BACKGROUND In 2018,the diagnosis-related groups prospective payment system(DRGs-PPS)was introduced in a trial operation in Beijing according to the requirements of medical and health reform.The implementation of the s...BACKGROUND In 2018,the diagnosis-related groups prospective payment system(DRGs-PPS)was introduced in a trial operation in Beijing according to the requirements of medical and health reform.The implementation of the system requires that more than 300 disease types pay through the DRGs-PPS for medical insurance.Colorectal cancer(CRC),as a common malignant tumor with high prevalence in recent years,was among the 300 disease types.AIM To investigate the composition and factors related to inpatient medical expenditure in CRC patients based on disease DRGs,and to provide a basis for the rational economic control of hospitalization expenses for the diagnosis and treatment of CRC.METHODS The basic material and cost data for 1026 CRC inpatients in a Grade-A tertiary hospital in Beijing during 2014-2018 were collected using the medical record system.A variance analysis of the composition of medical expenditure was carried out,and a multivariate linear regression model was used to select influencing factors with the greatest statistical significance.A decision tree model based on the exhaustiveχ^2 automatic interaction detector(E-CHAID)algorithm for DRG grouping was built by setting chosen factors as separation nodes,and the payment standard of each diagnostic group and upper limit cost were calculated.The correctness and rationality of the data were re-evaluated and verified by clinical practice.RESULTS The average hospital stay of the 1026 CRC patients investigated was 18.5 d,and the average hospitalization cost was 57872.4 RMB yuan.Factors including age,gender,length of hospital stay,diagnosis and treatment,as well as clinical operations had significant influence on inpatient expenditure(P<0.05).By adopting age,diagnosis,treatment,and surgery as the grouping nodes,a decision tree model based on the E-CHAID algorithm was established,and the CRC patients were divided into 12 DRG cost groups.Among these 12 groups,the number of patients aged≤67 years,and underwent surgery and chemotherapy or radiotherapy was largest;while patients aged>67 years,and underwent surgery and chemotherapy or radiotherapy had the highest medical cost.In addition,the standard cost and upper limit cost in the 12 groups were calculated and re-evaluated.CONCLUSION It is important to strengthen the control over the use of drugs and management of the hospitalization process,surgery,diagnosis and treatment to reduce the economic burden on patients.Tailored adjustments to medical payment standards should be made according to the characteristics and treatment of disease types to improve the comprehensiveness and practicability of the DRGs-PPS.展开更多
Background:The number of medical research publications by Chinese clinical investigators has risen substantially,contributing to 14.63%of the global total in 2019;however,their tangible impact on clinical decisionmaki...Background:The number of medical research publications by Chinese clinical investigators has risen substantially,contributing to 14.63%of the global total in 2019;however,their tangible impact on clinical decisionmaking remains limited.Various evaluation methods have been developed to measure hospital research competence in China,such as Fudan University's China hospital ranking and Science and Technology Evaluation Metrics(STEM)ranking,which predominantly focuses on factors such as academic reputation,volume of publications and patents,and research resources.However,composite indices may not fully capture the actual clinical value generated by medical research.To address this gap,we introduced the“Clinical Influence and Timeliness Evaluation(CITE)”metric to assess both the clinical importance of a given medical research study and the clinical influence of the hospital where it originated.The methodology used relies on the premise that influential medical research would be referenced in clinical guidelines,which serve as critical resources for clinicians.Methods:The CITE metric was applied for 78,636 medical studies concerning chronic obstructive pulmonary disease(COPD)published between 2000 and 2020 and referenced in both Chinese and international clinical guidelines for COPD.Specific indexes and formulas were derived to quantify the clinical weight of a medical research study(W)and its timeliness(T),enabling a dynamic assessment of the clinical value of each study and the overall contribution of a particular hospital.Results:In this analysis,we incorporated 499 hospitals in China and quantitatively identified their dynamic clinical influence in COPD from 2000 to 2020.Our findings offer objective and targeted evaluation metrics by focusing on clinical relevance and recognizing the collaborative nature of medical research.Conclusion:The CITE metric provides an innovative method to gauge the true impact of medical research in China,with potential applications across different medical specialties.CITE can serve as a useful tool for understanding the relationship between research input and practical clinical outcomes,ultimately promoting more clinically relevant research endeavors.展开更多
Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introd...Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers.This non-invasive technique not only facilitates prompt therapeutic intervention,but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence.The wealth of circulating exosomes present in body fluids is often enriched with proteins,lipids,microRNAs,and other RNAs derived from tumor cells.These specific cargo components are reflective of processes involved in GI tumorigenesis,tumor progression,and response to treatment.As such,they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer.In this review,we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles.We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application.Furthermore,we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.展开更多
Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which mi...Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.展开更多
Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.T...Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.展开更多
The use of synthetic biology technology to develop cosmetic ingredients is attracting widespread attention due to its effectiveness,safety,and environmental friendliness.This article explains the concept of synthetic ...The use of synthetic biology technology to develop cosmetic ingredients is attracting widespread attention due to its effectiveness,safety,and environmental friendliness.This article explains the concept of synthetic biology and its key technologies and current status in the production of cosmetic ingredients.It also briefly analyzes the regulatory approaches to synthetic biology-based cosmetic ingredients in different countries and regions,providing guidance for the management of this field in China.The goal is to ensure product safety,enhance consumer trust,and promote the healthy development of the industry.展开更多
Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working p...Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working populations and school-aged children at higher risk due to increased outdoor exposure[1].Dengue transmission in Sri Lanka is seasonal with two high transmission waves corresponding with the two monsoon rains every year.The estimated average annual incidence is 175/100000 population,and it was 407.5/100000 in 2023 with a case fatality rate of 0.07%[2].展开更多
Recently,a multitude of techniques that fuse deep learning with Retinex theory have been utilized in the field of low-light image enhancement,yielding remarkable outcomes.Due to the intricate nature of imaging scenari...Recently,a multitude of techniques that fuse deep learning with Retinex theory have been utilized in the field of low-light image enhancement,yielding remarkable outcomes.Due to the intricate nature of imaging scenarios,including fluctuating noise levels and unpredictable environmental elements,these techniques do not fully resolve these challenges.We introduce an innovative strategy that builds upon Retinex theory and integrates a novel deep network architecture,merging the Convolutional Block Attention Module(CBAM)with the Transformer.Our model is capable of detecting more prominent features across both channel and spatial domains.We have conducted extensive experiments across several datasets,namely LOLv1,LOLv2-real,and LOLv2-sync.The results show that our approach surpasses other methods when evaluated against critical metrics such as Peak Signal-to-Noise Ratio(PSNR)and Structural Similarity Index(SSIM).Moreover,we have visually assessed images enhanced by various techniques and utilized visual metrics like LPIPS for comparison,and the experimental data clearly demonstrate that our approach excels visually over other methods as well.展开更多
Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfen...Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfenidone treatment on lung function in 113 patients with IPF.In addition to other research,pirfeni-done has demonstrated efficacy in patients at all stages of IPF once correct diagnosis has been made.In advanced IPF,we include the requirement for pirfenidone.Therefore,it is essential to choose an appropriate method of adminis-tration method,such as inhalation.This may circumvent the drawbacks of the high cost and possible adverse effects of this drug.展开更多
By recruiting 30 participants with striae gravidarum and using anti-wrinkle skincare products as an intervention measure,skin elasticity testing,skin firmness testing,and stretch mark image collection were conducted b...By recruiting 30 participants with striae gravidarum and using anti-wrinkle skincare products as an intervention measure,skin elasticity testing,skin firmness testing,and stretch mark image collection were conducted before use the anti-wrinkle skincare products,on the 14th,28th,and 56th day of use the antiwrinkle skincare products,respectively.Combined with visual evaluation by researchers and self-assessment by participants,the role of anti-wrinkle skincare products in improving stretch marks during pregnancy was explored.The results showed that on the 14th,28th,and 56th day of using efficacy skincare products,the average depth,area,and volume of stretch marks in the test area decreased compared to the baseline values before use and showed statistical differences(P<0.05);The measured values of R5 and R7 parameters for evaluating skin elasticity at the test site were significantly higher than the baseline values before use(P<0.05).On the 28th and 56th day of using efficacy skincare products,the measured values of the skin firmness evaluation parameters in the test area decreased significantly compared to the baseline values before use,and there was a statistical difference(P<0.05).The scores of the number,depth,and skin laxity of abdominal stretch marks in the visual assessment of the researchers and self-assessment of the subjects were significantly reduced on days 14,28,and 56 compared to before using the anti-wrinkle skincare product(P<0.05).This suggests that the anti-wrinkle skincare product has the effect of improving the elasticity and firmness of the skin in subjects with striae gravidarum,as well as improving striae gravidarum.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseas...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.展开更多
Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and pro...Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.展开更多
