Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavio...Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.展开更多
In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a n...In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.展开更多
The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnos...The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients.展开更多
Vehicular beaconing plays an important role to facilitate various applications in the paradigm of Internet of Vehicles(IoV). Due to high dynamic and resource limitation in IoV, how to schedule the vehicular beacon bro...Vehicular beaconing plays an important role to facilitate various applications in the paradigm of Internet of Vehicles(IoV). Due to high dynamic and resource limitation in IoV, how to schedule the vehicular beacon broadcast is challenging, especially in dense scenarios. In this paper, we investigate the beacon broadcast scheduling problem considering the Age of Information(AoI). We first propose an algorithm minimizing the expected sum of AoI considering the limited communication resource and vehicle mobility. Then the performance of the proposed algorithm is analyzed. With the proposed algorithm, the optimal solution can be obtained under certain conditions. Extensive simulations are conducted to verify the efficiency, effectiveness and fairness of the proposed solution.展开更多
Purpose: Online reviews on tourism attractions provide important references for potential tourists to choose tourism spots. The main goal of this study is conducting sentiment analysis to facilitate users comprehendin...Purpose: Online reviews on tourism attractions provide important references for potential tourists to choose tourism spots. The main goal of this study is conducting sentiment analysis to facilitate users comprehending the large scale of the reviews, based on the comments about Chinese attractions from Japanese tourism website 4 Travel.Design/methodology/approach: Different statistics-and rule-based methods are used to analyze the sentiment of the reviews. Three groups of novel statistics-based methods combining feature selection functions and the traditional term frequency-inverse document frequency(TF-IDF) method are proposed. We also make seven groups of different rulesbased methods. The macro-average and micro-average values for the best classification results of the methods are calculated respectively and the performance of the methods are shown.Findings: We compare the statistics-based and rule-based methods separately and compare the overall performance of the two method. According to the results, it is concluded that the combination of feature selection functions and weightings can strongly improve the overall performance. The emotional vocabulary in the field of tourism(EVT), kaomojis, negative and transitional words can notably improve the performance in all of three categories. The rule-based methods outperform the statistics-based ones with a narrow advantage.Research limitation: Two limitations can be addressed: 1) the empirical studies to verify the validity of the proposed methods are only conducted on Japanese languages; and 2) the deep learning technology is not been incorporated in the methods.Practical implications: The results help to elucidate the intrinsic characteristics of the Japanese language and the influence on sentiment analysis. These findings also provide practical usage guidelines within the field of sentiment analysis of Japanese online tourism reviews.Originality/value: Our research is of practicability. Currently, there are no studies that focus on the sentiment analysis of Japanese reviews about Chinese attractions.展开更多
In order to accelerate the chronic wounds healing, we investigated the healing effects of bioactive glass and Yunnan baiyao ointments in streptozotocin-induced diabetic rats. The ointments were prepared by mixing 45S5...In order to accelerate the chronic wounds healing, we investigated the healing effects of bioactive glass and Yunnan baiyao ointments in streptozotocin-induced diabetic rats. The ointments were prepared by mixing 45S5 bioactive glass powder(16% weight) with Vaseline and different weight percentages of Yunnan baiyao. Full-thickness defect wounds were created on the back of 130 SD rats and were randomly divided into 8 groups. The wound healing rates were calculated at 4, 7, 10, 14 and 21 days after surgery. The samples were harvested for further observations. Considering the wound closure rate, group 6(with 5% Yunnan baiyao) has better wound healing performance than other diabetic groups. The lower infl ammatory response was observed by gross observation and confirmed by the results of H&E staining and TEM observation. Besides, the proliferation of fibroblasts, the formation of granulation tissue, as well as the vascularization, were improved in group 6 compared to other diabetic groups. All results suggest that bioactive glass and Yunnan baiyao ointments can accelerate the recovery of diabetes-impaired skin wounds, and comparing to other diabetic groups, group 6(with 5% Yunnan baiyao) has better healing effect.展开更多
Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains uncle...Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.展开更多
