Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to t...Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.展开更多
Compared to traditional liquid electrolyte batteries,solid metal batteries offer advantages such as a wide operating temperature range,high energy density,and improved safety,making them a promising energy storage tec...Compared to traditional liquid electrolyte batteries,solid metal batteries offer advantages such as a wide operating temperature range,high energy density,and improved safety,making them a promising energy storage technology.Solid electrolytes,as the core components of solid‐state batteries,are key factors in advancing solid‐state battery technology.Among various solid electrolytes,Na super ionic conductor(NASICON)‐type solid electrolytes exhibit high ionic conductivity(10−3 S·cm−1),a wide electrochemical window,and good thermal stability,providing room for the development of high energy‐density solid metal batteries.Since the discovery of NASICON‐type solid electrolytes in 1976,interest in their use in all‐solid‐state battery development has grown significantly.In this review,we comprehensively analyze the common features of NASICON lithium‐ion conductors and NASICON sodium‐ion conductors,review the historical development of NASICON‐type solid electrolytes,systematically summarize the transport mechanisms of metal cations in NASICON‐type solid electrolytes,discuss the latest strategies for enhancing ionic conductivity,elaborate on the latest methods for improving mechanical stability and interface stability,and point out the requirements of high energy density devices for NASICON‐type solid electrolytes as well as three types of in situ characterization techniques for interfaces.Finally,we highlight the challenges and potential solutions for the future development of NASICON‐type solid electrolytes and solid‐state metal batteries.展开更多
Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb to...Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.展开更多
It is very important in the field of bioinformatics to apply computer to perform the function annotation for new sequenced bio-sequences. Based on GO database and BLAST program, a novel method for the function annotat...It is very important in the field of bioinformatics to apply computer to perform the function annotation for new sequenced bio-sequences. Based on GO database and BLAST program, a novel method for the function annotation of new biological sequences is presented by using the variable-precision rough set theory. The proposed method is applied to the real data in GO database to examine its effectiveness. Numerical results show that the proposed method has better precision, recall-rate and harmonic mean value compared with existing methods.展开更多
An enriched environment is used as a behavio ral intervention therapy that applies sensory,motor,and social stimulation,and has been used in basic and clinical research of va rious neurological diseases.In this study,...An enriched environment is used as a behavio ral intervention therapy that applies sensory,motor,and social stimulation,and has been used in basic and clinical research of va rious neurological diseases.In this study,we established mouse models of photothrombotic stroke and,24 hours later,raised them in a standard,enriched,or isolated environment for 4 weeks.Compared with the mice raised in a standard environment,the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated.Furthermore,protein expression levels of tumor necrosis factor receptor-associated factor 6,nuclear factorκB p65,interleukin-6,and tumor necrosis factorα,and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower,while the expression level of miR-146a-5p was higher.Compared with the mice raised in a standard environment,changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment.These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stro ke.An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.展开更多
Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to selec...Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.展开更多
In the context of constructing Global Energy Interconnection(GEI), energy storage technology, as one of the important basic supporting technologies in power system, will play an important role in the energy configurat...In the context of constructing Global Energy Interconnection(GEI), energy storage technology, as one of the important basic supporting technologies in power system, will play an important role in the energy configuration and optimization. Based on the most promising battery energy storage technology, this paper introduces the current status of the grid technology, the application of large-scale energy storage technology and the supporting role of battery energy storage for GEI. Based on several key technologies of large-scale battery energy storage system, preliminary analysis of the standard system construction of energy storage system is made, and the future prospect is put forward.展开更多
