Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Impact of Action Observation Therapy along with Usual Physiotherapy Intervention of Individual with Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.

Photo-activated microtubule targeting drugs: Advancing therapies for colorectal cancer

Over the years immunotherapy has demonstrably improved the field of cancer treatment.However,achieving long-term survival for colorectal cancer(CRC)patients remains a significant unmet need.Combination immunotherapies incor-porating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative benefit.Nevertheless,substantial gaps remain in the current therapeutic armamentarium for CRC.In recent years,there has been a surge of interest in exploring novel treatment strategies,including the application of light-activated drugs in conjunction with optical devices.This approach holds promise for achie-ving localized and targeted delivery of cytotoxic agents,such as microtubule-targeting drugs,directly to cancerous cells within the colon.

The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

IMPACTS OF PENETRATION THERAPY WITH HEAD ELECTRICAL ACUPUNCTURE ON PROLIFERATION OF NEURAL STEM CELLS IN SUBSTANTIA NIGRA OF RAT MODEL OF PARKINSON'S DISEASE

Objective To probe into the function mechanism of penetration therapy with head electrical acupuncture on Parkinson＇s disease. Methods Microinjection of 6-hydroxydopamin （6-OHDA） on the left cor- pus striatum was adopted to prepare rotation model of Parkinson^s disease in rat. Penetration therapy with head electrical acupuncture was administered in treatment. Normal group, sham-operation group, model group and penetration therapy group were set up. （1）lmmunohistochemical （IHC） method was used to test the morphology and count of positive cell of tyrosine hydroxylase （TH）. （2）RT-PCR technology was used to detect the expression of nestin mRNA of neural stem cell （NSC）. Results （1）Compared with model group, in pene- tration therapy group, the expressions of TH-positive neurons in immune response were increased in areal density （AD）, numerical density （ND） and integrating optic density （P〈0.05）. （2）Compared with model group, in penetration therapy group, the expression of nestin mRNA was increased （P〈0. 05）. Conclusion Penetration therapy with head electrical acupuncture promotes the proliferation of endogenous neural stem cells in substantia nigra of rat model of Parkinson＇s disease.

Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

The practice of phage therapy, which uses bacterial viruses(phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage-or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection. Although much about phages and human health is still being discovered, the time to take phage therapy serious again seems to be rapidly approaching.

Treatment of inflammatory bowel disease:A review of medical therapy

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non- systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

Photodynamic therapy vs radiofrequency ablation for Barrett's dysplasia: Efficacy,safety and cost-comparison

AIM:To compare effectiveness,safety,and cost of photodynamic therapy(PDT)and radiofrequency ablation(RFA)in treatment of Barrett’s dysplasia(BD).METHODS:Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared.Thirty-three patients with high-grade dysplasia(HGD)had treatment with porfimer sodium photosensitzer and 630 nm laser(130 J/cm),with maximum of 3 treatment sessions.Fifty-three patients with BD(47 with low-grade dysplasia-LGD,6 with HGD)had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions.Both groups received proton pump inhibitors twice daily.Endoscopic biopsies were acquired at 2 and 12 mo after enrollment,with 4-quadrant biopsies every 1 cm of the original BE extent.A complete histological resolution response of BD(CR-D)was defined as all biopsies at the last endoscopy session negative for BD.Fisher’s exact test was used to assess differences between the two study groups for primary outcomes.For all outcomes,a two-sided P value of less than 0.05 was considered to indicate statistical significance.RESULTS:Thirty(91%)PDT patients and 39(74%)RFA were men(P=0.05).The mean age was 70.7±12.2 and 65.4±12.7(P=0.10)year and mean length of BE was 5.4±3.2 cm and 5.7±3.2 cm(P=0.53)for PDT and RFA patients,respectively.The CR-D was(18/33)54.5%with PDT vs(47/53)88.7%with RFA(P=0.001).One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA.PDT was five times more costly than RFA at our institution.The two groups were not randomized and had different BD grading are the limitations of the study.CONCLUSION:In our experience,RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Advances in Drug Therapy for Alzheimer’s Disease

Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.

Current medical therapy of inflammatory bowel disease

INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiology of IBD symptoms hasled to newer treatment modalities and streamlining oftherapy for specific subsets of patients.

