Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency(AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-ma...Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency(AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital,a major teaching hospital in Chinese Academy of Medical Sciences.Data of physicians' educational background,clinical training,patient workload per year and continuing medical education in AGHD were collected.Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents,endocrine fellows,attending physicians and visiting physicians responded to the survey.Among them,44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy.Moreover,56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD.Logistic regression analysis of physician demographic data,educational background,and work experience found no consistent independent factors associated with better decision-making,other than continued medical education,that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence.High quality continued medical education is required to improve Chinese physician management of AGHD.展开更多
Ischemic stroke is one of the leading causes of death worldwide,and effective treatment strategies in the chronic phase of this disease remain insufficient.Homeostasis of metals in the brain plays an important role in...Ischemic stroke is one of the leading causes of death worldwide,and effective treatment strategies in the chronic phase of this disease remain insufficient.Homeostasis of metals in the brain plays an important role in maintaining normal brain function.However,the dynamic spatial distributions of iron,zinc,calcium,potassium,and copper in a rat brain following ischemic stroke and the association between structural distribution and function remain to be elucidated.In this study,we used a synchrotron radiation-based micro-X-ray fluorescence technique to image element mapping changes in special rat brain regions after ischemic stroke,showing the distribution characteristics of iron,zinc,calcium,potassium,and copper.We demonstrated,for the first time,the consistent dynamic spatial distributions of metal elements at a series of time points(3 h,4.5 h,6 h,12 h,1 d,3 d,5 d,7 d,10 d,14 d,28 d)after brain ischemia,which revealed that the homeostasis of iron,zinc,calcium,potassium,and copper in the brain was disturbed with distinctive change trends,providing clear insights in understanding the underlying pathogenesis of stroke from a novel perspective,thus laying the foundation of further developing new drug targets for stroke treatment.展开更多
BACKGROUND Alpha-L-fucosidase-1(FUCA1)has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma.Moreover,recent studies reported that FUCA1 could decrease the invasion capability...BACKGROUND Alpha-L-fucosidase-1(FUCA1)has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma.Moreover,recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9(MMP-9)expression.However,the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma(ESCC)have not yet been explored.AIM To evaluate the status,association,and prognostic value of FUCA1 and MMP-9 expression in ESCC.METHODS Patients who underwent esophagectomy for ESCC between January 1,2014,and December 31,2014 at Sun Yat-Sen University Cancer Center were enrolled.The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry.In addition,the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas(TCGA)database.RESULTS High expression of FUCA1 and MMP-9 was found in 90 patients(75.6%)and 62 patients(52.1%),respectively.In the high FUCA1 expression group,the constituent ratios of patients with stage III disease(61.1%vs 37.9%,P=0.029),lymphatic invasion(62.2%vs 31.0%,P=0.003),and high MMP-9 expression(60.0%vs 27.6%,P=0.002)were significantly higher than those in the low FUCA1 expression group.In Kaplan-Meier univariate analysis,advanced tumor-nodemetastasis stage(III,P=0.001),positive regional lymph node metastasis(N+,P=0.002),high FUCA1 expression(P=0.001),and high MMP-9 expression(P=0.002)were potential predictors of shorter overall survival(OS),which was similar to the results analyzed based on the TCGA database.Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS[hazard ratio(HR):0.484,95%confidence interval(CI):0.239-0.979;P=0.044;and HR:0.591,95%CI:0.359-0.973,P=0.039,respectively].CONCLUSION FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability,and serve as a valuable prognostic biomarker in ESCC.展开更多
Wenzhou has improved its environmental quality because of comprehensive environmental remediation;nevertheless,the semen quality of infertile males remains unclear.This study determined whether better environmental qu...Wenzhou has improved its environmental quality because of comprehensive environmental remediation;nevertheless,the semen quality of infertile males remains unclear.This study determined whether better environmental quality improved semen quality in this region.We recorded semen quality data from 22962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University(Wenzhou,China).Patients were predominantly 30–35 years old(33.1%)and workers(82.0%),with high school education or lower(77.6%);more than a half of the patients(52.6%)were Wenzhou household registration;and most patients(77.5%)had abnormal semen quality.Patients who were older than 40 years and workers,and those with Wenzhou household registration,had significantly worse semen quality(all P<0.05).From 2014 to 2019,progressive sperm motility,total sperm motility,and semen volume showed increasing linear trends in all patients(P=0.021,0.030,and 0.005,respectively),yet normal sperm morphology showed a linearly decreasing trend(P=0.046).Sensitivity analyses for subgroups yielded similar results.In conclusion,the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility,total sperm motility,and semen volume.Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.展开更多