Acute spontaneous urticaria has a high incidence,with sudden and severe symptoms that can significantly impact daily life and work.If not properly managed,it may lead to severe reactions such as angioedema,gastrointes...Acute spontaneous urticaria has a high incidence,with sudden and severe symptoms that can significantly impact daily life and work.If not properly managed,it may lead to severe reactions such as angioedema,gastrointestinal symptoms,or even anaphylactic shock.Research on acute spontaneous urticaria is limited,with unclear etiology,and treatment largely relies on antihistamines and corticosteroids,which may not prevent progression to chronic urticaria.In this study,three patients with acute spontaneous urticaria,unresponsive to conventional treatments,chose a single 300mg subcutaneous injection of Omalizumab after evaluating the risks and benefits.Within 1-3 days,all patients showed significant symptom improvement,with near-complete resolution of lesions.Within a week,they resumed normal daily activities,and no recurrence was observed during 12 months of follow-up,with no adverse reactions.This study demonstrates the efficacy and safety of Omalizumab for acute spontaneous urticaria,particularly in cases resistant to antihistamines and corticosteroids.Early administration of Omalizumab can effectively control disease progression,reduce impact on daily life,and may lower the risk of developing chronic urticaria.These findings suggest that Omalizumab should be considered a valuable option in treating acute spontaneous urticaria,especially when conventional therapies fail,offering rapid symptom relief and long-term disease control.展开更多
Variable material screw-based material extrusion(S-MEX)3D printing technology provides a novel approach for fabricating composites with continuous material gradients.Nevertheless,achieving precise alignment between th...Variable material screw-based material extrusion(S-MEX)3D printing technology provides a novel approach for fabricating composites with continuous material gradients.Nevertheless,achieving precise alignment between the process parameters and material compositions is challenging because of fluctuations in the melt rheological state caused by material variations.In this study,an invertible extrusion prediction model for 0-40 wt% short carbon fiber reinforced polyether-ether-ketone(SCF/PEEK)in the S-MEX process was established using an invertible neural network(INN)that demonstrated the capabilities of forward flow rate prediction and inverse process optimization with accuracies of 0.852 and 0.877,respectively.Moreover,a strategy for adjusting the screw speeds using process parameters obtained from the INN was developed to maintain a consistent flow rate during the variable material printing process.Benefiting from uniform flow,the linewidth accuracy was improved by 77%,and the surface roughness was reduced by 51%.Adjusting the process parameters by using an INN offers significant potential for flow rate control and the enhancement of the overall performance of variable material 3D printing.展开更多
This work aims to compare the chemical composition and anti-inflammatory effects on RAW264.7 macrophages of Keemun black tea stems and leaves.A total of 50 volatile compounds were identified in tea stems and leaves,an...This work aims to compare the chemical composition and anti-inflammatory effects on RAW264.7 macrophages of Keemun black tea stems and leaves.A total of 50 volatile compounds were identified in tea stems and leaves,and aldehydes,alcohols,and esters were the main volatile compound categories.There were 11 key volatile compounds,including geraniol,benzeneacetaldehyde,methyl salicylate,linalool,etc.contributed to distinguishing the tea stems from the tea leaves.In the quantitative and liquid chromatography-mass spectrometry(LC-MS)-based metabolomics analysis,higher contents of amino acids,monosaccharides,and quinic acids were found in stems than those in leaves.Inversely,higher contents of tea pigments,flavan-3-ols,gallic acid,purine alkaloids,and flavonol glycosides were present in tea leaves than in stems.LC-MS-based metabolomics also revealed that organic acids were the most critical non-volatile compounds responsible for the differences between tea stems and leaves.Furthermore,tea stems had better inhibiting effects of pro-inflammatory cytokines(interleukin(IL)-1βand IL-6)in lipopolysaccharide-challenged RAW264.7 macrophages than tea leaves,while no significant differences exist between leaves and stems for inhibiting the secretion of tumor necrosis factorα(TNF-α)and NO.In conclusion,our results support using Keemun black tea stems as a novel source of anti-inflammatory compounds.展开更多
Through three millennia of practice,Traditional Chinese Medicine(TCM)has evolved by integrating knowledge from diverse disciplines,forging a distinct developmental path that respects its ancient foundations while inco...Through three millennia of practice,Traditional Chinese Medicine(TCM)has evolved by integrating knowledge from diverse disciplines,forging a distinct developmental path that respects its ancient foundations while incorporating innovation.TCM has achieved significant breakthroughs in elucidating its theoretical foundations using contemporary scientific methodologies,through the implementation of modernization initiatives over the past three decades.The TCM modernization program has yielded continuous innovations,propelling TCM into a high-quality development stage across both clinical practice and industrial applications.Notably,these advances have enhanced global recognition and adoption of TCM.展开更多
The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechani...The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.展开更多
In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2...In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95%of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.展开更多
