RESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder; the prevalence of which has been on the rise with unknown causes. Alterations in the gut-brain axis have been widely recognized in ASD patients, and probiotics are considered to potentially benefit the rescuing of autism-like behaviors. However, the effectiveness and mechanisms of multiple probiotics on zebrafish models are still not clearly revealed. This study aims to use the germ-free (GF) and conventionally raised (CR) AB wild-type zebrafish and the mutant Tbr1b-/- and Katnal2-/- lines as human-linked ASD animal models to evaluate the effects of multiple probiotics on mitigating developmental and behavioral defects. Results showed that the addition of probiotics increased the basic important developmental indexes, such as body length, weight, and survival rate of treated zebrafish. Moreover, the Lactobacillus plantarum and Lactobacillus rhamnosus affected the behavior of CR zebrafish by increasing their mobility, lowering the GF zebrafish manic, and mitigating transgenic zebrafish abnormal behavior. Moreover, the expression levels of key genes related to gamma-aminobutyric acid (GABA), dopamine (DA), and serotonin (5-HT) as important neuropathways to influence the appearance and development of autism-related disorders, including gad1b, tph1a, htr3a, th, and slc6a3, were significantly activated by some of the probiotics' treatment at some extent. Taken together, this study indicates the beneficial effects of different probiotics, which may provide a novel understanding of probiotic function in related diseases' therapy.
RESUMEN
Glioblastoma, a highly malignant intracranial tumor, has acquired slow progress in treatment. Previous clinical trials involving targeted therapy and immune checkpoint inhibitors have shown no significant benefits in treating glioblastoma. This ineffectiveness is largely due to the complex immunosuppressive environment of glioblastoma. Glioblastoma cells exhibit low immunogenicity and strong heterogeneity and the immune microenvironment is replete with inhibitory cytokines, numerous immunosuppressive cells, and insufficient effective T cells. Fortunately, recent Phase I clinical trials of CART therapy for glioblastoma have confirmed its safety, with a small subset of patients achieving survival benefits. However, CART therapy continues to face challenges, including blood-brain barrier obstruction, antigen loss, and an immunosuppressive tumor microenvironment (TME). This article provides a detailed examination of glioblastoma's immune microenvironment, both from intrinsic and extrinsic tumor cell factors, reviews current clinical and basic research on multi-targets CART treatment, and concludes by outlining the key challenges in using CART cells for glioblastoma therapy.
RESUMEN
OBJECTIVE: This study aimed to investigate the genomic alteration profiles of cervical cancer patients, examine the correlation between mutation patterns and clinical and immune attributes, and discover novel targets for treatment of individuals with cervical cancer. METHODS: We performed targeted next-generation sequencing of tumor tissues and blood samples obtained from 45 cervical cancer patients to analyze somatic alterations, mutation patterns, and HLA alleles comprehensively. Additionally, we used flow cytometry to assess expression levels of immune checkpoint genes. RESULTS: Notably, genes such as AR (78%), KMT2D (76%), and NOTCH1 (62%) exhibited higher mutation frequencies. Moreover, the tumor mutation burden (TMB) was significantly greater in HPV-positive cervical cancer patients than in HPV-negative patients (P=0.029). BMI (P=0.047) and mutations in BARD1 (P=0.034), CEP290 (P=4E-04), and SLX4 (P=0.0128) were identified as predictors of shorter overall survival in cervical cancer patients. Furthermore, the present study revealed significant upregulation of PD-1 (P=0.027) and Tim-3 (P=0.048) in the high mutant-allele tumor heterogeneity (MATH) cohort. In the elderly cervical cancer patient population, HLA-A03:01 emerged as a high-risk allele (OR=3.2, P<0.0001); HLA-C07:02 (OR=0.073, P=0.02) and HLA-B*07:02 (OR=0.257, P=0.037) were associated with a reduced risk among patients with low TMB. CONCLUSIONS: This study offers insights into the mutation characteristics of cervical cancer patients and identifies potential therapeutic.