The discovery of the clustered regularly interspaced short palindromic repeat(CRISPR)system has driven gene manipulation technology to a new era with applications reported in organisms that span the tree of life.The u...The discovery of the clustered regularly interspaced short palindromic repeat(CRISPR)system has driven gene manipulation technology to a new era with applications reported in organisms that span the tree of life.The utility of CRISPR-mediated editing was further expanded to mRNA following identification of the RNA-targeting Cas13 family of smaller endonuclease proteins.Application of this family to insect research,however,has been more limited.In this study,the smallest Cas13 family member,Cas13d,and guide RNAs(gRNAs)were complexed with a versatile nanomaterial(star polycation,SPc)to generate a proof-of-concept RNA-editing platform capable of disrupting mRNA expression of the eye pigmentation gene tryptophan 2,3-dioxygenase(SfTO)in white-backed planthoppers(WBPHs).The resulting red-eye phenotype was present in 19.76%(with SPc)and 22.99%(without SPc)of the treatment groups and was comparable to the red-eye phenotype generated following conventional RNA interference knockdown(22.22%).Furthermore,the Cas13/gRNA phenotype manifested more quickly than RNA interference.Consistent with the expected Cas13d mechanism,SfTO transcript levels were significantly reduced.Taken together,the results indicate that the SPc-CRISPR-Cas13d/gRNA complex negatively impacted expression of the target gene.These findings confirm the utility of this novel mRNA disruption system in insects and lay the foundation for further development of these tools in the implementation of green agricultural pest management tactics.展开更多
We study the mechanism design of facility location problems.The problem is to design mechanisms to select a set of locations on which to build a set of facilities,aiming to optimize some system objective and achieve d...We study the mechanism design of facility location problems.The problem is to design mechanisms to select a set of locations on which to build a set of facilities,aiming to optimize some system objective and achieve desirable properties based on the strategic agents'locations.The agents might have incentives to misreport their private locations,in order to minimize the costs(i.e.,the distance from the closest facility).We study the setting with limited locations,that is,the facilities can only be built on a given finite set of candidate locations,rather than the whole space.For locating a single facility and two facilities on a real line,we propose strategyproof mechanisms with tight approximation ratios,under the objectives of minimizing the total cost and the maximum cost.Further,we consider the problem of locating an obnoxious facility from which the agents want to stay as far away as possible,and derive tight bounds on the approximation ratio of strategyproof mechanisms.展开更多
Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques ...Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation(SR)-based X-ray in-line phase-contrast imaging (ILPCI)and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.展开更多
Objective: Haliotidis, the dried muscle of abalone, has long been used as a marine traditional Chinese medicine(TCM) due to its high medicinal and nutritive values, whereas few reports contributed to its quality contr...Objective: Haliotidis, the dried muscle of abalone, has long been used as a marine traditional Chinese medicine(TCM) due to its high medicinal and nutritive values, whereas few reports contributed to its quality control. This study aimed to establish the high-performance liquid chromatography(HPLC) fingerprints of Haliotidis. Materials and Methods: The HPLC fingerprints of Haliotidis, the manufacturing products of dried muscle of abalone, were analyzed by reverse-phase HPLC, using a YMC HPLC C18 column(250 mm × 4.6 mm, 5 μm).The gradient elution mode was applied with mobile phase starting from 5% acetonitrile and 0.1% phosphoric acid aqueous solution to 100%acetonitrile in 70 min at a flow rate of 1.0 mL/min. The detection wavelength was set at 190 nm. Results: Through compared the HPLC fingerprint chromatograms of 14 batches of Haliotidis, 25 peaks were assigned as the characteristic common peaks, of which one index component L-phenylalanine was identified by comparison with its standard substance. The established HPLC fingerprint analysis method of Haliotidis was validated with good precision, repeatability, and stability. Based on the above study, a reference HPLC fingerprint chromatogram of Haliotidis was proposed. Conclusions: It is the first time to establish the HPLC fingerprint chromatogram of TCM Haliotidis, which could contribute to the establishment of its quality control system.展开更多
基金Supported by National Natural Science Foundation of China(81400774)PUMC Youth Fund(33320140164 and 3332016128)
文摘Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency(AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital,a major teaching hospital in Chinese Academy of Medical Sciences.Data of physicians' educational background,clinical training,patient workload per year and continuing medical education in AGHD were collected.Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents,endocrine fellows,attending physicians and visiting physicians responded to the survey.Among them,44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy.Moreover,56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD.Logistic regression analysis of physician demographic data,educational background,and work experience found no consistent independent factors associated with better decision-making,other than continued medical education,that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence.High quality continued medical education is required to improve Chinese physician management of AGHD.
基金This work was supported by the National Natural Science Foundation of China(No.81501025)the Natural Science Foundation of Hunan Province(Nos.2020JJ4134 and 2016JJ3174).