基于MRI影像组学构建PD-1/PD-L1抑制剂治疗dMMR/MSI-H直肠癌疗效的预测模型

目的:探讨MRI影像组学模型在程序性细胞死亡蛋白-1(PD-1)/程序性细胞死亡-配体1(PD-L1)抑制剂联合全程新辅助治疗(TNT)局部进展期直肠癌(LARC)的疗效预测价值。方法:收集河南中医药大学第一附属医院PD-1/PD-L1抑制剂联合TNT治疗的80例错配修复基因缺陷(dMMR)/微卫星高度不稳定(MSI-H)基因型中低位LARC患者的临床和影像资料。将入组患者按7∶3比例分为训练集和测试集,提取影像组学特征,从中筛选并构建影像组学模型。描绘影像组学模型的Rad-score与病理金标准之间的受试者工作特征(ROC)曲线,计算曲线下面积(AUC),并评价模型的诊断效能。采用决策曲线分析(DCA)计算风险阈值的范围,并评估临床获益情况。收集湖南省人民医院25例dMMR/MSI-H基因型LARC患者的影像资料作为外部验证集。结果:训练集、测试集及外部验证集三者之间的临床特征无统计学差异(P>0.05)。经过降维处理、t检验及一致性检验以及LASSO交叉验证后,筛选出一阶偏度特征和体积2个特征构建影像组学模型。训练集、测试集和外部验证集的影像组学预测模型ROC曲线的AUC、灵敏度、特异度、阳性预测值和阴性预测值分别为0.920、97.1%、85.7%、91.9%、94.7%;0.885、80.0%、88.9%、92.3%、72.7%;0.875、87.5%、88.9%、93.3%、80.0%。DCA曲线显示,当风险阈值范围为0%~82%时,采用影像组学模型预测LARC患者为病理完全缓解(pCR)的获益大于将所有患者都视为pCR或者无病理完全缓解(npCR)。结论:基于MRI影像组学构建的dMMR/MSI-H型局部进展期直肠癌PD-1/PD-L1抑制剂联合全程新辅助放化疗疗效预测模型,有较大潜力为不同基因分型的直肠癌患者制定个体化治疗策略提供量化依据。

Extracorporeal shockwave therapy for Peyronie＇s disease： an alternative treatment？

Aim： To determine retrospectively the safety and efficacy of extracorporeal shock wave therapy （ESWT） in patients with Peyronie＇s disease. Methods： Fifty-three patients with stable Peyronie＇s disease underwent ESWT （group 1）. Fifteen patients matched with the baseline characteristic of the patients in group 1, who received no treatment, were used as the control （group 2）. The patients＇ erectile function （International Index of Erectile Function [IIEF-5] score）, pain severity （visual analog scale）, plaque size and degree of penile angulation were assessed before and after the treatment in group 1 and during the follow-up in group 2. Results： The mean follow-up time was 32 months （range： 6-64 months） in group 1 and 35 months （range： 9-48 months） in group 2. All the patients were available for the follow-up. Considering erectile function and plaque size, no significant changes （P 〉 0.05） were observed in group 1 before or after the ESWT. A total of 39 patients （74%） reported a significant effect in pain relief in group 1 after ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no significant differences were observed between the two groups. In 21 patients （40%） of group 1, the deviation angle was decreased more than 10° with a mean reduction in all patients of 11° （range： 6-20°）. No serious complications were noted considering ESWT procedure. Conclusion： ESWT is a minimally invasive and safe alternative procedure for the treatment of Peyronie＇s disease. However, the effect of ESWT on penile pain, sexual function and plaque size remains questionable.

Cryotherapy in the management of premalignant and malignant conditions of the esophagus

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Efficacy of endoscopic therapy for gastrointestinal bleeding from Dieulafoy’s lesion

AIM： To investigate the endoscopic hemostasis for gastrointestinal bleeding due to Dieulafoy＇s lesion. METHODS： One hundred and seven patients with gastrointestinal bleeding due to Dieulafoy＇s lesion were treated with three endoscopic hemostasis methods： aethoxysklerol injection （46 cases）, endoscopic hemoclip hemostasis （31 cases）, and a combination of hemoclip hemostasis with aethoxysklerol injection （30 cases）. RESULTS： The rates of successful hemostasis using the three methods were 71.7% （33/46）, 77.4% （24/31） and 96.7% （29/30）, respectively, with significant differences between the methods （P 〈 0.05）. Among those who had unsuccessful treatment with aethoxysklerol injection, 13 were treated with hemoclip hemostasis and 4 underwent surgical operation; 9 cases were successful in the injection therapy. Among the cases with unsuccessful treatment with hemoclip hemostasis,7 were treated with injection of aethoxysklerol and 3 cases underwent surgical operation; 4 cases were successful in the treatment with hemoclip hemostasis. Only 1 case had unsuccessful treatment with a combined therapy of hemoclip hemostasis and aeth- oxysklerol injection, and surgery was then performed. No serious complications of perforation occurred in the patients whose bleeding was treated with the endoscopic hemostasis, and no releeding was found during a 1-year follow-up. CONCLUSION： The combined therapy of hemoclip hemostasis with aethoxysklerol injection is the most effective method for gastrointestinal bleeding due to Dieulafoy＇s lesion.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.