Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Circular RNAs in breast cancer diagnosis,treatment and prognosis

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

Interface property of dissimilar Ti-6Al-4V/AA1050 composite laminate made by non-equal channel lateral co-extrusion and heat treatment

The purpose of this paper is to examine the effect of processing parameters and subsequent heat treatments on the microstructures and bonding strengths of Ti-6Al-4V/AA1050 laminations formed via a non-equal channel lateral co-extrusion process.The microstructural evolution and growth mechanism in the diffusion layer were discussed further to optimize the bonding quality by appropriately adjusting process parameters.Scanning electron microscopes(SEM),energy dispersive spectrometer(EDS),and X-ray diffraction(XRD)were used to characterize interfacial diffusion layers.The shear test was used to determine the mechanical properties of the interfacial diffusion layer.The experimental results indicate that it is possible to co-extrusion Ti-6Al-4V/AA1050 compound profiles using non-equal channel lateral co-extrusion.Different heat treatment processes affect the thickness of the diffusion layer.When the temperature and time of heat treatment increase,the thickness of the reaction layers increases dramatically.Additionally,the shear strength of the Ti-6Al-4V/AA1050 composite interface is proportional to the diffusion layer thickness.It is observed that a medium interface thickness results in superior mechanical performance when compared to neither a greater nor a lesser interface thickness.Microstructural characterization of all heat treatments reveals that the only intermetallic compound observed in the diffusion layers is TiAl_(3).Due to the inter-diffusion of Ti and Al atoms,the TiAl_(3) layer grows primarily at AA1050/TiAl_(3) interfaces.

Effect of annealing treatment on the microstructure and mechanical properties of warm-rolled Mg-Zn-Gd-Ca-Mn alloys

The basal texture of traditional magnesium alloy AZ31 is easy to form and exhibits poor plasticity at room temperature.To address these problems,a multi-micro-alloyed high-plasticity Mg-1.8Zn-0.8Gd-0.1Ca-0.2Mn(wt%)alloy was developed using the unique role of rare earth and Ca solute atoms.In addition,the influence of the annealing process on the grain size,second phase,texture,and mechanical properties of the warm-rolled sheet at room temperature was analyzed with the goal of developing high-plasticity mag-nesium alloy sheets and obtaining optimal thermal-mechanical treatment parameters.The results show that the annealing temperature has a significant effect on the microstructure and properties due to the low alloying content:there are small amounts of larger-sized block and long string phases along the rolling direction(RD),as well as several spherical and rodlike particle phases inside the grains.With increas-ing annealing temperature,the grain size decreases and then increases,and the morphology,number,and size of the second phase also change correspondingly.The particle phase within the grains vanishes at 450℃,and the grain size increases sharply.In the full recrystal-lization stage at 300-350℃,the optimum strength-plasticity comprehensive mechanical properties are presented,with yield strengths of 182.1 and 176.9 MPa,tensile strengths of 271.1 and 275.8 MPa in the RD and transverse direction(TD),and elongation values of 27.4%and 32.3%,respectively.Moreover,there are still some larger-sized phases in the alloy that influence its mechanical properties,which offers room for improvement.

Role of fullerenols derivative 3HFWC in the treatment of Alzheimer's disease

Fullerenes:The extensive development of nanoscience that has marked this century continues to evolve,producing new materials,structures,and devices for the treatments of diverse pathologies.Fullerenes are a family of nanoparticles with great applicative promise due to their small size(approximately 1 nm in diameter),structure,and capacity to cross biological barriers.

Chlorfenapyr poisoning:mechanisms,clinical presentations,and treatment strategies

BACKGROUND:Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides.Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.This article aims to review the mechanisms,clinical presentations,and treatment strategies for chlorfenapyr poisoning.DATA RESOURCES:We conducted a review of the literature using PubMed,Web of Science,and SpringerLink from their beginnings to the end of October 2023.The inclusion criteria were systematic reviews,clinical guidelines,retrospective studies,and case reports on chlorfenapyr poisoning that focused on its mechanisms,clinical presentations,and treatment strategies.The references in the included studies were also examined to identify additional sources.RESULTS:We included 57 studies in this review.Chlorfenapyr can be degraded into tralopyril,which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate.High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning.Once it occurs,respiratory failure occurs immediately,ultimately leading to cardiac arrest and death.Chlorfenapyr poisoning is diflcult to treat,and there is no specific antidote.CONCLUSION:Chlorfenapyr is a new pyrrole pesticide.Although it has been identified as a moderately toxic pesticide by the World Health Organization(WHO),the mortality rate of poisoned patients is extremely high.There is no specific antidote for chlorfenapyr poisoning.Therefore,based on the literature review,future efforts to explore rapid and effective detoxification methods,reconstitute intracellular oxidative phosphorylation couplings,identify early biomarkers of chlorfenapyr poisoning,and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The emerging role of exercise as a cancer treatment

Over the past few decades,exercise oncology has emerged as an important subfield within exercise science.Over that time,substantial progress has been made in understanding the role of exercise in people newly diagnosed with cancer,actively being treated for cancer,and recovering after cancer treatments.

Recent progresses in thermal treatment of β-Ga_(2)O_(3) single crystals and devices

In recent years,ultra-wide bandgap β-Ga_(2)O_(3) has emerged as a fascinating semiconductor material due to its great potential in power and photoelectric devices.In semiconductor industrial,thermal treatment has been widely utilized as a convenient and effective approach for substrate property modulation and device fabrication.Thus,a thorough summary of β-Ga_(2)O_(3) substrates and devices behaviors after high-temperature treatment should be significant.In this review,we present the recent advances in modulating properties of β-Ga_(2)O_(3) substrates by thermal treatment,which include three major applications:(ⅰ)tuning surface electrical properties,(ⅱ)modifying surface morphology,and(ⅲ)oxidating films.Meanwhile,regulating electrical contacts and handling with radiation damage and ion implantation have also been discussed in device fabrication.In each category,universal annealing conditions were speculated to figure out the corresponding problems,and some unsolved questions were proposed clearly.This review could construct a systematic thermal treatment strategy for various purposes and applications of β-Ga_(2)O_(3).