文摘Ischemic stroke is one of the leading causes of death worldwide,and effective treatment strategies in the chronic phase of this disease remain insufficient.Homeostasis of metals in the brain plays an important role in maintaining normal brain function.However,the dynamic spatial distributions of iron,zinc,calcium,potassium,and copper in a rat brain following ischemic stroke and the association between structural distribution and function remain to be elucidated.In this study,we used a synchrotron radiation-based micro-X-ray fluorescence technique to image element mapping changes in special rat brain regions after ischemic stroke,showing the distribution characteristics of iron,zinc,calcium,potassium,and copper.We demonstrated,for the first time,the consistent dynamic spatial distributions of metal elements at a series of time points(3 h,4.5 h,6 h,12 h,1 d,3 d,5 d,7 d,10 d,14 d,28 d)after brain ischemia,which revealed that the homeostasis of iron,zinc,calcium,potassium,and copper in the brain was disturbed with distinctive change trends,providing clear insights in understanding the underlying pathogenesis of stroke from a novel perspective,thus laying the foundation of further developing new drug targets for stroke treatment.
基金the Research Ethics Committee at the Sun Yat-Sen University Cancer Center(No.B2014-110)Shenzhen KeyMedical Discipline ConstructionFund, No. SZXK075and theSanming Project of Medicine inShenzhen, No. SZSM201612097.
文摘BACKGROUND Alpha-L-fucosidase-1(FUCA1)has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma.Moreover,recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9(MMP-9)expression.However,the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma(ESCC)have not yet been explored.AIM To evaluate the status,association,and prognostic value of FUCA1 and MMP-9 expression in ESCC.METHODS Patients who underwent esophagectomy for ESCC between January 1,2014,and December 31,2014 at Sun Yat-Sen University Cancer Center were enrolled.The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry.In addition,the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas(TCGA)database.RESULTS High expression of FUCA1 and MMP-9 was found in 90 patients(75.6%)and 62 patients(52.1%),respectively.In the high FUCA1 expression group,the constituent ratios of patients with stage III disease(61.1%vs 37.9%,P=0.029),lymphatic invasion(62.2%vs 31.0%,P=0.003),and high MMP-9 expression(60.0%vs 27.6%,P=0.002)were significantly higher than those in the low FUCA1 expression group.In Kaplan-Meier univariate analysis,advanced tumor-nodemetastasis stage(III,P=0.001),positive regional lymph node metastasis(N+,P=0.002),high FUCA1 expression(P=0.001),and high MMP-9 expression(P=0.002)were potential predictors of shorter overall survival(OS),which was similar to the results analyzed based on the TCGA database.Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS[hazard ratio(HR):0.484,95%confidence interval(CI):0.239-0.979;P=0.044;and HR:0.591,95%CI:0.359-0.973,P=0.039,respectively].CONCLUSION FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability,and serve as a valuable prognostic biomarker in ESCC.
基金This study was supported by the Project of Wenzhou Science and Technology Bureau(No.Y2020048)the Education Project of Zhejiang Province(No.Y202146906)+1 种基金the Science and Technology Planning Project of Wenzhou(S2020002)the Research Project of Wenzhou Medical University(KJHX2014).
文摘Wenzhou has improved its environmental quality because of comprehensive environmental remediation;nevertheless,the semen quality of infertile males remains unclear.This study determined whether better environmental quality improved semen quality in this region.We recorded semen quality data from 22962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University(Wenzhou,China).Patients were predominantly 30–35 years old(33.1%)and workers(82.0%),with high school education or lower(77.6%);more than a half of the patients(52.6%)were Wenzhou household registration;and most patients(77.5%)had abnormal semen quality.Patients who were older than 40 years and workers,and those with Wenzhou household registration,had significantly worse semen quality(all P<0.05).From 2014 to 2019,progressive sperm motility,total sperm motility,and semen volume showed increasing linear trends in all patients(P=0.021,0.030,and 0.005,respectively),yet normal sperm morphology showed a linearly decreasing trend(P=0.046).Sensitivity analyses for subgroups yielded similar results.In conclusion,the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility,total sperm motility,and semen volume.Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.
基金supported by the National Nat-ural Science Foundation of China(Grant No.32260671 for MH and No.31860617 for PH and MH)the Guizhou Provincial Science and Technology Project of China(Grant No.QKH-J[2020]1 Y077 for PH)+4 种基金the Scien-tific Research Foundation of Guizhou University of China(2017-33 for MH)the Program of talent culti-vation of Guizhou University([2019]05 for PH)the.Science and Technology Support of Guizhou province(QKH[2017]2956 for MH)the Program of Introducing Talents of Discipline to Universities of China(111 Pro-gram,D20023)the Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules,Depart-ment of Education,Guizhou Province[Qianjiaohe KY number(2020)004].