Based on the energy storage cloud platform architecture,this study considers the extensive configuration of energy storage devices and the future large-scale application of electric vehicles at the customer side to bu...Based on the energy storage cloud platform architecture,this study considers the extensive configuration of energy storage devices and the future large-scale application of electric vehicles at the customer side to build a new mode of smart power consumption with a flexible interaction,smooth the peak/valley difference of the load side power,and improve energy efficiency.A plug and play device for customer-side energy storage and an internet-based energy storage cloud platform are developed herein to build a new intelligent power consumption mode with a flexible interaction suitable for ordinary customers.Based on the load perception of the power grid,this study aims to investigate the operating state and service life of distributed energy storage devices.By selecting an integrated optimal control scheme,this study designs a kind of energy optimization and deployment strategy for stratified partition to reduce the operating cost of the energy storage device on the client side.The effectiveness of the system and the control strategy is verified through the Suzhou client-side distributed energy storage demonstration project.展开更多
Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids ...Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel FeeCu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under lowpower microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H_(2)O_(2) decomposition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTT and chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and provides a reference for developing new microwave sensitizers。展开更多
As part of the ongoing information revolution,smart power grid technology has become a key focus area for research into power systems.Intelligent electrical appliances are now an important component of power systems,p...As part of the ongoing information revolution,smart power grid technology has become a key focus area for research into power systems.Intelligent electrical appliances are now an important component of power systems,providing a smart power grid with increased control,stability,and safety.Based on the secure communication requirements of cloud energy storage systems,this paper presents the design and development of a node controller for a cloud energy storage network.The function division and system deployment processes were carried out to ensure the security of the communication network used for the cloud energy storage system.Safety protection measures were proposed according to the demands of the communication network,allowing the system to run safely and stably.Finally,the effectiveness of the system was verified through a client-side distributed energy storage demonstration project in Suzhou,China.The system was observed to operate safely and stably,demonstrating good peak-clipping and valley filling effects,and improving the system load characteristics.展开更多
To the Editor,Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for portal hypertension,particularly in cases of esophageal and gastric variceal bleeding.By reducing portal pressure,TIPS low...To the Editor,Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for portal hypertension,particularly in cases of esophageal and gastric variceal bleeding.By reducing portal pressure,TIPS lowers the risk of variceal bleeding and manages other complications associated with portal hypertension[1].It is also effective in addressing portal cavernous malformations[2].However,it does not resolve all issues related to portal hypertension.Its effectiveness is limited in conditions such as portal vein fibrosis[3],and those similar to this case,which is provisionally termed“dysfunctional portal vein.”展开更多
RSS fingerprint based indoor localization consists of two phases:offline phase and online phase.A RSS fingerprint database constructed at the offline phase may be outdated for online phase,which may significantly degr...RSS fingerprint based indoor localization consists of two phases:offline phase and online phase.A RSS fingerprint database constructed at the offline phase may be outdated for online phase,which may significantly degrade the localization performance.Furthermore,maintaining an RSS fingerprint database is a labor intensive and time-consuming task.In this paper,we proposes a robust and iterative indoor localization algorithm based on Wi-Fi RSS fingerprints,referred to as RIFi,which does not need to update the RSS fingerprint database and perform well even if the RSS fingerprint database is outdated.Specifically,we demonstrate that smaller localization area can provides better performance for outdated fingerprint database.Furthermore,we propose an iterative algorithm to determine the smaller localization area.Finally,the K-nearest neighbors(KNN)algorithm is invoked for the determined smaller localization area.Simulation results show that the proposed RIFi algorithm can significantly outperforms the traditional KNN algorithm for outdated RSS fingerprint database,and is more robust.展开更多
