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.

Circ RNA and ferroptosis in human disease:Insights for new treatments

Circular RNA(circ RNA),classified as a type of non-coding RNA,has gained significant attention in the field of biology due to its distinctive ring structure and functional properties.Recent research has provided evidence that specific circ RNAs have the ability to modulate disease progression through diverse mechanisms,one of which is by regulating cellular ferroptosis.Ferroptosis is a form of regulated cell death that is driven by iron dependency and lipid peroxidation,and extensive investigations have revealed a relationship between ferroptosis and disease development.In addition to evidence that both circ RNAs and ferroptosis exert critical roles in disease progression,circ RNAs have also been shown to actively mediate the process of ferroptosis.The relationship between circ RNAs and ferroptosis therefore influences disease progression and offers novel targets for disease treatment.By directly or indirectly modulating the expression of circ RNAs that regulate the expression of ferroptosisrelated proteins,it may be possible to impact disease progression by promoting or inhibiting ferroptosis.Current research indicates such approaches may hold significant value in a wide variety of common diseases across physiological systems.This review comprehensively summarizes the findings of recent studies investigating the roles of circ RNAs in the regulation of ferroptosis in various diseases.

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

The coronavirus disease 2019(COVID-19)pandemic has been a serious threat to global health for nearly 3 years.In addition to pulmonary complications,liver injury is not uncommon in patients with novel COVID-19.Although the prevalence of liver injury varies widely among COVID-19 patients,its incidence is significantly increased in severe cases.Hence,there is an urgent need to understand liver injury caused by COVID-19.Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes.Liver function tests,computed tomography scans,and ultrasound can help evaluate liver injury.Risk factors for liver injury in patients with COVID-19 include male sex,preexisting liver disease including liver transplantation and chronic liver disease,diabetes,obesity,and hypertension.To date,the mechanism of COVID-19-related liver injury is not fully understood.Its pathophysiological basis can generally be explained by systemic inflammatory response,hypoxic damage,ischemia-reperfusion injury,and drug side effects.In this review,we systematically summarize the existing literature on liver injury caused by COVID-19,including clinical features,underlying mechanisms,and potential risk factors.Finally,we discuss clinical management and provide recommendations for the care of patients with liver injury.

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.

Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

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.

Convergence of human and veterinary medicine:leveraging canine naturally occurring neurological disorders to develop regenerative treatments

In recent years,large animal models of naturally occurring diseases have become increasingly studied,with the rationale that their disease attributes may better recapitulate the pathological features of corresponding human diseases as compared to induced disease models(Hoffman and Dow,2016).Of the available naturally occurring disease models,the canine is increasingly recognized as a valuable pre-clinical animal model in translational medicine for numerous human diseases,including cancer.

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.

Do not lose the moon while counting the stars:Conventional IVF versus add-on treatments

When we look back at-more than four decades-the history of assisted reproductive treatments(ART),a continuous effort to optimise laboratory conditions and to improve treatment protocols can be seen.In basic terms,the aim of research about culture media and laboratory environments is to create as more physiological condition as possible,which means reducing the gap between the not-fully-known in vivo conditions and their in vitro counterparts.

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.

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.

Effect of Different Titanium Surface Treatments on the Adhesion Test Result:Dental Application

The aim of the study was to investigate the effect of different surface treatment of titanium(Ti)on the adhesion test results for dental application.Ti substrates roughened by 400 to 1500-grit SiC polish papers and alumina blasting,alkali treated by 5 molar(M)NaOH and KOH solutions and heat treated at the temperature range of 400-800℃were used in this study.The treated samples were subjected to the adhesion test.According to the results of the adhesion test,the adhesive strength showed the highest value for the blasted titanium among all polished and blasted samples.The Ti samples heated at 650℃showed the highest adhesive strength among all heat-treated samples.Further,the adhesion test results indicated the higher adhesive strength of chemically treated samples treated by NaOH rather than that by KOH.The polished and heated Ti samples showed the highest adhesive strength among all samples.

