Cotton(Gossypium spp.)is a pivotal crop in the global textile industry,providing essential natural fibers.Additionally,cottonseed offers significant value as a source of oil and as feed for livestock(Huang et al.2021;...Cotton(Gossypium spp.)is a pivotal crop in the global textile industry,providing essential natural fibers.Additionally,cottonseed offers significant value as a source of oil and as feed for livestock(Huang et al.2021;Wen et al.2023).The sector,dependent on cotton,features a comprehensive value chain extending from the processing of fibers to the production of finished textiles,and it employs tens of millions of individuals(Dorward et al.1970).展开更多
On March 3,2024,the prototype permeability logging instrument independently developed in China successfully completed its first downhole test in Ren 91 standard well in PetroChina Huabei Oilfield.In the open hole sect...On March 3,2024,the prototype permeability logging instrument independently developed in China successfully completed its first downhole test in Ren 91 standard well in PetroChina Huabei Oilfield.In the open hole section at a depth of 3925 metres and at a temperature of 148℃,the device collected high-quality permeability logging data.This marks a key technological breakthrough from 0 to 1 in permeability logging,and lays the foundation for the next step in developing a complete set of permeability logging equipment.展开更多
Purpose:To address the“anomalies”that occur when scientific breakthroughs emerge,this study focuses on identifying early signs and nascent stages of breakthrough innovations from the perspective of outliers,aiming t...Purpose:To address the“anomalies”that occur when scientific breakthroughs emerge,this study focuses on identifying early signs and nascent stages of breakthrough innovations from the perspective of outliers,aiming to achieve early identification of scientific breakthroughs in papers.Design/methodology/approach:This study utilizes semantic technology to extract research entities from the titles and abstracts of papers to represent each paper’s research content.Outlier detection methods are then employed to measure and analyze the anomalies in breakthrough papers during their early stages.The development and evolution process are traced using literature time tags.Finally,a case study is conducted using the key publications of the 2021 Nobel Prize laureates in Physiology or Medicine.Findings:Through manual analysis of all identified outlier papers,the effectiveness of the proposed method for early identifying potential scientific breakthroughs is verified.Research limitations:The study’s applicability has only been empirically tested in the biomedical field.More data from various fields are needed to validate the robustness and generalizability of the method.Practical implications:This study provides a valuable supplement to current methods for early identification of scientific breakthroughs,effectively supporting technological intelligence decision-making and services.Originality/value:The study introduces a novel approach to early identification of scientific breakthroughs by leveraging outlier analysis of research entities,offering a more sensitive,precise,and fine-grained alternative method compared to traditional citation-based evaluations,which enhances the ability to identify nascent breakthrough innovations.展开更多
Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identif...Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.展开更多
On August 28,salmon industry insiders and consumers shared insights and analysis on the salmon market and consumption at the 7th Global Salmon Industry Development Summit.An important component of the 18th Shanghai In...On August 28,salmon industry insiders and consumers shared insights and analysis on the salmon market and consumption at the 7th Global Salmon Industry Development Summit.An important component of the 18th Shanghai International Fisheries Expo,the event attracted more than100 salmon farming companies from around the globe to exchange views on the current situation and future development of the industry.展开更多
Facing dual challenges of climate change and energy crisis,the global iron and steel industry has been seeking to balance efficiency with energy conservation and environmental protection.Could the realities of blast f...Facing dual challenges of climate change and energy crisis,the global iron and steel industry has been seeking to balance efficiency with energy conservation and environmental protection.Could the realities of blast furnace operation possibly align with low-carbon circular development within China's iron and steel industry?Hydrogen-rich carbon circulating oxygen blast furnace (HyCROF)technology is gaining traction in the Chinese metallurgical industry.展开更多
The breakthrough of key core technology is a theoretical and practical strategic issue to realize the rise of the country.This paper analyzes the concept of key core technology and its breakthrough and analyzes its ch...The breakthrough of key core technology is a theoretical and practical strategic issue to realize the rise of the country.This paper analyzes the concept of key core technology and its breakthrough and analyzes its characteristics.Based on the perspective of participants,this paper summarizes the influencing factors of key core technology breakthroughs in enterprises:internal and external enterprises,universities and scientific research institutions,and government.This paper expands the relevant research on key core technology breakthroughs and provides inspiration for enterprises to carry out key core technology research and breakthrough practices.展开更多
