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

On August 31， 2025， the Asian Pacific Association for the Study of the Liver （APASL） updated and released management of acute variceal bleeding： updated APASL guidelines （2025 edition）， which systematically elaborates on the definition， diagnosis， assessment， and treatment of acute variceal bleeding. This article gives an excerpt of the recommendations in this guideline.

ObjectiveTo understand the prevalence of tobacco use among residents aged 15 years old and above in Jiading District of Shanghai, and to provide a scientific basis for formulating effective regional tobacco control policies. MethodsThe Probability Proportional to Size (PPS) sampling method was employed to select one neighborhood committee (village) from each of Jiading District’s 11 subdistricts as survey monitoring sites. From the household registry of each selected neighborhood committee (village), 50 residential households were randomly sampled, resulting in a total of 550 households surveyed. Within each selected household, one permanent resident aged 15 years old or above was randomly chosen to complete the questionnaire. The content covered general information, exposure to secondhand smoke, awareness of tobacco related health hazards, etc. Statistical analyses were performed using SPSS 27.0 software. ResultsA total of 550 questionnaires were distributed, with 549 valid responses collected, and the effective response rate was 99.82%. The survey findings revealed that in 2023, the current smoking rate among individuals aged 15 years old and above in Jiading District of Shanghai was 18.76%, with males accounting for 38.93% and females accounting for 2.62%. Male gender was identified as a relative factor for smoking (OR=34.108, 95%CI: 14.440‒80.722), whereas higher education attainment emerged as a protective factor against smoking (OR=0.388, 95%CI: 0.184‒0.820). Among non-smokers aged 15 years old and above in Jiading District, the secondhand smoke exposure rate was 46.86%, with statistically significant differences observed across different age groups and occupations (P<0.001). Restaurants exhibited the highest secondhand smoke exposure rate of 42.14%, followed by households bearing (36.79%). The overall awareness rate among individuals aged 15 years old and above in Jiading District regarding four smoking-related diseases, namely stroke, heart disease, lung cancer, and impotence, was 48.45%, while the awareness rate for three secondhand smoke-induced diseases, namely adult heart disease, pediatric pulmonary disease, and adult lung cancer, was 64.29%. ConclusionThere is still room for reduction in the prevalence of tobacco use among individuals aged 15 yeas old and above in Jiading District. The exposure to secondhand smoke is severe, and residents have low awareness of the harm of tobacco. Tobacco control law enforcement should be strengthened, smoke-free-home health education should be included in tobacco control efforts, and targeted health education should be carried out.

Objective:To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs.Methods:The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed.Results:There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation.Conclusions:For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

Objective·To explore EDAR(ectodysplasin A receptor)gene variants that lead to congenital tooth agenesis,and preliminarily analyze the reasons why variants in EDAR can cause both syndromic and non-syndromic tooth agenesis.Methods·Patients with congenital tooth agenesis admitted to the Department of 2nd Dental Center,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine and their family members were included,and genomic DNA from their peripheral blood was extracted for whole exome sequencing(WES).After preliminary screening,PolyPhen-2,Mutation Taster,and Provean were used to predict the harmfulness of potential variants.The screened variants in patients and their families were verified by Sanger sequencing.Conservation analysis of variants was performed,and Swiss-Model was used to analyze the changes in the three-dimensional structure of EDAR.The teeth and syndromic phenotype of the patients and their family members were investigated.Results·Among the included congenital tooth agenesis patients,five patients with EDAR mutations were found,one with EDAR frameshift mutation c.368_369insC(p.L123fs)and the other four with EDAR missense mutations.Two of these four patients were diagnosed as non-syndromic tooth agenesis(NSTA),resulted from c.77C＞A(p.A26E)homozygous mutation and c.380C＞T(p.P127L)heterozygous mutation,respectively.The other two patients with two variants were diagnosed as hypohidrotic ectodermal dysplasia(HED).One compound heterozygous missense mutation patient carried EDAR c.77C＞T(p.A26V)from her father andEDAR c.1281G＞C(p.L427F)from her mother;the other patient with both EDAR and EDA mutations carried EDAR c.1138A＞C(p.S380R)heterozygous mutation and EDA c.1013C＞T(p.T338M)hemizygous mutation.Both variants were from his mother and were reported to be related with NSTA.Two of these missense mutations,EDAR c.1281G＞C(p.L427F)and EDAR c.77C＞A(p.A26E),had not been reported before.The missense mutations affected the protein's spatial conformation by altering the polarity,charge,or volume of the amino acid residues.The frameshift mutation caused a non-triplet base addition,which probably led to protein truncation or degradation.Conclusion·Two new EDAR missense mutations are discovered.An NSTA patients with EDAR homozygous mutations and an HED patient with both EDA and EDAR mutations are reported.It expands the understanding of pathogenic mechanisms of EDAR mutations causing HED and NSTA.