The key enzymes involved in the flavonoid biosynthesis pathway have been extensively studied in seed plants,but relatively less in ferns.In this study,two 4-Coumarate:coenzyme A ligases(Sc4CL1 and Sc4CL2)and one novel...The key enzymes involved in the flavonoid biosynthesis pathway have been extensively studied in seed plants,but relatively less in ferns.In this study,two 4-Coumarate:coenzyme A ligases(Sc4CL1 and Sc4CL2)and one novel chalcone synthase(ScCHS1)were functionally characterized by mining the Stenoloma chusanum transcriptome database.Recombinant Sc4CLs were able to esterify various hydroxycinnamic acids to corresponding acyl-coenzyme A(CoA).ScCHS1could catalyze p-coumaroyl-CoA,cinnamoyl-CoA,caffeoyl-CoA,and feruloyl-CoA to form naringenin,pinocembrin,eriodictyol,and homoeriodictyol,respectively.Moreover,enzymatic kinetics studies revealed that the optimal substrates of ScCHS1were feruloyl-CoA and caffeoyl-CoA,rather than p-coumaroyl-CoA,which was substantially different from the common CHSs.Crystallographic and sitedirected mutagenesis experiments indicated that the amino acid residues,Leu87,Leu97,Met165,and Ile200,located in the substrate-binding pocket near the B-ring of products,could exert a significant impact on the unique catalytic activity of ScCHS1.Furthermore,overexpression of ScCHS1 in tt4 mutants could partially rescue the mutant phenotypes.Finally,ScCHS1 and Sc4CL1 were used to synthesize flavanones and flavones with multi-substituted hydroxyl and methoxyl B-ring in Escherichia coli,which can effectively eliminate the need for the cytochrome P450 hydroxylation/O-methyltransferase from simple phenylpropanoid acids.In summary,the identification of these important Stenoloma enzymes provides a springboard for the future production of various flavonoids in E.coli.展开更多
Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics,and developing the oxygen production nanoplatforms received the widespread attention.However,it is remaining a challenge to structure a nano...Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics,and developing the oxygen production nanoplatforms received the widespread attention.However,it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy.Herein,we present a novel theranostics nanoplatform(Au NPs/UCNPs/WO_(3)@C)comprising of tungsten trioxide(WO3)that loaded gold nanoparticles(Au NPs)and up-conversion nanoparticles(UCNPs)for improved photoacoustic(PA)imaging performance in the second near infrared window(NIR-Ⅱ,900-1,700 nm).Au NPs/UCNPs/WO_(3)@C exhibited superior oxygen-generation effect and doxorubicin loading capacity,thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy.Importantly,the accumulated Au NPs/UCNPs/WO_(3)@C in the tumor region led to the increased NIR-Ⅱ PA imaging signal and the blood oxygen saturation signal,which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues.This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO_(3)@C for NIR-Ⅱ PA imaging-guided tumor therapeutics.展开更多
Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertensio...Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows that TIPS is an essential part of the treatment of portal hypertension in China.TIPS is widely used in Chinese patients with portal hypertension,and this survey presents a more comprehensive picture of the options and difficulties encountered in the implementation of TIPS.In the future,it is necessary to promote TIPS technology and further standardize surgical indications,routine operations,and instrument application.展开更多
The treatment of digestive system tumors presents challenges,particularly in immunotherapy,owing to the advanced immune tolerance of the digestive system.Nanomaterials have emerged as a promising approach for addressi...The treatment of digestive system tumors presents challenges,particularly in immunotherapy,owing to the advanced immune tolerance of the digestive system.Nanomaterials have emerged as a promising approach for addressing these challenges.They provide targeted drug delivery,enhanced permeability,high bioavailability,and low toxicity.Additionally,nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment(TIME).Among the various cells in the TIME,tumor-associated macrophages(TAMs)are the most abundant and play a crucial role in tumor progression.Therefore,investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance.Here,we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer,colorectal cancer,hepatocellular carcinoma,and pancreatic cancer.We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system.Furthermore,this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors.Overall,this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.展开更多
Aims:Chronic liver disease(CLD)is increasingly recognized as a significant global public health threat,with morbidity and mortality rates remaining high.Evidence suggests that sarcopenia independently increases the ri...Aims:Chronic liver disease(CLD)is increasingly recognized as a significant global public health threat,with morbidity and mortality rates remaining high.Evidence suggests that sarcopenia independently increases the risk of CLD and negatively impacts various clinical outcomes,including survival,quality of life,and the emergence of additional complications in patients with CLD.This study aimed to give a bibliometric analysis to examine the correlation between sarcopenia and CLD from a literature perspective.Methods:To understand the structure of this research field,we employed VOSviewer.The research on the correlation between long‐term liver disease and sarcopenia was obtained from the Web of Science Core Collection.VOSviewer 1.6.19.0 was utilized to examine and illustrate these publications,encompassing yearly patterns in the domain,focal points of research,significant articles,authors,journals,and organizations.Moreover,according to the results of the cluster analysis of keywords,we further searched and classified related studies to discuss.Results:This study provides a comprehensive