Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic ker...Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.展开更多
Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical a...Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical approaches.This study aimed to investigate whether computed tomography(CT)-based radiomics analysis could help predict development of MaVI in HCC.Methods:A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups.CT-based radiomics signature was built via multi-strategy machine learning methods.Afterwards,MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model(CRIM,clinical-radiomics integrated model)via random forest modeling.Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development.Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development,progression-free survival(PFS),and overall survival(OS)based on the selected risk factors.Results:The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors(P<0.001).CRIM could predict MaVI with satisfactory areas under the curve(AUC)of 0.986 and 0.979 in the training(n=154)and external validation(n=72)datasets,respectively.CRIM presented with excellent generalization with AUC of 0.956,1.000,and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory.Peel9_fos_InterquartileRange[hazard ratio(HR)=1.98;P<0.001]was selected as the independent risk factor.The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development(P<0.001),PFS(P<0.001)and OS(P=0.002).Conclusions:The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.展开更多
In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cere...In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.展开更多
Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic chang...Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.展开更多
The value of a statistical life(VSL)is a crucial tool for monetizing health impacts.To explore the VSL in China,this study examines people’s willingness to pay(WTP)to reduce death risk from air pollution in six repre...The value of a statistical life(VSL)is a crucial tool for monetizing health impacts.To explore the VSL in China,this study examines people’s willingness to pay(WTP)to reduce death risk from air pollution in six representative cities in China based on face-to-face contingent valuation interviews(n=3936)from March 7,2019 to September 30,2019.The results reveal that the WTP varied from CNY 455 to 763 in 2019(USD 66-111),corresponding to a VSL range of CNY 3.79-6.36 million(USD 549395-921940).The VSL in China in 2019 is estimated to be CNY 4.76 million(USD 689659).The statistics indicate that monthly expenditure levels,environmental concerns,risk attitudes,and assumed market acceptance,which have seldom been dis‐cussed in previous studies,significantly impact WTP and VSL.These findings will serve as a reference for ana‐lyzing mortality risk reduction benefits in future research and for policymaking.展开更多
The LaBr3(Ce)detector has attracted much attention in recent years because of its superior characteristics compared with other scintillating materials in terms of resolution and efficiency.However,it has a relatively ...The LaBr3(Ce)detector has attracted much attention in recent years because of its superior characteristics compared with other scintillating materials in terms of resolution and efficiency.However,it has a relatively high intrinsic background radiation because of the naturally occurring radioisotopes in lanthanum,actinium,and their daughter nuclei.This limits its applications in low-counting rate experiments.In this study,we identified the radioactive isotopes in theφ3"x 3"Saint-Gobain B380 detector by a coincidence measurement using a Clover detector in a low-background shielding system.Moreover,we carried out a Geant4 simulation of the experimental spectra to evaluate the activities of the main internal radiation components.The total activity of the background radiation of B380 is determined to be 1.523(34)Bq/cm^3.The main sources include 138La at 1.428(34)Bq/cm^3,207Tl at 0.0135(13)Bq/cm^3,211Bi at 0.0136(15)Bq/cm^3,215Po at 0.0135(3)Bq/cm^3,219Rn at 0.0125(12)Bq/cm^3,223Fr at 0.0019(11)Bq/cm^3,223Ra at 0.0127(10)Bq/cm^3,227Th at 0.0158(22)Bq/cm^3,and 227Ac at 0.0135(13)Bq/cm^3.Of these,the activities of 207Tl,211Po,215Po,223Fr,and 227Ac are deduced for the first time from the secular equilibrium established in the decay chain of 227Ac.展开更多
Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Meth...Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.展开更多
A nuclear spin gyroscope based on an alkali-metal–noble-gas co-magnetometer operated in spin-exchange relaxationfree(SERF) regime is a promising atomic rotation sensor for its ultra-high fundamental sensitivity. Howe...A nuclear spin gyroscope based on an alkali-metal–noble-gas co-magnetometer operated in spin-exchange relaxationfree(SERF) regime is a promising atomic rotation sensor for its ultra-high fundamental sensitivity. However, the fluctuation of probe light intensity is one of the main technical error sources that limits the bias stability of the gyroscope. Here we propose a novel method to suppress the bias error induced by probe light intensity fluctuations. This method is based on the inherent magnetic field response characteristics of the gyroscope. By the application of a bias magnetic field, the gyroscope can be tuned to a working point where the output signal is insensitive to probe light intensity variation, referred to herein as ‘zero point’, thus the bias error induced by intensity fluctuations can be completely suppressed. The superiority of the method was verified on a K–Rb–21 Ne co-magnetometer, and a bias stability of approximately 0.01°/h was obtained. In addition, the method proposed here can remove the requirement of the closed-loop control of probe light intensity, thereby facilitating miniaturization of the gyroscope volume and improvement of reliability.展开更多