Objective To analyze the characteristics of breakthrough therapy designation(BTD)and its implementation in China,and to provide reference for the optimization of BTD system.Methods A comparative research method was us...Objective To analyze the characteristics of breakthrough therapy designation(BTD)and its implementation in China,and to provide reference for the optimization of BTD system.Methods A comparative research method was used to study the content and implementation effect of BTD system in China and the relevant policies and implementation of the same procedures of drug regulatory authorities in the United States,Japan and the European Union.Then,the differences in policies and implementation results among these countries were analyzed to provide suggestions for the implementation and optimization of this system in China.Results and Conclusion China’s BTD system is implemented late and a small number of drugs has been approved.At the same time,there are problems such as insufficient guidance and communication from the agency to applicants,a broad application condition,single review mode,and lack of full-time personnel.Both the agencies and the applicants have limited experience due to the short implementation time of BTD system in China.There are still some problems despite we have learned a lot from the experience of other drug regulatory agencies.Therefore,based on our national conditions,we should strengthen the guidance of evaluation agency to applicants,optimize the eligibility criteria of BTD system,introduce the rolling review,and increase the number of professional liaisons,which can accelerate the development and marketing process of drugs with obvious clinical value,and finally to address unmet medical need.展开更多
AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had ...AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.展开更多
Scaled physical model tests for steam breakthrough were conducted based on the analysis of mechanisms and influence factors of steam breakthrough. Physical simulation results showed that at the initial steam breakthro...Scaled physical model tests for steam breakthrough were conducted based on the analysis of mechanisms and influence factors of steam breakthrough. Physical simulation results showed that at the initial steam breakthrough, preferential flow channels were formed in narrow sand packs and most residual oil left in these channels was immobile. This shortened the steam breakthrough time of follow-up steam flooding and decreased the increment of oil recovery efficiency. Steam breakthrough occurred easily for a smaller producer-injector spacing, and a bigger difference in physical properties between fluids and rock. Steam breakthrough is more likely to occur at a larger formation permeability (k), greater steam displacement velocity (u) and smaller producer-injector spacing (L). Steam breakthrough time is a function of the parameter group (uk/L), i.e. tb=3.2151 (uk/L)^-0.5142. A non piston-like displacement model was built based on steam breakthrough observation for a steam stimulated well in the Jinglou Oilfield, Henan Oilfield Company. The steam volume swept in different directions could be obtained from inter-well permeability capacity and breakthrough angle, and the steam swept pore volume (SSPV) was also determined. Numerical simulation showed that steam sweep efficiency reached its peak value when a slug of profile control agent (slug size 10%-15% SSPV) was set at one half of the inter-well spacing. Field test with 12.5% SSPV of profile control agents in the Jinglou Oilfield achieved success in sealing breakthrough channels and good production performance of adjacent producers.展开更多
Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the...Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the lesion is subject to hemorrhage,a phenomenon termed normal perfusion pressure breakthrough(NPPB) syndrome.According to this theory,arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure.Acutely after removal of a cerebral AVM,excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed.However,this theory remains controversial.We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.展开更多
AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS...AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB.RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3±2.6 vs 3.8±3.4 mo,P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03).CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment,compared to baseline ones, might be a predictor of risk for VB.展开更多
It is well known that the complicated channeling of fluid flow and heat transfer is strongly related with the intricate natural fracture system.However,it is still challenging to set up the fracture network model whic...It is well known that the complicated channeling of fluid flow and heat transfer is strongly related with the intricate natural fracture system.However,it is still challenging to set up the fracture network model which is strong heterogeneous.Compared with other methods(e.g.equivalent continuum model(ECM),discrete fracture model(DFM),and ECM-DFM),the fracture flow module in the COMSOL Multiphysics simulator is powerful in definition of fractures as the inner flow boundary existing in the porous media.Thus it is selected to simulate the fluid flow and heat transfer in the geothermal-developed fractured granite of Sanguliu area located at Liaodong Peninsula,Eastern China.The natural faults/fractures based on field investigation combined with the discrete fracture network(DFN)generated by the MATLAB are used to represent the two-dimensional geological model.Numerical results show that early thermal breakthrough occurs at the production well caused by quick flow of cold water along the highly connected fractures.Suitable hydraulic fracturing treatments with proper injection rates,locations,etc.can efficiently hinder the thermal breakthrough time in the natural fracture system.Large well spacing helps the long-term operation of geothermal production,but it is highly dependent on the geometrical morphology of the fracture network.The enhancement of reservoir properties at the near-well regions can also increase the geothermal production efficiency.The results in this study can provide references to achieve a sustainable geothermal exploitation in fractured granitic geothermal reservoirs or hot dry rocks at depth.展开更多