analysis of current research trends,international collaboration models,fundamental understandings,key focus areas,and future research areas in the field of sarcopenia and CLD by reviewing publications from January 1,2000 to December 31,2023.Over the past 24 years,research in the field of sarcopenia and CLD has deepened,with a gradual increase in publications and citations from various countries,institutions,and authors.Keyword analysis of sarcopenia and CLD indicates that current research predominantly focuses on several key areas,including obesity,metabolic syndrome,hepatic steatosis,insulin resistance,inflammation,and nutrition therapy.Conclusion:This study provided a visual representation of the current research on the correlation between CLD and sarcopenia,including publication trends,global collaboration patterns,and research hotspots.This research contributes significantly by summarizing and discussing current research trends in sarcopenia and CLD,offering valuable insights into the complex relationship,and highlighting research trends,collaborations,and future directions in clinical treatment.展开更多
Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to in...Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.展开更多
Hepatocellular carcinoma(HCC)remains the most common malignancy to threaten public health globally.With advances in artificial intelligence techniques,radiomics for HCC management provides a novel perspective to solve...Hepatocellular carcinoma(HCC)remains the most common malignancy to threaten public health globally.With advances in artificial intelligence techniques,radiomics for HCC management provides a novel perspective to solve unmet needs in clinical settings,and reveals pixel-level radiological information for medical imaging big data,correlating the radiological phenotype with targeted clinical issues.Conventional radiomics pipelines depend on handcrafted engineering features,and further deep learning-based radiomics pipelines are supplemented with deep features calculated via self-learning strategies.During the past decade,radiomics has been widely applied in accurate diagnoses and pathological or biological behavior evaluation,as well as in prognosis prediction.In this review,we systematically introduce the main pipelines of artificial intelligence-based radiomics and their efficacy in the clinical studies of HCC.展开更多
To the Editor,Cirrhosis develops histologically as regenerative nodules surrounded by fibrous bands because of chronic liver injury,resulting in portal hypertension and end‐stage liver failure.Liver cirrhosis imposes...To the Editor,Cirrhosis develops histologically as regenerative nodules surrounded by fibrous bands because of chronic liver injury,resulting in portal hypertension and end‐stage liver failure.Liver cirrhosis imposes a heavy health and economic burden on many countries.In 2014,Mokdad et al.1 reported the results of the 2010 Global Burden of Disease Study(GBD).Global deaths from cirrhosis increased monotonically from just over 676,000 deaths in 1980(1.54%of global deaths)to more than 1 million deaths in 2010,or 1.95%.Portal hypertension is a group of disorders characterized by symptoms,such as hepatic encephalopathy.Cirrhosis is the main cause of portal hypertension,accounting for 80%–90%of cases.In addition,cirrhosis has fatal complications that greatly affect the quality of life of patients.展开更多
基金supported by National Natural Science Foundation of China(No.82161138029)Liaoning Revitalization Talents Program(No.XLYC2402040)the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007).
文摘Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.
基金supported by the National Natural Science Foundation of China(No.52472137)the Talent Introduction Research Project of Hebei University(No.521100224231)the Shanghai Magnolia Talent Plan Pujiang Project(23PJ1415600)。
文摘Compared to traditional liquid electrolyte batteries,solid metal batteries offer advantages such as a wide operating temperature range,high energy density,and improved safety,making them a promising energy storage technology.Solid electrolytes,as the core components of solid‐state batteries,are key factors in advancing solid‐state battery technology.Among various solid electrolytes,Na super ionic conductor(NASICON)‐type solid electrolytes exhibit high ionic conductivity(10−3 S·cm−1),a wide electrochemical window,and good thermal stability,providing room for the development of high energy‐density solid metal batteries.Since the discovery of NASICON‐type solid electrolytes in 1976,interest in their use in all‐solid‐state battery development has grown significantly.In this review,we comprehensively analyze the common features of NASICON lithium‐ion conductors and NASICON sodium‐ion conductors,review the historical development of NASICON‐type solid electrolytes,systematically summarize the transport mechanisms of metal cations in NASICON‐type solid electrolytes,discuss the latest strategies for enhancing ionic conductivity,elaborate on the latest methods for improving mechanical stability and interface stability,and point out the requirements of high energy density devices for NASICON‐type solid electrolytes as well as three types of in situ characterization techniques for interfaces.Finally,we highlight the challenges and potential solutions for the future development of NASICON‐type solid electrolytes and solid‐state metal batteries.