Osteosarcoma(OS)is the most common primary malignant pediatric bone tumor and is characterized by high heterogeneity.Studies have revealed a wide range of phenotypic differences among OS cell lines in terms of their i...Osteosarcoma(OS)is the most common primary malignant pediatric bone tumor and is characterized by high heterogeneity.Studies have revealed a wide range of phenotypic differences among OS cell lines in terms of their in vivo tumorigenicity and in vitro colony-forming abilities.However,the underlying molecular mechanism of these discrepancies remains unclear.The potential role of mechanotransduction in tumorigenicity is of particular interest.To this end,we tested the tumorigenicity and anoikis resistance of OS cell lines both in vitro and in vivo.We utilized a sphere culture model,a soft agar assay,and soft and rigid hydrogel surface culture models to investigate the function of rigidity sensing in the tumorigenicity of OS cells.Additionally,we quantified the expression of sensor proteins,including four kinases and seven cytoskeletal proteins,in OS cell lines.The upstream core transcription factors of rigidity-sensing proteins were further investigated.We detected anoikis resistance in transformed OS cells.The mechanosensing function of transformed OS cells was also impaired,with general downregulation of rigidity-sensing components.We identified toggling between normal and transformed growth based on the expression pattern of rigidity-sensing proteins in OS cells.We further uncovered a novel TP53 mutation(R156P)in transformed OS cells,which acquired gain of function to inhibit rigidity sensing,thus sustaining transformed growth.Our findings suggest a fundamental role of rigidity-sensing components in OS tumorigenicity as mechanotransduction elements through which cells can sense their physical microenvironment.In addition,the gain of function of mutant TP53 appears to serve as an executor for such malignant programs.展开更多
BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plu...BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81801236(to ZX),81974189(to HT)a grant from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.ynlc201719(to QZ).
文摘Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.
基金supported(in part)by the Entrusted Project of National Center for Medical Service Administration,National Health and Family Planning Commission China(No.[2019]099)the First Level Funding of the Second Medical Leading Talent Project in Hubei Provincethe Special Project for Emergency of the Ministry of Science and Technology(2020YFC0841300)。
文摘In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
基金supported(in part)by the National Key Research and Development Program of China(2020YFC0845500)the Special Project for Emergency of Hubei Province(2020FCA008)the First Level Funding of the Second Medical Leading Talent Project in Hubei Province。
文摘The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
基金supported in part by the Natural Sciences and Engineering Research Council of Canada (NSERC)China Scholarship Council (CSC)
文摘Vehicular beaconing plays an important role to facilitate various applications in the paradigm of Internet of Vehicles(IoV). Due to high dynamic and resource limitation in IoV, how to schedule the vehicular beacon broadcast is challenging, especially in dense scenarios. In this paper, we investigate the beacon broadcast scheduling problem considering the Age of Information(AoI). We first propose an algorithm minimizing the expected sum of AoI considering the limited communication resource and vehicle mobility. Then the performance of the proposed algorithm is analyzed. With the proposed algorithm, the optimal solution can be obtained under certain conditions. Extensive simulations are conducted to verify the efficiency, effectiveness and fairness of the proposed solution.
基金supported by the National Natural Science Foundation of China under the grant #71373286 and # 71603189the Major Project of the Ministry of Education of China (Grant No. 17JZD034)
文摘Purpose: Online reviews on tourism attractions provide important references for potential tourists to choose tourism spots. The main goal of this study is conducting sentiment analysis to facilitate users comprehending the large scale of the reviews, based on the comments about Chinese attractions from Japanese tourism website 4 Travel.Design/methodology/approach: Different statistics-and rule-based methods are used to analyze the sentiment of the reviews. Three groups of novel statistics-based methods combining feature selection functions and the traditional term frequency-inverse document frequency(TF-IDF) method are proposed. We also make seven groups of different rulesbased methods. The macro-average and micro-average values for the best classification results of the methods are calculated respectively and the performance of the methods are shown.Findings: We compare the statistics-based and rule-based methods separately and compare the overall performance of the two method. According to the results, it is concluded that the combination of feature selection functions and weightings can strongly improve the overall performance. The emotional vocabulary in the field of tourism(EVT), kaomojis, negative and transitional words can notably improve the performance in all of three categories. The rule-based methods outperform the statistics-based ones with a narrow advantage.Research limitation: Two limitations can be addressed: 1) the empirical studies to verify the validity of the proposed methods are only conducted on Japanese languages; and 2) the deep learning technology is not been incorporated in the methods.Practical implications: The results help to elucidate the intrinsic characteristics of the Japanese language and the influence on sentiment analysis. These findings also provide practical usage guidelines within the field of sentiment analysis of Japanese online tourism reviews.Originality/value: Our research is of practicability. Currently, there are no studies that focus on the sentiment analysis of Japanese reviews about Chinese attractions.