Based on exploration and development results and evaluation of marine shale gas in South China in the past ten years, in view of the features of "high maturity, strong tectonic reformation and high shear stress&q...Based on exploration and development results and evaluation of marine shale gas in South China in the past ten years, in view of the features of "high maturity, strong tectonic reformation and high shear stress" of the shale in Zhaotong exploration zone in the Yunnan and Guizhou Plateau, as well as the key issues of long time diffusion and leakage of shallow shale gas, and the preservation conditions, the factors controlling shallow shale gas sweet spot and key zone selection evaluation technology of shale gas are investigated. From 2017 to 2018, the first significant exploration breakthrough was made in the Taiyang anticline at a buried depth of 700 to 2 000 m, discovering large-scale proved geological reserves of shallow shale gas. By examining the accumulation conditions and sweet spot control factors of the shallow shale gas in this area, it is found that the accumulation and productivity potential of shale gas in the mountainous area with complex structure outside basin are controlled by five factors:(1) The gas-rich area has weak tectonic reformation and good preservation conditions on the whole, taking on typical anticline trap occurrence mode.(2) The gas-rich area is in over-pressure state and high in shale gas content.(3) The gas-rich area has high quality shale and thus superior source rock condition.(4) The gas-rich area has high quality reservoirs dominated by class I.(5) The shale gas reservoir in the gas-rich area has high content of brittle minerals and small difference between maximum and minimum horizontal stresses which are conducive to hydraulic fracturing. The innovative practice and core technologies formed during the exploration and production capacity construction of shallow shale gas in the Zhaotong demonstration zone have great reference significance for shallow shale gas exploration and development in other areas.展开更多
Dimensional analysis and numerical simulations were carried out to research prediction method of breakthrough time of horizontal wells in bottom water reservoir. Four dimensionless independent variables and dimensionl...Dimensional analysis and numerical simulations were carried out to research prediction method of breakthrough time of horizontal wells in bottom water reservoir. Four dimensionless independent variables and dimensionless time were derived from 10 influencing factors of the problem by using dimensional analysis. Simulations of horizontal well in reservoir with bottom water were run to find the prediction correlation. A general and concise functional relationship for predicting breakthrough time was established based on simulation results and theoretical analysis. The breakthrough time of one conceptual model predicted by the correlation is very close to the result by Eclipse with less than 2% error. The practical breakthrough time of one well in Helder oilfield is 10 d, and the predicted results by the method is 11.2 d, which is more accurate than the analytical result. Case study indicates that the method could predict breakthrough time of horizontal well under different reservoir conditions accurately. For its university and ease of use, the method is suitable for quick prediction of breakthrough time.展开更多
The regeneration of a spent packing is crucial with respect to the development of circular economy and abstemious society.Thus,the effects of regeneration temperature,resistant time,heating rate,and regeneration cycle...The regeneration of a spent packing is crucial with respect to the development of circular economy and abstemious society.Thus,the effects of regeneration temperature,resistant time,heating rate,and regeneration cycle on the breakthrough performance of methylene blue(MB)dye⁃exhausted ceramsite in a two⁃stage fixed⁃bed column were studied in this work.Results illustrate that the ceramsite exhibited excellent potential regeneration properties under the following optimal regeneration conditions:treatment temperature was 600°C,resistant time was 15 min,heating rate was 20℃/min,regeneration cycle was over 9 cycles,and the breakthrough time,saturation time,regeneration efficiency(RE),and regeneration loss rate(RLR)were 540 min,1020 min,64.61%,and 17.73%,respectively.The RE declined by 35.14%in over 1 cycle,while the RLR increased by 3.15 times in over 9 cycles.Besides,Thomas model was suitable to describe the two⁃stage fixed⁃bed column adsorption and thermal regeneration process with R2=0.978.In conclusion,a thorough understanding of the regeneration behavior of the two⁃stage fixed⁃bed column packed with ceramsite provides reference to obtain an effective and feasible regeneration approach,and it is beneficial for further application in water treatment.展开更多
The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can r...The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can regrow to normal size even after resection of 90%of the liver volume because of its strong regeneration ability2.Changes in diet,viral infection(HBV and/or HCV)。展开更多