基金supported by National Key Research and Development Program of China Grant under No.2019YFC0118100。
文摘Locoregional therapies(LRTs)of hepatocellular carcinoma(HCC)represented by ablation and TACE has become the main means for the clinical treatment of unresectable HCC.Among these,TACE is used throughout the stageⅠb toⅢb of HCC treatment.In recent years,immunotherapy led by immune checkpoint inhibitors has become a hot direction in clinical research.At the same time,targeted drugs such as Sorafenib and Apatinib have played an important role in the treatment and complementary therapy of advanced HCC,and their clinical application has been quite mature.HCC is the sixth most common malignant tumor in the world.When it comes to its treatment,different therapies have different indications,and their individual efficacies are not satisfactory,which makes the exploration of the use of combination therapy in HCC treatment become a new trend.In this paper,the status of the three therapies and the progress of their combined application are briefly reviewed.
基金the support of the National Natural Science Foundation of China under Grant No.60673023,60433020,10501017,3040016the European Commission for TH/Asia Link/010 under Grant No.111084.
文摘It is very important in the field of bioinformatics to apply computer to perform the function annotation for new sequenced bio-sequences. Based on GO database and BLAST program, a novel method for the function annotation of new biological sequences is presented by using the variable-precision rough set theory. The proposed method is applied to the real data in GO database to examine its effectiveness. Numerical results show that the proposed method has better precision, recall-rate and harmonic mean value compared with existing methods.
基金financially the National Natural Science Foundation of China,No.82072533the China Postdoctoral Science Foundation,No.2017M621675+1 种基金Huxin Foundation of Jiangsu Key Laboratory of Zoonosis of China,No.HX2003Yangzhou Science and Technology Development Plan Project of China,No.YZ2020201(all to XW)。
文摘An enriched environment is used as a behavio ral intervention therapy that applies sensory,motor,and social stimulation,and has been used in basic and clinical research of va rious neurological diseases.In this study,we established mouse models of photothrombotic stroke and,24 hours later,raised them in a standard,enriched,or isolated environment for 4 weeks.Compared with the mice raised in a standard environment,the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated.Furthermore,protein expression levels of tumor necrosis factor receptor-associated factor 6,nuclear factorκB p65,interleukin-6,and tumor necrosis factorα,and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower,while the expression level of miR-146a-5p was higher.Compared with the mice raised in a standard environment,changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment.These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stro ke.An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.
基金supported in part by grants from the National Key Research and Development Program (2019YFC0118100 and 2017YFC0110903)the National Natural Science Foundation of China (12026602 and 81802649)+2 种基金the Guangdong Key Area Re-search and Development Program (2020B010165004)the Shen-zhen Key Basic Science Program (JCYJ20180507182437217)the Shenzhen Key Laboratory Program (ZDSYS201707271637577)
文摘Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.
基金supported by National Key R&D Program of China(2017YFB0903504)
文摘In the context of constructing Global Energy Interconnection(GEI), energy storage technology, as one of the important basic supporting technologies in power system, will play an important role in the energy configuration and optimization. Based on the most promising battery energy storage technology, this paper introduces the current status of the grid technology, the application of large-scale energy storage technology and the supporting role of battery energy storage for GEI. Based on several key technologies of large-scale battery energy storage system, preliminary analysis of the standard system construction of energy storage system is made, and the future prospect is put forward.
