OBJECTIVE: To investigate the expression of co-inhibitory molecules TIGIT/CD155 and PD-1 on CD4⁺T cells and Treg cells in peripheral blood of patients with chronic lymphocytic leukemia (CLL) and analyze their clinical significance. METHODS: The expression of PD-1 and TIGIT on CD4⁺T cells and Treg cells was detected by flow cytometry in 40 CLL patients and 20 healthy controls. Additionally, the expression of CD155 on peripheral blood B cells and DC cells of the enrolled subjects was detected. RESULTS: The proportions of PD-1⁺TIGIT⁺CD4⁺T cells, PD-1⁺TIGIT⁺Treg cells and CD155⁺DC cells in peripheral blood of CLL patients were significantly higher than those of healthy controls ( P < 0.05). The proportions of PD-1⁺TIGIT⁺CD4⁺T cells and PD-1⁺TIGIT⁺Treg cells in CLL patients were significantly higher than those of PD-1⁺TIGIT^-CD4⁺T cells and PD-1⁺TIGIT^-Treg cells, respectively ( P < 0.05). Both PD-1⁺TIGIT⁺CD4⁺T cells and PD-1⁺TIGIT⁺Treg cells were positively correlated with the level of CD155⁺DC cells (r =0.742, r =0.766). With the progression of Binet stage, the proportions of PD-1⁺TIGIT⁺CD4⁺T cells, PD-1⁺TIGIT⁺Treg cells, and CD155⁺DC cells gradually increased ( P < 0.05), and the aforementioned three types cells were all increased in patients with CD38≥30%, IGVH unmutated, or poor prognosis due to chromosomal abnormalities ( P < 0.05). CONCLUSION Co-inhibitory molecules PD-1 and TIGIT may be involved in immunodepletion in patients with advanced CLL, which has clinical prognostic value. Dual inhibitor molecular targeted therapy provides a new direction for the individualized treatment of CLL.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology* ; Receptors, Immunologic/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; T-Lymphocytes, Regulatory/metabolism* ; Receptors, Virus/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Flow Cytometry ; Clinical Relevance

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective:To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings.Methods:The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated.Results:In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot ( P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion:Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.

Objective:To evaluate the disinfection effect of high-energy pulse ultraviolet disinfection equipment in medical institution settings.Methods:The disinfection effect was evaluated through field tests and laboratory tests. Among them, 135 high-frequency contact points were selected from nine departments in the field test. Samples were collected before and after disinfection, and the disinfection effects of 75% alcohol wipes wiping disinfection, high-energy pulse ultraviolet disinfection robot disinfection and high-energy pulse ultraviolet handheld disinfection instrument were compared. In the laboratory test, 30 infected areas of the simulated test table were exposed to vertical ultraviolet irradiation and the bacterial-killing rate before and after disinfection was calculated.Results:In the field test, the bacteria-killing rates of 75% alcohol wipes, high-energy pulse ultraviolet disinfection robot and high-energy pulse ultraviolet handheld disinfection instrument were 94.99%, 91.53% and 95.94%, respectively, and the difference was statistically significant. The disinfection effect of the high-energy pulse ultraviolet handheld disinfection instrument was better than that of the high-energy pulse ultraviolet disinfection robot ( P values <0.05). In the laboratory test, the killing log value of Staphylococcus aureus and Escherichia coli on the carrier were both greater than 3.00. In the simulated field test, the killing log value of Staphylococcus aureus on the surface samples were 4.99. Conclusion:Both the high-energy pulse ultraviolet handheld disinfection instrument and the high-energy pulse ultraviolet disinfection robot have good disinfection effects, which are similar to the disinfection effects of conventional 75% alcohol wipes.

Respiratory syncytial virus（RSV）is the most common reason for lower respiratory tract infections in children's hospitalization.The burden of RSV disease is widely recognized.Main risk factors for severe disease，such as extreme age（<3 months），chronic cardiopulmonary conditions，and immunosuppression，typically coincide with poorer outcomes.While most RSV hospitalizations involve healthy children，a higher proportion of hospitalized infants with underlying conditions need intensive care.Lower respiratory tract disease caused by RSV may present as bronchiolitis or pneumonitis，a large intrapulmonary shunt and acute respiratory distress syndrome（ARDS）.The bronchiolitis clinical assessment scales were used to determine the severity of the children.Presently，treatment primarily consists of supportive measures.Non-invasive mechanical ventilation and high-flow oxygen therapy represented significant advancements in the management of severe RSV disease in children.Severe respiratory distress and ARDS need invasive mechanical ventilatory support and/or extracorporeal membrane oxygenation therapy.New vaccines for RSV under development and immune passive strategies involving Nirsevimab are expected to reduce the medical burden of severe RSV disease.

Objective:To analyze the effects of highdose methotrexate(HD-MTX)and lenalidomide as central nervous system(CNS)prophylaxis strategies in patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively.The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies.Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement.The CNS relapse-free survival(CRFS)rate,adverse effects,and the effects of different prophylaxis strategies on overall survival(OS)rate and progression-free survival(PFS)rate were evaluated in different groups and subgroups.Results:There were 200 patients enrolled in this study,80 cases in lenalidomide group and 120 cases in HD-MTX group.According to the delivery timing of prophylactic HD-MTX,the patients in HD-MTX group were further divided into two groups:80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval.At a median follow-up of 48(14-133)months,the 4-year CRFS rate,4-year PFS rate,and 4-year OS rate of the HD-MTX group was 93.6％,57.2％,and 68.8％,respectively,while that of the lenalidomide group was 90.4％,69.4％and 75.6％.There were no significant differences in 4-year CRFS rate,4-year PFS rate,and 4-year OS rate between HD-MTX group and lenalidomide group(all P＞0.05),but lenalidomide group showed a trend of improvement in PFS.Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups(91.7％vs 83.4％,P＞0.05),while 4-year PFS rate showed difference(49.5％vs 64.2％,P＜0.05).A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group,and 25 cycles occurred neutropenia accompanied with infection(10.1％),while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection(8.3％).Both the two groups had no treatment-related deaths.Conclusion:Compared with HD-MTX,lenalidomide combined with immunochemotherapy can prevent CNS relapse,at the same time,improve prognosis,which is a safe and well tolerated central prophylaxis strategy.

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

Purpose::This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects.Methods::Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct 3-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean ± standard deviation and compared using independent sample t-tests. Results::In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment.Conclusion::Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.