Brain,the material foundation of human intelligence,is the most complex tissue in the human body.Brain diseases are among the leading threats to human life,yet our understanding of their pathogenic mechanisms and drug...Brain,the material foundation of human intelligence,is the most complex tissue in the human body.Brain diseases are among the leading threats to human life,yet our understanding of their pathogenic mechanisms and drug development remains limited,largely due to the lack of accurate brain-like tissue models that replicate its complex structure and functions.Therefore,constructing brain-like models—both in morphology and function—possesses significant scientific value for advancing brain science and pathological pharmacology research,representing the frontiers in the biomanufacturing field.This review outlines the primary requirements and challenges in biomanufacturing brain-like tissue,addressing its complex structures,functions,and environments.Also,the existing biomanufacturing technologies,strategies,and characteristics for brain-like models are depicted,and cutting-edge developments in biomanufacturing central neural repair prosthetics,brain development models,brain disease models,and brain-inspired biocomputing models are systematically reviewed.Finally,the paper concludes with future perspectives on the biomanufacturing of brain-like tissue transitioning from structural manufacturing to intelligent functioning.展开更多
The bioinert nature of polyether ether ketone(PEEK)material limits the widespread clinical application of PEEK implants.Although the porous structure is considered to improve osseointegration of PEEK implants,it is ha...The bioinert nature of polyether ether ketone(PEEK)material limits the widespread clinical application of PEEK implants.Although the porous structure is considered to improve osseointegration of PEEK implants,it is hardly used due to its mechanical properties.This study investigated the combined influence of the porous structure and in vivo mechanical stimulation on implantation safety and bone growth based on finite element analysis of the biomechanical behavior of the implantation system.The combined control of pore size and screw preloads allows the porous PEEK implant to achieve good osseointegration while maintaining a relatively high safety level.A pore size of 600μm and a preload of 0.05 N·m are the optimal combination for the long-term stability of the implant,with which the safety factor of the implant is>2,and the predicted percentage of effective bone growth area of the bone-implant interface reaches 97%.For further clinical application,PEEK implants were fabricated with fused filament fabrication(FFF)three-dimensional(3D)printing,and clinical outcomes demonstrated better bone repair efficacy and long-term stability of porous PEEK implants compared to solid PEEK implants.Moreover,good osteointegration performance of 3D-printed porous PEEK implants was observed,with an average bone volume fraction>40%three months after implantation.In conclusion,3D-printed porous PEEK implants have great potential for clinical application,with validated implantation safety and good osseointegration.展开更多
文摘BACKGROUND In 2018,the diagnosis-related groups prospective payment system(DRGs-PPS)was introduced in a trial operation in Beijing according to the requirements of medical and health reform.The implementation of the system requires that more than 300 disease types pay through the DRGs-PPS for medical insurance.Colorectal cancer(CRC),as a common malignant tumor with high prevalence in recent years,was among the 300 disease types.AIM To investigate the composition and factors related to inpatient medical expenditure in CRC patients based on disease DRGs,and to provide a basis for the rational economic control of hospitalization expenses for the diagnosis and treatment of CRC.METHODS The basic material and cost data for 1026 CRC inpatients in a Grade-A tertiary hospital in Beijing during 2014-2018 were collected using the medical record system.A variance analysis of the composition of medical expenditure was carried out,and a multivariate linear regression model was used to select influencing factors with the greatest statistical significance.A decision tree model based on the exhaustiveχ^2 automatic interaction detector(E-CHAID)algorithm for DRG grouping was built by setting chosen factors as separation nodes,and the payment standard of each diagnostic group and upper limit cost were calculated.The correctness and rationality of the data were re-evaluated and verified by clinical practice.RESULTS The average hospital stay of the 1026 CRC patients investigated was 18.5 d,and the average hospitalization cost was 57872.4 RMB yuan.Factors including age,gender,length of hospital stay,diagnosis and treatment,as well as clinical operations had significant influence on inpatient expenditure(P<0.05).By adopting age,diagnosis,treatment,and surgery as the grouping nodes,a decision tree model based on the E-CHAID algorithm was established,and the CRC patients were divided into 12 DRG cost groups.Among these 12 groups,the number of patients aged≤67 years,and underwent surgery and chemotherapy or radiotherapy was largest;while patients aged>67 years,and underwent surgery and chemotherapy or radiotherapy had the highest medical cost.In addition,the standard cost and upper limit cost in the 12 groups were calculated and re-evaluated.CONCLUSION It is important to strengthen the control over the use of drugs and management of the hospitalization process,surgery,diagnosis and treatment to reduce the economic burden on patients.Tailored adjustments to medical payment standards should be made according to the characteristics and treatment of disease types to improve the comprehensiveness and practicability of the DRGs-PPS.