基金supported by the State Grid Corporation of China Science and Technological Project(Research and demonstration application of key technology of energy storage cloud for mobile energy storage application of electric vehicles 5419-20197121 7a-0-0-00)
文摘Based on the energy storage cloud platform architecture,this study considers the extensive configuration of energy storage devices and the future large-scale application of electric vehicles at the customer side to build a new mode of smart power consumption with a flexible interaction,smooth the peak/valley difference of the load side power,and improve energy efficiency.A plug and play device for customer-side energy storage and an internet-based energy storage cloud platform are developed herein to build a new intelligent power consumption mode with a flexible interaction suitable for ordinary customers.Based on the load perception of the power grid,this study aims to investigate the operating state and service life of distributed energy storage devices.By selecting an integrated optimal control scheme,this study designs a kind of energy optimization and deployment strategy for stratified partition to reduce the operating cost of the energy storage device on the client side.The effectiveness of the system and the control strategy is verified through the Suzhou client-side distributed energy storage demonstration project.
基金supported by the National Key R&D Program of China(Grant No.:2018YFC0115500)the National Natural Science Foundation of China(Grant No.:U21A20378)+2 种基金Liaoning Revitalization Talents Program,China(Grant No.:XLYC1802098)the Natural Science Foundation of Shaanxi Provincical Department of Education,China(Grant No.:21JK0593)the Key Research and Development Plan of Science and Technology Department of Xianyang City,China(Grant No.:L2023-ZDYF-SF-054).
文摘Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel FeeCu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under lowpower microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H_(2)O_(2) decomposition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTT and chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and provides a reference for developing new microwave sensitizers。
基金supported by the Technical Project of the State Grid Corporation of China(research and demonstration application of key technology of energy storage cloud for mobile energy storage application of electric vehicles 5419-201971217a-0-0-00)。
文摘As part of the ongoing information revolution,smart power grid technology has become a key focus area for research into power systems.Intelligent electrical appliances are now an important component of power systems,providing a smart power grid with increased control,stability,and safety.Based on the secure communication requirements of cloud energy storage systems,this paper presents the design and development of a node controller for a cloud energy storage network.The function division and system deployment processes were carried out to ensure the security of the communication network used for the cloud energy storage system.Safety protection measures were proposed according to the demands of the communication network,allowing the system to run safely and stably.Finally,the effectiveness of the system was verified through a client-side distributed energy storage demonstration project in Suzhou,China.The system was observed to operate safely and stably,demonstrating good peak-clipping and valley filling effects,and improving the system load characteristics.
基金funded by the National Natural Science Foundation of China(General Program,Award No.62371474)National Key Researchand Development Program of China(Award No.2023YFC2308405)。
文摘To the Editor,Transjugular intrahepatic portosystemic shunt(TIPS)is an effective treatment for portal hypertension,particularly in cases of esophageal and gastric variceal bleeding.By reducing portal pressure,TIPS lowers the risk of variceal bleeding and manages other complications associated with portal hypertension[1].It is also effective in addressing portal cavernous malformations[2].However,it does not resolve all issues related to portal hypertension.Its effectiveness is limited in conditions such as portal vein fibrosis[3],and those similar to this case,which is provisionally termed“dysfunctional portal vein.”
基金supported by the Key Research and Development Program of Shaanxi under Grant(2017DCXL-GY-04-02).
文摘RSS fingerprint based indoor localization consists of two phases:offline phase and online phase.A RSS fingerprint database constructed at the offline phase may be outdated for online phase,which may significantly degrade the localization performance.Furthermore,maintaining an RSS fingerprint database is a labor intensive and time-consuming task.In this paper,we proposes a robust and iterative indoor localization algorithm based on Wi-Fi RSS fingerprints,referred to as RIFi,which does not need to update the RSS fingerprint database and perform well even if the RSS fingerprint database is outdated.Specifically,we demonstrate that smaller localization area can provides better performance for outdated fingerprint database.Furthermore,we propose an iterative algorithm to determine the smaller localization area.Finally,the K-nearest neighbors(KNN)algorithm is invoked for the determined smaller localization area.Simulation results show that the proposed RIFi algorithm can significantly outperforms the traditional KNN algorithm for outdated RSS fingerprint database,and is more robust.
