Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune respons...BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune responses.Numerous studies have investigated links between AS and various infections-bacterial,viral,fungal,and other microorganism infections.However,limited attention has been given to the association between AS and Clonorchis sinensis(C.sinensis)infection.CASE SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation.Ten years ago,the patient had achieved a stable condition after treatment with biological agents.However,he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission.A lumbosacral magnetic resonance imaging(MRI)scan revealed bone marrow edema in the left sacroiliac joint,and laboratory indicators were elevated.Moreover,the presence of C.sinensis eggs was detected in the stool.The patient was prescribed praziquantel,resulting in the disap-pearance of C.sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain.A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint.CONCLUSION C.sinensis infections could potentially trigger the exacerbation of AS.Clinicians should pay attention to investigating the presence of infections.INTRODUCTION Ankylosing spondylitis(AS)is a chronic inflammatory and rheumatic disease resulting from an imbalance between innate and acquired immune responses[1].While it can affect any part of the spine,its primary symptoms are persistent back pain and stiffness in the lower back and pelvis.The prevalence of AS per 10000 individuals is 23.8 in Europe,31.9 in North America,16.7 in Asia,10.2 in Latin America,and 7.4 in Africa[2].Infections commonly occur in the first 3 months and may act as potential triggers for the first symptoms of AS,often manifesting as gastrointestinal,urinary tract,and respiratory infections of microbiological origin[3,4].Clonorchis sinensis(C.sinensis)infection is a severe parasitic disease affecting millions globally,especially prevalent in China,South Korea,the Far East of Russia,and Vietnam,with an estimated 15 million cases[5].Transmission occurs through the consumption of undercooked freshwater fish containing metacercariae.Adult C.sinensis parasites then establish themselves within the human hepatobiliary system[6].C.sinensis infection triggers the activation of sphingosine 1-phosphate receptor 2,leading to the injury and fibrosis of the hepatobiliary[7].Recent research in a rat model found that C.sinensis infection increases the risk of hepatocellular carcinoma by stimulating hepatic progenitor cell proliferation[8].Complications of C.sinensis infection include cholestasis,cholangitis,biliary system fibrosis,and in severe cases,the development of cholangiocarcinoma[9].Consequently,the primary preventive measure is to abstain from consuming raw or undercooked freshwater fish.Praziquantel is the recommended and effective treatment for this infection[10].While there is existing literature on the coexistence of AS and parasitic infections,there is limited research specifically addressing the simultaneous presence of AS and C.sinensis infection.This case report details a rare scenario of AS coexisting with C.sinensis infection,underscoring the potential impact of C.sinensis infection on AS disease activity.展开更多
Objective:To explore the relationships among ambient temperature,ischemic stroke severity,and blood pressure.Methods:Meteorological data(2005–2015)were collected from the Guangzhou Meteorological Data Service.Ischemi...Objective:To explore the relationships among ambient temperature,ischemic stroke severity,and blood pressure.Methods:Meteorological data(2005–2015)were collected from the Guangzhou Meteorological Data Service.Ischemic stroke patients from the Department of Neurology of the First Affiliated Hospital,Sun Yat-sen University were retrospectively evaluated,each winter from 2005 to 2015.Patient demographics,baseline measurements,and National Institute of Health Stroke Scale(NIHSS)score were evaluated.Results:Three hundred sixty-two patients were included.The median latency from symptom onset to admission was 2 d(IQR:1–3 d).During recruitment,the highest and lowest temperatures were 39℃and 1.3℃,respectively.Hypertension was the most common comorbidity(75.1%).NIHSS scores at admission and discharge were higher in the cold-exposed group than in the controls regardless of the average temperature at admission.In addition,systolic and diastolic blood pressure values at admission were higher in the cold-exposed group than in the controls.When stratified by hypertensive status,the average and minimum temperatures at admission were negatively associated with systolic and diastolic blood pressure values in hypertensive patients.Reductions in the average and minimum temperatures at symptom onset were associated with more severe stroke.Conclusion:Ischemic stroke patients with symptom onset in winter had higher systolic blood pressure values and more serious neurologic deficits upon admission.展开更多
