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Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor (HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy (HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better (HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.
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Leucemia de Células Plasmáticas , Humanos , Persona de Mediana Edad , Leucemia de Células Plasmáticas/terapia , Leucemia de Células Plasmáticas/diagnóstico , Adulto , Anciano , Pronóstico , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas , Masculino , Femenino , Tasa de Supervivencia , Inducción de RemisiónRESUMEN
OBJECTIVE: To analyze the epidemiological characteristics of visceral leishmaniasis in Gansu Province from 2017 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy in the province. METHODS: All epidemiological features of confirmed and clinically diagnosed cases of visceral leishmaniasis reported in Gansu Province from January 1, 2017 to December 31, 2023 were retrieved from the Chinese Disease Prevention and Control Information System, and the epidemiological characteristics of visceral leishmaniasis cases were analyzed descriptively. RESULTS: A total of 280 visceral leishmaniasis cases were reported in 39 counties (cities and districts) of Gansu Province from 2017 to 2023, including 258 local cases reported in 21 endemic counties (districts) and 22 imported cases reported in 18 non-endemic areas. Of the 280 cases, there were 262 cases with mountain type zoonotic visceral leishmaniasis (MT-ZVL), 12 cases with desert-type zoonotic visceral leishmaniasis (DT-ZVL), and 6 cases with unknown type. Re-emerging MT-ZVL occurred in Maiji District, Qinzhou District, Lixian County, Kangxian County, Zhenyuan County, Qin'an County and Yongjing County, and re-emerging DT-ZVL occurred in Dunhuang City, while emerging DT-ZVL occurred in Yumen City. The five counties (districts) reporting the highest number of visceral leishmaniasis cases included Wudu District, Wenxian County, Tanchang County, Zhouqu County and Diebu County, and a total of 220 cases were reported in these five counties, accounting for 78.57% of all visceral leishmaniasis cases in the province. Visceral leishmaniasis cases were reported each month throughout the year, with the peak in July. All reported visceral leishmaniasis cases had ages of 6 months to 81 years, including 50.71% (142/280) under 15 years of age, 49.29% (138/280) at ages of 15 years and older, and of all cases under 15 years of age, children at ages of 0 to 3 years were the most commonly affected (27.14%, 76/280). Among 280 visceral leishmaniasis cases, there were 173 males and 107 females with a male to female ratio of 1.62â¶1, and farmer was the most common occupation (40.36%), followed by diaspora children (37.86%). CONCLUSIONS: The prevalence of visceral leishmaniasis appeared an overall tendency towards a decline in Gansu Province from 2017 to 2023; however, there are still multiple challenges for visceral leishmaniasis control in the province. Reinforced dog monitoring and management, intensified human health education and improved capability building among professionals are recommended to manage the rebounding and spread of visceral leishmaniasis.
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Leishmaniasis Visceral , Leishmaniasis Visceral/epidemiología , Humanos , China/epidemiología , Masculino , Femenino , Adulto , Adolescente , Niño , Persona de Mediana Edad , Adulto Joven , Preescolar , Anciano , LactanteRESUMEN
OBJECTIVE: To investigate the spatiotemporal clustering characteristics of the reported incidence of visceral leishmaniasis (VL) in Gansu Province from 1993 to 2023, so as to provide insights into the containment of VL and prevention of VL recurrence. METHODS: County (district)-level epidemical data of VL in Gansu Province from 1993 to 2023 were collected, and the geographical information database of reported VL incidence in Gansu Province was created according to the county-level administrative code and electronic maps in Gansu Province. In addition, the spatial autocorrelation analysis and hot spot analysis of the reported VL incidence were performed in Gansu Province using the software ArcGIS 10.8. RESULTS: A total of 2 597 VL cases were reported in Gansu Province from 1993 to 2023, with an annual average incidence rate of 3.036/105. Spatial autocorrelation analysis showed spatial clustering of the reported VL incidence in Gansu Province (Moran's I = 0.605, Z = 5.240, P < 0.001), appearing high-high clustering features (Getis-Ord G = 0.080, Z = 4.137, P < 0.001), and high-high clustering of the reported incidence of VL was identified in Diebu County, Tanchang County, Zhouqu County and Wenxian County. Hot spot analysis showed hot-spot areas of the reported VL incidence in Tanchang County, Zhouqu County, Wudu District and Wenxian County along the Bailong River basins and cold-spot areas in Qin'an County and Gangu County. CONCLUSIONS: There was spatial clustering and hot spots of the reported VL incidence in Gansu Province from 1993 to 2023. Intensified surveillance and control is required to prevent the spread of VL.
