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The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.
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BACKGROUND: Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions. AIM: To develop a 2D-SWE-based predictive model for preoperative identification of HCC. METHODS: A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms. RESULTS: In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003). CONCLUSION: 2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.
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Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Neoplasias Hepáticas , Hígado , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Valor Predictivo de las Pruebas , Hepatectomía , Nomogramas , Adulto , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/patología , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.
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Pueblo Asiatico , Enfermedad de Crohn , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Células Th17 , Humanos , Enfermedad de Crohn/genética , Masculino , Femenino , Adulto , Estudios de Casos y Controles , Pueblo Asiatico/genética , China , Persona de Mediana Edad , Adulto Joven , Receptores de Interleucina/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Adolescente , Factores de Riesgo , Pueblos del Este de AsiaRESUMEN
Background: Studies have indicated an association between gut microbiota (GM) and non-Hodgkin lymphoma (NHL). However, the causality between GM and NHL remains unclear. This study aims to investigate the causality between GM and NHL using Mendelian randomization (MR). Methods: Data on GM is sourced from the MiBioGen consortium, while data on NHL and its subtypes is sourced from the FinnGen consortium R10 version. Inverse variance weighted (IVW) was employed for the primary MR analysis method, with methods such as Bayesian weighted Mendelian randomisation (BWMR) as an adjunct. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO, and the "Leave-one-out" method. Results: The MR results showed that there is a causality between 27 GMs and NHL. Among them, 20 were negatively associated (OR < 1), and 7 were positively associated (OR > 1) with the corresponding diseases. All 27 MR results passed sensitivity tests, and there was no reverse causal association. Conclusion: By demonstrating a causal link between GM and NHL, this research offers novel ideas to prevent, monitor, and cure NHL later.
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With the widespread presence of plastic waste in ecosystems, it is imperative to understand the response of natural processes to micro- and nanoplastic pollution pressures. However, the effects of nanoplastics on biogeochemical cycles are still overlooked and controversial. This study investigated the effects of three particle sizes (100 µm, 7 µm, and 80 nm) of polystyrene (PS) micro/nanoplastics (0.08 % of mass concentration) on denitrification processes and nirS/nirK denitrifying bacterial communities in wetland soils. The results indicated that PS nanoplastics were found to significantly enhance denitrification rates from 21.30 to 54.73 µmol N2·h-1·kg-1, increasing by 1.57 times compared to the control. Exposure to nanoplastics caused shifts in the composition and structure of the nirS-type denitrifier community. LEfSe analysis, random forest, and Mantel tests revealed that nirS denitrifying bacteria, especially Sideroxydans, played a pivotal role in driving denitrification rates (Mantel's R = 0.24, p = 0.002), likely due to the faster release of organic substrates from nanoplastics. Microbial co-occurrence networks demonstrated that nanoplastic amendments fostered a denser denitrifier network and led to shifts in keystone species. Sideroxydans appeared more likely to cooperate with other bacteria, such as Burkholderiales, to complete denitrification processes. This study suggests that nanoplastics are a potentially stronger driver of denitrification than microplastics, providing insight into the impact of plastic pollutants on biogeochemical cycling in natural wetland ecosystems. Given the widespread distribution of wetlands, the potential increase in gaseous nitrogen emissions due to nanoplastics pollution warrants attention.
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Desnitrificación , Microbiología del Suelo , Suelo , Humedales , Suelo/química , Interacciones Microbianas , Bacterias/metabolismo , PlásticosRESUMEN
Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50â¯mg·kg-1·d-1, ig) or the positive control sulfasalazine (500â¯mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.