基金Funded by the National Natural Science Foundation of China(Nos.50830101,51172073)the National Program on Key Basic Research Project(973 Program)(Nos.2011CB606204,2012CB619100)
文摘In order to accelerate the chronic wounds healing, we investigated the healing effects of bioactive glass and Yunnan baiyao ointments in streptozotocin-induced diabetic rats. The ointments were prepared by mixing 45S5 bioactive glass powder(16% weight) with Vaseline and different weight percentages of Yunnan baiyao. Full-thickness defect wounds were created on the back of 130 SD rats and were randomly divided into 8 groups. The wound healing rates were calculated at 4, 7, 10, 14 and 21 days after surgery. The samples were harvested for further observations. Considering the wound closure rate, group 6(with 5% Yunnan baiyao) has better wound healing performance than other diabetic groups. The lower infl ammatory response was observed by gross observation and confirmed by the results of H&E staining and TEM observation. Besides, the proliferation of fibroblasts, the formation of granulation tissue, as well as the vascularization, were improved in group 6 compared to other diabetic groups. All results suggest that bioactive glass and Yunnan baiyao ointments can accelerate the recovery of diabetes-impaired skin wounds, and comparing to other diabetic groups, group 6(with 5% Yunnan baiyao) has better healing effect.
基金supported by the National Nature Science Foundation of China,Nos.81671207 and 81974189(both to HLT)。
文摘Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.
基金sponsored by the National Natural Science Foundation of China(82202767)。
文摘Osteosarcoma(OS)is the most common primary malignant pediatric bone tumor and is characterized by high heterogeneity.Studies have revealed a wide range of phenotypic differences among OS cell lines in terms of their in vivo tumorigenicity and in vitro colony-forming abilities.However,the underlying molecular mechanism of these discrepancies remains unclear.The potential role of mechanotransduction in tumorigenicity is of particular interest.To this end,we tested the tumorigenicity and anoikis resistance of OS cell lines both in vitro and in vivo.We utilized a sphere culture model,a soft agar assay,and soft and rigid hydrogel surface culture models to investigate the function of rigidity sensing in the tumorigenicity of OS cells.Additionally,we quantified the expression of sensor proteins,including four kinases and seven cytoskeletal proteins,in OS cell lines.The upstream core transcription factors of rigidity-sensing proteins were further investigated.We detected anoikis resistance in transformed OS cells.The mechanosensing function of transformed OS cells was also impaired,with general downregulation of rigidity-sensing components.We identified toggling between normal and transformed growth based on the expression pattern of rigidity-sensing proteins in OS cells.We further uncovered a novel TP53 mutation(R156P)in transformed OS cells,which acquired gain of function to inhibit rigidity sensing,thus sustaining transformed growth.Our findings suggest a fundamental role of rigidity-sensing components in OS tumorigenicity as mechanotransduction elements through which cells can sense their physical microenvironment.In addition,the gain of function of mutant TP53 appears to serve as an executor for such malignant programs.
基金Supported by The Twelfth Five-Year Project on Tackling Key Problems of National Science and Technology,No2012ZX10001-003Sichuan Province Health Commission,No. 130430 and No. 17PJ070Chengdu Municipal Health Commission,No. 2019079
文摘BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.
