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.

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.

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.

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.

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.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Multivariate analysis of oral mucosal ulcers during orthodontic treatment

BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis:A network meta-analysis

BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

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.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

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.

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.

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.

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.

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.

Deciding on life-saving treatment after a violent suicide attempt:an ethical case report

To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods are used.2 These methods include jumping from heights,using a firearm,crashing a motor vehicle,and lying down or jumping in front of a moving object.