In this paper, we report the results of quality control based in pbysicochemical characteriza- tion and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were supplied by different pharmaceuticals companies. The sample A, as the discovered product, was supplied by Pfizer, while samples B and C （generics）, were manufactured by two different Indian industries. Solid-state characterization of the three samples was realized with different physicochemical methods as： X-ray powder diffraction, Fourier-transformation infrared spectroscopy, differential scanning calorimetry. High performance liquid chromatography was used to quantify the impurities in the different samples. The results from the physicochemical methods cited above, showed difference in polymorph structure of the three drug substances. Sample A consisted in pure polymorph II1, sample B consisted in pure polymorph I1, sample C consisted in a mixture of fluconazole Form Ili, form II and the monohydrate. This result was confirmed by differential scanning calorimetry. Also it was demonstrated that solvents used during the re-crystallization step were among the origins of these differences in the structure form. On the other hand, the result of the stability study under humidity and temperature showed that fluconazole polymorphic transformation could be owed to the no compliance with the conditions of storage. The HPLC analysis of these compounds showed the presence of specific
文摘Perceptions of Chinese pharmacists towards generic drugs were evaluated by a cross-sectional study from Aug.2018 to Dec.2018.Online survey tool Sojump was adopted to release the questionnaires using convenience sampling.A total of 577 questionnaires by pharmacists were analyzed.A meaningful proportion of pharmacists expressed negative perceptions of generic drugs,such as perceiving generics as less effective,less safe and more likely to cause side effects compared to their branded equivalents.Educational campaigns that focus on misperceptions of generic drugs may be necessary.
基金supported by the National Natural Science Foundation of China(No.71373089).
文摘Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and perception can promote the quality use of generic drugs.The objective of this study was to investigate the knowledge,attitudes,and perception of pharmacists from tertiary hospitals in China regarding generic drugs.Methods:A cross-sectional survey using a postal questionnaire was conducted,which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province.A total of 125 questionnaires out of 200 were received.Of the respondents,80 were female and 45 were male.Results:The majority of respondents(87.2%)could clearly distinguish between original and generic drugs.Pharmacists agreed that generic drugs were less effective(52.8%)and produced more side effects(52%).Forty-nine respondents thought that generic drug products were not adequately tested.Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases,respectively.Most of them supported the recommendation of generic drugs based on professional judgment.Conclusion:Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs.Interventions to improve pharmacists'knowledge of generic drugs are needed.
基金the National Key Research and Development Plan of China(No.2016YFB0101601-7)the Science Foundation of Chinese Academy of Sciences(No.51175214)the Special Planning Project of Jilin Province(No.SXGJSF2017-2-1-5)
文摘In the present study, the subcritical flow past a generic side mirror on a base plane is investigated at the Reynolds number of 5.2 × 10~5 using delayed detached eddy simulation(DDES) turbulence model. Asides from the capability of capturing main features of the large recirculation vortex in the wake of the side mirror and the front horseshoe vortex, the accuracy of DDES estimation of recirculation length is significantly increased by over20%, compared to the detached eddy simulation(DES) estimation using the same grid. And DDES prediction of pressure coefficient at the trailing edge of the mirror is in good agreement with the experiments, which is more accurate than both DES and large eddy simulation(LES) results. The results verify the capacity of DDES turbulence model to solve the turbulent flow around the side mirror. This is a key foundation for possible future study of full simulation of external flow field of vehicle.
基金The National Key Development Plan for Precision Medicine Research(Grant No.2017YFC0910004)Jinan Science Project(Grant No.201602171)
文摘In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage~? and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation. Adult male Zucker diabetes fatty rats received Glucophage~? or the generic metformin through gastric gavage at a dose of 180 mg/kg(n = 6 per condition). Both pharmacokinetic parameters(AUC0–t, AUC0–∞, Cmax) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage~? or the generic metformin at doses of 180 and 300 mg·kg–1·d–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein(GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05. In single dosing experiments, pharmacokinetic parameters(t1/2, AUC0–t and Cmax) did not differ between Glucophage~? and the generic metformin(P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h(P = 0.03) and 4 h(P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage~? were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin(P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage~? group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage~?. However, Glucophage~? was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.
基金supported by by the National Natural Science Foundation of China under Grant Nos.11271034,11290141the Project SYSKF1207 from SKLCS,IOS,the Chinese Academy of Sciences
文摘This paper presents a generalization of the authors＇ earlier work. In this paper, the two concepts, generic regular decomposition （GRD） and regular-decomposition-unstable （RDU） variety introduced in the authors＇ previous work for generic zero-dimensional systems, are extended to the case where the parametric systems are not necessarily zero-dimensional. An algorithm is provided to compute GRDs and the associated RDU varieties of parametric systems simultaneously on the basis of the algorithm for generic zero-dimensional systems proposed in the authors＇ previous work. Then the solutions of any parametric system can be represented by the solutions of finitely many regular systems and the decomposition is stable at any parameter value in the complement of the associated RDU variety of the parameter space. The related definitions and the results presented in the authors＇ previous work are also generalized and a further discussion on RDU varieties is given from an experimental point of view. The new algorithm has been implemented on the basis of DISCOVERER with Maple 16 and experimented with a number of benchmarks from the literature.
