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Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.
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Aprendizaje Profundo , Encefalopatía Hepática , Humanos , Estudios Transversales , Encéfalo , Cirrosis Hepática , Imagen por Resonancia MagnéticaRESUMEN
In the past decades,a dramatic development of navigation technology in orthopaedic surgery has been witnessed. By assisting the localization of surgical region,verification of target bony structure,preoperative planning of fixation,intraoperative identification of planned entry point and direction of instruments or even automated insertion of implants,its ability and potential to reduce operation time,intraoperative radiation,surgical trauma,and improve accuracy has been proved. However,in contrast to the widespread use of navigation technology in arthroplasty,orthopaedic tumor,and spine surgery,its application in orthopaedic trauma is relatively less. In this manuscript,the main purpose is to introduce the technical principles of navigation devices,outline the current clinical application of navigation systems in orthopaedic trauma,analyze the current challenges confronting its further application in clinical practice and its prospect in the future.
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Procedimientos Ortopédicos , Ortopedia , Cirugía Asistida por Computador , Humanos , Cirugía Asistida por Computador/métodos , Procedimientos Ortopédicos/métodos , Tempo OperativoRESUMEN
Objective: To explore the application value of T lymphocyte subsets combined with procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and white blood cell count (WBC) in the auxiliary diagnosis and prognosis evaluation of sepsis. Methods: In a retrospective study, seventy-two patients with sepsis diagnosed and treated in Tianjin First Central Hospital from June 2018 to April 2021 were selected as the research objects, and included in the sepsis group were 46 males and 26 females, aged 68 (57.3, 80.3) years. In addition, 111 patients with local infection admitted to hospital during the same period were included in the local infection group, including 62 males and 49 females, aged 68 (51, 77) years. Sepsis patients were divided into survival group (43 cases) and death group (29 cases) according to the 28-day outcome. CD3+, CD4+, CD8+, CD4+/CD8+ ratio were detected by flow cytometry within 24 h after admission, PCT was detected by ELISA, CRP was detected by immunoturbidimetry, blood routine examination, blood lactic acid (Lac) and oxygen partial pressure (PO2) were detected by instrumental method. Multivariate Logistic regression analysis was used to evaluate the correlation between each indicator and sepsis, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of each indicator for sepsis. Multivariate Logistic regression analysis and Kaplan Meier survival analysis were used to evaluate the prognostic value of each index for patients with sepsis. Results: Peripheral blood CD3+, CD4+, CD8+, CD4+/CD8+ ratio and PLT in sepsis group were significantly lower than those in local infection group(Z=-8.184,P<0.001;Z=-7.210,P<0.001;Z=-5.936,P<0.001;Z=-2.700,P=0.007;Z=-6.381,P<0.001); PCT, CRP, NLR and Lac levels were significantly higher than those in local infection group(Z=-8.262,P<0.001;Z=-3.094,P=0.002;Z=-9.004,P<0.001;Z=-4.770,P<0.001). Multivariate Logistic regression model showed that PCT, NLR, CD3+, CD8+, CD4+/CD8+ were independent risk factors for sepsis. According to ROC curve analysis, AUC of sepsis patients diagnosed by each indicator were 0.862, 0.894, 0.858, 0.760 and 0.618, respectively. The cut-off values were 3.075 ng/ml, 10.715, 44.935×109/L, 27.463×109/L and 0.750, respectively. The NLR sensitivity was 80.6%, and the CD3+ specificity was 94.6%. The AUC of combined detection of PCT and NLR was 0.947, sensitivity was 87.5% and specificity was 91.9%. The combined detection AUC of PCT, NLR, CD3+, CD4+/CD8+ was 0.958, the sensitivity and specificity were 90.3% and 91.0% respectively(P<0.001). PCT and Lac in death group were significantly higher than those in survival group(Z=-2.302,P=0.021;Z=-3.095,P=0.002);Peripheral blood CD4+/CD8+ levels were significantly lower than those in survival group(Z=-3.691,P<0.001),Multivariate Logistic regression model showed that CD4+/CD8+ ratio was an independent risk factor for 28 d mortality in patients with sepsis (P<0.001). The ROC curve showed that the AUC was 0.758, and the Youden index reached the maximum when the cut-off value was 1.27, the sensitivity and specificity were 79.3% and 60.5%, respectively. Compared with patients with CD4+/CD8+ ≥1.27, 28-day mortality was significantly increased in patients with CD4+/CD8+<1.27 (P=0.032). Conclusion: The combined detection of PCT, NLR, CD3+ and CD4+/CD8+ can improve the auxiliary diagnostic efficiency of sepsis, and the ratio of CD4+/CD8+ in peripheral blood may have certain predictive value for the prognosis of sepsis.
