B and T lymphocyte attenuator (BTLA) is an inhibitory immune checkpoint, which typically interacts with herpesvirus entry mediator (HVEM) and plays a crucial role in regulating immune balance. BTLA interacts with its ligand HVEM in a cis manner on the surface of the same immune cell to maintain immune tolerance, while trans interactions on the surface of different immune cells mediate immunosuppressive effects. Dysregulation of the BTLA/HVEM axis can impair the functions of immune cells, particularly T lymphocytes, promoting immune escape of tumor cells and ultimately leading to tumor progression. Researchers have found that BTLA and HVEM are abnormally expressed in various tumors and are associated with prognosis, suggesting that they may be potential targets for tumor immunotherapy. This review summarizes the molecular structures of BTLA and HVEM, immunomodulatory mechanisms, recent advances in hematologic malignancies, potential inhibitors of BTLA/HVEM interaction, and their applications in immunotherapy for hematologic malignancies.
Humans ; Receptors, Tumor Necrosis Factor, Member 14/chemistry* ; Receptors, Immunologic/immunology* ; Hematologic Neoplasms/genetics* ; Immunotherapy/methods* ; Animals

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Poliovirus receptor(PVR)family includes several immune checkpoint receptors such as T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif structural domains(TIGIT),CD96 and CD226,and their ligands CD155 and CD112,etc.PVR family members have sequence homology and highly interact with each other for synergistic stimulatory or inhibitory effects,forming a complex immunomodulatory network together.The co-signaling network formed by PVR family members is of great significance and has become a major hot spot in hematologic tumor immunotherapy in recent years.This review describes the structure of PVR family members,their mechanism of action,research progress in hematological tumors,and their prospects for application in the immunotherapy of hematologic tumors.

Objective To study whether there are differences in immunological and hematological indexes in patients with extramed-ullary multiple myeloma(EMM).Methods The medical records of 150 newly diagnosed multiple myeloma(MM)patients admitted to Department of Hematology,the Second Hospital of Lanzhou University from January 2019 to January 2024 were retrospectively analyzed,to compare and analyze the differences in immunological and some hematological indexes between the EMM group(n=60)and the non-EMM group(n=90),and the two subgroups of the different risk stratification DS stages and Mayo myeloma risk stratification.Results The peripheral blood erythrocyte count,hemoglobin level,lactic acid dehydrogenase(LDH)level and interleukins-8(IL-8)levels of the patients in the EMM group were higher than those in the non-EMM group(P＜0.05),the interleukins-10(IL-10)and the pro-portion of CD4+T cells in the EMM group were lower than those in the non-EMM group(P＜0.05).Lymphocyte counts were signifi-cantly higher(P＜0.05)and the proportion of CD8+T cells was significantly lower(P＜0.05)in the EMM group of patients with stand-ard-risk MM.The proportion of peripheral blood CD8+T cells was significantly lower in the EMM group compared with the non-EMM group of patients with high-risk MM(P＜0.05).LDH levels were higher in the EMM group than that in the non-EMM group in both DS-Ⅰ and DS-Ⅱ MM patients(P＜0.05).Peripheral blood erythrocyte count,monocyte count,and hemoglobin level were higher in the EMM group than those in the non-EMM group in DS-Ⅲ MM patients(P＜0.05).Conclusion Immune abnormalities may be one of the factors contributing to the occurrence,development and poor prognosis of EMM.This study suggest that CD8+T cells,as immune effector cells,can be further studied in the occurrence and progression of MM to EMM,providing a new basis for clinical treatment.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

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NLRP3 inflammasome plays an important role in immune microenvironment of myelodysplastic syndromes(MDS)and is a key component of innate immune system.NLRP3 inflammasome participates in inflammatory regulation of MDS by producing pro-inflammatory factors IL-1β and IL-18 and Caspase-1-mediated cell pyroptosis.In bone marrow microenvironment,DAMPs and related genes can activate inflammasome,leading to dysregulation of innate immune system.Therefore,NLRP3 inflammasome may be an effective therapeutic target for MDS.This review studies structure,function,activation mechanism and immune regulation of NLRP3 inflammasome in MDS and explored its potential as a therapeutic target for MDS.

