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

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

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.

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.

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 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.