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Sepsis , Anciano , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina , Estudios Retrospectivos , Sepsis/diagnóstico , Subgrupos de Linfocitos T/químicaRESUMEN
Objective: To investigate the expression of type â collagen α1 chain protein (COL1A1) in triple negative breast cancer (TNBC), and its relationship with clinicopathological features and prognosis of TNBC. Methods: A total of 148 TNBC specimens were collected from the Affiliated Cancer Hospital of Xinjiang Medical University from 2013 to 2015. The mRNA expression of COL1A1 was detected by fluorescence quantitative RT-PCR and the protein expression of COL1A1 was detected by Western blot. The expression of COL1A1 and α-smooth muscle actin (α-SMA) in TNBC were detected by immunohistochemistry. The relationship between the expression of COL1A1 and clinicopathological parameters and prognosis of TNBC patients was analyzed. Results: The mRNA and protein expression of COL1A1 in MDA-MB-231 cells were 1.696±0.486 and 0.550±0.088, respectively, which were higher than those in MCF-10A cells (1.020±0.231 and 0.350±0.083, P=0.032, P=0.046). The mRNA and protein expression of COL1A1 in TNBC tissues were 1.632 ±0.598 and 0.733 ±0.068, respectively, which were higher than those in paracancerous tissues (1.041±0.316 and 0.612±0.016, P=0.003, P=0.039). The high expression rates of COL1A1 and α-SMA in TNBC tissues were 35.8% and 56.7% respectively, which were higher than those in paracancerous tissues (16.7% and 30.0%, P=0.041, P=0.037). The expression of COL1A1 was correlated with tumor size, TNM stage, lymph node metastasis, vascular invasion and α-SMA expression (all P<0.05). The median survival time in COL1A1 high expression group was 64 months, which was lower than that in low expression group (73 months, P<0.05). Multivariate analysis of Cox proportional hazard regression model showed that COL1A1 expression was an independent influencing factor for the survival of TNBC patients (HR=3.952, P=0.004). Conclusion: The high expression of COL1A1 in TNBC is an independent prognostic factor of TNBC patients.
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Colágeno Tipo I/biosíntesis , Neoplasias de la Mama Triple Negativas/metabolismo , Actinas/biosíntesis , Humanos , Inmunohistoquímica , Metástasis Linfática , Pronóstico , Biosíntesis de Proteínas , ARN Mensajero/biosíntesis , Neoplasias de la Mama Triple Negativas/patologíaAsunto(s)
Neoplasias Pulmonares , Macrófagos , Macrófagos Asociados a Tumores , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Macrófagos/patología , Macrófagos/inmunología , Macrófagos Asociados a Tumores/patología , Macrófagos Asociados a Tumores/inmunología , Monocitos/patología , Animales , Antígenos CD/metabolismoAsunto(s)
Adenocarcinoma , Neoplasias del Apéndice , Factor de Transcripción CDX2 , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/metabolismo , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Anciano , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adenocarcinoma/metabolismo , Factor de Transcripción CDX2/metabolismo , ColectomíaRESUMEN
Nasal cancer has not been included in the current list of legal occupational diseases in China. There is also a lack of systematic and in-depth study on the relationship between nasal cancer and occupational exposure factors in China. In September 2018, the department for work and pensions of UK released the latest edition of the "List of diseases covered by industrial injuries disablement benefit", which lists nasal cancer and nasopharyngeal carcinoma associated with wood dust exposure on the UK's occupational disease list. In order to better protect the health of workers, the relationship between occupational wood dust exposure and nasal cancer is reviewed, which provides a reference for further revision and improvement of occupational disease catalogue.
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Polvo , Neoplasias Nasales , Enfermedades Profesionales , Exposición Profesional , Madera , China/epidemiología , Humanos , Neoplasias Nasales/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/estadística & datos numéricosRESUMEN
Myasthenia gravis (MG) is an autoimmune disease characterized by fatigue and muscle weakness. Artemisinin and its derivatives were reported to be experimentally used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and experimental allergic encephalomyelitis (EAE). Here, we tested the effects of artemisinin on experimental autoimmune myasthenia gravis (EAMG). Our data confirmed that artemisinin markedly ameliorated the symptoms of EAMG rats. There was a decreased level of tumor necrosis factor-α (TNF-α) and IL-17+ cells in mononuclear cells (MNCs), and an increased level of transforming growth factor-ß1 (TGF-ß1) and Treg cells in MNCs. These findings indicate that artemisinin may be a new choice for MG treatment.