Objective To investigate alterations in plasma complement levels and white matter imaging characteristics,along with their relationship in patients with first-episode schizophrenia(SCZ).Methods Thirty-eight patients with first-episode schizophrenia and 42 healthy controls were enrolled.Whole-brain diffusion tensor imaging(DTI)was performed using a Philips 3.0 T MRI scanner.Tract-based spatial statistics(TBSS)combined with the Johns Hopkins University(JHU)white matter labels atlas was used to extract and compare white matter characteristics between the two groups.Plasma levels of complement components(C1q,C3,C4,factor B,factor H,and factor P)were measured using the MILLIPLEX? human complement assay kit via multiplex analysis.Spearman correlation analysis was conducted to examine the association between plasma complement levels and white matter features.Results The radial diffusivity(RD)of the left fornix/stria terminalis was significantly higher in the patient group compared to the control group[(0.62±0.04)×10-3mm2/s vs.(0.60±0.03)×10-3mm2/s,PFDR=0.048)].Factor H[677.71(551.58,846.21)ng/mL vs.582.76(513.93,729.71)ng/mL,P=0.041]and factor P[71.36(57.30,95.99)ng/mL vs.60.08(46.67,80.03)ng/mL,P=0.011]were both significantly elevated compared to the control group.Moreover,RD values in the left fornix/stria terminalis were negatively correlated with plasma C3 levels in the patient group(r=-0.362,P=0.025).Conclusion Patients with first-episode schizophrenia exhibit white matter microstructural abnormalities in left fornix/stria terminalis,which are significantly associated with plasma complement levels.

Objective To study whether there are differences in immunological and hematological indexes in patients with extramed-ullary multiple myeloma(EMM).Methods The medical records of 150 newly diagnosed multiple myeloma(MM)patients admitted to Department of Hematology,the Second Hospital of Lanzhou University from January 2019 to January 2024 were retrospectively analyzed,to compare and analyze the differences in immunological and some hematological indexes between the EMM group(n=60)and the non-EMM group(n=90),and the two subgroups of the different risk stratification DS stages and Mayo myeloma risk stratification.Results The peripheral blood erythrocyte count,hemoglobin level,lactic acid dehydrogenase(LDH)level and interleukins-8(IL-8)levels of the patients in the EMM group were higher than those in the non-EMM group(P＜0.05),the interleukins-10(IL-10)and the pro-portion of CD4+T cells in the EMM group were lower than those in the non-EMM group(P＜0.05).Lymphocyte counts were signifi-cantly higher(P＜0.05)and the proportion of CD8+T cells was significantly lower(P＜0.05)in the EMM group of patients with stand-ard-risk MM.The proportion of peripheral blood CD8+T cells was significantly lower in the EMM group compared with the non-EMM group of patients with high-risk MM(P＜0.05).LDH levels were higher in the EMM group than that in the non-EMM group in both DS-Ⅰ and DS-Ⅱ MM patients(P＜0.05).Peripheral blood erythrocyte count,monocyte count,and hemoglobin level were higher in the EMM group than those in the non-EMM group in DS-Ⅲ MM patients(P＜0.05).Conclusion Immune abnormalities may be one of the factors contributing to the occurrence,development and poor prognosis of EMM.This study suggest that CD8+T cells,as immune effector cells,can be further studied in the occurrence and progression of MM to EMM,providing a new basis for clinical treatment.

NLRP3 inflammasome plays an important role in immune microenvironment of myelodysplastic syndromes(MDS)and is a key component of innate immune system.NLRP3 inflammasome participates in inflammatory regulation of MDS by producing pro-inflammatory factors IL-1β and IL-18 and Caspase-1-mediated cell pyroptosis.In bone marrow microenvironment,DAMPs and related genes can activate inflammasome,leading to dysregulation of innate immune system.Therefore,NLRP3 inflammasome may be an effective therapeutic target for MDS.This review studies structure,function,activation mechanism and immune regulation of NLRP3 inflammasome in MDS and explored its potential as a therapeutic target for MDS.