Persimmon （ Diospyros kaki Thunb. ） , a member of Ebenaceae family, is known as ＂woody grain＂ and ＂iron-stem crop＂. However, the epigenetie research has been rarely reported. In this study, tannin content in lat...Persimmon （ Diospyros kaki Thunb. ） , a member of Ebenaceae family, is known as ＂woody grain＂ and ＂iron-stem crop＂. However, the epigenetie research has been rarely reported. In this study, tannin content in late fruit development periods was determined. Moreover, the MSAP （methylation-sensitive amplified polymorphism） method was used to analyze methylation profile, and 13 primer combinations were selected. In total, 5 differential fragments were cloned and sequenced. This research would be helpful for further gene cloning, research on deastringency mechanism, as well as molecular breeding of D. kaki.展开更多
Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spi...Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spinal cord injury.However,the precise mechanism remains unclear.To investigate the effect of photo biomodulation on mitochondrial fission imbalance after spinal cord injury,in this study,we treated rat models of spinal co rd injury with 60-minute photo biomodulation(810 nm,150 mW) every day for 14 consecutive days.Transmission electron microscopy results confirmed the swollen and fragmented alte rations of mitochondrial morphology in neurons in acute(1 day) and subacute(7 and 14 days) phases.Photo biomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase,reduced neuronal cell death,and improved rat posterior limb motor function in a time-dependent manner.These findings suggest that photobiomodulation targets neuronal mitochondria,alleviates mitochondrial fission imbalance-induced neuronal apoptosis,and thereby promotes the motor function recovery of rats with spinal cord injury.展开更多
The interpretability of deep learning models has emerged as a compelling area in artificial intelligence research.The safety criteria for medical imaging are highly stringent,and models are required for an explanation...The interpretability of deep learning models has emerged as a compelling area in artificial intelligence research.The safety criteria for medical imaging are highly stringent,and models are required for an explanation.However,existing convolutional neural network solutions for left ventricular segmentation are viewed in terms of inputs and outputs.Thus,the interpretability of CNNs has come into the spotlight.Since medical imaging data are limited,many methods to fine-tune medical imaging models that are popular in transfer models have been built using massive public Image Net datasets by the transfer learning method.Unfortunately,this generates many unreliable parameters and makes it difficult to generate plausible explanations from these models.In this study,we trained from scratch rather than relying on transfer learning,creating a novel interpretable approach for autonomously segmenting the left ventricle with a cardiac MRI.Our enhanced GPU training system implemented interpretable global average pooling for graphics using deep learning.The deep learning tasks were simplified.Simplification included data management,neural network architecture,and training.Our system monitored and analyzed the gradient changes of different layers with dynamic visualizations in real-time and selected the optimal deployment model.Our results demonstrated that the proposed method was feasible and efficient:the Dice coefficient reached 94.48%,and the accuracy reached 99.7%.It was found that no current transfer learning models could perform comparably to the ImageNet transfer learning architectures.This model is lightweight and more convenient to deploy on mobile devices than transfer learning models.展开更多
Two-dimensional (2D)Ni(OH)_(2) nanosheets can theoretically expose their active sites of 100%.Whereas,their intrinsic easy accumulation and low conductivity lead to weak and unsustainable reaction kinetics.Herein,we p...Two-dimensional (2D)Ni(OH)_(2) nanosheets can theoretically expose their active sites of 100%.Whereas,their intrinsic easy accumulation and low conductivity lead to weak and unsustainable reaction kinetics.Herein,we propose a novel halogen chlorine-triggered electrochemical etching strategy to controllably manage the reaction kinetics of 2D Ni(OH)_(2) nanosheets(EE/Cl-Ni(OH)_(2)).It is found that halogen chlorine doping can adjust the interlamellar spacing flexibly and promote the lattice oxygen activation to achieve controlled construction of superficial oxygen defects at the adjustable voltage.The optimal EE/Cl-Ni(OH)_(2) electrode exhibits a high rate capability and excellent specific capacity of 206.9 mA h g^(-1) at 1 A g^(-1) in a three-electrode system,which is more than twice as high as the pristine Ni(OH)_(2).Furthermore,EE/Cl-Ni(OH)_(2) cathode and FeOOH@rGO anode are employed for developing an aqueous Ni-Fe battery with an excellent energy density of 83 W h kg^(-1),a high power density of 17051 W kg^(-1),and robust durability over 20,000 cycles.This strategy exploits a fresh channel for the ingenious fabrication of highefficiency and stable nickel-based deficiency materials for energy storage.展开更多