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Artemisininas/uso terapéutico , Miastenia Gravis Autoinmune Experimental/tratamiento farmacológico , Miastenia Gravis Autoinmune Experimental/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Células Th17/inmunología , Animales , Artemisininas/farmacología , Ratas , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Células TH1/citología , Células TH1/inmunología , Células Th17/citologíaRESUMEN
AIM: To determine the clinical non-inferiority of recombinant glargine-Basalin vs glargine-Lantus, in treatment of type 2 diabetes mellitus (T2DM) using continuous glucose monitoring system (CGMS). METHODS: One hundred patients with T2DM were recruited. They were either regularly taking Basalin (Basalin group) or Lantus (Lantus group) (n = 50 each). CGMS was employed to real-time monitor blood glucose profile for 4 days (from day 1 to day 5). To exclude the effect of patient background, the study design was to have a blinded crossover from glargine-Basalin to glargine-Lantus on day 3, and vice versa. 24-hour mean blood glucose (24hMBG), 24-hour standard deviation of blood glucose (24hSDBG), 24-hour mean amplitude of glycemic excursion (24hMAGE), and number of glycemic excursion (NGE) every 24 h (24hNGE) were calculated for each glargine from 100 patients. RESULTS: No significant difference of 24hMBG, 24hSDBG, 24hMAGE, and 24hNGE (p > 0.05 for all) was found between Basalin and Lantus treatments. The glucose area under the curve and time when blood glucose was below 3.9 mmol/L, between 3.9 and 10.0 mmol/L, or above 10.0 mmol/L were similar between Basalin and Lantus treatment. The frequency of hypoglycemic episodes was also similar. However, the mean cost of Basalin was only 72% of Lantus's in one treatment course. CONCLUSION: Glargine-Basalin is non-inferior in clinical efficacy compared to glargine-Lantus. In view of the large difference in the cost of glargine-Basalin, it would be much more cost-effective for our patients.
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Compuestos de Anilina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Hipoglucemiantes/uso terapéutico , Insulina Glargina/uso terapéutico , Monitoreo Fisiológico , Adolescente , Adulto , Compuestos de Anilina/economía , Estudios Cruzados , Femenino , Humanos , Insulina Glargina/economía , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
We aimed to investigate the role of FUT1 gene in Taxol resistance and to explore its mechanism in epithelial ovarian cancer. Three ovarian cancer cell lines, ES-2, SK-OV-3 and OVCAR-3 were selected from epithelial ovarian cancer in this experiment. Western blot was used to validate the protein expression level of FUT1 and the apoptosis proteins. The expression level of the corresponding carrier was validated by RT-PCR. Transfection and isolation of stable transfectants were carried out to establish the cell line models. The different concentrations of Taxol on the inhibition of cell growth rate was measured by MTT, in which Taxol resistance profiling in ovarian cancer cells was determined by IC50 data. Flow cytometry was conducted to compare cell apoptosis ability. Caspase-3 activity and the apoptosis proteins were measured by colorimetry and western blot, respectively, to further compare the cell apoptosis ability in different groups. To demonstrate the inhibition of miR-FUT1 combined with Taxol therapy against ovarian cancer, xenograft assay was carried out for the in vivo effect. The western blot results indicate that FUT1 is expressed in all of the ovarian cancer cells with different expression level: ES-2 > SK-OV-3 > OVCAR-3. Besides, FUT1 siRNA was used in the maximum expression of FUT1 cell line ES-2, or over-expression plasmid was used in the minimum expression of FUT1 cell line OVCAR-3, to establish stable expression cell lines. After the treatment with Taxol, the inhibition rate of Taxol was obviously decreased with the established cell model above, and the IC50 level was significantly increased in the FUT1 over-expression + Taxol group (p Keywords: FUT1, Lewis y, Taxol resistance, ovarian cancer, apoptosis.
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Resistencia a Antineoplásicos , Fucosiltransferasas/genética , Neoplasias Ováricas/enzimología , Paclitaxel/farmacología , Animales , Apoptosis , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
Objective: To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). Methods: Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed. Results: The levels of IL-6 mRNA were significantly higher in peripheral blood of SLE.DNA methylation levels of IL-6 promoter were reduced in SLE patients as compared with healthy controls.The methylation status and expression of IL-6 in peripheral blood reflected the levels in peripheral blood mononuclear cells (PBMCs). Significantly positive correlation was found between IL-6 hypomethylation and renal disorder, as well as hypocomplementemia in patients with SLE. Conclusion: Hypomethylation of interleukin-6 promoter in peripheral blood might be involved in the etiology of SLE.