文摘Background:The number of medical research publications by Chinese clinical investigators has risen substantially,contributing to 14.63%of the global total in 2019;however,their tangible impact on clinical decisionmaking remains limited.Various evaluation methods have been developed to measure hospital research competence in China,such as Fudan University's China hospital ranking and Science and Technology Evaluation Metrics(STEM)ranking,which predominantly focuses on factors such as academic reputation,volume of publications and patents,and research resources.However,composite indices may not fully capture the actual clinical value generated by medical research.To address this gap,we introduced the“Clinical Influence and Timeliness Evaluation(CITE)”metric to assess both the clinical importance of a given medical research study and the clinical influence of the hospital where it originated.The methodology used relies on the premise that influential medical research would be referenced in clinical guidelines,which serve as critical resources for clinicians.Methods:The CITE metric was applied for 78,636 medical studies concerning chronic obstructive pulmonary disease(COPD)published between 2000 and 2020 and referenced in both Chinese and international clinical guidelines for COPD.Specific indexes and formulas were derived to quantify the clinical weight of a medical research study(W)and its timeliness(T),enabling a dynamic assessment of the clinical value of each study and the overall contribution of a particular hospital.Results:In this analysis,we incorporated 499 hospitals in China and quantitatively identified their dynamic clinical influence in COPD from 2000 to 2020.Our findings offer objective and targeted evaluation metrics by focusing on clinical relevance and recognizing the collaborative nature of medical research.Conclusion:The CITE metric provides an innovative method to gauge the true impact of medical research in China,with potential applications across different medical specialties.CITE can serve as a useful tool for understanding the relationship between research input and practical clinical outcomes,ultimately promoting more clinically relevant research endeavors.
文摘Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers.This non-invasive technique not only facilitates prompt therapeutic intervention,but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence.The wealth of circulating exosomes present in body fluids is often enriched with proteins,lipids,microRNAs,and other RNAs derived from tumor cells.These specific cargo components are reflective of processes involved in GI tumorigenesis,tumor progression,and response to treatment.As such,they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer.In this review,we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles.We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application.Furthermore,we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.
基金supported by grants from the National Key Research and Development Program of China,No.2017YFA0105400(to LR)the Key Research and Development Program of Guangdong Province,No.2019B020236002(to LR)the National Natural Science Foundation of China,Nos.81972111(to LZ),81772349(to BL).
文摘Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.
基金supported by National Key R&D Program of China(Grant No.2022YFB4600500)Fundamental Research Funds for the Central Universities,and the Program for Innovation Team of Shaanxi Province(Grant No.2023-CX-TD-17).
文摘Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.
文摘The use of synthetic biology technology to develop cosmetic ingredients is attracting widespread attention due to its effectiveness,safety,and environmental friendliness.This article explains the concept of synthetic biology and its key technologies and current status in the production of cosmetic ingredients.It also briefly analyzes the regulatory approaches to synthetic biology-based cosmetic ingredients in different countries and regions,providing guidance for the management of this field in China.The goal is to ensure product safety,enhance consumer trust,and promote the healthy development of the industry.
文摘Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working populations and school-aged children at higher risk due to increased outdoor exposure[1].Dengue transmission in Sri Lanka is seasonal with two high transmission waves corresponding with the two monsoon rains every year.The estimated average annual incidence is 175/100000 population,and it was 407.5/100000 in 2023 with a case fatality rate of 0.07%[2].
