ABSTRACT
Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.
Subject(s)
Mutation , Humans , Male , Prognosis , Female , Middle Aged , Cell Proliferation , Adult , Aged , Leukemia, Large Granular Lymphocytic/diagnosisABSTRACT
Objective: To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. Methods: PV patients with JAK2V617F gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age M (Q1, Q3) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [M (Q1, Q3)] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Results: Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all P<0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all P<0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (P=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (P<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (HR=2.031, 95%CI: 1.297-3.179, P=0.002), V617F%≥50% (HR=2.141, 95%CI: 1.370-3.347, P=0.001), ASXL1 mutation (HR=4.632, 95%CI: 1.497-14.336, P=0.008), spleen subcostal≥5 cm (HR=1.771, 95%CI: 1.047-2.996, P=0.033) are the risk factors of venous thrombosis in PV patients. According to HR values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95%CI: 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Conclusions: Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.
Subject(s)
Polycythemia Vera , Venous Thromboembolism , Humans , Polycythemia Vera/complications , Male , Risk Factors , Middle Aged , Female , Venous Thromboembolism/etiology , Adult , Janus Kinase 2/genetics , Mutation , Venous Thrombosis/etiologyABSTRACT
To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage â ¢ to â £. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.
Subject(s)
Intestinal Perforation , Humans , Male , Female , Child , Retrospective Studies , Adolescent , Child, Preschool , Infant , Prognosis , Intestinal Perforation/etiology , Lymphoma, B-Cell , Burkitt Lymphoma , Gastrointestinal Tract , Lymphoma, Non-Hodgkin , Lymphoma, Large B-Cell, DiffuseABSTRACT
Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage â £ and 5 cases of stage â ¢. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Brentuximab Vedotin , Hodgkin Disease , Humans , Hodgkin Disease/drug therapy , Female , Male , Child , Adolescent , Retrospective Studies , Child, Preschool , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Treatment Outcome , Immunoconjugates/administration & dosageABSTRACT
Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageâ ¡, 33(53.2%)patients in stage â ¢ and 18(29.1%)patients in stage â £. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, B-Cell , Humans , Retrospective Studies , Child , Lymphoma, B-Cell/drug therapy , China , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , Female , Male , Proto-Oncogene Proteins c-bcl-6/genetics , Cohort Studies , Proto-Oncogene Proteins c-bcl-2/genetics , Child, Preschool , In Situ Hybridization, Fluorescence , Treatment Outcome , Proto-Oncogene Proteins c-myc/geneticsABSTRACT
Objective: To summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage â and 1 case in stage â ¡ (0.7% each), 41 cases (28.1%) cases in stage â ¢ and 103 cases(70.5%) in stage â £. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Humans , Child , Female , Male , Adolescent , Prognosis , Retrospective Studies , Child, Preschool , Beijing , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Infant , Treatment Outcome , Hospitals, Pediatric , Survival Rate , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapyABSTRACT
OBJECTIVES: Evidence on the association between garden work and risk of incident dementia in the older Chinese population is limited. This study aimed to explore the association between the frequency of garden work and risk of incident dementia in an older population in China. STUDY DESIGN: This was a national cohort study. METHODS: This study analysed data from 8676 participants (median age: 86 years) from the Chinese Longitudinal Healthy Longevity Survey. Cox proportional hazard models were used to assess the association between the frequency of garden work and risk of incident dementia using hazard ratios (HRs) and 95% confidence intervals (CIs). Multiplicative and additive interaction effects were calculated between the frequency of garden work and age, sex or residence on incident dementia; subgroup analyses of the association were also conducted by age, sex and residence. In addition, sensitivity analyses were performed to assess the robustness of the results. RESULTS: During 4.31 years (median) of follow-up, 633 participants developed dementia. Compared with participants who did not engage in garden work, the adjusted risk of incident dementia for those who regularly or almost daily engaged in garden work decreased by 28% (HR = 0.72, 95% CI: 0.57-0.93). An additive interaction effect between frequency of garden work and age on incident dementia was observed, with subgroup analyses demonstrating similar statistically significant associations among participants aged ≥85 years, women and city or town residents. Sensitivity analyses were consistent with the primary analysis in the present study. CONCLUSIONS: Frequent engagement in garden work may be associated with a reduced risk of dementia and may be an effective measure to prevent incident dementia in the older population in China.