RESUMEN
Cholestatic liver diseases encompass a range of organic damages, metabolic disorders, and dysfunctions within the hepatobiliary system, arising from various pathogenic causes. These factors contribute to disruptions in bile production, secretion, and excretion. Cholestatic liver diseases can be classified into intrahepatic and extrahepatic cholestasis, according to the location of occurrence. The etiology of cholestatic liver diseases is complex, and includes drugs, poisons, viruses, parasites, bacteria, autoimmune responses, tumors, and genetic metabolism. The pathogenesis of cholelstatic liver disease is not completely clarified, and effective therapy is lacking. Clarifying its mechanism to find more effective therapeutic targets and drugs is an unmet need. Increasing evidence demonstrates that miRNA and long noncoding RNA are involved in the progression of cholestatic liver diseases. This review provides a comprehensive summary of the research progress on the roles of miRNA and long noncoding RNA in cholestatic liver diseases. The aim of the review is to enhance the understanding of their potential diagnostic, therapeutic, and prognostic value for patients with cholestasis.
Asunto(s)
Colestasis , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Colestasis/genética , Colestasis/metabolismo , Colestasis/patología , Animales , Hepatopatías/genética , Hepatopatías/metabolismo , Hepatopatías/patologíaRESUMEN
Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a conductive polymer commonly used in various technological applications. However, its impact on aquatic ecosystems remains largely unexplored. In this study, we investigated the toxicity effects of PEDOT:PSS on zebrafish. We first determined the lethal concentration (LC50) of PEDOT:PSS in zebrafish and then exposed AB-type zebrafish embryos to different concentrations of PEDOT:PSS for 120 h. Our investigation elucidated the toxicity effects of zebrafish development, including morphological assessments, heart rate measurements, behavioral analysis, transcriptome profiling, and histopathological analysis. We discovered that PEDOT:PSS exhibited detrimental effects on the early developmental stages of zebrafish, exacerbating the oxidative stress level, suppressing zebrafish activity, impairing cardiac development, and causing intestinal cell damage. This study adds a new dimension to the developmental toxicity of PEDOT:PSS in zebrafish. Our findings contribute to our understanding of the ecological repercussions of PEDOT:PSS and highlight the importance of responsible development and application of novel materials in our rapidly evolving technological landscape.
RESUMEN
Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).
RESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most important curative method for intermediate- and high-risk adult acute myeloid leukemia (AML) patients. We aimed to identify the clinical outcomes of haploidentical related donor (HID) peripheral blood stem cell transplantation (PBSCT) who receiving peripheral blood (G-PB) harvest, and the patients receiving bone marrow (BM) plus G-PB harvest (BM + PB) as grafts were enrolled as control. The engraftments of neutrophil and platelet in G-PB group were both faster than those in BM + PB group. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD), and moderate to severe chronic GVHD (cGVHD) were all comparable between G-PB and BM + PB groups. The cumulative incidence of relapse and non-relapse mortality at 3 years after HID HSCT was 12.6% versus 13.7% (p = 0.899) and 3.6% versus 7.3% (p = 0.295), respectively, in G-PB and BM + PB group. While the probabilities of GVHD-free/relapse-free survival, leukemia-free survival, and overall survival at 3 years after HID HSCT were 60.6% versus 53.4% (p = 0.333), 83.8% versus 79.0% (p = 0.603), and were 87.3% versus 82.9% (p = 0.670), respectively. We confirmed the safety and efficacy of HID PBSCT in intermediate- and high-risk AML patients in a large cohort.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante de Células Madre de Sangre Periférica , Humanos , Adulto , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Recurrencia , Leucemia Mieloide Aguda/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: Because of the deficiencies of traditional methods in multivalent rotavirus vaccine potency detection, a cell-based quantitative RT-qPCR assay (C-QPA) was established and validated for specificity, precision, and accuracy. METHODS: In order to further validate the robustness of this method in actual titer detection, the linear range and the practical application under different conditions were tested using monovalent and trivalent rotavirus samples and standards. RESULTS: Results showed that the linear range was 2.0-6.5, 3.9-8.3, and 3.5-8.1 UI (unit of infectivity) for