Influence of heat treatments on incipient melting structures of DD5 nickel-based single crystal superalloy

The evolution of microstructure and formation mechanism of incipient melting microstructure of DD5 single crystal superalloy during solution heat treatment were studied by scanning electron microscopy(SEM),electron probe microanalysis(EPMA),and energy dispersive spectroscopy(EDS).The solidus and liquidus of single crystal alloy were obtained by differential scanning calorimetry(DSC).Results show that the mosaic-like eutectic and fan-like eutectic are dissolved at first,and the coarseγ'phase is dissolved later during the solution heat treatment of 1,390°C/2 h+1,310°C/4 h+1,320°C/10 h+air cooling(AC).The composition segregations of Al,Ta,W and Re are 0.99,0.96,1.04 and 1.16,respectively,which close to 1.The incipient melting is caused by the low local temperature of the alloy,and the micropore region with a lower melting point is the preferred position for incipient melting.

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.

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.

Assessing the effects of alternative fuel treatments to reduce wildfire exposure

Effective landscape-scale fuel management strategies are essential for reducing wildfire risk in Mediterranean fire-prone areas.In this study,the minimum travel time(MTT)fire-spread algorithm as implemented in FlamMap was applied to assess the potential of alternative fuel treatments for lowering wildfire losses in a 5,740-ha study area in eastern Sardinia,Italy.Twenty-seven wildfires at 10-m resolution were simulated considering three wind speeds(15,18,and 21 km h-1)to compare fuel treatments:no treatment(NT),irrigated agroforestry areas with shrub clearing(T1),prescribed fire in eucalyptus stands(T2),and irrigated grasslands(T3).The simulations replicated a recent large wildfire that occurred in the study area(Orrìwildfire,2019)and considered the weather and fuel moisture conditions associated with this event.The average wildfire exposure outputs(burned area,probability of burning,conditional flame length,potential crown fire occurrence,and surfaces withflame lengths above 2.5 m)decreased after fuel treatments,compared to no treatment.T1 was the most effective strategy in mitigating wildfire hazards and provided the most significant performance for several wildfire exposure indicators.Treating only 0.5%of the study area(~30 ha)resulted in a decrease in all wildfire exposure metrics to~10%within the study area.In addition,the total surface characterized by high flame length(average>2.5 m)was the lowest in the T1 treatment.This study can help land and fire managers optimize fuel treatment opportunities and wildfire risk mitigation strategies in Mediterranean areas.

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.

Impact of Heat Treatments and Hole Density (p) on the Structural, Electrical, and Superconducting Properties of LnSrBaCu3O6+z (Ln = Eu, Sm, Nd) Compounds

In this study, we thoroughly examined the impact of heat treatments and hole count (p) on the properties of LnSrBaCu3O6+z (Ln = Eu, Sm, Nd) compounds. We focused on preparation, X-ray diffraction with Rietveld refinement, AC susceptibility, DC resistivity measurements, and heat treatment effects. Two heat treatment types were applied: oxygen annealing [O] and argon annealing followed by oxygen annealing [AO]. As the rare earth Ln’s ionic radius increased, certain parameters notably changed. Specifically, c parameter, surface area S, and volume V increased, while critical temperature Tc and holes (p) in the CuO2 plane decreased. The evolution of these parameters with rare earth Ln’s ionic radius in [AO] heat treatment is linear. Regardless of the treatment, the structure is orthorhombic for Ln = Eu, tetragonal for Ln = Nd, orthorhombic for Ln = Sm [AO], and pseudo-tetragonal for Sm [O]. The highest critical temperature is reached with Ln = Eu (Tc [AO] = 87.1 K). Notably, for each sample, Tc [AO] surpasses Tc [O]. Observed data stems from factors including rare earth ionic size, improved cationic and oxygen chain order, holes count p in Cu(2)O2 planes, and in-phase purity of [AO] samples. Our research strives to clearly demonstrate that the density of holes (p) within the copper plane stands as a determinant impacting the structural, electrical, and superconducting properties of these samples. Meanwhile, the other aforementioned parameters contribute to shaping this density (p).

Systemic treatments for resectable carcinoma of the esophagus

One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.