Subject(s)
Dementia , Gardening , Humans , Dementia/epidemiology , China/epidemiology , Female , Male , Aged , Aged, 80 and over , Gardening/statistics & numerical data , Risk Factors , Longitudinal Studies , Incidence , Proportional Hazards Models , Cohort Studies , Age FactorsABSTRACT
Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase â ¡ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1â¶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Male , Female , Humans , Adult , Middle Aged , Aged , Carcinoma, Squamous Cell/drug therapy , Cisplatin/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Squamous Cell Carcinoma of Head and Neck/drug therapy , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mouth Neoplasms/drug therapy , Paclitaxel/therapeutic use , Albumins/therapeutic useABSTRACT
Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7â¶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.
Subject(s)
Central Nervous System Neoplasms , Lymphoma , Humans , Male , Female , Child , Central Nervous System Neoplasms/drug therapy , Retrospective Studies , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/drug therapy , Methotrexate/therapeutic use , Lymphoma/drug therapy , Central Nervous System/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
This study was to determine the effects of the mixture of glycerol monolaurate and cinnamaldehyde (GCM) supplementation on the intestinal morphology, immunity, antioxidant status and cecal microbiota of laying hens. A total of 1,120 healthy laying hens (Jingfen-1 strain) at the age of 14 wk were randomly divided into 4 groups with 10 replicates of 28 layers in each and layers were fed diets containing 0 (control group), or 250, 500, and 1,000 mg/kg GCM for 12 wk. The results showed that dietary supplementation with GCM significantly increased intestinal villus height and villus height/crypt depth, duodenal villus area, total superoxide disumutase activities in the liver and jejunum, jejunal glutathione peroxidase activities while decreased duodenal and jejunal crypt depth, hydrogen peroxide content in the liver and jejunal malondialdehyde content of laying hens aging 28 wk (P < 0.05). Meanwhile, GCM addition significantly increased serum immunoglobulin A and immunoglobulin M concentration of layers at the age of 20, 24, and 28 wk (P < 0.05). Moreover, it was observed in the 16S rRNA sequencing that the addition of GCM elevated the abundance and diversity of gut microbiota in laying hens. The predominant bacteria from each group were Bacteroidota and Firmicutes at the phylum level and Bacteroides and Lactobacillus were the dominant genera. The composition and structure of cecal microflora were changed by the addition of GCM to the diet of laying hens. In conclusion, the addition of GCM (500-1,000 mg/kg diet) can improve intestinal morphology, immune function, intestinal and liver antioxidant status and intestinal flora of laying hens, thereby improving intestinal digestion and absorption capacity. These findings provide a new way to further explore the mechanism of GCM improving intestinal health.
Subject(s)
Acrolein , Animal Feed , Antioxidants , Cecum , Chickens , Diet , Dietary Supplements , Gastrointestinal Microbiome , Intestines , Laurates , Animals , Chickens/physiology , Chickens/growth & development , Chickens/immunology , Gastrointestinal Microbiome/drug effects , Female , Antioxidants/metabolism , Diet/veterinary , Dietary Supplements/analysis , Animal Feed/analysis , Acrolein/analogs & derivatives , Acrolein/pharmacology , Acrolein/administration & dosage , Intestines/drug effects , Intestines/anatomy & histology , Intestines/microbiology , Cecum/microbiology , Cecum/drug effects , Laurates/pharmacology , Laurates/administration & dosage , Random Allocation , Dose-Response Relationship, Drug , MonoglyceridesABSTRACT
The slow transition from an out-of-equilibrium glass towards a supercooled liquid is a complex relaxation phenomenon. In this Letter, we study the correlation between mechanical relaxation and equilibration kinetics in a Pd_{20}Pt_{20}Cu_{20}Ni_{20}P_{20} high-entropy metallic glass. The evolution of stress relaxation with aging time was obtained with an unprecedented detail, allowing us to pinpoint new interesting features. The long structural relaxation towards equilibrium contains a wide distribution of activation energies, instead of being just associated to the ß relaxation as commonly accepted. The stress relaxation time can be correlated with the equilibration rate and we observe a decrease of microstructural heterogeneity which contrasts with an increase of dynamic heterogeneity. These results significantly enhance our insight of the interplay between relaxation dynamics and thermodynamics in metallic glasses.