Objective To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.Methods The isolation and culture of human endometrial endothelial cells(HEECs)was performed with t...Objective To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.Methods The isolation and culture of human endometrial endothelial cells(HEECs)was performed with the method established in our laboratory.The content and activity of urokinase-type plasminogen activator(uPA)and the content of plasminogen activator inhibitor-1(PAI-1)in cell supernatants after incubated with different concentrations of progesterone(0-5 μmol/L)and 17β-estradiol(0,0.1,or 1 nmol/L)were measured by method of ELISA.Apoptosis rate of HEECs was measured by flow cytometry.Viable cell count was measured by MTT.Results The increased level of progesterone(0.5-5 μmol/L)combined with 17β-estradiol elevated content and activity of uPA while the production of PAI-1 remained unchanged.The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher concentrations of progesterone with 17β-estradiol.Conclusion The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent.展开更多
In recent years,U.S.tight oil exploration and development have achieved significant progress,with rapidly increasing production,which has significantly changed the U.S.A.energy supply pattern(Fig.1).Compared with th...In recent years,U.S.tight oil exploration and development have achieved significant progress,with rapidly increasing production,which has significantly changed the U.S.A.energy supply pattern(Fig.1).Compared with the North American marine to marginal marine-continental transitional facies,China’s tight oil(Fig.1)展开更多
Lacustrine shale oil resources are abundant in many petroliferous basins in China.The shale oil formations are characterized by low API gravity,high viscosity,poor mobility,high clay content,low brittleness and etc.Ex...Lacustrine shale oil resources are abundant in many petroliferous basins in China.The shale oil formations are characterized by low API gravity,high viscosity,poor mobility,high clay content,low brittleness and etc.Exploration of lacustrine shale oil started relatively late in China,but its progress is very rapid and breakthroughs have been made successively.In this short communication,we introduced the most significant shale oil discovery which is made recently in the Qingshankou Formation of the Gulong sag in the Songliao Basin.Key exploratory wells including Guye 1H(GY1H),Yingye 1H(YY1H)and Guye 2HC(GY2HC)tested stable and high oil flow in shale reservoirs,revealing the relatively stable and high oil production capacity of shale in the Gulong sag of Daqing Oilfield.It marks a leap of petroleum theoretical recognition from lacustrine shale generating oil to producing oil and from the theory of traditional oil migration and accumulation to the theory of indigenous oil accumulation in organic-rich shale.Although lacustrine shale oil exploration and development still faces many challenges in China,its prospect is quite promising.展开更多
文摘Cotton(Gossypium spp.)is a pivotal crop in the global textile industry,providing essential natural fibers.Additionally,cottonseed offers significant value as a source of oil and as feed for livestock(Huang et al.2021;Wen et al.2023).The sector,dependent on cotton,features a comprehensive value chain extending from the processing of fibers to the production of finished textiles,and it employs tens of millions of individuals(Dorward et al.1970).
文摘On March 3,2024,the prototype permeability logging instrument independently developed in China successfully completed its first downhole test in Ren 91 standard well in PetroChina Huabei Oilfield.In the open hole section at a depth of 3925 metres and at a temperature of 148℃,the device collected high-quality permeability logging data.This marks a key technological breakthrough from 0 to 1 in permeability logging,and lays the foundation for the next step in developing a complete set of permeability logging equipment.
基金supported by the major project of the National Social Science Foundation of China“Big Data-driven Semantic Evaluation System of Science and Technology Literature”(Grant No.21&ZD329)。
文摘Purpose:To address the“anomalies”that occur when scientific breakthroughs emerge,this study focuses on identifying early signs and nascent stages of breakthrough innovations from the perspective of outliers,aiming to achieve early identification of scientific breakthroughs in papers.Design/methodology/approach:This study utilizes semantic technology to extract research entities from the titles and abstracts of papers to represent each paper’s research content.Outlier detection methods are then employed to measure and analyze the anomalies in breakthrough papers during their early stages.The development and evolution process are traced using literature time tags.Finally,a case study is conducted using the key publications of the 2021 Nobel Prize laureates in Physiology or Medicine.Findings:Through manual analysis of all identified outlier papers,the effectiveness of the proposed method for early identifying potential scientific breakthroughs is verified.Research limitations:The study’s applicability has only been empirically tested in the biomedical field.More data from various fields are needed to validate the robustness and generalizability of the method.Practical implications:This study provides a valuable supplement to current methods for early identification of scientific breakthroughs,effectively supporting technological intelligence decision-making and services.Originality/value:The study introduces a novel approach to early identification of scientific breakthroughs by leveraging outlier analysis of research entities,offering a more sensitive,precise,and fine-grained alternative method compared to traditional citation-based evaluations,which enhances the ability to identify nascent breakthrough innovations.