In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a s...In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a significant negative impact to the health status of human populations.This review covers type 1 diabetes and type 2 diabetes.We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases.It appears that the human oral and gut microbiota are deeply interdigitated with diabetes.It is that simple.Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes.These studies focus on the role and the potential impact of intestinal microflora in diabetes.We paint a clear picture of how strongly microbes are linked and associated,both positively and negatively,with the fundamental and essential parts of diabetes in humans.The microflora seems to have an endless capacity to impact and transform diabetes.We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.展开更多
Both the prevalence of atrial fibrillation(AF)and frailty are increasing with age,and they often occur simultaneously,leading them to become the central concerns in this aging society.The incidence of frailty in patie...Both the prevalence of atrial fibrillation(AF)and frailty are increasing with age,and they often occur simultaneously,leading them to become the central concerns in this aging society.The incidence of frailty in patients with AF is highly variable,ranging from 4.4%to 75.4%,depending on different evaluating instruments used.Moreover,the incidence of frailty among patients with AF is on the rise,which indicated that patients with AF are more prone to frailty compared to patients without AF.The relationship between AF and frailty is complicated.Frailty elevates the risk of stroke and mortality in AF patients and is also associated with longer hospitalizations.On the other hand,it may reduce the appropriate anticoagulation in AF patients.However,the evidence of the effects of frailty on anti-arrhythmic and interventional therapy in patients with AF is scarce.Frailty affects both the management and the prognosis of AF in the geriatric population.Vice versa,AF could worsen the frail state and may represent a marker of frailty.However,there are still questions need to be resolved,for example,the impact of frailty on the interventional therapy of patients with AF.Therefore,the geriatric assessment of frailty should be considered when planning individualized management of AF in older patients.展开更多
Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous system.However,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is cu...Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous system.However,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown.In this study,we established a mouse model of bilateral sciatic nerve crush injury.Two weeks before injury,AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord.Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve,and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury,arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle.By 1 month after injury,extensive neuromuscular reinnervation occurred.In addition,the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered,and their latency was shortened.These findings suggest that Id2 can accelerate axonal regeneration,promote neuromuscular reinnervation,and enhance functional improvement following sciatic nerve injury.Therefore,elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury.The study was approved by the Experimental Animal Ethics Committee of Jinan University(approval No.20160302003)on March 2,2016.展开更多
An 6 Li+89Y experiment was conducted at the Laboratori Nazinali di Legnaro,INFN,Italy.The 550μg/cm^2 thick^89Y target was backed on a 340μg/cm^2 thick 12C foil.The severalγrays in the experiment with energies highe...An 6 Li+89Y experiment was conducted at the Laboratori Nazinali di Legnaro,INFN,Italy.The 550μg/cm^2 thick^89Y target was backed on a 340μg/cm^2 thick 12C foil.The severalγrays in the experiment with energies higher than 3000 keV can most likely be ascribed to the transitions in the 13C nuclei,which can be formed through various interactions between the 6 Li beam and the 12C foil.The high-energy properties ofγrays in 13C are employed for energy calibrating HPGe detectors,especially for the>3000 keV region,which is impossible to reach by common standard sources(152Eu,133Ba,etc.).Furthermore,γ-γand particle-γcoincidence measurements were performed to investigate the formation of 13C.展开更多