The emergence of power dispatching automation systems has greatly improved the efficiency of power industry operations and promoted the rapid development of the power industry.However,with the convergence and increase...The emergence of power dispatching automation systems has greatly improved the efficiency of power industry operations and promoted the rapid development of the power industry.However,with the convergence and increase in power data flow,the data dispatching network and the main station dispatching automation system have encountered substantial pressure.Therefore,themethod of online data resolution and rapid problemidentification of dispatching automation systems has been widely investigated.In this paper,we performa comprehensive review of automated dispatching of massive dispatching data from the perspective of intelligent identification,discuss unresolved research issues and outline future directions in this area.In particular,we divide intelligent identification over power big data into data acquisition and storage processes,anomaly detection and fault discrimination processes,and fault tracing for dispatching operations during communication.A detailed survey of the solutions to the challenges in intelligent identification over power big data is then presented.Moreover,opportunities and future directions are outlined.展开更多
Extreme learning machine (ELM) is a feedforward neural network-based machine learning method that has the benefits of short training times, strong generalization capabilities, and will not fall into local minima. Howe...Extreme learning machine (ELM) is a feedforward neural network-based machine learning method that has the benefits of short training times, strong generalization capabilities, and will not fall into local minima. However, due to the traditional ELM shallow architecture, it requires a large number of hidden nodes when dealing with high-dimensional data sets to ensure its classification performance. The other aspect, it is easy to degrade the classification performance in the face of noise interference from noisy data. To improve the above problem, this paper proposes a double pseudo-inverse extreme learning machine (DPELM) based on Sparse Denoising AutoEncoder (SDAE) namely, SDAE-DPELM. The algorithm can directly determine the input weight and output weight of the network by using the pseudo-inverse method. As a result, the algorithm only requires a few hidden layer nodes to produce superior classification results when classifying data. And its combination with SDAE can effectively improve the classification performance and noise resistance. Extensive numerical experiments show that the algorithm has high classification accuracy and good robustness when dealing with high-dimensional noisy data and high-dimensional noiseless data. Furthermore, applying such an algorithm to Miao character recognition substantiates its excellent performance, which further illustrates the practicability of the algorithm.展开更多
The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, p...The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.展开更多
The influences of different directional solidification processes, i.e., the high rate solidification(HRS) and liquid metal cooling(LMC), on microstructure and stress rupture property of DD488 alloy were investigated. ...The influences of different directional solidification processes, i.e., the high rate solidification(HRS) and liquid metal cooling(LMC), on microstructure and stress rupture property of DD488 alloy were investigated. The DD488 alloy was directional solidified by both HRS and LMC processes. The microstructure and stress rupture properties at 980 ℃/250 MPa were investigated by using optical microscopy(OM), scanning electron microscopy(SEM), electron microprobe analyzer(EPMA), transmission electron microscopy(TEM) and stress rupture testing. The results indicated that the LMC process refined the primary dendrite arm and decreased the microporosity volume fraction and solidification segregations of Cr and Co in as-cast DD488 alloy. After standard heat treatment of 1,260 ℃/4 h, AC(air cooling) + 1,080 ℃/4 h, AC + 870 ℃/24 h, AC, the γ′ morphology in LMC alloy was more cuboidal than that in HRS alloy, and the γ′ volume fraction of LMC alloy was higher than that of HRS alloy. The stress rupture life at 980 ℃/250 MPa of HRS alloy was 76.8 h, and it increased to 110.0 h in LMC al oy. The LMC process increased the stress rupture life due to the higher γ′ volume fraction, more perfect rafting structure and finer interfacial dislocation networks.展开更多
AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice ...AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.展开更多
BACKGROUND Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease(MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy(IMT) for MS-CD relative to ...BACKGROUND Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease(MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy(IMT) for MS-CD relative to conventional maintenance therapy remained unclarified.AIM To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer.METHODS A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy(CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs.RESULTS Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications(odds ratio: 0.527, P = 0.010), higher utility value for quality of life(coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management(coefficient-0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers $55260 to gain one quality-adjusted life year(QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita(GDPPC)] was 86.4%.CONCLUSION IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.展开更多
Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming t...Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy.Nanoparticles are ideal candidates as carriers for theranostic agents,which is attributed to their extraordinary physicochemical properties,including nanoscale sizes,functional properties,prolonged blood circulation,active or passive tumor targeting,specific cellular uptake,and in some cases,excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time.Overall,with the development of nanotechnology,theranostics has become a reality,and is now in the transition stage of"bench to bedside."In this review,we summarize recent progress on nanotechnology-based theranostics,i.e.,nanotheranostics,that has greatly assisted traditional therapies,and has provided therapeutic strategies emerging in recent decades,as well as"cocktail"theranostics mixing various treatment modalities.展开更多
The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients.Programmable delivery of immunotherapy-involving combinations through a singl...The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients.Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising,yet greatly challenging,to reverse postoperative immunosuppression.Here,an injectable hierarchical gel matrix,composed of dual lipid gel(DLG)layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios,was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy.The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide(GO)nanoparticles.GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages(TAMs)and promote an immunogenic tumor microenvironment.The inner layer,loaded with anti-CD47 antibody(aCD47),could maintain the gel state for a much longer time,enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory proteinα(SIRPα)pathway for a long-term antitumor effect.In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape,thereby boosting the systemic immune responses.展开更多
Significant and persistent trajectory-to-trajectory variance are commonly observed in particle tracking experiments,which have become a major challenge for the experimental data analysis.In this theoretical paper we i...Significant and persistent trajectory-to-trajectory variance are commonly observed in particle tracking experiments,which have become a major challenge for the experimental data analysis.In this theoretical paper we investigate the ergodicity recovery behavior,which helps clarify the origin and the convergence of trajectory-to-trajectory fluctuation in various heterogeneous disordered media.The concepts of self-averaging and ergodicity are revisited in the context of trajectory analysis.The slow ergodicity recovery and the non-Gaussian diffusion in the annealed disordered media are shown as the consequences of the central limit theorem in different situations.The strange ergodicity recovery behavior is reported in the quenched disordered case,which arises from a localization mechanism.The first-passage approach is introduced to the ergodicity analysis for this case,of which the central limit theorem can be employed and the ergodicity is recovered in the length scale of diffusivity correlation.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.
基金Supported by Chongqing Municipal Health Commission's Key Discipline Construction Project of Traditional Chinese Medicine Bi Disease,Yu Traditional Chinese Medicine(2021),No.16.