基金Supported by National Key Research and Development Program of China,No.2022YFE0209900.
文摘Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.
文摘On August 28,salmon industry insiders and consumers shared insights and analysis on the salmon market and consumption at the 7th Global Salmon Industry Development Summit.An important component of the 18th Shanghai International Fisheries Expo,the event attracted more than100 salmon farming companies from around the globe to exchange views on the current situation and future development of the industry.
文摘Facing dual challenges of climate change and energy crisis,the global iron and steel industry has been seeking to balance efficiency with energy conservation and environmental protection.Could the realities of blast furnace operation possibly align with low-carbon circular development within China's iron and steel industry?Hydrogen-rich carbon circulating oxygen blast furnace (HyCROF)technology is gaining traction in the Chinese metallurgical industry.
文摘The breakthrough of key core technology is a theoretical and practical strategic issue to realize the rise of the country.This paper analyzes the concept of key core technology and its breakthrough and analyzes its characteristics.Based on the perspective of participants,this paper summarizes the influencing factors of key core technology breakthroughs in enterprises:internal and external enterprises,universities and scientific research institutions,and government.This paper expands the relevant research on key core technology breakthroughs and provides inspiration for enterprises to carry out key core technology research and breakthrough practices.
基金Special Fund for Academy of Pharmaceutical Regulatory Sciences of Research Base for Drug Regulatory Science of National Medical Products Administration-Shenyang Pharmaceutical University(2021jgkx004).
文摘Objective To analyze the characteristics of breakthrough therapy designation(BTD)and its implementation in China,and to provide reference for the optimization of BTD system.Methods A comparative research method was used to study the content and implementation effect of BTD system in China and the relevant policies and implementation of the same procedures of drug regulatory authorities in the United States,Japan and the European Union.Then,the differences in policies and implementation results among these countries were analyzed to provide suggestions for the implementation and optimization of this system in China.Results and Conclusion China’s BTD system is implemented late and a small number of drugs has been approved.At the same time,there are problems such as insufficient guidance and communication from the agency to applicants,a broad application condition,single review mode,and lack of full-time personnel.Both the agencies and the applicants have limited experience due to the short implementation time of BTD system in China.There are still some problems despite we have learned a lot from the experience of other drug regulatory agencies.Therefore,based on our national conditions,we should strengthen the guidance of evaluation agency to applicants,optimize the eligibility criteria of BTD system,introduce the rolling review,and increase the number of professional liaisons,which can accelerate the development and marketing process of drugs with obvious clinical value,and finally to address unmet medical need.
基金Supported by the research grant of the Chungbuk National University in 2004
文摘AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.
文摘Scaled physical model tests for steam breakthrough were conducted based on the analysis of mechanisms and influence factors of steam breakthrough. Physical simulation results showed that at the initial steam breakthrough, preferential flow channels were formed in narrow sand packs and most residual oil left in these channels was immobile. This shortened the steam breakthrough time of follow-up steam flooding and decreased the increment of oil recovery efficiency. Steam breakthrough occurred easily for a smaller producer-injector spacing, and a bigger difference in physical properties between fluids and rock. Steam breakthrough is more likely to occur at a larger formation permeability (k), greater steam displacement velocity (u) and smaller producer-injector spacing (L). Steam breakthrough time is a function of the parameter group (uk/L), i.e. tb=3.2151 (uk/L)^-0.5142. A non piston-like displacement model was built based on steam breakthrough observation for a steam stimulated well in the Jinglou Oilfield, Henan Oilfield Company. The steam volume swept in different directions could be obtained from inter-well permeability capacity and breakthrough angle, and the steam swept pore volume (SSPV) was also determined. Numerical simulation showed that steam sweep efficiency reached its peak value when a slug of profile control agent (slug size 10%-15% SSPV) was set at one half of the inter-well spacing. Field test with 12.5% SSPV of profile control agents in the Jinglou Oilfield achieved success in sealing breakthrough channels and good production performance of adjacent producers.