G2, G3, and G4, respectively. Besides, unknown sample with high titer exceeding the linear range can be calculated by dilution. The UIs of serotypes G2, G3, and G4 in monovalent and trivalent rotavirus samples showed a relative deviation ≤4.10%, and the monovalent samples of the same serotype with or without protective agents showed a relative deviation ≤4.28%; the coefficient of variation (CV) of at least 176 tests (548 individual runs) of 3 in vitro-transcribed RNA standards with certain concentrations was not higher than 6.50%; the results of the trivalent samples tested by more than 149 times in 5 years (467 individual runs) showed the CVs lower than 12.66%; 15 samples detected by one laboratory showed a CV lower than 9.83%, while other three samples tested by two independent laboratories showed a CV lower than 6.90%. CONCLUSION: In summary, the C-QPA has good linearity, durability, repeatability, and reproducibility in practical application and has been proved by the authority to be widely used in the production, quality control and release of the recently licensed trivalent vaccine in China.
Asunto(s)
Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Humanos , Reproducibilidad de los Resultados , Rotavirus/genética , Infecciones por Rotavirus/diagnóstico , ChinaRESUMEN
Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at environmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1ß and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds.
RESUMEN
Verticillium wilt (VW), Fusarium wilt (FW) and Root-knot nematode (RKN) are the main diseases affecting cotton production. However, many reported quantitative trait loci (QTLs) for cotton resistance have not been used for agricultural practices because of inconsistencies in the cotton genetic background. The integration of existing cotton genetic resources can facilitate the discovery of important genomic regions and candidate genes involved in disease resistance. Here, an improved and comprehensive meta-QTL analysis was conducted on 487 disease resistant QTLs from 31 studies in the last two decades. A consensus linkage map with genetic overall length of 3006.59 cM containing 8650 markers was constructed. A total of 28 Meta-QTLs (MQTLs) were discovered, among which nine MQTLs were identified as related to resistance to multiple diseases. Candidate genes were predicted based on public transcriptome data and enriched in pathways related to disease resistance. This study used a method based on the integration of Meta-QTL, known genes and transcriptomics to reveal major genomic regions and putative candidate genes for resistance to multiple diseases, providing a new basis for marker-assisted selection of high disease resistance in cotton breeding.
RESUMEN
Background: Postoperative complications are common after major surgical procedures, leading to increased morbidity and mortality. Regional cerebral oxygen saturation (rScO2) reflects cerebral and global perfusion, and thus it can be used to guide hemodynamic management. We aim to explore the effect of rScO2-guided blood pressure management strategy on postoperative major complications in older adults who undergo major noncardiac surgery. Methods: This randomized controlled clinical trial includes a total of 400 elderly patients receiving major noncardiac surgery and general anesthesia. Patients will be randomized (1:1) to one of two blood pressure management groups: a standard care group (targeting mean arterial pressure >65 mmHg or within 20% of baseline value), and a rScO2-guided group (absolute value of rScO2 >60% or decrease in rScO2 <10% of baseline). The primary outcome is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. Secondary outcomes include the individual components of the primary outcome by day 7 after surgery and 30-day mortality. Data will be analyzed in the modified intention-to-treat population. Discussion: This study will provide evidence for improving postoperative outcomes using the rScO2-guided blood pressure management among older adults who undergo major noncardiac surgery. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2200060816).
This is a protocol for a prospective, randomized, controlled clinical trial to evaluate the use of intraoperative individualized regional cerebral oxygen saturation (rScO2) optimization for blood pressure management in older adults undergoing major noncardiac surgery. The primary focus of this trial is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. The secondary outcomes are the individual components of the primary outcome by day 7 after surgery and 30-day mortality. The findings of this trial will provide clinical evidence for the rScO2-guided blood pressure management to improve postoperative outcomes in older patients who are scheduled for major noncardiac surgery.
