Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Research on optimal immunization strategies for hepatitis B in different endemic areas in China

INTRODUCTION At present hepatitis B vaccine immunization is an unique effective measure for controlling hepatitis B.It is important o determine optimal immunization

Random walk immunization strategy on scale-free networks

A novel immunization strategy called the random walk immunization strategy on scale-free networks is proposed. Different from other known immunization strategies, this strategy works as follows： a node is randomly chosen from the network. Starting from this node, randomly walk to one of its neighbor node; if the present node is not immunized, then immunize it and continue the random walk; otherwise go back to the previous node and randomly walk again. This process is repeated until a certain fraction of nodes is immunized. By theoretical analysis and numerical simulations, we found that this strategy is very effective in comparison with the other known immunization strategies.

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

An Immunization Strategy for Social Network Worms Based on Network Vertex Influence

Along with the rapid development of social networks, social network worms have constituted one of the major internet security problems. The root of worm is the inevitable software vulnerability during the design and implementation process of software. So it is hard to completely avoid worms in the existing software engineering systems. Due to lots of bandwidth consumption, the patch cannot be transmitted simultaneously by the network administrator to all hosts. This paper studies how to prevent the propagation of social network worms through the immunization of key nodes. Unlike existing containment models for worm propagation, a novel immunization strategy is proposed based on network vertex influence. The strategy selects the critical vertices in the whole network. Then the immunization is applied on the selected vertices to achieve the maximal effect of worm containment with minimal cost. Different algorithms are implemented to select vertices. Simulation experiments are presented to analyze and evaluate the performance of different algorithms.

Rethinking Strategies to Address Inequity in Immunization Services towards Achieving Universal Immunization Coverage (UIC) in Karachi, Pakistan

Karachi, the largest city in Pakistan, having high population growth and a complex health care environment, has highest density of unimmunized (zero dose) and under-immunized children. The main reasons of low immunization coverage in Karachi were lack of governance and accountability in a duplicative and fragmented health management structure, weak and inequitable immunization services, and lack of demand and trust among people for immunization services. The Expanded Programme on Immunization (EPI), Ministry of Health (MOH) in Sindh Province spearheaded a structured and collaborative process to develop strategies for addressing inequity in immunization services towards achieving Universal Immunization Coverage (UIC) in Karachi. The process included a situation analysis with gathering quantitative and qualitative information on the root causes of zero-dose and inequity of the immunization services. The strategies and interventions were developed with multi-layer input and feedback of the stakeholders and partners, and focusing primarily to address gaps in three program areas: governance, leadership and accountability;immunization service delivery;and building demand and trust among the people. The interventions were further prioritized for high-risk areas;identified based on maximum number zero-dose children, presence of large slum areas, measles outbreak and on-going circulation of wild poliovirus. Finally, costing for the Roadmap activities was done through consultation with partners and aligning domestic and external (donor) resources. In this paper, we have highlighted the unique process the Sindh Government undertook in collaboration with the stakeholders and partners to develop strategies and interventions for addressing inequity in urban immunization services in Karachi towards achieving Universal Immunization Coverage (UIC). Similar processes can be adapted, as a potential model, for developing strategies to achieve universal health coverage in the cities of Pakistan and in other countries.

Immunization for scale-free networks by random walker

Based on the random walk and the intentional random walk, we propose two types of immunization strategies which require only local connectivity information. On several typical scale-free networks, we demonstrate that these strategies can lead to the eradication of the epidemic by immunizing a small fraction of the nodes in the networks. Particularly, the immunization strategy based on the intentional random walk is extremely efficient for the assortatively mixed networks.

Immune Control Strategies for Vaccinia Virus-related Laboratory-acquired Infections

While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections.

Synthesis of TP3 FragmentviaOne Pot Strategy and Its Immune Regulatory Activity

We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.

Stator Winding Turn Faults Diagnosis for Induction Motor by Immune Memory Dynamic Clonal Strategy Algorithm

Quick detection of a small initial fault is important for an induction motor to prevent a consequent large fault.The mathematical model with basic motor equations among voltages,currents,and fluxes is analyzed and the motor model equations are described.The fault related features are extracted.An immune memory dynamic clonal strategy(IMDCS)system is applied to detecting the stator faults of induction motor.Four features are obtained from the induction motor,and then these features are given to the IMDCS system.After the motor condition has been learned by the IMDCS system,the memory set obtained in the training stage can be used to detect any fault.The proposed method is experimentally implemented on the induction motor,and the experimental results show the applicability and effectiveness of the proposed method to the diagnosis of stator winding turn faults in induction motors.