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Colitis Ulcerosa , Modelos Animales de Enfermedad , Inflamasomas , Isotiocianatos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Sulfóxidos , Animales , Isotiocianatos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sulfóxidos/farmacología , Estrés Oxidativo/efectos de los fármacos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colitis Ulcerosa/inducido químicamente , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Ratones , Masculino , Sulfato de Dextran , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Células RAW 264.7RESUMEN
INTRODUCTION: This study aimed to elucidate the mechanisms underlying endothelial injury in the context of intracranial aneurysm formation and development, which are associated with vascular endothelial injury caused by hemodynamic abnormalities. Specifically, we focus on the involvement of PKCα, an intracellular signaling transmitter closely linked to vascular diseases, and its role in activating MAPK. Additionally, we investigate the protective effects of PPARγ, a vasculoprotective factor known to attenuate vascular injury by mitigating the inflammatory response in the vessel wall. METHODS: The study employs a modified T-chamber to replicate fluid flow conditions at the artery bifurcation, allowing us to assess wall shear stress effects on human umbilical vein endothelial cells in vitro. Through experimental manipulations involving PKCα knockdown and Ca2+ and MAPK inhibitors, we evaluated the phosphorylation status of PKCα, NF-κB, ERK5, ERK1/2, JNK1/2/3, and P38, as well as the expression levels of PPARγ, NF-κB, and MMP2 via Western blot analysis. The cellular localization of phosphorylated NF-κB was determined using immunofluorescence. RESULTS: Our results showed that impinging flow resulted in the activation of PKCα, followed by the phosphorylation of ERK5, ERK1/2, and JNK1/2/3, leading to a decrease in PPARγ expression, an increase in the expression of NF-κB and MMP2, and the induction of apoptotic injury. Inhibition of PKCα activation or knockdown of PKCα using shRNA leads to a suppression of ERK5, ERK1/2, JNK1/2/3, and P38 phosphorylation, an elevation in PPARγ expression, and a reduction in NF-κB and MMP2 expression, alleviated apoptotic injury. Furthermore, we observe that the regulation of PPARγ, NF-κB, and MMP2 expression is influenced by ERK5 and ERK1/2 phosphorylation, and activation of PPARγ effectively counteracts the elevated expression of NF-κB and MMP2. CONCLUSION: Our findings suggest that the PKCα/ERK/PPARγ pathway plays a crucial role in mediating endothelial injury under conditions of impinging flow, with potential implications for vascular diseases and intracranial aneurysm development.
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In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species, Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed in Escherichia coli and self-activated in vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolytic activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed in E. coli, but failed to activate itself. To resolve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via ion-exchange chromatography. After the noncovalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolytic activity and could efficiently catalyze inter-molecular protein ligation and intramolecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.
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Cisteína Endopeptidasas , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/química , Ingeniería de Proteínas/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Ligasas/genética , Ligasas/metabolismo , Ligasas/química , Bambusa/genética , Bambusa/enzimología , Mutagénesis Sitio-Dirigida , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Secuencia de AminoácidosRESUMEN
In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100 µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (â3-α-L-fucp(2-SO3-)-1â4-α-L-fucp(2,3-SO3-)-1âsection), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.
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Acetilcolinesterasa , Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Simulación del Acoplamiento Molecular , Oligosacáridos , Sargassum , Sargassum/química , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/uso terapéutico , Ratones , Acetilcolinesterasa/metabolismo , Oligosacáridos/farmacología , Oligosacáridos/química , Oligosacáridos/aislamiento & purificación , Masculino , Sulfatos/química , Sulfatos/farmacología , Butirilcolinesterasa/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Relación Dosis-Respuesta a DrogaRESUMEN
The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients. KEY POINTS: ⢠The detection results of M1-method had a high coincidence rate with that of standard method ⢠M1 method detected many pathogens which had not been found by standard clinic method.
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Lectina de Unión a Manosa , Humanos , Líquido del Lavado Bronquioalveolar , Bacterias , Huésped Inmunocomprometido , Fenómenos Magnéticos , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.
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Drastic changes in hydrological conditions within floodplain ecosystems create distinct microbial habitats. However, there remains a lack of exploration regarding the variations in microbial function potentials across the flooding and drought seasons. In this study, metagenomics and environmental analyses were employed in floodplains that experience hydrological variations across four seasons. Analysis of functional gene composition, encompassing nitrogen, carbon, and sulfur metabolisms, revealed apparent differences between the flooding and drought seasons. The primary environmental drivers identified were water level, overlying water depth, submergence time, and temperature. Specific modules, e.g., the hydrolysis of ß-1,4-glucosidic bond, denitrification, and dissimilatory/assimilatory nitrate reduction to ammonium, exhibited higher relative abundance in summer compared to winter. It is suggested that cellulose degradation was potentially coupled with nitrate reduction during the flooding season. Phylogenomic analysis of metagenome-assembled genomes (MAGs) unveiled that the Desulfobacterota lineage possessed abundant nitrogen metabolism genes supported by pathway reconstruction. Variation of relative abundance implied its environmental adaptability to both the wet and dry seasons. Furthermore, a novel order was found within Methylomirabilota, containing nitrogen reduction genes in the MAG. Overall, this study highlights the crucial role of hydrological factors in modulating microbial functional diversity and generating genomes with abundant nitrogen metabolism potentials.