文摘BACKGROUND Ankylosing spondylitis(AS)is a chronic immune-mediated inflammatory disease.The prevailing theory links AS onset to infections in susceptible individuals.Furthermore,infections may impair the immune responses.Numerous studies have investigated links between AS and various infections-bacterial,viral,fungal,and other microorganism infections.However,limited attention has been given to the association between AS and Clonorchis sinensis(C.sinensis)infection.CASE SUMMARY A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation.Ten years ago,the patient had achieved a stable condition after treatment with biological agents.However,he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission.A lumbosacral magnetic resonance imaging(MRI)scan revealed bone marrow edema in the left sacroiliac joint,and laboratory indicators were elevated.Moreover,the presence of C.sinensis eggs was detected in the stool.The patient was prescribed praziquantel,resulting in the disap-pearance of C.sinensis eggs in subsequent routine stool tests and relief from lumbosacral pain.A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint.CONCLUSION C.sinensis infections could potentially trigger the exacerbation of AS.Clinicians should pay attention to investigating the presence of infections.INTRODUCTION Ankylosing spondylitis(AS)is a chronic inflammatory and rheumatic disease resulting from an imbalance between innate and acquired immune responses[1].While it can affect any part of the spine,its primary symptoms are persistent back pain and stiffness in the lower back and pelvis.The prevalence of AS per 10000 individuals is 23.8 in Europe,31.9 in North America,16.7 in Asia,10.2 in Latin America,and 7.4 in Africa[2].Infections commonly occur in the first 3 months and may act as potential triggers for the first symptoms of AS,often manifesting as gastrointestinal,urinary tract,and respiratory infections of microbiological origin[3,4].Clonorchis sinensis(C.sinensis)infection is a severe parasitic disease affecting millions globally,especially prevalent in China,South Korea,the Far East of Russia,and Vietnam,with an estimated 15 million cases[5].Transmission occurs through the consumption of undercooked freshwater fish containing metacercariae.Adult C.sinensis parasites then establish themselves within the human hepatobiliary system[6].C.sinensis infection triggers the activation of sphingosine 1-phosphate receptor 2,leading to the injury and fibrosis of the hepatobiliary[7].Recent research in a rat model found that C.sinensis infection increases the risk of hepatocellular carcinoma by stimulating hepatic progenitor cell proliferation[8].Complications of C.sinensis infection include cholestasis,cholangitis,biliary system fibrosis,and in severe cases,the development of cholangiocarcinoma[9].Consequently,the primary preventive measure is to abstain from consuming raw or undercooked freshwater fish.Praziquantel is the recommended and effective treatment for this infection[10].While there is existing literature on the coexistence of AS and parasitic infections,there is limited research specifically addressing the simultaneous presence of AS and C.sinensis infection.This case report details a rare scenario of AS coexisting with C.sinensis infection,underscoring the potential impact of C.sinensis infection on AS disease activity.
文摘Objective:To explore the relationships among ambient temperature,ischemic stroke severity,and blood pressure.Methods:Meteorological data(2005–2015)were collected from the Guangzhou Meteorological Data Service.Ischemic stroke patients from the Department of Neurology of the First Affiliated Hospital,Sun Yat-sen University were retrospectively evaluated,each winter from 2005 to 2015.Patient demographics,baseline measurements,and National Institute of Health Stroke Scale(NIHSS)score were evaluated.Results:Three hundred sixty-two patients were included.The median latency from symptom onset to admission was 2 d(IQR:1–3 d).During recruitment,the highest and lowest temperatures were 39℃and 1.3℃,respectively.Hypertension was the most common comorbidity(75.1%).NIHSS scores at admission and discharge were higher in the cold-exposed group than in the controls regardless of the average temperature at admission.In addition,systolic and diastolic blood pressure values at admission were higher in the cold-exposed group than in the controls.When stratified by hypertensive status,the average and minimum temperatures at admission were negatively associated with systolic and diastolic blood pressure values in hypertensive patients.Reductions in the average and minimum temperatures at symptom onset were associated with more severe stroke.Conclusion:Ischemic stroke patients with symptom onset in winter had higher systolic blood pressure values and more serious neurologic deficits upon admission.