The aim of this study was to determine the attenuation of gamma and X-rays with different energies caused by passage through different materials.To this end,different materials with a range of atomic numbers were chos...The aim of this study was to determine the attenuation of gamma and X-rays with different energies caused by passage through different materials.To this end,different materials with a range of atomic numbers were chosen to measure gamma and X-ray attenuation coefficients and to explore the mechanisms of interaction of gamma and X-rays with matter of various kinds.It is shown that the attenuation coefficients first decrease and then increase with increase in the radiation(photon)energy.The attenuation of gamma and X-rays passing through materials with high atomic number is greater than that in materials with low atomic number.The attenuation minimum is related to the atomic number of the irradiated materials.The larger the atomic number is,the lower the energy corresponding to attenuation minimum is.Photoelectric and Compton effects are the main processes when gamma rays pass through individual materials with high and low atomic numbers,respectively.Therefore,for radiotherapy and radiation protection,different methods should be considered and selected for the use of gamma and X-rays of different energies for use in different materials.展开更多
Statistical analysis is critical in medical research.The objective of this article is to summarize the appropriate use and reporting of commonly used statistical methods in medical research,on the basis of existing st...Statistical analysis is critical in medical research.The objective of this article is to summarize the appropriate use and reporting of commonly used statistical methods in medical research,on the basis of existing statistical guidelines and the authors’experience in reviewing manuscripts,to provide recommendations for statistical applications and reporting.展开更多
The total effective spin-exchange relaxation of naturally abundant Rb in a K–Rb–21Ne comagnetometer is analyzed,and the results show that the coexistence of 87Rb and 85Rb isotopes in the same volume can lead to a la...The total effective spin-exchange relaxation of naturally abundant Rb in a K–Rb–21Ne comagnetometer is analyzed,and the results show that the coexistence of 87Rb and 85Rb isotopes in the same volume can lead to a large extra spinexchange broadening compared to pure 87Rb.This broadening mainly comes from the contribution of the equivalent reduction in the Rb spin-exchange rate.On this basis,an approximate relaxation model is proposed and experimentally demonstrated to be more accurate than that from a previous work.This study also provides a method for determining the properties of alkali-metal vapor cells.展开更多
This paper investigates the atomic spin polarization controllability of spin-exchange relaxation-free co-magnetometers(SERFCMs).This is the first work in the field of controllability analysis for the atomic spin ensem...This paper investigates the atomic spin polarization controllability of spin-exchange relaxation-free co-magnetometers(SERFCMs).This is the first work in the field of controllability analysis for the atomic spin ensembles systems,whose dynamic behaviors of spin polarization are described by the Bloch equations.Based on the Bloch equations,a state-space model of the atomic spin polarization for SERFCM is first established,which belongs to a particular class of nonlinear systems.For this class of nonlinear systems,a novel determination method for the global state controllability is proposed and proved.Then,this method is implemented in the process of controllability analysis on the atomic spin polarization of an actual SERFCM.Moreover,a theoretically feasible and reasonable solution of the control input is proposed under some physical constraints,with whose limitation of realistic conditions,the controller design can be accomplished more practically and more exactly.Finally,the simulation results demonstrate the feasibility and validation of the proposed controllability determination method.展开更多
An elongated trap potential for cold atoms is designed based on a quadrupole-Ioffe configuration.Phase fluctuations in a Bose-Einstein condensate(BEC),which is confined by the trap,are studied.We simulate the atom den...An elongated trap potential for cold atoms is designed based on a quadrupole-Ioffe configuration.Phase fluctuations in a Bose-Einstein condensate(BEC),which is confined by the trap,are studied.We simulate the atom density distribution induced by fluctuation after time of flight from this elongated trap potential and study the temperature measurement method related to the distribution.Furthermore,taking advantage of the tight confinement and radio frequency dressing technique,we propose a double well potential for splitting BECs.Our results are helpful for improving understanding of low-dimensional quantum gases and provide important guidance for atomic interferometry.展开更多
Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivi...Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivity, information transmission, and physiological functions of neural circuits in vivo. However, current techniques for optogenetic stimulation and neuronal activity recording mostly operate independently. Here, we report an all-fiber-transmission photometry system for simultaneous optogenetic manipulation and multi-color recording of neuronal activities and the neurotransmitter release in a freely moving animal. We have designed and manufactured a wavelength-independent multi-branch fiber bundle to enable simultaneous optogenetic manipulation and multi-color recording at different wavelengths. Further, we combine a laser of narrow linewidth with the lock-in amplification method to suppress the optogenetic stimulation-induced artifacts and channel crosstalk. We show that the collection efficiency of our system outperforms a traditional epi-fluorescence system. Further, we demonstrate successful recording of dynamic dopamine(DA) responses to unexpected rewards in the nucleus accumbens(NAc) in a freely moving mouse. We also show simultaneous dual-color recording of neuronal Ca2+ signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location. Thus, our multi-function fiber photometry system provides a compatible, efficient, and flexible solution for neuroscientists to study neural circuits and neurological diseases.展开更多
Objective To examine increases in average height among Chinese children and adolescents.Methods The data were obtained from the China Health and Nutrition Survey conducted during the period 1989–2015. A stratified mu...Objective To examine increases in average height among Chinese children and adolescents.Methods The data were obtained from the China Health and Nutrition Survey conducted during the period 1989–2015. A stratified multistage cluster sampling method was utilized to select participants aged 2–22 years in each province. Linear regression was used to examine the effects of age, birth cohort, and survey period on height.Results A total of 15,227 males and 13,737 females were included in the final analysis. Age(A) showed a continuous effect on height. The average heights of the investigated groups increased continuously during the investigation period. By 2015, the average height of the overall group increased by 7.87 cm compared to the average height during the 1989 survey. Moreover, birth year(cohort, C) also had a stable effect on height. Using the height of individuals born in or before 1975 as a reference, the average height of each birth cohort increased in comparison to the previous birth cohort.Conclusions The height of Chinese children and adolescents was affected by age, period, and cohort effects, and this effect is governed by certain rules. The age-period-cohort model can be used to analyze the trends of children’s and adolescent’s heights. The findings provide a scientific basis for the formulation of children’s and adolescents’ growth and development policies in China.展开更多
Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced volta...Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced voltage signal into the image of superparamagnetic iron oxide particles concentration distribution.MPI reconstruction primarily involves system matrix-and x-space-based methods.In this review,we provide a detailed overview of the research status and future research trends of these two methods.In addition,we review the application of deep learning methods in MPI reconstruction and the current open sources of MPI.Finally,research opinions on MPI reconstruction are presented.We hope this review promotes the use of MPI in clinical applications.展开更多
基金supported by PLA General Hospital Program,No.LB20201A010024(to LW).
文摘Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy,being convenient and cost effective.
基金supported by grants from the National Key R&D Program of China(2017YFA0205200,2017YFC1308701,and 2017YFC1309100)National Natural Science Foundation of China(82001917,81930053,81227901,81771924,81501616,81571785,81771957,and 61671449)the Natural Science Foundation of Guangdong Province,China(2016A030311055 and 2016A030313770)。
文摘Background:Macrovascular invasion(MaVI)occurs in nearly half of hepatocellular carcinoma(HCC)patients at diagnosis or during follow-up,which causes severe disease deterioration,and limits the possibility of surgical approaches.This study aimed to investigate whether computed tomography(CT)-based radiomics analysis could help predict development of MaVI in HCC.Methods:A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups.CT-based radiomics signature was built via multi-strategy machine learning methods.Afterwards,MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model(CRIM,clinical-radiomics integrated model)via random forest modeling.Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development.Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development,progression-free survival(PFS),and overall survival(OS)based on the selected risk factors.Results:The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors(P<0.001).CRIM could predict MaVI with satisfactory areas under the curve(AUC)of 0.986 and 0.979 in the training(n=154)and external validation(n=72)datasets,respectively.CRIM presented with excellent generalization with AUC of 0.956,1.000,and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory.Peel9_fos_InterquartileRange[hazard ratio(HR)=1.98;P<0.001]was selected as the independent risk factor.The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development(P<0.001),PFS(P<0.001)and OS(P=0.002).Conclusions:The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.