文摘The discovery of the clustered regularly interspaced short palindromic repeat(CRISPR)system has driven gene manipulation technology to a new era with applications reported in organisms that span the tree of life.The utility of CRISPR-mediated editing was further expanded to mRNA following identification of the RNA-targeting Cas13 family of smaller endonuclease proteins.Application of this family to insect research,however,has been more limited.In this study,the smallest Cas13 family member,Cas13d,and guide RNAs(gRNAs)were complexed with a versatile nanomaterial(star polycation,SPc)to generate a proof-of-concept RNA-editing platform capable of disrupting mRNA expression of the eye pigmentation gene tryptophan 2,3-dioxygenase(SfTO)in white-backed planthoppers(WBPHs).The resulting red-eye phenotype was present in 19.76%(with SPc)and 22.99%(without SPc)of the treatment groups and was comparable to the red-eye phenotype generated following conventional RNA interference knockdown(22.22%).Furthermore,the Cas13/gRNA phenotype manifested more quickly than RNA interference.Consistent with the expected Cas13d mechanism,SfTO transcript levels were significantly reduced.Taken together,the results indicate that the SPc-CRISPR-Cas13d/gRNA complex negatively impacted expression of the target gene.These findings confirm the utility of this novel mRNA disruption system in insects and lay the foundation for further development of these tools in the implementation of green agricultural pest management tactics.
基金the National Natural Science Foundation of China(No.12101069)Innovation Foundation of BUPT for Youth(No.500421358)Ying-Chao Zhao was partially supported by the Research Grants Council of the HKSAR,China(No.UGC/FDS11/E03/21).
文摘We study the mechanism design of facility location problems.The problem is to design mechanisms to select a set of locations on which to build a set of facilities,aiming to optimize some system objective and achieve desirable properties based on the strategic agents'locations.The agents might have incentives to misreport their private locations,in order to minimize the costs(i.e.,the distance from the closest facility).We study the setting with limited locations,that is,the facilities can only be built on a given finite set of candidate locations,rather than the whole space.For locating a single facility and two facilities on a real line,we propose strategyproof mechanisms with tight approximation ratios,under the objectives of minimizing the total cost and the maximum cost.Further,we consider the problem of locating an obnoxious facility from which the agents want to stay as far away as possible,and derive tight bounds on the approximation ratio of strategyproof mechanisms.
基金the BL13W1 beamline of the Shanghai Synchrotron Radiation Facility(SSRF)in China and was supported by Key Research Project of the Ministry of Science and Technology of China(2016YFC0904400)the National Natural Science Foundation of China(81501025&81671299)+1 种基金the Natural Science Foundation of Hunan Province(2016JJ3174)the Science and Technology Department Funds of Hunan Province Key Project(2016JC2057).
文摘Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation(SR)-based X-ray in-line phase-contrast imaging (ILPCI)and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.
基金financially supported by the National Natural Science Fund of China (No. 41806191)the National High Technology Research and Development Program of China (863 Program)(No. 2013AA093001)+2 种基金the Taishan Scholars Program,Chinathe Program of Open Studio for Druggability Research of Marine Natural ProductsPilot National Laboratory for Marine Science and Technology (Qingdao, China) Directed by Kai-Xian Chen and Yue-Wei Guo。
文摘Objective: Haliotidis, the dried muscle of abalone, has long been used as a marine traditional Chinese medicine(TCM) due to its high medicinal and nutritive values, whereas few reports contributed to its quality control. This study aimed to establish the high-performance liquid chromatography(HPLC) fingerprints of Haliotidis. Materials and Methods: The HPLC fingerprints of Haliotidis, the manufacturing products of dried muscle of abalone, were analyzed by reverse-phase HPLC, using a YMC HPLC C18 column(250 mm × 4.6 mm, 5 μm).The gradient elution mode was applied with mobile phase starting from 5% acetonitrile and 0.1% phosphoric acid aqueous solution to 100%acetonitrile in 70 min at a flow rate of 1.0 mL/min. The detection wavelength was set at 190 nm. Results: Through compared the HPLC fingerprint chromatograms of 14 batches of Haliotidis, 25 peaks were assigned as the characteristic common peaks, of which one index component L-phenylalanine was identified by comparison with its standard substance. The established HPLC fingerprint analysis method of Haliotidis was validated with good precision, repeatability, and stability. Based on the above study, a reference HPLC fingerprint chromatogram of Haliotidis was proposed. Conclusions: It is the first time to establish the HPLC fingerprint chromatogram of TCM Haliotidis, which could contribute to the establishment of its quality control system.