文摘Recently,a multitude of techniques that fuse deep learning with Retinex theory have been utilized in the field of low-light image enhancement,yielding remarkable outcomes.Due to the intricate nature of imaging scenarios,including fluctuating noise levels and unpredictable environmental elements,these techniques do not fully resolve these challenges.We introduce an innovative strategy that builds upon Retinex theory and integrates a novel deep network architecture,merging the Convolutional Block Attention Module(CBAM)with the Transformer.Our model is capable of detecting more prominent features across both channel and spatial domains.We have conducted extensive experiments across several datasets,namely LOLv1,LOLv2-real,and LOLv2-sync.The results show that our approach surpasses other methods when evaluated against critical metrics such as Peak Signal-to-Noise Ratio(PSNR)and Structural Similarity Index(SSIM).Moreover,we have visually assessed images enhanced by various techniques and utilized visual metrics like LPIPS for comparison,and the experimental data clearly demonstrate that our approach excels visually over other methods as well.
文摘Idiopathic pulmonary fibrosis(IPF)has a poor prognosis if left untreated;therefore,early treatment with pirfenidone is crucial.Lei et al conducted a retrospective analysis to evaluate the effectiveness of early pirfenidone treatment on lung function in 113 patients with IPF.In addition to other research,pirfeni-done has demonstrated efficacy in patients at all stages of IPF once correct diagnosis has been made.In advanced IPF,we include the requirement for pirfenidone.Therefore,it is essential to choose an appropriate method of adminis-tration method,such as inhalation.This may circumvent the drawbacks of the high cost and possible adverse effects of this drug.
文摘By recruiting 30 participants with striae gravidarum and using anti-wrinkle skincare products as an intervention measure,skin elasticity testing,skin firmness testing,and stretch mark image collection were conducted before use the anti-wrinkle skincare products,on the 14th,28th,and 56th day of use the antiwrinkle skincare products,respectively.Combined with visual evaluation by researchers and self-assessment by participants,the role of anti-wrinkle skincare products in improving stretch marks during pregnancy was explored.The results showed that on the 14th,28th,and 56th day of using efficacy skincare products,the average depth,area,and volume of stretch marks in the test area decreased compared to the baseline values before use and showed statistical differences(P<0.05);The measured values of R5 and R7 parameters for evaluating skin elasticity at the test site were significantly higher than the baseline values before use(P<0.05).On the 28th and 56th day of using efficacy skincare products,the measured values of the skin firmness evaluation parameters in the test area decreased significantly compared to the baseline values before use,and there was a statistical difference(P<0.05).The scores of the number,depth,and skin laxity of abdominal stretch marks in the visual assessment of the researchers and self-assessment of the subjects were significantly reduced on days 14,28,and 56 compared to before using the anti-wrinkle skincare product(P<0.05).This suggests that the anti-wrinkle skincare product has the effect of improving the elasticity and firmness of the skin in subjects with striae gravidarum,as well as improving striae gravidarum.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.
基金supported by the National Natural Science Foundation of China(No.82372001,82171973,82171980)the Youth Talent Support Program(No.A002863)Scientific Research Foundation of Peking University Cancer Hospital(No.BJCH2024CZ02)。
文摘Objective:This study aimed to evaluate the clinical utility of[^(68)Ga]Ga-RM2 positron emission tomography/computed tomography(PET/CT),in comparison with^(18)F-fluorodeoxyglucose([^(18)F]FDG)PET/CT,for staging and prognosis in patients with estrogen receptor-positive(ER+)breast cancer.Methods:This prospective study enrolled nine female patients with breast cancer(mean age 45.5±11.5 years).Eight patients were confirmed to have ER+disease.All participant underwent both[^(68)Ga]Ga-RM2 PET/CT and[^(18)F]FDG PET/CT scans within a one-week interval.The maximum standardized uptake values(SUV_(max))was measured for primary tumors,lymph nodes,and metastatic lesions.The physiological distribution of[^(68)Ga]GaRM2 was also evaluated.Results:No adverse events were observed.Metastatic were identified in lymph nodes(n=29 lesions),bone(n=19),liver(n=7),brain(n=3),and multiple other sites.[^(68)Ga]Ga-RM2 demonstrated a significantly higher median SUV_(max)than[^(18)F]FDG across all lesions[7.5(interquartile range,IQR,3.4-14.0)vs.4.0(IQR,2.3-6.1);P<0.001].Similarly,the tumor-to-background ratio(TBR)was significantly superior with[^(68)Ga]Ga-RM2 for all type of lesions:primary tumors[12.3(IQR,10.4-18.3)vs.7.0(IQR,6.0-10.0);P<0.001],lymph node metastases[17.8(IQR,4.4-39.0)vs.4.7(IQR,2.7-10.2);P<0.001],hepatic metastases[5.4(IQR,3.7-8.3)vs.1.0(IQR,0.9-1.5);P<0.001],and osseous metastases[13.9(IQR,7.3-18.0)vs.4.3(IQR,1.6-5.9);P<0.001].Physiological uptake of[^(68)Ga]Ga-RM2 was the highest in the pancreas(SUV_(max),77.82±22.64),with moderate uptake in the kidneys(2.82±0.62),heart(1.83±0.29),and liver(1.33±0.41).Conclusions:[^(68)Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions,particularly in the brain and breast,suggesting its potential as a valuable complementary imaging modality to[^(18)F]FDG PET/CT.These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.