ABSTRACT
OBJECTIVE: During menopause, women are more likely to develop coronary heart disease (CHD) due to the significant changes in body metabolism brought on by the loss of estrogen. The purpose of this study was to investigate the independent association between platelet parameters and blood urea nitrogen (BUN) in postmenopausal patients with coronary artery disease in order to clarify the function performed by platelet parameters and BUN in thrombosis. PATIENTS AND METHODS: We took information from the NHANES between 2003 and 2016. Platelet count (PC), mean platelet volume (MPV), and PC/MPV were the independent variables, BUN was the dependent variable, and age, race, marital status, body mass index (BMI), inflammation indicators, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were the covariates. RESULTS: BUN decreased with increasing PC in postmenopausal heart disease patients after controlling for other factors. When PC/MPV was less than 30.5, there was a strong negative correlation with BUN. In addition, there was a strong positive correlation with BUN when MPV was less than 9.3 fL. CONCLUSIONS: The findings of this study will contribute to a better understanding of the mechanisms underlying thrombosis in postmenopausal women with CHD and offer fresh perspectives on how to create novel antithrombotic medications for an aging population.
Subject(s)
Coronary Artery Disease , Thrombosis , Humans , Female , Aged , Blood Urea Nitrogen , Postmenopause , Nutrition Surveys , Blood Platelets , Mean Platelet VolumeABSTRACT
The interface heat transfer of two layers induced by van der Waals (vdW) contacts is theoretically investigated, based on first-principles calculations at low temperatures. The results suggest that out-of-plane acoustic phonons with low frequencies dominate the interface thermal transport due to the vdW interaction. The interface thermal conductivity is proportional to the cubic of temperature at very low temperatures, but becomes linearly proportional to temperature as temperature increases. We show that manipulating the strain alters vdW coupling, leading to increased interfacial thermal conductivity at the interface. Our findings provide valuable insights into the interface heat transport in vdW heterostructures and support further design and optimization of electronic and optoelectronic nanodevices based on vdW contacts.
ABSTRACT
Objective: To explore the trend and influencing factors of serum lipoprotein (a) (Lp(a)) concentration over time in Chinese community populations. Methods: This study is a prospective cohort study. The participants were enrolled from Chinese Multi-provincial Cohort Study- Beijing projects, completed the cardiovascular disease risk factor surveys in 2002 and 2007, and the serum Lp (a) concentration were measured. Based on the Lp(a) concentration at baseline (2002) and follow-up (2007), the participants were classified into subgroups of <30.0 mg/dl (1 mg/dl=0.01 g/L) group, 30.0 to 49.9 mg/dl group, and ≥50.0 mg/dl group, respectively. Multivariable logistic regression analysis was used to identify influencing factors associated with Lp (a) absolute change (≥20 mg/dl) and relative change (≥20%) within 5 years. Results: Among 1 955 participants with age of (56.5±8.0) years old and 821 male (42.0%) at baseline, there were 1 657 (84.8%), 184 (9.4%) and 114 (5.8%) participants in Lp(a)<30.0 mg/dl group, 30.0 to 49.9 mg/dl group and ≥50.0 mg/dl group, respectively. Among the baseline Lp(a) concentration of 30.0-49.9 mg/dl group, 68 (37.0%) participants progressed to Lp(a) ≥50.0 mg/dl after 5 years follow-up, and 102 (55.4%) remained at this level. Participants with baseline Lp(a)<30.0 mg/dl (92%, 1 524/1 657) or Lp(a)≥50.0 mg/dl (94.7%, 108/114) tended to be maintained at their respective levels. The results of the multivariate logistic regression analysis showed that, in addition to the high level of baseline Lp(a) concentration, family history of cardiovascular disease, elevated fasting blood glucose and usage of oral lipid-lowering drugs were the influencing factors of Lp(a) changes over time (P<0.05). Conclusions: Adults with borderline-high Lp(a) concentrations (30.0 to 49.9 mg/dl) could be considered for repeated testing, especially for those with a family history of cardiovascular disease, elevated fasting blood glucose and usage of statins.
Subject(s)
Cardiovascular Diseases , Lipoprotein(a) , Adult , Humans , Male , Middle Aged , Blood Glucose , Cohort Studies , Prospective Studies , Biomarkers , Risk FactorsABSTRACT
The construction and analysis of the topic of traditional Chinese medicine is an important social and cultural landscape since the founding of New China, and media for party afairs is an important field for this process. Authoritative media such as People's Daily expressed respect to TCM practitioners, reflected the national system, urban-rural relations, cultural concepts, etc. behind the development of TCM, and clarified the determination and confidence of the Party and the country to adhere to the development of TCM through its content,specific situations and line of reasoning logic.