文摘Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the lesion is subject to hemorrhage,a phenomenon termed normal perfusion pressure breakthrough(NPPB) syndrome.According to this theory,arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure.Acutely after removal of a cerebral AVM,excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed.However,this theory remains controversial.We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.
文摘AIM: Predictive value of serum b2-microglobulin (b2m)levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM).METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB.RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3±2.6 vs 3.8±3.4 mo,P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03).CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment,compared to baseline ones, might be a predictor of risk for VB.
基金financial support from the projects of the National Natural Science Foundation of China(NSFC)(Grant Nos.51809259,51774056,and 51774095)the CAS Pioneer Hundred Talents Program in China。
文摘It is well known that the complicated channeling of fluid flow and heat transfer is strongly related with the intricate natural fracture system.However,it is still challenging to set up the fracture network model which is strong heterogeneous.Compared with other methods(e.g.equivalent continuum model(ECM),discrete fracture model(DFM),and ECM-DFM),the fracture flow module in the COMSOL Multiphysics simulator is powerful in definition of fractures as the inner flow boundary existing in the porous media.Thus it is selected to simulate the fluid flow and heat transfer in the geothermal-developed fractured granite of Sanguliu area located at Liaodong Peninsula,Eastern China.The natural faults/fractures based on field investigation combined with the discrete fracture network(DFN)generated by the MATLAB are used to represent the two-dimensional geological model.Numerical results show that early thermal breakthrough occurs at the production well caused by quick flow of cold water along the highly connected fractures.Suitable hydraulic fracturing treatments with proper injection rates,locations,etc.can efficiently hinder the thermal breakthrough time in the natural fracture system.Large well spacing helps the long-term operation of geothermal production,but it is highly dependent on the geometrical morphology of the fracture network.The enhancement of reservoir properties at the near-well regions can also increase the geothermal production efficiency.The results in this study can provide references to achieve a sustainable geothermal exploitation in fractured granitic geothermal reservoirs or hot dry rocks at depth.
基金Supported by the China National Science and Technology Major Project(2017ZX05063).
文摘Based on exploration and development results and evaluation of marine shale gas in South China in the past ten years, in view of the features of "high maturity, strong tectonic reformation and high shear stress" of the shale in Zhaotong exploration zone in the Yunnan and Guizhou Plateau, as well as the key issues of long time diffusion and leakage of shallow shale gas, and the preservation conditions, the factors controlling shallow shale gas sweet spot and key zone selection evaluation technology of shale gas are investigated. From 2017 to 2018, the first significant exploration breakthrough was made in the Taiyang anticline at a buried depth of 700 to 2 000 m, discovering large-scale proved geological reserves of shallow shale gas. By examining the accumulation conditions and sweet spot control factors of the shallow shale gas in this area, it is found that the accumulation and productivity potential of shale gas in the mountainous area with complex structure outside basin are controlled by five factors:(1) The gas-rich area has weak tectonic reformation and good preservation conditions on the whole, taking on typical anticline trap occurrence mode.(2) The gas-rich area is in over-pressure state and high in shale gas content.(3) The gas-rich area has high quality shale and thus superior source rock condition.(4) The gas-rich area has high quality reservoirs dominated by class I.(5) The shale gas reservoir in the gas-rich area has high content of brittle minerals and small difference between maximum and minimum horizontal stresses which are conducive to hydraulic fracturing. The innovative practice and core technologies formed during the exploration and production capacity construction of shallow shale gas in the Zhaotong demonstration zone have great reference significance for shallow shale gas exploration and development in other areas.
基金Project(2011ZX05009-004)supported by the National Science and Technology Major Projects of China
文摘Dimensional analysis and numerical simulations were carried out to research prediction method of breakthrough time of horizontal wells in bottom water reservoir. Four dimensionless independent variables and dimensionless time were derived from 10 influencing factors of the problem by using dimensional analysis. Simulations of horizontal well in reservoir with bottom water were run to find the prediction correlation. A general and concise functional relationship for predicting breakthrough time was established based on simulation results and theoretical analysis. The breakthrough time of one conceptual model predicted by the correlation is very close to the result by Eclipse with less than 2% error. The practical breakthrough time of one well in Helder oilfield is 10 d, and the predicted results by the method is 11.2 d, which is more accurate than the analytical result. Case study indicates that the method could predict breakthrough time of horizontal well under different reservoir conditions accurately. For its university and ease of use, the method is suitable for quick prediction of breakthrough time.