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Metilación de ADN , Interleucina-6/metabolismo , Lupus Eritematoso Sistémico/genética , Humanos , Leucocitos Mononucleares , Lupus Eritematoso Sistémico/fisiopatología , Regiones Promotoras GenéticasRESUMEN
Objective: To investigate the clinical phenotype and genotype characteristics of a Chinese hereditary factor â ª deficiency pedigree. Methods: The activated partial thromboplastin time (APTT), prothrombin time (PT), Fâ ª activity (Fâ ª: C) were measured by clotting method using automatic coagulation analyzer. The Fâ ª antigen (Fâ ª: Ag) was assayed by enzyme-linked immunosorbent assay (ELISA). Fifteen exons of F11 from the proband and his pedigree members were amplified by polymerase chain reaction (PCR), then sequenced. Pymol software was used to analyze the novel mutations. Results: APTT, Fâ ª: C and Fâ ª: Ag of proband was 74.2 s, 4.0% and 2.9%, respectively. For his older sister, APTT, Fâ ª: C and Fâ ª: Ag was 67.1 s, 3.0% and 1.8%, respectively. APTT, Fâ ª: C and Fâ ª: Ag of healthy controls were 34.5 s, 100.0% and 100.0%. Fâ ª: C of proband's father, mother and brother were 72.0%, 62.0%, and 78.0%, respectively. Fâ ª: Ag of them were 50.0%, 43.0%, and 51.8%, respectively. The other coagulant parameters of the proband and his pedigree were all in the normal range. Sequence analysis showed two heterozygous gene mutations in F11 of the proband and his older sister. One was a deletion of T at nucleotide 1 491 in exon 12, resulting in a frameshift. A substitution of leucine 465 by tryptophan and a terminal coden after 7 amino acid: F11NM_13142c.1491delT (p.Leu465Trp.fs*7). The other was a G to A substitution at nucleotide 1 815 in exon 15, resulting in a substitution of glycine 573 by aspartic acid: F11 NM_13142c.1815G>A (p.Gly573Asp). F11NM_13142c.1491delT (p.Leu465Trp.fs*7) heterozygotes were found both in the proband's father and his brother while p. Gly573Asp heterozygote was only found in his mother. F11 of the proband's uncle was wild. Conclusion: The novel compound heterozygous mutations of F11NM_13142c.1491delT (p.Leu465Trp.fs*7) and F11 NM_13142 c. 1815G>A (p.Gly573Asp) are responsible for Fâ ª deficiency to the proband, which induced the decrease of Fâ ª: C and Fâ ª: Ag.
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Deficiencia del Factor XI/genética , Factor XI/genética , Mutación , Exones , Femenino , Heterocigoto , Humanos , Masculino , LinajeRESUMEN
Escherichia coli is the most common cause of Gram-negative peritonitis resulting in peritoneal function deterioration as well as poor clinical outcome in continuous ambulatory peritoneal dialysis (PD) patients. In this study, we analyzed the phylogenetic background and genetic profile of the E. coli isolates and sought to determine the characteristics of specific bacteria associated with peritonitis. E. coli isolates from 56 episodes of peritonitis in 46 PD patient cases and rectal isolates from 57 matched PD control patient cases were compared for both phylogenetic groups and the presence of virulence factors (VFs). There were no significant differences in terms of demographic data between the peritonitis and control groups. Peritonitis isolates exhibited a significantly greater prevalence of 8 VFs. In multivariate logistic regression analysis, kpsMT II (group 2 capsule synthesis) was the strongest VF predictor of peritonitis (OR = 8.02; 95%CI = 3.18-20.25; P < 0.001), followed by traT (serum-resistance-associated outer membrane protein) (OR = 3.83; 95%CI = 1.33-11.03; P = 0.013). The pathogenic groups of E. coli contained a higher concentration of individual VFs compared to the commensal groups. The prevalence of pathogenic E. coli was much higher in peritoneal isolates than rectal isolates (64.3 vs 31.6%, P = 0.001). Our results indicate that the E. coli peritonitis and rectal isolates are different in PD patients. The specific VFs associated with peritonitis isolates may directly contribute to the pathogenesis of peritonitis.