基金supported by the National Natural Science Foundation of China,No.81730050(to WH).
文摘In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.
基金supported by the National Natural Science Foundation of China,Nos.82271963(to HJL),81771806(to HJL),61936013(to HJL),82001914(to ZCT),81871511(to HZ)National Key R&D Program of China,No.2021YFA1301603(to ZCT)the Natural Science Foundation of Beijing,No.7212051(to HJL).
文摘Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.
基金supported by the National Natural Science Foun‐dation of China[Grant No.71773061].
文摘The value of a statistical life(VSL)is a crucial tool for monetizing health impacts.To explore the VSL in China,this study examines people’s willingness to pay(WTP)to reduce death risk from air pollution in six representative cities in China based on face-to-face contingent valuation interviews(n=3936)from March 7,2019 to September 30,2019.The results reveal that the WTP varied from CNY 455 to 763 in 2019(USD 66-111),corresponding to a VSL range of CNY 3.79-6.36 million(USD 549395-921940).The VSL in China in 2019 is estimated to be CNY 4.76 million(USD 689659).The statistics indicate that monthly expenditure levels,environmental concerns,risk attitudes,and assumed market acceptance,which have seldom been dis‐cussed in previous studies,significantly impact WTP and VSL.These findings will serve as a reference for ana‐lyzing mortality risk reduction benefits in future research and for policymaking.
基金This work was supported by the National Key R&D program of China(No.2016YFA0400504)by the National Natural Science Foundation of China(Nos.U1832211,U1867210,11922501,11961141004,11575018,11790322,and U1932209).
文摘The LaBr3(Ce)detector has attracted much attention in recent years because of its superior characteristics compared with other scintillating materials in terms of resolution and efficiency.However,it has a relatively high intrinsic background radiation because of the naturally occurring radioisotopes in lanthanum,actinium,and their daughter nuclei.This limits its applications in low-counting rate experiments.In this study,we identified the radioactive isotopes in theφ3"x 3"Saint-Gobain B380 detector by a coincidence measurement using a Clover detector in a low-background shielding system.Moreover,we carried out a Geant4 simulation of the experimental spectra to evaluate the activities of the main internal radiation components.The total activity of the background radiation of B380 is determined to be 1.523(34)Bq/cm^3.The main sources include 138La at 1.428(34)Bq/cm^3,207Tl at 0.0135(13)Bq/cm^3,211Bi at 0.0136(15)Bq/cm^3,215Po at 0.0135(3)Bq/cm^3,219Rn at 0.0125(12)Bq/cm^3,223Fr at 0.0019(11)Bq/cm^3,223Ra at 0.0127(10)Bq/cm^3,227Th at 0.0158(22)Bq/cm^3,and 227Ac at 0.0135(13)Bq/cm^3.Of these,the activities of 207Tl,211Po,215Po,223Fr,and 227Ac are deduced for the first time from the secular equilibrium established in the decay chain of 227Ac.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81873450)the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,Beijing Tongren Hospital,Beihang University&Capital Medical University(Grant No.BHTR-KFJJ-202009)The authors thank Life-Ontology Biological Technology Co.,Ltd for assistance with bioinfbrmatics analysis.