考虑碳排放带时间窗的商超配送路径优化

针对商超配送多批次、小批量的实际情况,综合考虑了需求点的服务时间窗、最小配送量、访问次数等要求,设计了一种新的拆分策略,即“最大车辆载重量—最小配送量”需求拆分策略,构建相关商超配送车辆路径优化模型,并使用人工免疫算法对该模型进行求解。由于需求拆分车辆路径问题是一个复杂的组合优化过程,考虑到传统人工免疫算法局部搜索能力不足的局限,设计了多种变邻域操作改进人工免疫算法,并采用轮盘赌选择法将变邻域操作用于抗体突变,形成变邻域人工免疫算法。通过数值仿真实验,结果显示,变邻域人工免疫算法比人工免疫算法求得的综合成本平均优化3%~5%,碳排放相关成本平均降低5%~10%。

集成生物信息学与机器学习分析特应性皮炎差异表达基因及其与免疫细胞浸润的关系

目的利用生物信息学和机器学习策略,初步探索特应性皮炎(AD)差异表达基因(DEGs)及其与免疫细胞浸润的关系,以提高对该疾病的认识和诊治水平。方法从基因表达谱数据库(GEO)中检索了两个基因表达数据集,分别包括20名健康志愿者的正常皮肤和51例未经治疗的AD患者病损皮肤进行建模,以及22名健康志愿者的正常皮肤和30例AD病损皮肤用于验证,以确定DEGs。使用最小绝对收缩和选择算法回归模型和支持向量机-递归特征消除对DEGs进行了验证。通过CIBERSORT来评估AD的炎症状态,进一步探讨DEGs与免疫细胞之间的相关性。结果与健康志愿者比较,AD患者中MAPKAPK5反义RNA 1(MAPKAPK5-AS1)的表达有差异。此外,AD与健康志愿者之间皮肤的6种免疫细胞比例也存在显著差异。同时MAPKAPK5-AS1的表达水平与初始B细胞、活化的CD4^(+)记忆T细胞和活化的肥大细胞的数量之间均呈正相关。结论MAPKAPK5-AS1可能是AD的一个重要的DEGs,并且与免疫细胞浸润特征存在关联,为AD的诊断和治疗提供了新的思路。

老年肝癌患者系统治疗策略

衰老是促进慢性肝病不同阶段发展的主要风险因素,与肝细胞癌的发生密切相关,老年和年轻肝癌患者的临床病理学特征及肿瘤微环境有显著区别。肝癌系统治疗领域发展日新月异,免疫检查点抑制剂联合靶向治疗极大改善了晚期肝癌患者的预后。老年肝癌患者治疗决策的选择需要考虑年龄相关的独特问题,在决策前需进行充分沟通和必要评估。通过大型临床研究的年龄亚组分析,可以推测老年肝癌患者能够从免疫联合治疗中获益,不应将高龄作为治疗策略选择的限制因素。然而,将临床试验中获得的疗效和安全性数据外推到真实世界中的老年人群具有一定局限性,针对老年肝癌患者的最佳诊疗方案仍有待大规模前瞻性临床研究进一步探索。

网联环境中基于免疫思想的公交通行策略

在V2X网联环境中,公交系统能够获取全局的动态信息,以相邻公交车站之间的道路为场景开展网联公交的通行策略研究。以绿信比之差为主要参数,构建公交快速通行的数学模型;遗传算法与免疫思想相结合,设计亲和度,选取优秀抗体,提出一种混合遗传算子;改进自适应交叉、变异概率,提出一种基于免疫思想的公交通行策略。仿真结果表明:对比固定相位时长,采用遗传算法和基于免疫思想的通行策略均可较大程度地减少公交车的运行时间、等待时间和停车次数等重要指标;对比遗传算法的通行策略,基于免疫思想的通行策略绿信比变化降低了约8.8%,收敛速度提升了约26.8%,改进的策略减少了陷入局部最优的风险,能实现网联公交的快速通行,提升公交系统的运行效率。