Subject(s)
Medicine, Chinese Traditional , Rural Population , Humans , ChinaABSTRACT
Tenofovir disoproxil fumarate (TDF) is a novel nucleotide reverse transcriptase inhibitor that is mainly used to treat human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. In recent years, an increasing number of studies have demonstrated that TDF treatment can reduce blood lipid levels in patients with AIDS and chronic hepatitis B and has a close correlation with the severity of the disease and the occurrence of cardiovascular events. This article reviews the research progress on the effect of TDF on blood lipid profiles, with the aim of providing a basis for rational use of TDF.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Tenofovir/pharmacology , Tenofovir/therapeutic use , Antiviral Agents/therapeutic use , Adenine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Hepatitis B, Chronic/drug therapy , Hepatitis B/drug therapy , Hepatitis B virus , Lipids , DNA, Viral , Treatment OutcomeABSTRACT
How to promote high-quality wound healing is a common problem for plastic surgery and burn physicians. In recent years, numerous animal studies have demonstrated that mesenchymal stem cell-derived exosomes promote wound repair through multiple mechanisms and are promising cell-free therapeutic agents with broad prospect of application. How to enhance the therapeutic efficacy of exosomes, optimize their drug delivery strategy, and improve their biological properties are the challenges to be overcome in order to move from basic research to clinical application of exosome therapy for wound repair. This article focuses on methods to improve the wound repair potential of mesenchymal stem cell-derived exosomes, and reviews the recent research advances on improving the therapeutic efficacy of mesenchymal stem cell-derived exosomes in wound repair from three aspects, including pretreatment of parental mesenchymal stem cells, hydrogel bio-scaffold loaded with exosomes, and engineered exosomes, to provide a reference for further clinical studies.
Subject(s)
Exosomes , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Plastic Surgery Procedures , Animals , Wound HealingABSTRACT
Objective: To investigate the influence of family with sequence similarity 134, member B (FAM134B)-mediated reticulophagy on lipopolysaccharide (LPS)-induced apoptosis of mouse dendritic cells (DCs), so as to provide a basis for improving the immune suppression of sepsis caused by wound infection and other factors. Methods: The experimental research methods were used. The DC line DC2.4 of the 3rd to 10th passage in the logarithmic growth stage was collected for experiments. DCs were divided into LPS stimulation 0 h (no stimulation) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 24 h group, and LPS stimulation 72 h group, which were cultured with 1 µg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of FAM134B, microtubule-associated protein 1 light chain 3B (LC3B), and transporter protein SEC61B were determined by Western blotting, and the ratio of LC3B-â ¡/LC3B-â was calculated (n=3). DCs were divided into phosphate buffer solution (PBS) group and LPS group for corresponding treatment. After 24 hours of culture, the expression of FAM134B and its co-localization with lysosomal probes and LC3B were detected using immunofluorescence method, while the number of autolysosomes in cells were observed through transmission electron microscope. DCs were divided into the FAM134B-knockdown group that were transfected with lentivirus containing small interfering RNA (siRNA) sequence of FAM134B gene and the empty vector group with empty lentivirus transfected. At post transfection hour 72, the fluorescence expression of cells was observed under the inverted fluorescence phase contrast microscope, meanwhile, the normally cultured DCs were set as blank control group, and the same observation was performed at the corresponding time point. DCs were divided into PBS alone group and LPS alone group, DCs successfully transfected with lentivirus containing siRNA sequence of FAM134B gene were divided into FAM134B-knockdown+PBS group and FAM134B-knockdown+LPS group, and DCs successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. These cells were stimulated correspondingly and cultured for 24 hours. The protein expression of FAM134B was detected using Western blotting (n=3); the apoptotic rate of cells was determined by flow cytometry (n=3); the situation of apoptosis was observed by Hoechst staining, and the apoptotic rate was calculated (n=5); the protein expressions of cleaved cysteine aspartic acid specific protease-3 (caspase-3), B cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were detected using Western blotting, and the ratio of Bax/Bcl-2 was