文摘Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2016YFB0501600 and 2017YFB0503100)the National Natural Science Foundation of China(Grant Nos.61773043,61673041,and 61721091)
文摘A nuclear spin gyroscope based on an alkali-metal–noble-gas co-magnetometer operated in spin-exchange relaxationfree(SERF) regime is a promising atomic rotation sensor for its ultra-high fundamental sensitivity. However, the fluctuation of probe light intensity is one of the main technical error sources that limits the bias stability of the gyroscope. Here we propose a novel method to suppress the bias error induced by probe light intensity fluctuations. This method is based on the inherent magnetic field response characteristics of the gyroscope. By the application of a bias magnetic field, the gyroscope can be tuned to a working point where the output signal is insensitive to probe light intensity variation, referred to herein as ‘zero point’, thus the bias error induced by intensity fluctuations can be completely suppressed. The superiority of the method was verified on a K–Rb–21 Ne co-magnetometer, and a bias stability of approximately 0.01°/h was obtained. In addition, the method proposed here can remove the requirement of the closed-loop control of probe light intensity, thereby facilitating miniaturization of the gyroscope volume and improvement of reliability.
基金Supported by Shandong Provincial Key Research and Development Program,No.2018CXGC1219City of Weihai Technique Extension Project,No.2016GNS023+1 种基金TaiShan Scholars Program of Shandong Province,No.tshw20120206TaiShan Industrial Experts Program,No.tscy20190612.
文摘In this review,we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes.On a global scale,diabetes causes a significant negative impact to the health status of human populations.This review covers type 1 diabetes and type 2 diabetes.We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases.It appears that the human oral and gut microbiota are deeply interdigitated with diabetes.It is that simple.Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes.These studies focus on the role and the potential impact of intestinal microflora in diabetes.We paint a clear picture of how strongly microbes are linked and associated,both positively and negatively,with the fundamental and essential parts of diabetes in humans.The microflora seems to have an endless capacity to impact and transform diabetes.We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.
文摘Both the prevalence of atrial fibrillation(AF)and frailty are increasing with age,and they often occur simultaneously,leading them to become the central concerns in this aging society.The incidence of frailty in patients with AF is highly variable,ranging from 4.4%to 75.4%,depending on different evaluating instruments used.Moreover,the incidence of frailty among patients with AF is on the rise,which indicated that patients with AF are more prone to frailty compared to patients without AF.The relationship between AF and frailty is complicated.Frailty elevates the risk of stroke and mortality in AF patients and is also associated with longer hospitalizations.On the other hand,it may reduce the appropriate anticoagulation in AF patients.However,the evidence of the effects of frailty on anti-arrhythmic and interventional therapy in patients with AF is scarce.Frailty affects both the management and the prognosis of AF in the geriatric population.Vice versa,AF could worsen the frail state and may represent a marker of frailty.However,there are still questions need to be resolved,for example,the impact of frailty on the interventional therapy of patients with AF.Therefore,the geriatric assessment of frailty should be considered when planning individualized management of AF in older patients.
基金This work was supported by the National Natural Science Foundation of China,Nos.82071369(to PY)and 81971198(to BZ)Guangdong grant‘Key Technologies for Treatment of Brain Disorders’of China,No.2018B030332001(to LZ and PY)+2 种基金Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology,China,No.20200730090(to LZ)the Natural Science Foundation of Beijing of China,No.7192103(to BZ)the Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR0201006(to PY).
文摘Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous system.However,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown.In this study,we established a mouse model of bilateral sciatic nerve crush injury.Two weeks before injury,AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord.Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve,and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury,arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle.By 1 month after injury,extensive neuromuscular reinnervation occurred.In addition,the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered,and their latency was shortened.These findings suggest that Id2 can accelerate axonal regeneration,promote neuromuscular reinnervation,and enhance functional improvement following sciatic nerve injury.Therefore,elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury.The study was approved by the Experimental Animal Ethics Committee of Jinan University(approval No.20160302003)on March 2,2016.
基金supported by the National Natural Science Foundation of China(Nos.11975040,U1832130,11475013)the HIRFL User Project,CAS.