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Microbiota , Agua , Nitratos , Microbiota/genética , Metagenoma , Nitrógeno/metabolismoRESUMEN
Objective:To summarize the application of pectoralis major flap in complex defects after maxillofacial " frozen neck" surgery.Methods:The clinical data of 7 patients with maxillofacial " frozen neck" admitted to the Department of Stomatology of the Xuzhou Central Hospital from October 2020 to October 2022 were retrospectively analyzed. The pectoralis major flap was used to repair the complex defects after surgery and the treatment effect was observed.Results:All 7 patients had survived flap transplantation with no serious complications. After 3 to 24 months of follow-up, the patients were basically satisfied with the treatment effect.Conclusions:The pectoralis major flap has reliable blood supply, abundant tissue, and can be applied flexibly with a high survival rate and significant repair effect. It is a good choice for repairing complex defects after " frozen neck" surgery, and it has clinical application value.
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Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.
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Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.
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Objective:To evaluate the efficacy of 3D printed patients-specific guide plates in assisting Ilizarov bone transport in the treatment of tibial bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 24 patients with tibial bone defects who had been admitted to Institute of Trauma Orthopedics, The 80th Army Group Hospital of PLA from January 2018 to March 2022. There were 9 males and 15 females with an age of (49.8±6.5) years, and 4 upper tibial defects, 5 middle tibial defects, and 15 lower tibial defects. According to the methods of repairing bone defects, the patients were divided into 2 groups: a 3D printing group of 10 cases where a 3D printed patient-specific guide plate was used to assist Ilizarov bone transport in the treatment of tibial bone defects, and a traditional group of 14 cases where Ilizarov bone transport was performed in a traditional manner. The 2 groups were compared in terms of operation time, frequency of intraoperative fluoroscopy, axial angulation of the tibia at postoperation and the last follow-up, external fixation time (EFT) and external fixation index (EFI). At the last follow-up, healing of bone defects was evaluated according to the criteria of The Association for the Study and Application of the Method of Ilizarov (ASAMI), functional outcomes were evaluated according to the Paley criteria, and needle infection was recorded according to the Paley classification for complications.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (11.3±2.0) months on average after operation. The 3D printing group had significantly shorter operation time [(19.9±2.6) min] and significantly lower frequency of intraoperative fluoroscopy [(3.0±0.8) times] than the traditional group [(38.1±2.2) min and (8.9±1.3) times] (P<0.05), and had significantly better axial angulation of the tibia at postoperation and the last follow-up than the traditional group ( P<0.05). There was no significant difference in EFT or EFI between the 2 groups ( P>0.05), and the last follow-up revealed no significant difference either in bone healing, functional outcomes, or needle infection between the 2 groups ( P>0.05). Conclusion:In the treatment of tibial bone defects, compared with conventional Ilizarov bone transport, the Ilizarov bone transport assisted by a 3D printed patient-specific guide plate demonstrates advantages of shorter operation time, lower intraoperative fluoroscopy, and higher reduction accuracy.
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Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.
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This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital’s electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%).Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.
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@#The chemical constituents of solid rice culture of the endophytic fungus Aspergillus sp.Dq-25 from barnacle were isolated and purified by silica gel, Sephadex LH-20, C18 reversed silica gel column chromatography and recrystallization.Their structures were identified by the physical and chemical properties, and by various spectroscopic methods.Six compounds were isolated and identified as: demethyldihydropenicillic acid (1), dihydropenicillic acid (2), penicillic acid (3), fortisterol (4), 22E, 24R-3P, 5a-dihydroxyerogosta-7, 22-diene-6-one (5), and (22E, 24R)-ergosterol-7, 22-diene-3β, 5α, 9α-triol-6-one (6).Compound 1 was a new butyrolactone.MTT method was used to analyze cytotoxicity, and the result showed that compound 3 exhibited inhibitory activity on five cell lines, including K562, HeLa, SGC-7901, A542 and BEL-7402, with IC50 values of 38.0 ~ 105.0 μmol/L.