Objective:To screen the differentially expressed immune-related genes(DEIRGs)in in-stent restenosis(ISR),and to analyze the immune cell infiltration in ISR,and to clarify the mechanism of occurrence and development of ISR.Methods:The mRNA gene expression data of GSE46560 dataset samples were downloaded from the Gene Expression Omnibus(GEO),and divided into ISR group and non-ISR group.The"Limma"package in R software was used to identify the differentially expressed genes(DEGs)which were then intersected with immune-related genes(IRGs)to identify the DEIRGs in ISR;R software was used for Gene Ontology(GO)functional enrichment andalysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis on DEIRGs;the STRING database was used to construct the protein-protein interaction(PPI)network,which was visualized and analyzed for Hub genes by Cytoscape software;the receiver operating characteristic(ROC)curve of the Hub genes were plotted,and the area under the curve(AUC)was calculated and the diagnostic value was evaluated;CIBERSORT software was used to analyze the immune cell infiltration in ISR;Pearson correlation analysis was used to analyze the relationships between the immune cells and the relationships between the immune cells and key genes.Results:A total of 331 DEGs were identified(P<0.05,|log2FC|>1),including 176 upregulated genes and 155 downregulated genes,and 38 DEIRGs were obstained.The GO functional enrichment analysis results showed that the DEIRGs were mainly enriched in biological processes(BP)such as defense response,immune response,and immune system;in cellular components(CC),the DEIRGs were located primarily in the extracellular region and cytoplasmic membrane;and in molecular functions(MF),the DEIRGs were mainly involved in regulating signaling receptor binding and cytokine receptor activity.The KEGG signaling pathway enrichment analysis results indicated that the DEIRGs in ISR were primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and transforming growth factor-β(TGF-β)signaling pathways.In the PPI network,CD19 had the highest node among the top 10 Hub genes.Compared with non-ISR group,the expression level of the CD19 gene in the samples in ISR group was increased(P<0.05).The AUC value in the ROC curve of CD19 gene expression was 0.92(P<0.05).The immune cell infiltration analysis results showed that compared with non-ISR group,the infiltration level of T lymphocyte follicular helper(Tfh)cells in the patients in ISR group were increased(P<0.05),the infiltration levels of immature B lymphocytes,CD8+T lymphocytes,naive CD4+T lymphocytes,and M0 macrophages were increased,but the differences were not statistically significant(P>0.05),while the infiltration levels of memory B lymphocytes,activated memory CD4+T lymphocytes,regulatory T cells,resting natural killer(NK)cells,activated NK cells,monocytes,resting mast cells,and neutrophils were decreased,but the differences were not statistically significant(P>0.05).There were positive correlations between Tfh cells and M0 macrophages and resting mast cells(r=0.88,P<0.05;r=0.68,P<0.05),and there were negative correlations between Tfh cells and monocytes and neutrophils(r=-0.49,P<0.05;r=-0.42,P<0.05).Conclusion:CD19 may influence the occurrence and development of ISR by regulating the activation of the PI3K-AKT signaling pathway to affect the Tfh and B lymphocytes.CD19 can serve as a biomarker for the diagnosis of ISR.

Objective:To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs.Methods:The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed.Results:There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation.Conclusions:For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

OBJECTIVE To identify the chemical constituents of the modified Yupingfengsan formula. METHODS UPLC-Q- Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS & CONCLUSIONS Totally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O- glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.