文摘An 6 Li+89Y experiment was conducted at the Laboratori Nazinali di Legnaro,INFN,Italy.The 550μg/cm^2 thick^89Y target was backed on a 340μg/cm^2 thick 12C foil.The severalγrays in the experiment with energies higher than 3000 keV can most likely be ascribed to the transitions in the 13C nuclei,which can be formed through various interactions between the 6 Li beam and the 12C foil.The high-energy properties ofγrays in 13C are employed for energy calibrating HPGe detectors,especially for the>3000 keV region,which is impossible to reach by common standard sources(152Eu,133Ba,etc.).Furthermore,γ-γand particle-γcoincidence measurements were performed to investigate the formation of 13C.
基金supported by the National Natural Science Foundation of China(Nos.11475013,11975040 and U1832130)
文摘The aim of this study was to determine the attenuation of gamma and X-rays with different energies caused by passage through different materials.To this end,different materials with a range of atomic numbers were chosen to measure gamma and X-ray attenuation coefficients and to explore the mechanisms of interaction of gamma and X-rays with matter of various kinds.It is shown that the attenuation coefficients first decrease and then increase with increase in the radiation(photon)energy.The attenuation of gamma and X-rays passing through materials with high atomic number is greater than that in materials with low atomic number.The attenuation minimum is related to the atomic number of the irradiated materials.The larger the atomic number is,the lower the energy corresponding to attenuation minimum is.Photoelectric and Compton effects are the main processes when gamma rays pass through individual materials with high and low atomic numbers,respectively.Therefore,for radiotherapy and radiation protection,different methods should be considered and selected for the use of gamma and X-rays of different energies for use in different materials.
文摘Statistical analysis is critical in medical research.The objective of this article is to summarize the appropriate use and reporting of commonly used statistical methods in medical research,on the basis of existing statistical guidelines and the authors’experience in reviewing manuscripts,to provide recommendations for statistical applications and reporting.
基金Project supported by the National Key R&D Program of China(Grant Nos.2016YFB0501600 and 2017YFB0503100)the National Natural Science Foundation of China(Grant Nos.61773043,61673041,61721091,and 61703025)the National Science Fund for Distinguished Young Scholars of China(Grant No.61925301)。
文摘The total effective spin-exchange relaxation of naturally abundant Rb in a K–Rb–21Ne comagnetometer is analyzed,and the results show that the coexistence of 87Rb and 85Rb isotopes in the same volume can lead to a large extra spinexchange broadening compared to pure 87Rb.This broadening mainly comes from the contribution of the equivalent reduction in the Rb spin-exchange rate.On this basis,an approximate relaxation model is proposed and experimentally demonstrated to be more accurate than that from a previous work.This study also provides a method for determining the properties of alkali-metal vapor cells.
基金supported in part by the National Natural Science Foundation of China(61673041,62003022)the Beijing Academy of Quantum Information Science Research Program(Y18G34)。
文摘This paper investigates the atomic spin polarization controllability of spin-exchange relaxation-free co-magnetometers(SERFCMs).This is the first work in the field of controllability analysis for the atomic spin ensembles systems,whose dynamic behaviors of spin polarization are described by the Bloch equations.Based on the Bloch equations,a state-space model of the atomic spin polarization for SERFCM is first established,which belongs to a particular class of nonlinear systems.For this class of nonlinear systems,a novel determination method for the global state controllability is proposed and proved.Then,this method is implemented in the process of controllability analysis on the atomic spin polarization of an actual SERFCM.Moreover,a theoretically feasible and reasonable solution of the control input is proposed under some physical constraints,with whose limitation of realistic conditions,the controller design can be accomplished more practically and more exactly.Finally,the simulation results demonstrate the feasibility and validation of the proposed controllability determination method.