基金supported by the National Natural Science Foundation of China (No. 31770330 and 31870720)supported by the Foundation of Youth Innovation Promotion Association of the Chinese Academy of Sciences
文摘The key enzymes involved in the flavonoid biosynthesis pathway have been extensively studied in seed plants,but relatively less in ferns.In this study,two 4-Coumarate:coenzyme A ligases(Sc4CL1 and Sc4CL2)and one novel chalcone synthase(ScCHS1)were functionally characterized by mining the Stenoloma chusanum transcriptome database.Recombinant Sc4CLs were able to esterify various hydroxycinnamic acids to corresponding acyl-coenzyme A(CoA).ScCHS1could catalyze p-coumaroyl-CoA,cinnamoyl-CoA,caffeoyl-CoA,and feruloyl-CoA to form naringenin,pinocembrin,eriodictyol,and homoeriodictyol,respectively.Moreover,enzymatic kinetics studies revealed that the optimal substrates of ScCHS1were feruloyl-CoA and caffeoyl-CoA,rather than p-coumaroyl-CoA,which was substantially different from the common CHSs.Crystallographic and sitedirected mutagenesis experiments indicated that the amino acid residues,Leu87,Leu97,Met165,and Ile200,located in the substrate-binding pocket near the B-ring of products,could exert a significant impact on the unique catalytic activity of ScCHS1.Furthermore,overexpression of ScCHS1 in tt4 mutants could partially rescue the mutant phenotypes.Finally,ScCHS1 and Sc4CL1 were used to synthesize flavanones and flavones with multi-substituted hydroxyl and methoxyl B-ring in Escherichia coli,which can effectively eliminate the need for the cytochrome P450 hydroxylation/O-methyltransferase from simple phenylpropanoid acids.In summary,the identification of these important Stenoloma enzymes provides a springboard for the future production of various flavonoids in E.coli.
基金This research was supported by the National Natural Science Foundation of China(Nos.22027805 and 21874024)the National Key R&D Program of China(No.2020YFA0210800)+1 种基金the joint research projects of Health and Education Commission of Fujian Province(No.2019-WJ-20)the Natural Science Foundation of Fujian Province(No.2020J02012).
文摘Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics,and developing the oxygen production nanoplatforms received the widespread attention.However,it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy.Herein,we present a novel theranostics nanoplatform(Au NPs/UCNPs/WO_(3)@C)comprising of tungsten trioxide(WO3)that loaded gold nanoparticles(Au NPs)and up-conversion nanoparticles(UCNPs)for improved photoacoustic(PA)imaging performance in the second near infrared window(NIR-Ⅱ,900-1,700 nm).Au NPs/UCNPs/WO_(3)@C exhibited superior oxygen-generation effect and doxorubicin loading capacity,thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy.Importantly,the accumulated Au NPs/UCNPs/WO_(3)@C in the tumor region led to the increased NIR-Ⅱ PA imaging signal and the blood oxygen saturation signal,which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues.This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO_(3)@C for NIR-Ⅱ PA imaging-guided tumor therapeutics.
文摘Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows that TIPS is an essential part of the treatment of portal hypertension in China.TIPS is widely used in Chinese patients with portal hypertension,and this survey presents a more comprehensive picture of the options and difficulties encountered in the implementation of TIPS.In the future,it is necessary to promote TIPS technology and further standardize surgical indications,routine operations,and instrument application.
基金supported by National Natural Science Foundation of China,62371474(MN)Natural Science Foundation of Liaoning Province,2023JH2/101600006(MN).
文摘The treatment of digestive system tumors presents challenges,particularly in immunotherapy,owing to the advanced immune tolerance of the digestive system.Nanomaterials have emerged as a promising approach for addressing these challenges.They provide targeted drug delivery,enhanced permeability,high bioavailability,and low toxicity.Additionally,nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment(TIME).Among the various cells in the TIME,tumor-associated macrophages(TAMs)are the most abundant and play a crucial role in tumor progression.Therefore,investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance.Here,we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer,colorectal cancer,hepatocellular carcinoma,and pancreatic cancer.We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system.Furthermore,this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors.Overall,this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.