calculated (n=5). Data were statistically analyzed with one-way analysis of variance (ANOVA), least significant difference test, and ANOVA for factorial design. Results: Compared with those in LPS stimulation 0 h group, the protein expressions of FAM134B of cells in LPS stimulation 12 h group and LPS stimulation 24 h group were significantly increased (P<0.05), the protein expressions of SEC61B of cells in LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 24 h group, and LPS stimulation 72 h group were significantly decreased (P<0.05), and the ratios of LC3B-â ¡/LC3B-â of cells in LPS stimulation 24 h group and LPS stimulation 72 h group were obviously increased (P<0.05). As the most significant changes of three proteins were seen in the cells of LPS stimulation 24 h group, 24 h was used as the duration of subsequent LPS stimulation. After 24 hours of culture, the expression of FAM134B and its co-localization with LC3B and lysosomal probes in the cells of LPS group were all significantly enhanced, with a significant increase in the number of autolysosomes in comparison with those in PBS group. Both the empty vector group and the FAM134B-knockdown group showed high intensity fluorescence in the cells at post transfection hour 72, but the blank control group showed no fluorescence in the cells at the corresponding time point. After 24 hours of culture, the protein expression of FAM134B of cells in FAM134B-knockdown+PBS group was significantly lower than the expressions in PBS alone group and empty vector+PBS group (with P values all <0.05), the protein expression of FAM134B of cells in FAM134B-knockdown+LPS group was significantly lower than the expressions in LPS alone group and empty vector+LPS group (with P values all <0.05), the protein expression of FAM134B of cells in LPS alone group was significantly higher than that in PBS alone group (P<0.05), while the protein expression of FAM134B of cells in empty vector+LPS group was significantly higher than that in empty vector+PBS group (P<0.05). After 24 hours of culture, flow cytometry assay revealed that the apoptotic rate of cells in PBS alone group, LPS alone group, empty vector+PBS group, empty vector+LPS group, FAM134B-knockdown+PBS group, and FAM134B-knockdown+LPS group were (13.3±0.8)%, (32.6±4.3)%, (17.0±1.5)%, (51.7±3.3)%, (52.4±3.1)%, and (62.3±2.6)%, respectively. After 24 hours of culture, compared with those in LPS alone group and empty vector+LPS group, the protein expression of cleaved caspase-3, the ratio of Bax/Bcl-2, and the apoptotic rates of cells detected by flow cytometry and Hoechst staining were significantly increased in FAM134B-knockdown+LPS group (P<0.05); compared with those in the corresponding PBS treatment group, namely, PBS alone group, empty vector+PBS group, and FAM134B-knockdown+PBS group, the protein expression of cleaved caspase-3, the ratio of Bax/Bcl-2, and the apoptotic rates of cells detected by flow cytometry and Hoechst staining were significantly increased in LPS alone group, empty vector+LPS group, and FAM134B-knockdown+LPS group (P<0.05). Conclusions: The activation of reticulophagy mediated by FAM134B in mouse DCs is enhanced and peaked in 24 hours under LPS stimulation, and the activated reticulophagy has a significant inhibitory effect on cell apoptosis.
Subject(s)
Apoptosis , Dendritic Cells , Lipopolysaccharides , Animals , Mice , Autophagy , bcl-2-Associated X Protein , Caspase 3 , Dendritic Cells/pathology , Lipopolysaccharides/pharmacology , RNA, Small InterferingABSTRACT
Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.
Subject(s)
Calcinosis , Mediastinitis , Pulmonary Atelectasis , Humans , Constriction, Pathologic/diagnostic imaging , Perfusion , Lung/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
Nucleoside analogues and nucleotide analogues can not only achieve long-term viral suppression in the treatment of most CHB patients but also have a positive impact on other CHB therapeutic goals and an improved prognosis. A certain difference can be observed in the impact of nucleotide analogues such as TDF and TAF and nucleoside analogues such as ETV on the clinical outcomes of CHB. Studies on the mechanism of action indicate that apart from inhibiting the direct antiviral effects of HBV reverse transcriptase, these two categories of drugs exhibit distinct impacts on immune-related signaling pathways, gene expression, genome stability, and other non-antiviral mechanisms. This article reviews the evidence on the potential non-antiviral mechanism of action of nucleoside analogues and nucleotide analogues and proposes a preliminary explanation for the observation trend of nucleotide analogues having a comparative advantage in clinical outcomes in CHB patients based on the latest research advancement.