文摘Acute spontaneous urticaria has a high incidence,with sudden and severe symptoms that can significantly impact daily life and work.If not properly managed,it may lead to severe reactions such as angioedema,gastrointestinal symptoms,or even anaphylactic shock.Research on acute spontaneous urticaria is limited,with unclear etiology,and treatment largely relies on antihistamines and corticosteroids,which may not prevent progression to chronic urticaria.In this study,three patients with acute spontaneous urticaria,unresponsive to conventional treatments,chose a single 300mg subcutaneous injection of Omalizumab after evaluating the risks and benefits.Within 1-3 days,all patients showed significant symptom improvement,with near-complete resolution of lesions.Within a week,they resumed normal daily activities,and no recurrence was observed during 12 months of follow-up,with no adverse reactions.This study demonstrates the efficacy and safety of Omalizumab for acute spontaneous urticaria,particularly in cases resistant to antihistamines and corticosteroids.Early administration of Omalizumab can effectively control disease progression,reduce impact on daily life,and may lower the risk of developing chronic urticaria.These findings suggest that Omalizumab should be considered a valuable option in treating acute spontaneous urticaria,especially when conventional therapies fail,offering rapid symptom relief and long-term disease control.
基金supported by National Natural Science Foundation of China(Grant Nos.12202547,62461160259)Shaanxi Province Qingchuangyuan“Scientist and Engineering”Team Construction Project(Grant Nos.2022KXJ-102,2022KXJ-106)+1 种基金Fundamental Research Funds for the Central UniversitiesProgram for Innovation Team of Shaanxi Province(Grant No.2023-CX-TD-17).
文摘Variable material screw-based material extrusion(S-MEX)3D printing technology provides a novel approach for fabricating composites with continuous material gradients.Nevertheless,achieving precise alignment between the process parameters and material compositions is challenging because of fluctuations in the melt rheological state caused by material variations.In this study,an invertible extrusion prediction model for 0-40 wt% short carbon fiber reinforced polyether-ether-ketone(SCF/PEEK)in the S-MEX process was established using an invertible neural network(INN)that demonstrated the capabilities of forward flow rate prediction and inverse process optimization with accuracies of 0.852 and 0.877,respectively.Moreover,a strategy for adjusting the screw speeds using process parameters obtained from the INN was developed to maintain a consistent flow rate during the variable material printing process.Benefiting from uniform flow,the linewidth accuracy was improved by 77%,and the surface roughness was reduced by 51%.Adjusting the process parameters by using an INN offers significant potential for flow rate control and the enhancement of the overall performance of variable material 3D printing.
基金supported by the Natural Science Foundation of China(32122079,32072633)Earmarked Fund for China Agriculture Research System(CARS-19)+2 种基金Anhui Key Research and Development Plan(202104b11020001)Young Elite Scientist Sponsorship Program by National CAST(2016QNRC001)High-level Introduced Talent Sponsorship Program by Anhui Agricultural University(rc352203)。
文摘This work aims to compare the chemical composition and anti-inflammatory effects on RAW264.7 macrophages of Keemun black tea stems and leaves.A total of 50 volatile compounds were identified in tea stems and leaves,and aldehydes,alcohols,and esters were the main volatile compound categories.There were 11 key volatile compounds,including geraniol,benzeneacetaldehyde,methyl salicylate,linalool,etc.contributed to distinguishing the tea stems from the tea leaves.In the quantitative and liquid chromatography-mass spectrometry(LC-MS)-based metabolomics analysis,higher contents of amino acids,monosaccharides,and quinic acids were found in stems than those in leaves.Inversely,higher contents of tea pigments,flavan-3-ols,gallic acid,purine alkaloids,and flavonol glycosides were present in tea leaves than in stems.LC-MS-based metabolomics also revealed that organic acids were the most critical non-volatile compounds responsible for the differences between tea stems and leaves.Furthermore,tea stems had better inhibiting effects of pro-inflammatory cytokines(interleukin(IL)-1βand IL-6)in lipopolysaccharide-challenged RAW264.7 macrophages than tea leaves,while no significant differences exist between leaves and stems for inhibiting the secretion of tumor necrosis factorα(TNF-α)and NO.In conclusion,our results support using Keemun black tea stems as a novel source of anti-inflammatory compounds.