RESUMEN
The experiment investigated the impacts of FA on the proliferation of bovine mammary gland epithelial cells (BMECs) and to investigate the underlying mechanisms. Supplementation of 10 µM FA elevated the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin A2 and cyclin D1, and protein expression of PCNA and Cyclin A1. The mRNA and protein expression of B-cell lymphoma-2 (BCL2) and the BCL2 to BCL2 associated X 4 (BAX4) ratio elevated, while that of BAX, Caspase-3 and Caspase-9 reduced by FA. Both Akt and mTOR signaling pathways were activated by FA. Moreover, the stimulation of BMECs proliferation, the alteration of proliferative genes and protein expression, the change of apoptotic genes and protein expression, and the activation of mTOR signaling pathway caused by FA were obstructed by Akt inhibitor. Suppression of mTOR with Rapamycin reversed the FA-modulated promotion of BMECs proliferation and change of proliferous genes and protein expression, with no impact on mRNA or proteins expression related to apoptosis and FA-activated Akt signaling pathway. Supplementation of rumen-protected FA in cow diets evaluated milk yields and serum insulin-like growth factor-1 and estradiol levels. The results implied that the proliferation of BMECs was stimulated by FA through the Akt-mTOR signaling pathway.
Asunto(s)
Glándulas Mamarias Animales , Proteínas Proto-Oncogénicas c-akt , Femenino , Bovinos , Animales , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Nuclear de Célula en Proliferación/farmacología , Glándulas Mamarias Animales/metabolismo , Serina-Treonina Quinasas TOR/genética , Dieta/veterinaria , Leche/metabolismo , Células Epiteliales/metabolismo , ARN Mensajero/genética , Lactancia/genética , Suplementos Dietéticos , Ácido Fólico/farmacología , Ácido Fólico/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/farmacologíaRESUMEN
We aimed to identify the efficacy of haploidentical related donor (HID) haematopoietic stem cell transplantation (HSCT) in adolescent and young adults (AYAs) with acute myeloid leukaemia (AML) in a large cohort. Consecutive AML AYAs (15-39 years old, n = 599) receiving HID HSCT in complete remission (CR) were included. The 3-year cumulative incidence of measurable residual disease occurrence, relapse and non-relapse mortality after HID HSCT was 28.6% (95% CI: 25.0-32.2), 11.6% (95% CI: 9.0-14.2) and 6.7% (95% CI: 4.7-8.7) respectively. The 3-year probability of event-free survival, leukaemia-free survival (LFS) and overall survival (OS) after HID HSCT was 60.7% (95% CI: 56.9-64.8), 81.7% (95% CI: 78.7-84.9) and 85.6% (95% CI: 82.8-88.4) respectively. In multivariable analysis, AML risk category at diagnosis and comorbidity burdens before HID HSCT were independently associated with LFS and OS. Compared to the older adults (≥ 40 years, n = 355) with AML receiving HID HSCT in CR during the same time period, AYAs have a lower incidence of non-relapse mortality and higher probabilities of LFS and OS. Thus, we firstly confirmed the safety and efficacy of HID HSCT in AYAs with AML-CR.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Adolescente , Adulto Joven , Anciano , Adulto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inducción de Remisión , Estudios RetrospectivosRESUMEN
Antibiotics, due to their stability and persistence in the environment, can have chronic impacts on various ecosystems and organisms. However, the molecular mechanisms underlying antibiotic toxicity at environmental concentrations, particularly the neurotoxic effects of sulfonamides (SAs), remain poorly understood. In this study, we assessed the neurotoxicity of six SAs including the sulfadiazine (SD), sulfathiazole (ST), sulfamethoxazole (SMX), sulfisoxazole (SIZ), sulfapyridine (SPD), and sulfadimethoxine (SDM) by exposing zebrafish to environmentally relevant concentrations (ERCs). The SAs exhibited concentration-dependent effects on zebrafish behavior, including spontaneous movement, heartbeat, survival rate, and body metrics, ultimately leading to depressive-like symptoms and sublethal toxicity during early life stages. Notably, even the lowest SA concentration (0.05 µg/L) induced neurotoxicity and behavioral impairment in zebrafish. We observed a dose-dependent increase in melancholy behavior as indicated by increased resting time and decreased motor activity in zebrafish larvae. Following exposure to SAs from 4 to 120 h post-fertilization (hpf), key