基金Supported by the National Natural Science Foundation of China under Grant Nos 61703025,91736028 and 61673041
文摘An elongated trap potential for cold atoms is designed based on a quadrupole-Ioffe configuration.Phase fluctuations in a Bose-Einstein condensate(BEC),which is confined by the trap,are studied.We simulate the atom density distribution induced by fluctuation after time of flight from this elongated trap potential and study the temperature measurement method related to the distribution.Furthermore,taking advantage of the tight confinement and radio frequency dressing technique,we propose a double well potential for splitting BECs.Our results are helpful for improving understanding of low-dimensional quantum gases and provide important guidance for atomic interferometry.
基金supported by Beijing Municipal Governmentsupported by the National Natural Science Foundation of China(Grant Nos.61890952)the Director Fund of WNLO。
文摘Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivity, information transmission, and physiological functions of neural circuits in vivo. However, current techniques for optogenetic stimulation and neuronal activity recording mostly operate independently. Here, we report an all-fiber-transmission photometry system for simultaneous optogenetic manipulation and multi-color recording of neuronal activities and the neurotransmitter release in a freely moving animal. We have designed and manufactured a wavelength-independent multi-branch fiber bundle to enable simultaneous optogenetic manipulation and multi-color recording at different wavelengths. Further, we combine a laser of narrow linewidth with the lock-in amplification method to suppress the optogenetic stimulation-induced artifacts and channel crosstalk. We show that the collection efficiency of our system outperforms a traditional epi-fluorescence system. Further, we demonstrate successful recording of dynamic dopamine(DA) responses to unexpected rewards in the nucleus accumbens(NAc) in a freely moving mouse. We also show simultaneous dual-color recording of neuronal Ca2+ signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location. Thus, our multi-function fiber photometry system provides a compatible, efficient, and flexible solution for neuroscientists to study neural circuits and neurological diseases.
基金supported by 2020 Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Key research topicThe research of varicella disease burden and economic evaluation of vaccination [L202008]+2 种基金Beihang University & Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan [BHME-201801]Study on the current situation, change trend, nutrition and related factors of diabetes in children and adolescents,National Key R&D Program of China [2016YFC1305201]Study on the influencing factors of herpes zoster, Chinese Center for Disease Control and Prevention surplus project [59911917]。
文摘Objective To examine increases in average height among Chinese children and adolescents.Methods The data were obtained from the China Health and Nutrition Survey conducted during the period 1989–2015. A stratified multistage cluster sampling method was utilized to select participants aged 2–22 years in each province. Linear regression was used to examine the effects of age, birth cohort, and survey period on height.Results A total of 15,227 males and 13,737 females were included in the final analysis. Age(A) showed a continuous effect on height. The average heights of the investigated groups increased continuously during the investigation period. By 2015, the average height of the overall group increased by 7.87 cm compared to the average height during the 1989 survey. Moreover, birth year(cohort, C) also had a stable effect on height. Using the height of individuals born in or before 1975 as a reference, the average height of each birth cohort increased in comparison to the previous birth cohort.Conclusions The height of Chinese children and adolescents was affected by age, period, and cohort effects, and this effect is governed by certain rules. The age-period-cohort model can be used to analyze the trends of children’s and adolescent’s heights. The findings provide a scientific basis for the formulation of children’s and adolescents’ growth and development policies in China.
基金This work was supported in part by the National Key Research and Development Program of China,Nos.2017YFA0700401 and 2017YFA0205200the National Natural Science Foundation of China,Nos.62027901,81827808,81527805,and 81671851+2 种基金the CAS Youth Innovation Promotion Association,No.2018167the CAS Key Technology Talent Programand the Project of High-Level Talents Team Introduction in Zhuhai City,No.Zhuhai HLHPTP201703。
文摘Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced voltage signal into the image of superparamagnetic iron oxide particles concentration distribution.MPI reconstruction primarily involves system matrix-and x-space-based methods.In this review,we provide a detailed overview of the research status and future research trends of these two methods.In addition,we review the application of deep learning methods in MPI reconstruction and the current open sources of MPI.Finally,research opinions on MPI reconstruction are presented.We hope this review promotes the use of MPI in clinical applications.