单细胞RNA测序技术在胶质母细胞瘤研究中的应用

胶质母细胞瘤是成人脑部最常见的原发恶性肿瘤,尽管近年来在改善预后方面做出了巨大的努力,其中位生存期仍低于20个月,且存活时间超过20个月的患者不到5%。胶质母细胞瘤的标准治疗方案为最大限度的手术切除,联合放疗及替莫唑胺化疗。单细胞RNA测序(scRNA-seq)技术精准分析每个独特的细胞,使我们能够更好地理解肿瘤的异质性、肿瘤细胞的演化过程、肿瘤免疫微环境中各类细胞的特殊功能及细胞间相互作用,从而为临床的个体化治疗提供新思路。该综述重点关注scRNA-seq技术在胶质母细胞瘤的异质性、肿瘤免疫微环境、细胞通讯以及治疗研究中的应用。

集束化管理策略对脓毒症患者免疫功能及预后的影响

目的分析集束化管理策略对脓毒症患者免疫功能及预后的影响。方法选取2022年4月至2023年4月收治的82例脓毒症患者作为研究对象,按入院就医时间的不同将所有患者分为对照组和观察组,每组41例。对照组接受常规治疗和干预措施,观察组在对照组基础上接受集束化管理策略干预,评估和比较2组患者免疫功能指标、炎症指标、血流动力学指标以及预后效果。结果干预后观察组CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+)高于对照组(P<0.05),而CD_(8)^(+)、白细胞计数(WBC)水平低于对照组(P<0.05);干预后2组IL-6、CRP以及PCT水平均有所降低,组间比较,观察组低于对照组(P<0.05);观察组心率(HR)较于对照组低(P<0.05),而其平均动脉压(MAP)和中心静脉压(CVP)高于对照组(P<0.05);观察组在血管活性药物使用时间、机械通气时间以及总住院时间方面与对照组相比,显示明显地缩短且差异有统计学意义(P<0.05)。结论在脓毒症患者干预中,采取集束化管理策略可取得显著的干预效果,能有效改善免疫功能、降低炎症因子水平、稳定血流动力学,并促进预后效果提高。

The role of cholesterol metabolism in lung cancer

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer.Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells.Inhibiting tumor cell cholesterol uptake or biosynthesis pathways,through the modulation of receptors and enzymes such as liver X receptor and sterolregulatory element binding protein 2,effectively restrains lung tumor growth.Similarly,promoting cholesterol excretion yields comparable effects.Cholesterol metabolites,including oxysterols and isoprenoids,play a crucial role in regulating cholesterol metabolism within tumor cells,consequently impacting cancer progression.In lung cancer patients,both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth,proliferation,and metastasis.The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells,B cells,macrophages,myeloid-derived suppressor cells,among others.Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments.Statins,targeting the cholesterol biosynthesis pathway,are widely employed in lung cancer treatment,either as standalone agents or in combination with other drugs.Additionally,drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer.In this review,we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.

Converting“cold”to“hot”:epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells

Significant developments in cancer treatment have been made since the advent of immune therapies.However,there are still some patientswithmalignant tumors who do not benefit from immunotherapy.Tumors without immunogenicity are called“cold”tumors which are unresponsive to immunotherapy,and the opposite are“hot”tumors.Immune suppressive cells(ISCs)refer to cells which can inhibit the immune response such as tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),regulatory T(Treg)cells and so on.The more ISCs infiltrated,the weaker the immunogenicity of the tumor,showing the characteristics of“cold”tumor.The dysfunction of ISCs in the tumor microenvironment(TME)may play essential roles in insensitive therapeutic reaction.Previous studies have found that epigeneticmechanisms play an important role in the regulation of ISCs.Regulating ISCs may be a new approach to transforming“cold”tumors into“hot”tumors.Here,we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs.In addition,we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in“cold”tumor.

Mechanism of mesenchymal stem cells in liver regeneration:Insights and future directions

Mesenchymal stem cells(MSCs)are a prevalent source for stem cell therapy and play a crucial role in modulating both innate and adaptive immune responses.Non-alcoholic fatty liver disease(NAFLD)is characterized by the accumulation of triglycerides in liver cells and involves immune system activation,leading to histological changes,tissue damage,and clinical symptoms.A recent publication by Jiang et al,highlighted the potential of MSCs to mitigate in NAFLD progression by targeting various molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.In this editorial,we comment on their research and discuss the efficacy of MSC therapy in treating NAFLD.