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.

Significance of Primary Treatment Selection in the Efficiency of Wastewater Treatment in Constructed Wetlands (CWs)

This research explores strategies to enhance the efficiency of secondary treatment in Vertical Flow Constructed Wetlands (CW) in Montenegro. The focus is on selecting appropriate primary treatment methods alongside three distinct substrate types to improve wastewater treatment efficacy. The study examines the combination of two primary treatments with different substrate types in constructed wetlands (CW1, CW2, and CW3). The primary treatments include the existing wastewater treatment plant (WWTP) in Podgorica, involving coarse material removal through screens, inert material separation in aerated sand traps, and sediment and suspended matter removal in primary sedimentation tanks. The Extreme Separator (ExSep) was employed to evaluate its efficacy as a primary treatment method. The research demonstrates that the efficiency of CW can be significantly enhanced by selecting suitable primary treatment methods and substrates in Podgorica’s conditions. The most promising results were achieved by combining ExSep as a primary treatment with secondary treatment in CW-3. The removal efficiencies after CW3 for COD, BOD, and TSS exceeded 89%, 93%, and 91%, respectively. The outcomes underscore the significance of primary treatment in mitigating pollutant loads before discharge into the constructed wetlands, emphasizing potential areas for further optimization in wastewater treatment practices to enhance environmental sustainability and water quality management.

Has Coca-Cola treatment become the first-line therapy for gastric bezoars,both in general and specifically for western countries?

Phytobezoars is a rare disease and less common in Western countries.The stomach is the primary site for these formations,and endoscopic treatment involving fragmentation and extraction has traditionally been the most effective approach.However,medical treatments using enzymatic and chemical agents,such as cellulase and Coca-Cola,aimed at dissolving the bezoars,have also been utilized,showing varying degrees of resolution success.Notably,the oral dissolution treatment with Coca-Cola has emerged as a promising,simpler,and more costeffective method.The study by Liu et al represents an important step in clinical research on this topic,despite some limitations that need addressing for a more comprehensive understanding of its findings.Key considerations for future research include sample size calculation,endoscopic procedure details,outpatient vs.inpatient treatment,and detailed cost calculations.The study's exclusions,such as patients with upper gastric surgery,phytobezoars older than 14 d,and cases of gastroparesis,limit its applicability to broader populations,especially in Western countries.Given the promising outcomes of the Coca-Cola treatment,it's advocated as a first-line therapy for phytobezoars.Nonetheless,further research is essential to overcome these limitations.However special situations such as perforation or small bowel obstruction will require surgical treatment.

Cost of Medical Treatment for Primary Open-Angle Glaucoma in Relation to Patients’ Income and Its Impact on the Prognosis of the Disease, in Bouaké University Hospital

Introduction: Medical treatment for POAG is continuous and lifelong treatment. The aim of this study was to evaluate the relationship between the cost of this treatment and patients’ income and the impact of this relationship on treatment compliance. Materials and Methods: Prospective cross-sectional study with a descriptive aim covering sociodemographic data, average incomes, and direct and indirect costs of treatment of 57 patients followed for POAG during the period from January 1, 2012, to December 31, 2016 (5 years). Results: The patients were aged 25 to 77 years (mean = 54.4 years) with a male predominance (sex ratio = 1.5). Retirees were the most represented (26.32%), followed by workers in the informal sector (14.04%) and housewives (12.28%). Patients who had an annual income less than or equal to 900,000 CFA francs (€1370.83) per year represented 56.14% and those who did not have health coverage represented 57.89%. The treatment was monotherapy (64.91%), dual therapy (31.58%) or triple therapy (3.05%) and the average ratio of “annual cost of treatment to annual income” was 0.56 with for maximum 2.23 and 0.02 as minimum. Patients who considered the cost of treatment unbearable for their income represented 78.95%. Conclusion: Prevention of blindness due to glaucoma requires early detection but also the establishment of health coverage mechanisms to improve compliance with medical treatment. In addition, consideration should be given to the development of glaucoma surgery in our country, the indication of which could be the first intention in certain patients, considering for those patients, the geographical and financial accessibility of medical treatment. .

Research Progress on Integrated Chinese and Western Medicine Treatment of Tourette Syndrome in Children

Tourette syndrome is a common neuropsychiatric disorder that affects the physical and mental health of children.Early detection,diagnosis,and treatment are crucial to prevent serious impacts on the affected children,their families,and society.In recent years,there has been an increasing trend towards using a combination of methods in the clinical treatment of children with Tourette syndrome.This approach has achieved remarkable results,leading to a reduction in the rate of Tourette syndrome symptoms in children.In recent years,a combination of clinical methods has been used to treat children with Tourette syndrome,resulting in significant improvement in control rates.This article reviews the etiology of infantile Tourette syndrome and the progress made in Chinese and Western medicine treatments,providing a reference for further treatment of the condition.

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.

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).

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.

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.

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.

Hodgkin's lymphoma:2023 update on treatment

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all lymphomas.HL comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predominant HL.

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.

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.

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.

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).

Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment

To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].

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.

Community-based prevention and treatment of cardiovascular diseases

The Annual Report on Cardiovascular Health and Diseases in China(2022)intricate landscape of cardiovascular health in China.This is the third section of the report with a specific focus on community-based prevention and treatment of cardiovascular diseases(CVD).This section of the report underscores the importance of initiatives outlined in the"Healthy China 2030 Plan,"emphasizing the comprehensive prevention and control strategy for chronic diseases.A key aspect of this plan involves the establishment of national demonstration areas aimed at comprehensive prevention and control of chronic diseases.By 2020,488 such areas had been set up across China,surpassing the initial target and covering a significant proportion of counties and districts.The report highlights the successful implementation of these strategies in Lishan district,Anshan city,where demonstration areas for comprehensive prevention and control of chronic diseases were launched in 2013.Over the course of seven years,the number of healthy units increased substantially,leading to improvements in managing risk factors for CVD among residents.Significant reductions in prevalence rates of overweight,obesity,smoking,passive smoking,and drinking were observed,along with the development of healthier behaviors among residents.Similarly,Qiaokou district in Wuhan City,designated as a national demonstration area in 2014,implemented comprehensive public health promotion initiatives.Notably,special clinics for hypertension intervention were established,contributing to an increase in self-reported rates of hypertension,a slight decrease in prevalence,and a remarkable improvement in the control rate among treated patients.Overall,these efforts underscore the effectiveness of community-based approaches in driving positive health outcomes and advancing the comprehensive prevention and control of chronic diseases,particularly cardiovascular diseases,in China.

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.