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Escherichia coli/genética , Peritonitis/microbiología , Adulto , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/métodos , Filogenia , Factores de VirulenciaRESUMEN
In this experiment, the test materials were 'Red Fuji' apple trees grafted onto three interstocks (No. 53, No. 111, and No. 236), which were chosen from SH40 seeding interstocks. The content of malic acid, the enzyme activities, and the expression of genes related to malic acid metabolism were determined during fruit development.The results showed that malic acid content in the ripe fruit on interstock No. 53 was higher than that in the interstock No. 111 fruit. The malate dehydrogenase (NAD-MDH) activity in apples on interstock No. 53 was highest on Day 30, Day 100, and Day 160 after bloom, and the malic enzyme (NADP-ME) activity in apples on interstock No. 111 was higher than in the interstock No. 53 fruit from Day 70 to Day 100 after bloom. The relative expression of NAD-MDH genes in interstock No. 53 fruit was higher than in No. 236 fruit on Day 100 after bloom, but the relative expression of NADP-ME in No. 236 interstock fruit was lower than in No. 53 fruit. The relative expression of NAD-MDH genes in No. 53 interstock fruit was highest on Day 160 after bloom. This might have been the main reason for the difference in the accumulation of malic acid in the ripe apples.There was a positive correlation between the relative expression of phosphoenolpyruvate carboxylase (PEPC) and the malic acid content of the fruit, and the content of malic acid in the apples was affected by the PEPC activity during the early developmental stage.
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Frutas/genética , Malato Deshidrogenasa/biosíntesis , Malatos/metabolismo , Malus/genética , Frutas/enzimología , Frutas/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Malato Deshidrogenasa/genética , Malus/enzimología , Malus/crecimiento & desarrolloRESUMEN
Microscopic images of curvilinear fibre network structure like cytoskeleton are traditionally analysed by qualitative observation, which can hardly provide quantitative information of their morphological properties. However, such information is crucially contributive to the understanding of important biological events, even helps to learn about the inner relations hard to perceive. Individual fibre segmentation-based curvilinear structure detector proposed in this study can identify each individual fibre in the network, as well as connections between different fibres. Quantitative information of each individual fibre, including length, orientation and position, can be extracted; so are the connecting modes in the fibre network, such as bifurcation, intersection and overlap. Distribution of fibres with different morphological properties is also presented. No manual intervening or subjective judging is required in the analysing process. Both synthesized and experimental microscopic images have verified that the detector is capable to segment curvilinear network at the subcellular level with strong noise immunity. The proposed detector is finally applied to the morphological study on cytoskeleton. It is believed that the individual fibre segmentation-based curvilinear structure detector can greatly enhance our understanding of those biological images generated from tons of biological experiments.
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Citoesqueleto/ultraestructura , Microscopía/métodos , Algoritmos , Estudios de Evaluación como Asunto , HumanosRESUMEN
Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade â ¡-â £ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade â or â ¡. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
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Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Neoplasias Hematológicas/terapia , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Crónica , Donante no Emparentado , Trasplante Homólogo , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: Excessive accumulation of long-chain fatty acids in the pancreatic islets is associated with beta cell dysfunction and ultimately contributes to the pathogenesis of type 2 diabetes. It has been well proved that the cell death-inducing DFF45-like effector b (Cideb) is involved in cell apoptosis and lipid metabolism. However, the expression and function of Cideb in endocrine pancreas remain to be investigated. METHODS: By using reverse transcript polymerase chain reaction, immunohistochemistry and Western blot, we observed the expression of Cideb in pancreas tissues and clonal beta-cell lines. The physiological role of Cideb was examined under the free fatty acid (FFA) administration and Cideb ribonucleic acid interference, and further analysis on apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay and caspase-3 activity. Nile red staining and quantitative evaluation of triglyceride were used to detect the lipid accumulation. The changes in esterification of FFA were traced by radiolabelled palmitate. RESULTS: Cideb was abundantly expressed in pancreas and mainly localized in beta cells. FFAs, especially palmitate, induced an obvious increase of Cideb expression in beta cell lines. Adenoviral-mediated overexpression of Cideb increased the apoptosis, whereas ribonucleic acid interference-based Cideb depletion in beta-TC3 cells had no effect on apoptosis in normal condition. Palmitate supplementation led to beta cell lipoapoptosis, and Cideb silencing exacerbated the apoptosis induced by palmitate, reduced intracellular triglyceride content and aggravated FFA overload in beta cells. CONCLUSIONS: The present results suggest that increased Cideb expression upon palmitate exposure may be involved in beta cell lipoapoptosis through its influence on conversion of FFAs to lipid esters in lipid droplets.