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1.
Zhonghua Gan Zang Bing Za Zhi ; 32(2): 133-139, 2024 Feb 20.
Artículo en Chino | MEDLINE | ID: mdl-38514262

RESUMEN

Objective: To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs. Methods: An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD- t test was used for pairwise comparison. Results: ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2(+/+)), heterozygous mutant (ALDH2(+/-)), and homozygous mutant (ALDH2(-/-)), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group (P < 0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT (P  = 0.004), AST (P = 0.002), and TBil (P = 0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group (P = 0.003, 0 and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group (P = 0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice (P = 0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion: APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.


Asunto(s)
Aldehído Oxidorreductasas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Ratones , Acetaminofén/efectos adversos , Acetaminofén/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Hígado/patología , Ratones Noqueados , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Alanina Transaminasa
2.
Nanoscale ; 16(6): 3081-3090, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38240724

RESUMEN

A BaTiO3/SrCoO2.5 (BTO/SCO) bilayer and a BTO single film were prepared by radio frequency magnetron sputtering on La0.7Sr0.3MnO3 (LSMO) buffered SrTiO3 (001) substrates. Interestingly, compared with reported BTO-based films, the BTO/SCO/LSMO heterostructure has a maximum ON/OFF current ratio of ∼945. More interestingly, compared with the BTO single layer, a larger Pr (∼18.4 µC cm-2) and larger dielectric tunability (∼71.9%) were achieved in the BTO/SCO bilayer. The improved performance may be attributed to the large tetragonality and improved oxygen vacancy concentrations in the BTO/SCO/LSMO heterostructure. Furthermore, our BTO/SCO/LSMO stacks exhibit potential for flexible electronic informational devices.

3.
Zhonghua Yi Xue Za Zhi ; 104(3): 205-211, 2024 Jan 16.
Artículo en Chino | MEDLINE | ID: mdl-38220446

RESUMEN

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.


Asunto(s)
Artritis Reumatoide , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Femenino , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Hepatitis B Crónica/complicaciones , Estudios Retrospectivos , Estudios Transversales , Artritis Reumatoide/complicaciones , Virus de la Hepatitis B , Hepatitis B/epidemiología
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(1): 136-140, 2024 Jan 06.
Artículo en Chino | MEDLINE | ID: mdl-38228561

RESUMEN

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.


Asunto(s)
Sistema Cardiovascular , Neoplasias Pulmonares , Humanos , Proteínas de la Membrana , Factor de Crecimiento Epidérmico , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patología
5.
Anim Genet ; 54(6): 803-807, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37705287

RESUMEN

Semen is a measure of the reproductive efficiency of roosters, which affects the economic benefits of white-feathered broilers. Over the years, research in this field has mainly focused on hens, while there have been fewer studies on the reproductive traits of roosters. To identify the genes related to the semen traits of roosters, we used a chicken 55 K SNP chip to genetically type the white-feathered population (220) and performed imputation with resequencing data from 97 roosters. In total, 1 048 576 SNPs were obtained and used for genome-wide association analysis of semen volume, from which 197 genome-wide significant markers were identified, all within the interval of 13.82-16.12 Mb on chromosome 7. By combining our results with the biological functions of genes in the interval, four candidate genes were identified that potentially relate to semen volume: FAPP1, OSBPL6, SESTD1 and SSFA2. Our findings may provide a basis for further research on the genetic mechanism and marker-assisted selection of semen volume in white-feathered broilers.


Asunto(s)
Pollos , Estudio de Asociación del Genoma Completo , Animales , Masculino , Femenino , Estudio de Asociación del Genoma Completo/veterinaria , Pollos/genética , Semen , Análisis de Semen , Fenotipo , Polimorfismo de Nucleótido Simple
6.
Waste Manag ; 171: 195-206, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37660632