基金Supported by College Students’Innovation and Entrepreneurship Training Program of Huanggang Normal University(zx201425)Fund of Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains(2015TD07)
文摘Persimmon （ Diospyros kaki Thunb. ） , a member of Ebenaceae family, is known as ＂woody grain＂ and ＂iron-stem crop＂. However, the epigenetie research has been rarely reported. In this study, tannin content in late fruit development periods was determined. Moreover, the MSAP （methylation-sensitive amplified polymorphism） method was used to analyze methylation profile, and 13 primer combinations were selected. In total, 5 differential fragments were cloned and sequenced. This research would be helpful for further gene cloning, research on deastringency mechanism, as well as molecular breeding of D. kaki.
基金supported by the National Natural Science Foundation of China,Nos.81070996 (to ZW) and 815 72151 (to XYH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05 (to ZW),2021ZDLSF02-10 (to XYH)。
文摘Increasing evidence indicates that mitochonarial lission imbalance plays an important role in derayed neuronal cell death. Our previous study round that photo biomodulation improved the motor function of rats with spinal cord injury.However,the precise mechanism remains unclear.To investigate the effect of photo biomodulation on mitochondrial fission imbalance after spinal cord injury,in this study,we treated rat models of spinal co rd injury with 60-minute photo biomodulation(810 nm,150 mW) every day for 14 consecutive days.Transmission electron microscopy results confirmed the swollen and fragmented alte rations of mitochondrial morphology in neurons in acute(1 day) and subacute(7 and 14 days) phases.Photo biomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase,reduced neuronal cell death,and improved rat posterior limb motor function in a time-dependent manner.These findings suggest that photobiomodulation targets neuronal mitochondria,alleviates mitochondrial fission imbalance-induced neuronal apoptosis,and thereby promotes the motor function recovery of rats with spinal cord injury.
基金The National Natural Science Foundation of China (62176048)provided funding for this research.
文摘The interpretability of deep learning models has emerged as a compelling area in artificial intelligence research.The safety criteria for medical imaging are highly stringent,and models are required for an explanation.However,existing convolutional neural network solutions for left ventricular segmentation are viewed in terms of inputs and outputs.Thus,the interpretability of CNNs has come into the spotlight.Since medical imaging data are limited,many methods to fine-tune medical imaging models that are popular in transfer models have been built using massive public Image Net datasets by the transfer learning method.Unfortunately,this generates many unreliable parameters and makes it difficult to generate plausible explanations from these models.In this study,we trained from scratch rather than relying on transfer learning,creating a novel interpretable approach for autonomously segmenting the left ventricle with a cardiac MRI.Our enhanced GPU training system implemented interpretable global average pooling for graphics using deep learning.The deep learning tasks were simplified.Simplification included data management,neural network architecture,and training.Our system monitored and analyzed the gradient changes of different layers with dynamic visualizations in real-time and selected the optimal deployment model.Our results demonstrated that the proposed method was feasible and efficient:the Dice coefficient reached 94.48%,and the accuracy reached 99.7%.It was found that no current transfer learning models could perform comparably to the ImageNet transfer learning architectures.This model is lightweight and more convenient to deploy on mobile devices than transfer learning models.
基金supported by the Opening Project of State Key Laboratory of Advanced Chemical Power Sourcesthe Guizhou Provincial Science and Technology Projects(QKHJC-ZK[2021]YB057)+1 种基金the Growth Project of Young Scientific and Technological Talents in Colleges and Universities of Guizhou Province(QKHJCKYZ[2021]252)the Reward and Subsidy Fund Project of Guizhou Education University(Z20210108)。
文摘Two-dimensional (2D)Ni(OH)_(2) nanosheets can theoretically expose their active sites of 100%.Whereas,their intrinsic easy accumulation and low conductivity lead to weak and unsustainable reaction kinetics.Herein,we propose a novel halogen chlorine-triggered electrochemical etching strategy to controllably manage the reaction kinetics of 2D Ni(OH)_(2) nanosheets(EE/Cl-Ni(OH)_(2)).It is found that halogen chlorine doping can adjust the interlamellar spacing flexibly and promote the lattice oxygen activation to achieve controlled construction of superficial oxygen defects at the adjustable voltage.The optimal EE/Cl-Ni(OH)_(2) electrode exhibits a high rate capability and excellent specific capacity of 206.9 mA h g^(-1) at 1 A g^(-1) in a three-electrode system,which is more than twice as high as the pristine Ni(OH)_(2).Furthermore,EE/Cl-Ni(OH)_(2) cathode and FeOOH@rGO anode are employed for developing an aqueous Ni-Fe battery with an excellent energy density of 83 W h kg^(-1),a high power density of 17051 W kg^(-1),and robust durability over 20,000 cycles.This strategy exploits a fresh channel for the ingenious fabrication of highefficiency and stable nickel-based deficiency materials for energy storage.