基金the Natural Science Foundation Training Project of Shandong Province,China(Grant No.ZR2018PEE026)the Science and Technology Planning Project of Zaozhuang City,Shandong Province,China(Grant No.2018GX12)+1 种基金the Project of Science Research Foundation of Zaozhuang University,China(Grant No.2017ZX16)the Doctoral Scientific Research Foundation of Zaozhuang University,China(Grant No.2017BS01).
文摘The regeneration of a spent packing is crucial with respect to the development of circular economy and abstemious society.Thus,the effects of regeneration temperature,resistant time,heating rate,and regeneration cycle on the breakthrough performance of methylene blue(MB)dye⁃exhausted ceramsite in a two⁃stage fixed⁃bed column were studied in this work.Results illustrate that the ceramsite exhibited excellent potential regeneration properties under the following optimal regeneration conditions:treatment temperature was 600°C,resistant time was 15 min,heating rate was 20℃/min,regeneration cycle was over 9 cycles,and the breakthrough time,saturation time,regeneration efficiency(RE),and regeneration loss rate(RLR)were 540 min,1020 min,64.61%,and 17.73%,respectively.The RE declined by 35.14%in over 1 cycle,while the RLR increased by 3.15 times in over 9 cycles.Besides,Thomas model was suitable to describe the two⁃stage fixed⁃bed column adsorption and thermal regeneration process with R2=0.978.In conclusion,a thorough understanding of the regeneration behavior of the two⁃stage fixed⁃bed column packed with ceramsite provides reference to obtain an effective and feasible regeneration approach,and it is beneficial for further application in water treatment.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81970459)。
文摘The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can regrow to normal size even after resection of 90%of the liver volume because of its strong regeneration ability2.Changes in diet,viral infection(HBV and/or HCV)。
文摘Objective To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.Methods The isolation and culture of human endometrial endothelial cells(HEECs)was performed with the method established in our laboratory.The content and activity of urokinase-type plasminogen activator(uPA)and the content of plasminogen activator inhibitor-1(PAI-1)in cell supernatants after incubated with different concentrations of progesterone(0-5 μmol/L)and 17β-estradiol(0,0.1,or 1 nmol/L)were measured by method of ELISA.Apoptosis rate of HEECs was measured by flow cytometry.Viable cell count was measured by MTT.Results The increased level of progesterone(0.5-5 μmol/L)combined with 17β-estradiol elevated content and activity of uPA while the production of PAI-1 remained unchanged.The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher concentrations of progesterone with 17β-estradiol.Conclusion The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent.
文摘In recent years,U.S.tight oil exploration and development have achieved significant progress,with rapidly increasing production,which has significantly changed the U.S.A.energy supply pattern(Fig.1).Compared with the North American marine to marginal marine-continental transitional facies,China’s tight oil(Fig.1)
基金Natural Science Foundation of China(42090020,42090025,42172151)Z.Jin,X.Liang and Z.Bai Energy Geoscience 3(2022)120e125124 National Key Research and Development Program(2019YFA0708504)thank the anonymous reviewers for constructive comments that have greatly improved this paper.
文摘Lacustrine shale oil resources are abundant in many petroliferous basins in China.The shale oil formations are characterized by low API gravity,high viscosity,poor mobility,high clay content,low brittleness and etc.Exploration of lacustrine shale oil started relatively late in China,but its progress is very rapid and breakthroughs have been made successively.In this short communication,we introduced the most significant shale oil discovery which is made recently in the Qingshankou Formation of the Gulong sag in the Songliao Basin.Key exploratory wells including Guye 1H(GY1H),Yingye 1H(YY1H)and Guye 2HC(GY2HC)tested stable and high oil flow in shale reservoirs,revealing the relatively stable and high oil production capacity of shale in the Gulong sag of Daqing Oilfield.It marks a leap of petroleum theoretical recognition from lacustrine shale generating oil to producing oil and from the theory of traditional oil migration and accumulation to the theory of indigenous oil accumulation in organic-rich shale.Although lacustrine shale oil exploration and development still faces many challenges in China,its prospect is quite promising.