基金National Natural Science Foundation of China,Grant/Award Number:62371474National Key Research and Development Program of China,Grant/Award Number:2023YFC2308405Natural Science Foundation of Liaoning Province,Grant/Award Number:2023JH2/101600006。
文摘Aims:Chronic liver disease(CLD)is increasingly recognized as a significant global public health threat,with morbidity and mortality rates remaining high.Evidence suggests that sarcopenia independently increases the risk of CLD and negatively impacts various clinical outcomes,including survival,quality of life,and the emergence of additional complications in patients with CLD.This study aimed to give a bibliometric analysis to examine the correlation between sarcopenia and CLD from a literature perspective.Methods:To understand the structure of this research field,we employed VOSviewer.The research on the correlation between long‐term liver disease and sarcopenia was obtained from the Web of Science Core Collection.VOSviewer 1.6.19.0 was utilized to examine and illustrate these publications,encompassing yearly patterns in the domain,focal points of research,significant articles,authors,journals,and organizations.Moreover,according to the results of the cluster analysis of keywords,we further searched and classified related studies to discuss.Results:This study provides a comprehensive analysis of current research trends,international collaboration models,fundamental understandings,key focus areas,and future research areas in the field of sarcopenia and CLD by reviewing publications from January 1,2000 to December 31,2023.Over the past 24 years,research in the field of sarcopenia and CLD has deepened,with a gradual increase in publications and citations from various countries,institutions,and authors.Keyword analysis of sarcopenia and CLD indicates that current research predominantly focuses on several key areas,including obesity,metabolic syndrome,hepatic steatosis,insulin resistance,inflammation,and nutrition therapy.Conclusion:This study provided a visual representation of the current research on the correlation between CLD and sarcopenia,including publication trends,global collaboration patterns,and research hotspots.This research contributes significantly by summarizing and discussing current research trends in sarcopenia and CLD,offering valuable insights into the complex relationship,and highlighting research trends,collaborations,and future directions in clinical treatment.
文摘Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.
基金This study has received funding by the National Key Research and Development Program of China under Grant 2017YFA0700401 and 2021YFC2500402Ministry of Science and Technology of China under Grant No.2017YFA0205200+2 种基金National Natural Science Foundation of China under Grant No.82001917,81930053,82090052,82090051,82093219055,81227901,92159202 and 81527805Beijing Natural Science Foundation under Grant No.L192061the Project of High-Level Talents Team Introduction in Zhuhai City。
文摘Hepatocellular carcinoma(HCC)remains the most common malignancy to threaten public health globally.With advances in artificial intelligence techniques,radiomics for HCC management provides a novel perspective to solve unmet needs in clinical settings,and reveals pixel-level radiological information for medical imaging big data,correlating the radiological phenotype with targeted clinical issues.Conventional radiomics pipelines depend on handcrafted engineering features,and further deep learning-based radiomics pipelines are supplemented with deep features calculated via self-learning strategies.During the past decade,radiomics has been widely applied in accurate diagnoses and pathological or biological behavior evaluation,as well as in prognosis prediction.In this review,we systematically introduce the main pipelines of artificial intelligence-based radiomics and their efficacy in the clinical studies of HCC.
文摘To the Editor,Cirrhosis develops histologically as regenerative nodules surrounded by fibrous bands because of chronic liver injury,resulting in portal hypertension and end‐stage liver failure.Liver cirrhosis imposes a heavy health and economic burden on many countries.In 2014,Mokdad et al.1 reported the results of the 2010 Global Burden of Disease Study(GBD).Global deaths from cirrhosis increased monotonically from just over 676,000 deaths in 1980(1.54%of global deaths)to more than 1 million deaths in 2010,or 1.95%.Portal hypertension is a group of disorders characterized by symptoms,such as hepatic encephalopathy.Cirrhosis is the main cause of portal hypertension,accounting for 80%–90%of cases.In addition,cirrhosis has fatal complications that greatly affect the quality of life of patients.