文摘The emergence of power dispatching automation systems has greatly improved the efficiency of power industry operations and promoted the rapid development of the power industry.However,with the convergence and increase in power data flow,the data dispatching network and the main station dispatching automation system have encountered substantial pressure.Therefore,themethod of online data resolution and rapid problemidentification of dispatching automation systems has been widely investigated.In this paper,we performa comprehensive review of automated dispatching of massive dispatching data from the perspective of intelligent identification,discuss unresolved research issues and outline future directions in this area.In particular,we divide intelligent identification over power big data into data acquisition and storage processes,anomaly detection and fault discrimination processes,and fault tracing for dispatching operations during communication.A detailed survey of the solutions to the challenges in intelligent identification over power big data is then presented.Moreover,opportunities and future directions are outlined.
文摘Extreme learning machine (ELM) is a feedforward neural network-based machine learning method that has the benefits of short training times, strong generalization capabilities, and will not fall into local minima. However, due to the traditional ELM shallow architecture, it requires a large number of hidden nodes when dealing with high-dimensional data sets to ensure its classification performance. The other aspect, it is easy to degrade the classification performance in the face of noise interference from noisy data. To improve the above problem, this paper proposes a double pseudo-inverse extreme learning machine (DPELM) based on Sparse Denoising AutoEncoder (SDAE) namely, SDAE-DPELM. The algorithm can directly determine the input weight and output weight of the network by using the pseudo-inverse method. As a result, the algorithm only requires a few hidden layer nodes to produce superior classification results when classifying data. And its combination with SDAE can effectively improve the classification performance and noise resistance. Extensive numerical experiments show that the algorithm has high classification accuracy and good robustness when dealing with high-dimensional noisy data and high-dimensional noiseless data. Furthermore, applying such an algorithm to Miao character recognition substantiates its excellent performance, which further illustrates the practicability of the algorithm.
文摘The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.
基金financially supported by the National Key R&D Program of China(Grant No.2016YFB0701402)National Natural Science Foundation of China(Grant No.51771020)Aeronautical Science Foundation of China(Grant No.2015ZE21006)
文摘The influences of different directional solidification processes, i.e., the high rate solidification(HRS) and liquid metal cooling(LMC), on microstructure and stress rupture property of DD488 alloy were investigated. The DD488 alloy was directional solidified by both HRS and LMC processes. The microstructure and stress rupture properties at 980 ℃/250 MPa were investigated by using optical microscopy(OM), scanning electron microscopy(SEM), electron microprobe analyzer(EPMA), transmission electron microscopy(TEM) and stress rupture testing. The results indicated that the LMC process refined the primary dendrite arm and decreased the microporosity volume fraction and solidification segregations of Cr and Co in as-cast DD488 alloy. After standard heat treatment of 1,260 ℃/4 h, AC(air cooling) + 1,080 ℃/4 h, AC + 870 ℃/24 h, AC, the γ′ morphology in LMC alloy was more cuboidal than that in HRS alloy, and the γ′ volume fraction of LMC alloy was higher than that of HRS alloy. The stress rupture life at 980 ℃/250 MPa of HRS alloy was 76.8 h, and it increased to 110.0 h in LMC al oy. The LMC process increased the stress rupture life due to the higher γ′ volume fraction, more perfect rafting structure and finer interfacial dislocation networks.