RESUMEN

Styrene-butadiene rubber (SBR) is widely used in tires, which brings great challenge to the disposal and reclaiming of the used tires. The ring-opening reaction pathways of benzene rings in hydrothermal gasification of styrene-butadiene rubber were revealed based on reactive force field molecular dynamics (ReaxFF-MD) simulation. H-abstraction reaction that OH radicals capture H atom from the vinyl group of styrene was critical to the degrading of the styrene monomers. The energy barrier of H2O2 converted to OH radicals was lower than that of O2 and pure water converted to OH radicals. The oxidants that can urge OH radical formed in reaction were beneficial to SBR degradation, which could be assigned to confirm that SBR degradation with H2O2 was better than that with oxygen at the same concentration. The addition of oxidant could be helpful for decreasing the degradation temperature of styrene monomers. At oxidant equivalent ratio (ER) of 0.1, H2 yield at 2500 K lifted after 135 ps and increased by 75% at 500 ps compared with that without oxidants. According to the chemical equilibrium analysis, the optimal ER for H2 was 0.4 between 350 and 600 °C (real temperatures). The results could provide theoretic support and experiment guidance for adding oxidants in reclaiming waste rubber products.

7.
Zhonghua Xue Ye Xue Za Zhi ; 44(5): 418-423, 2023 May 14.
Artículo en Chino | MEDLINE | ID: mdl-37550193

RESUMEN

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Estudios Retrospectivos , Translocación Genética , Aberraciones Cromosómicas , Cariotipificación
8.
Eur Rev Med Pharmacol Sci ; 27(10): 4570-4577, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37259738

RESUMEN

BACKGROUND: The prognosis of natural killer/T cell lymphoma (NKTCL) with multifocal small intestine involvement complicated by intestinal perforation is extremely poor. There is no evidence-based treatment strategy for this intractable condition. CASE PRESENTATION: A 30-year-old male was admitted to our hospital in April 2017 and presented with recurrent fever for three months and multiple painless subcutaneous nodules in the abdominal wall. An excision biopsy of the subcutaneous nodules in the abdominal wall revealed NKTCL. The patient was diagnosed with stage IVB NKTCL with skin and multifocal small intestinal involvement according to the imaging results. The first intestinal perforation occurred due to tumor infiltration before the initial treatment. The second intestinal perforation occurred after receiving two cycles of chemotherapy with a modified SMILE regimen. The histone deacetylase inhibitor (HDACi) chidamide was administered as a single-agent therapy after recovery from the second intestinal perforation. Complete remission was achieved. Unfortunately, five months later, the patient was confirmed to have relapsed and received the salvage chemotherapy. The patient suffered from disease progression again after the fourth cycle of chemotherapy. At this point, from May 29, 2018, the patient started to receive injections of the anti-programmed death 1 (PD-1) antibody camrelizumab as a salvage treatment. Two months after the initial anti-PD-1 antibody camrelizumab injection, the response was partial remission. Disease progression was confirmed in March 2021, with a progression-free survival time of 34 months. CONCLUSIONS: NKTCL patients with multifocal small intestine involvement have a high risk of intestinal perforation. The possible etiologies of bowel perforation include tumor infiltration, tumor necrosis in response to therapy, and acute inflammation. The anti-PD-1 antibody camrelizumab may be a new candidate agent for treating this type of intractable NKTCL. Further observations are necessary to identify the efficacy and safety of new agents in the future.


Asunto(s)
Perforación Intestinal , Linfoma de Células T , Linfoma , Masculino , Humanos , Adulto , Perforación Intestinal/tratamiento farmacológico , Progresión de la Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
9.
Zhonghua Yi Xue Za Zhi ; 103(21): 1617-1622, 2023 Jun 06.
Artículo en Chino | MEDLINE | ID: mdl-37248061

RESUMEN

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 µmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) µmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) µmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 µmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.


Asunto(s)
Artritis Gotosa , Gota , Adulto , Humanos , Masculino , Persona de Mediana Edad , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/inducido químicamente , Estudios de Cohortes , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Estudios Retrospectivos , Ácido Úrico , Femenino
10.
Zhonghua Nei Ke Za Zhi ; 62(4): 374-383, 2023 Apr 01.
Artículo en Chino | MEDLINE | ID: mdl-37032132

RESUMEN

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.


Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio sin Elevación del ST , Masculino , Femenino , Humanos , Anciano , Péptido Natriurético Encefálico , Simendán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Fragmentos de Péptidos , Arritmias Cardíacas , Biomarcadores , Pronóstico
12.
Eur Rev Med Pharmacol Sci ; 26(18): 6536-6549, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36196702

RESUMEN

OBJECTIVE: The aim of our study was to determine whether abnormal hyperplasia of chondrocytes occurs in glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) using a well-established rat model. MATERIALS AND METHODS: Rats were injected with lipopolysaccharide and methylprednisolone to induce GC-ONFH, while control animals were injected with saline (12 animals per group). Establishment of the disease model was confirmed using micro-computed tomography and hematoxylin-eosin (HE) staining of femoral head tissue sections. Chondrocyte hyperplasia was detected using HE staining and semi-quantitated using toluidine blue and saffron O staining. Expression of the autophagy marker LC3B was assessed in cartilage tissues of femoral head using immunohistochemistry. RESULTS: GC-ONFH animals showed significantly greater area of abnormal chondrocyte hyperplasia in femoral head tissue sections than control animals. They also showed significantly higher expression of LC3B in articular cartilage of the femoral head. CONCLUSIONS: GC-ONFH may be associated with abnormal chondrocyte hyperplasia in articular surface cartilage, which may be related to glucocorticoid-induced overactivation of autophagy.


Asunto(s)
Necrosis de la Cabeza Femoral , Cabeza Femoral , Animales , Condrocitos , Eosina Amarillenta-(YS)/efectos adversos , Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Glucocorticoides , Hematoxilina , Hiperplasia/inducido químicamente , Lipopolisacáridos/efectos adversos , Metilprednisolona/efectos adversos , Ratas , Cloruro de Tolonio/efectos adversos , Microtomografía por Rayos X
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(7): 1134-1139, 2022 Jul 10.
Artículo en Chino | MEDLINE | ID: mdl-35856211

RESUMEN

Birth cohort is an important platform to study the effect of early-life exposure on health outcome, but large cohorts to investigate the effect of preconception exposure, especially paternal exposure, on reproductive health and birth outcome are limited. The Preconception Reproductive Health and Birth Outcome Cohort (PREBIC) is a prospective birth cohort study which pays equal attention to the contribution of environmental, psychological, behavioral as well as other factors to reproductive health and adverse birth outcomes in both men and women in Chongqing, China. PREBIC started in 2019 and plans to recruit 20 800 reproductive-age couples with child-bearing willingness. Followed up was conducted to understand the conception status of the women within two years. Women in pregnancy would be visited at first, second, third trimesters and after delivery. The offspring would be monitored until 2 years old to understand the incidences of preterm birth, low birth weight, birth defects, neurodevelopmental disorders and other outcomes. Related information and biospecimen collections (including semen, peripheral blood, urine, placenta, umbilical cord, cord blood and oral swab) were scheduled in each period. By January 2022, PREBIC had recruited 8 698 participants from all 38 districts in Chongqing. The goal of PREBIC is to establish one of the largest prospective preconception birth cohorts covering both men and women, which might provide a unique insight to understand the effects of the full reproductive cycle on reproductive health and adverse outcomes, with especial emphasis on preconception exposures.


Asunto(s)
Nacimiento Prematuro , Preescolar , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Masculino , Exposición Paterna/efectos adversos , Embarazo , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Salud Reproductiva
16.
Scand J Rheumatol ; 50(4): 280-289, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33554691

RESUMEN

Objective: Little is known about muscle wasting in elderly patients with rheumatoid arthritis (RA). We examined muscle characteristics and their clinical significance in this group.Method: Consecutive RA patients were recruited and clinical data were collected. Muscle mass and distribution were assessed using bioelectric impedance analysis. Myopenia was defined as an appendicular skeletal muscle mass index (ASMI) ≤ 7.0 kg/m2 (men) and ≤ 5.7 kg/m2 (women).Results: Among the 643 RA patients recruited, 165 (25.7%) were elderly patients (age ≥ 60 years) with a mean age of 65.1 ± 4.5 years. Compared with young patients (age < 60 years), elderly RA patients had significantly higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) (median 3.4 vs 3.2), Health Assessment Questionnaire Disability Index (HAQ-DI) (0.38 vs 0.13), and modified total Sharp score (mTSS) (16 vs 9), and a higher proportion of myopenia (54.5% vs 41.4%; all p < 0.01). Elderly RA patients with myopenia (n = 90, 14.0%) had significantly higher DAS28-CRP (3.6 vs 3.0), HAQ-DI (0.50 vs 0.12), and mTSS (21 vs 7) than young RA patients without myopenia (n = 280, 43.5%; all p < 0.0083). Multivariate logistic and linear regression analyses showed that myopenia, high HAQ-DI, active smoking, hypertension, diabetes, and coronary atherosclerotic heart disease were the main relevant characteristics of elderly RA patients. Age positively correlated with HAQ-DI, and ASMI negatively correlated with HAQ-DI (both p < 0.01). Further mediation analysis showed that ASMI partially mediated the association between age and HAQ-DI.Conclusion: Our data reveal that half of elderly RA patients manifest myopenia which aggravates physical dysfunction as a mediator of age. Myopenia, a neglected complication in elderly RA patients, should be recognized and further investigated.