文摘Through three millennia of practice,Traditional Chinese Medicine(TCM)has evolved by integrating knowledge from diverse disciplines,forging a distinct developmental path that respects its ancient foundations while incorporating innovation.TCM has achieved significant breakthroughs in elucidating its theoretical foundations using contemporary scientific methodologies,through the implementation of modernization initiatives over the past three decades.The TCM modernization program has yielded continuous innovations,propelling TCM into a high-quality development stage across both clinical practice and industrial applications.Notably,these advances have enhanced global recognition and adoption of TCM.
基金financially supported by the National Natural Science Foundation of China(Nos.52125501,52405325)the Key Research Project of Shaanxi Province(Nos.2021LLRH-08,2024SF2-GJHX-34)+5 种基金the Program for Innovation Team of Shaanxi Province(No.2023-CX-TD17)the Postdoctoral Fellowship Program of CPSF(No.GZB20230573)the Postdoctoral Project of Shaanxi Province(No.2023BSHYDZZ30)the Basic Research Program of Natural Science in Shaanxi Province(No.2021JQ-906)the China Postdoctoral Science Foundationthe Fundamental Research Funds for the Central Universities。
文摘The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.
基金support from the Science Research Program Project for Drug Regulation,Jiangsu Medical Products Administration,China(Grant No.:202207)the National Drug Standards Revision Project,China(Grant No.:2023Y41)+1 种基金the National Natural Science Foundation of China(Grant No.:22276080)the Foreign Expert Project,China(Grant No.:G2022014096L).
文摘In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95%of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.
基金supported by the Program of the National Natural Science Foundation of China(52275291)(52435006)the Program for Innovation Team of Shaanxi Province(2023CX-TD-17)the Fundamental Research Funds for the Central Universities。
文摘Brain,the material foundation of human intelligence,is the most complex tissue in the human body.Brain diseases are among the leading threats to human life,yet our understanding of their pathogenic mechanisms and drug development remains limited,largely due to the lack of accurate brain-like tissue models that replicate its complex structure and functions.Therefore,constructing brain-like models—both in morphology and function—possesses significant scientific value for advancing brain science and pathological pharmacology research,representing the frontiers in the biomanufacturing field.This review outlines the primary requirements and challenges in biomanufacturing brain-like tissue,addressing its complex structures,functions,and environments.Also,the existing biomanufacturing technologies,strategies,and characteristics for brain-like models are depicted,and cutting-edge developments in biomanufacturing central neural repair prosthetics,brain development models,brain disease models,and brain-inspired biocomputing models are systematically reviewed.Finally,the paper concludes with future perspectives on the biomanufacturing of brain-like tissue transitioning from structural manufacturing to intelligent functioning.
基金supported by the National Key R&D Program of China(No.2023YFB4603500)the Program for Innovation Team of Shaanxi Province(No.2023-CX-TD-17)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Shaanxi Province Qinchuangyuan“Scientist+Engineer”Team Construction Project(No.2022KXJ-106).
文摘The bioinert nature of polyether ether ketone(PEEK)material limits the widespread clinical application of PEEK implants.Although the porous structure is considered to improve osseointegration of PEEK implants,it is hardly used due to its mechanical properties.This study investigated the combined influence of the porous structure and in vivo mechanical stimulation on implantation safety and bone growth based on finite element analysis of the biomechanical behavior of the implantation system.The combined control of pore size and screw preloads allows the porous PEEK implant to achieve good osseointegration while maintaining a relatively high safety level.A pore size of 600μm and a preload of 0.05 N·m are the optimal combination for the long-term stability of the implant,with which the safety factor of the implant is>2,and the predicted percentage of effective bone growth area of the bone-implant interface reaches 97%.For further clinical application,PEEK implants were fabricated with fused filament fabrication(FFF)three-dimensional(3D)printing,and clinical outcomes demonstrated better bone repair efficacy and long-term stability of porous PEEK implants compared to solid PEEK implants.Moreover,good osteointegration performance of 3D-printed porous PEEK implants was observed,with an average bone volume fraction>40%three months after implantation.In conclusion,3D-printed porous PEEK implants have great potential for clinical application,with validated implantation safety and good osseointegration.