文摘AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.
基金Supported by Zhejiang Medical and Health Science and Technology Project,No. 2020KY608Natural Science Foundation of Zhejiang Province,No. LQ19H030013。
文摘BACKGROUND Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease(MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy(IMT) for MS-CD relative to conventional maintenance therapy remained unclarified.AIM To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer.METHODS A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy(CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs.RESULTS Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications(odds ratio: 0.527, P = 0.010), higher utility value for quality of life(coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management(coefficient-0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers $55260 to gain one quality-adjusted life year(QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita(GDPPC)] was 86.4%.CONCLUSION IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.22077038 and 21702070)the National Basic Research Plan of China(Grant No.2018YFA0208903)+2 种基金the Postdoctoral Research Foundation of China(Grant No.2017M612461)the National Undergraduate Program for Innovation and Entrepreneurship of China(Grant No.19YA06)the Shenzhen Science and Technology Project(Grant No.JCYJ20170818161I36779)。
文摘Theranostics that integrates therapy and diagnosis in one system to achieve accurate cancer diagnosis and treatment has attracted tremendous interest,and has been recognized as a potential breakthrough in overcoming the challenges of conventional oncotherapy.Nanoparticles are ideal candidates as carriers for theranostic agents,which is attributed to their extraordinary physicochemical properties,including nanoscale sizes,functional properties,prolonged blood circulation,active or passive tumor targeting,specific cellular uptake,and in some cases,excellent optical properties that ideally meet the needs of phototherapy and imaging at the same time.Overall,with the development of nanotechnology,theranostics has become a reality,and is now in the transition stage of"bench to bedside."In this review,we summarize recent progress on nanotechnology-based theranostics,i.e.,nanotheranostics,that has greatly assisted traditional therapies,and has provided therapeutic strategies emerging in recent decades,as well as"cocktail"theranostics mixing various treatment modalities.
基金This work was funded by the budgets from the National Basic Research Plan of China(2018YFA0208903)National Natural Science Foundation of China(21877042,22077038,81972894,81673364)+2 种基金the Ministry of Science and Technology of the People’s Republic of China(2017ZX09101001006)the Fundamental Research Funds for the Central Universities(2632018ZD13)the startup fund of Huazhong University of Science and Technology,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.The authors also thank the assistance from the Research Core Facilities for Life Science(HUST).
文摘The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients.Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising,yet greatly challenging,to reverse postoperative immunosuppression.Here,an injectable hierarchical gel matrix,composed of dual lipid gel(DLG)layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios,was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy.The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide(GO)nanoparticles.GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages(TAMs)and promote an immunogenic tumor microenvironment.The inner layer,loaded with anti-CD47 antibody(aCD47),could maintain the gel state for a much longer time,enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory proteinα(SIRPα)pathway for a long-term antitumor effect.In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape,thereby boosting the systemic immune responses.
基金Project supported by the National Natural Science Foundation of China(Grants Nos.11705064,11675060,and 91730301).
文摘Significant and persistent trajectory-to-trajectory variance are commonly observed in particle tracking experiments,which have become a major challenge for the experimental data analysis.In this theoretical paper we investigate the ergodicity recovery behavior,which helps clarify the origin and the convergence of trajectory-to-trajectory fluctuation in various heterogeneous disordered media.The concepts of self-averaging and ergodicity are revisited in the context of trajectory analysis.The slow ergodicity recovery and the non-Gaussian diffusion in the annealed disordered media are shown as the consequences of the central limit theorem in different situations.The strange ergodicity recovery behavior is reported in the quenched disordered case,which arises from a localization mechanism.The first-passage approach is introduced to the ergodicity analysis for this case,of which the central limit theorem can be employed and the ergodicity is recovered in the length scale of diffusivity correlation.