Asunto(s)
Artritis Reumatoide/complicaciones , Atrofia Muscular/etiología , Adulto , Anciano , Artritis Reumatoide/fisiopatología , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia Muscular/fisiopatología
17.
Zhonghua Xue Ye Xue Za Zhi ; 42(11): 911-916, 2021 Nov 14.
Artículo en Chino | MEDLINE | ID: mdl-35045652

RESUMEN

Objective: To investigate the effect of genetic polymorphisms of TPMT*2 rs1800462, TPMT*3B rs1800460, TPMT*3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) . Methods: A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed. Results: Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT*2 rs1800462 and TPMT*3B rs1800460. The number of TT and TC genotypes for TPMT*3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT*3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT*3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) (P=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) (OR=9.559, 95% CI 1.135-80.475, P=0.038) . The durations of white blood cells (WBC) <1×10(9)/L and absolute neutrophil count (ANC) <0.5×10(9)/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) (P=0.005, P=0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) (P=0.014) . Conclusion: Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.


Asunto(s)
Mercaptopurina , Metiltransferasas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pirofosfatasas , Antimetabolitos Antineoplásicos/uso terapéutico , Genotipo , Humanos , Mercaptopurina/uso terapéutico , Metiltransferasas/genética , Metiltransferasas/uso terapéutico , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatasas/genética , Pirofosfatasas/uso terapéutico
19.
Zhonghua Yi Xue Za Zhi ; 100(42): 3296-3302, 2020 Nov 17.
Artículo en Chino | MEDLINE | ID: mdl-33202490

RESUMEN

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anciano de 80 o más Años , Ciclofosfamida/uso terapéutico , Doxorrubicina , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del Tratamiento
20.
Zhonghua Xue Ye Xue Za Zhi ; 41(6): 502-505, 2020 Jun 14.
Artículo en Chino | MEDLINE | ID: mdl-32654465

RESUMEN

Objective: This study aimed to explore the efficacy and safety of rituximab combined with short-course and intensive regimens in the treatment of adult patients with Burkitt leukemia. Methods: The clinical data of 11 Burkitt leukemia patients in our hospital from January 30, 2006, to September 12, 2018, were collected. The clinical details, complete remission (CR) rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were evaluated. Results: The median age of 11 patients was 34 (15-54) years, of which six were males and five were females (M∶F, 1.2∶1) . The median white blood cell (WBC) count was 12.28 (2.21-48.46) ×10(9)/L, and the median blast percent of peripheral blood and bone marrow were 40% (3%-76%) and 84.0% (29.5%-94.5%) , respectively. Ten patients were administered with rituximab combined with a short-course and intensive regimens, and two patients underwent autologous hematopoietic stem cell transplantation following consolidation chemotherapy. The CR rate after one cycle of induction therapy was 100%, the four-year OS was 90%, and RFS was 90%. Out of the ten treated patients, only one patient suffered from tumor lysis syndrome during the induction chemotherapy. Consequently, renal function recovered after hemodialysis and other treatments. The regimen is safe with no treatment-related deaths. Conclusions: Rituximab combined with short-course and intensive chemotherapy regimens is effective and well-tolerated in adult Burkitt leukemia.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Rituximab/uso terapéutico , Adolescente , Adulto , Linfoma de Burkitt/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Adulto Joven
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