genes involved in folate synthesis [sepiapterin reductase a (spra), phenylalanine hydroxylase (pah), tyrosine hydroxylase (th), and tryptophan hydroxylase 1 (tryptophan 5-monooxygenase) a tryptophan hydroxylase (tph1a)] and carbonic anhydrase (CA) metabolism [carbonic anhydrase II (ca2), carbonic anhydrase IV a (ca4a), carbonic anhydrase VII (ca7), and carbonic anhydrase XIV (ca14)] were significantly downregulated or inhibited at different concentrations. Our findings demonstrate that acute exposure to six SAs at environmentally relevant concentrations induces developmental and neurotoxic effects in zebrafish, impacting folate synthesis pathways and CA metabolism. These results provide valuable insights into the potential role of antibiotics in depressive disorders and neuroregulatory pathways.
Asunto(s)
Anhidrasas Carbónicas , Contaminantes Químicos del Agua , Animales , Sulfonamidas/toxicidad , Pez Cebra , Triptófano Hidroxilasa/farmacología , Ecosistema , Contaminantes Químicos del Agua/toxicidad , Sulfanilamida/farmacología , Antibacterianos/farmacología , Larva , Ácido Fólico/farmacologíaRESUMEN
Desert carbon sequestration plays an active role in promoting carbon neutralization. However, the current understanding of the effect of hydrothermal interactions and soil properties on desert carbon sequestration after precipitation remains unclear. Based on the experiment in the hinterland of the Taklimakan Desert, we found that the heavy precipitation will accelerate the weakening of abiotic carbon sequestration in deserts under the background of global warming and intensified water cycle. The high soil moisture can significantly stimulate sand to release CO2 at an incredible speed by rapidly increasing microbial activity and organic matter diffusion. At this time, the CO2 flux in the shifting sand was synergistically affected by soil temperature and soil moisture. As far as soil properties are concerned, with less organic carbon substrate and stronger soil alkalinity, the carbon sequestration of shifting sand is gradually highlighted and strengthened at low temperature. On the contrary, the carbon sequestration of shifting sand is gradually weakened. Our study provides a new way to assess the contribution of desert to the global carbon cycle and improve the accuracy and scope of application.
Asunto(s)
Secuestro de Carbono , Ecosistema , Clima Desértico , Dióxido de Carbono , Suelo/química , Carbono , ChinaRESUMEN
As a special geographical unit on the earth, deserts have certain differences in planetary boundary layer (PBL) characteristics from other surface types. In order to find out the long-term evolution law of the Gurbantünggüt Desert, on the basis of evaluating the availability of reanalysis data, using the most effective reanalysis data and situ measured data in this area, the evolution law of the atmospheric boundary layer in the desert area was studied. The results show that among the ERA5, MERRA2, JRA-55 and NCEP-FNL reanalysis data, the ERA5 data has the smallest error with the measured data in the comparison of ground elements or high-altitude meteorology parameters, and can be used for the long-term evolution of the atmospheric boundary layer in desert areas. Based on the ERA5 dataset, the annual planetary boundary layer height (PBLH) of the desert fluctuated between 1979 and 1985, but showed a downward trend overall. From 1986 to 2019, the PBLH generally shows an upward trend, and by 2020, the PBLH decreases again. The PBLH in the summer of the desert was contrary to the inter-annual change trend of the PBLH throughout the year. The spatial distribution shows that the PBLH has the characteristics of north-south anisotropy. The characteristics of the ABL in the Gurbantünggüt Desert in different thermal states in summer vary greatly. Based on the sounding observational data, the average PBLH of the stable boundary layer in the Gurbantünggüt Desert in summer is 496 m, the average PBLH of the convective boundary layer is 1693 m, and the average PBLH of the neutral boundary layer is 1208 m. The ABL in desert areas from 02:00 to 08:00 and 23:00 is dominated by stable boundary layers, of which the proportion of stable boundary layers at 05:00 is as high as 67%. During the day, the boundary layer from 14:00 to 17:00 is mainly the convective boundary layer, accounting for more than 50%, and the boundary layer at 20:00 is mainly a neutral boundary layer, accounting for 55%.
RESUMEN
BACKGROUND: Trend pattern analysis are lacking for hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B (CHB) patients during nucleos(t)ide analogue (Nuc) therapy. We evaluated the trend patterns of HBsAg kinetics by time series analysis and forecasting times to HBsAg seroclearance accordingly. METHODS: A total of 116 CHB patients with documented three-month HBsAg levels during the previous more than five years of Nuc therapy were included. The piecewise linear trends of the autoregressive-moving average (ARMA) model were used for time series analysis of HBsAg kinetics trends. Best fitted models were created for each patient using HBsAg datasets with backtracking capability. Predicted time to HBsAg seroclearance was calculated accordingly. RESULTS: Four trend patterns of HBsAg kinetics were found: no trend (n = 22, 19.0%), single trend (n = 16, 13.8%), biphasic trend with rapid-slow decline (n = 56, 48.2%) and biphasic trend with rise-decline (n = 22, 19.0%). Except for no-trend patients, the trend became slow reduction as HBsAg declined. Only 6.1% of patients continued rapid decline when the initial HBsAg of the last trend reached <100 IU/mL. Last trend slopes < -10 and rise-decline patterns indicate greater chances of achieving HBsAg seroclearance within two years. CONCLUSION: Best fitted ARMA models of HBsAg kinetics can be created individually for patients during Nuc therapy. About 67.2% patients have biphasic trend patterns, suggesting the dynamic nature of HBsAg kinetics over time. Trend patterns and last trend slopes predict individual times to HBsAg seroclearance.
Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Virus de la Hepatitis B/genética , Antivirales/uso terapéutico , ADN Viral , Antígenos e de la Hepatitis BRESUMEN
The rate of intensive care unit (ICU) mortality in patients with hematologic malignancies is high. The risk factors for this were inconsistent across several previous studies, and there is currently no accepted consensus around risk factors for these patients. We aimed to identify which prognostic factors were associated with ICU mortality in critically ill patients with hematologic malignancies, nearly half of which were allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. In addition, we aimed to compare the characteristics and clinical outcomes of patients with and without allogenic allo-HSCT. In total, 217 patients with hematologic malignancies were enrolled consecutive, 119 (54.8%) of whom underwent HSCT (allo-HSCT: n = 115). All survivors were followed up with until August 1, 2022. The rate of ICU mortality in this cohort was 54.4%: 55.5 and 53.1% for the patients with and without HSCT, respectively (p = 0.724). The probabilities of survival after ICU admission were also comparable between the patients who had allo-HSCT and those who did not. A multivariable analysis revealed that cerebrovascular disease, hyperlactic acidemia on the day of ICU admission, lower platelet count, use of vasoactive drugs, and absence of noninvasive ventilation on the day of ICU admission were independent risk factors for ICU mortality. For patients with three to five of these risk factors, the rate of ICU mortality was as high as 84.6%, which was significantly higher than that of other patients. In this study, the ICU mortality rate in patients with hematologic malignancies was still high, particularly for those with multiple risk factors. However, allo-HSCT was not found to be a risk factor for ICU mortality.
Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Pronóstico , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Trasplante Homólogo , Factores de Riesgo , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.