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Leishmaniasis Visceral , Análisis Espacio-Temporal , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/parasitología , Humanos , China/epidemiología , Análisis por Conglomerados , IncidenciaRESUMEN
Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are highly active in MYD88-mutated (MYD88Mut) Waldenstrom's macroglobulinaemia and suppress nuclear factor kappa-light-chain-enhancer of activated B cells and extracellular signal-regulated kinases-1/2 (ERK1/2)-related signalling. BTKCys481 mutations are associated with cBTK-i acquired resistance and are accompanied by reactivation of ERK1/2 that promotes inflammatory cytokine secretion and paracrine-mediated resistance of BTK wild-type (BTKWT) tumour cells. Pirtobrutinib is a non-covalent BTK-inhibitor that binds at non-BTKCys481 sites. We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.
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Objective: To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center. Methods: This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children's Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results: Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157);χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) (χ2=8.33, P=0.004). According to imaging data, Crawford type â £ was the most common type, with 321 limbs (63.3%), followed by type â ¡ in 100 limbs (19.7%), type â ¢ in 54 limbs (10.7%) and type â in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times;t=14.93,P<0.01). Conclusions: Crawford type â £ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.
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Seudoartrosis , Tibia , Humanos , Estudios Retrospectivos , Femenino , Masculino , Seudoartrosis/congénito , Seudoartrosis/diagnóstico , Tibia/anomalías , Tibia/cirugía , Preescolar , Niño , LactanteRESUMEN
Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1â¶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: â Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. â¡Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. â¢Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
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Ciclofosfamida , Etopósido , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Mieloma Múltiple , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Etopósido/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Ciclofosfamida/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Estudios Retrospectivos , Células Madre de Sangre Periférica , Trasplante de Células Madre de Sangre Periférica/métodos , Femenino , Masculino , Persona de Mediana EdadRESUMEN
Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage â ¢C and 47 cases (77.0%) classified as stage â £ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antígeno B7-H1/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , Adulto , Anciano de 80 o más AñosRESUMEN
Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
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Antituberculosos , Nitroimidazoles , Oxazoles , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Masculino , Femenino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios Prospectivos , Rifampin/efectos adversos , Persona de Mediana Edad , Oxazoles/efectos adversos , Oxazoles/uso terapéutico , Oxazoles/administración & dosificación , Antituberculosos/efectos adversos , Tuberculosis Pulmonar/tratamiento farmacológico , Nitroimidazoles/efectos adversos , Nitroimidazoles/uso terapéutico , Nitroimidazoles/administración & dosificación , Anciano , China , Adulto Joven , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiologíaRESUMEN
Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.
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Detección Precoz del Cáncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Pronóstico , Biopsia Líquida , Sensibilidad y EspecificidadRESUMEN
While 2D metal-organic hybrids have emerged as promising solar absorbers due to their improved moisture stability, their inferior transport properties limit their potential translation into devices. We report a new hybrid containing 2-(2-ammonioethyl)pyridine [(2-AEP)+], forming a 2D hybrid with the composition (2-AEP)2PbI4. The organic bilayer comprises of (2-AEP)+, which is arranged in a face-to-face stacking that promotes π-π interactions between neighboring pyridyl rings. We also demonstrate the structural diversity of 2-(2-aminoethyl)pyridine-based lead iodide hybrids in solution-processed films. This report highlights the importance of solution-processing conditions in trying to obtain single-phase films of hybrids containing dibasic organic species.
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Long-term inhalation of silica dust can cause silicosis, but also may induce autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, anti-histidyl tRNA synthetase antibody (JO-1 antibody) syndrome. These two diseases can be isolated or combined. In this paper, the clinical characteristics of 5 cases of silicosis complicated with connective tissue diseases were analyzed and summarized to strengthen the clinical understanding of silicosis complicated with connective tissue diseases, so as to reduce its misdiagnosis and missed diagnosis, and provide reference for clinicians in diagnosis and treatment.
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Enfermedades del Tejido Conjuntivo , Lupus Eritematoso Sistémico , Esclerodermia Sistémica , Silicosis , Síndrome de Sjögren , Humanos , Enfermedades del Tejido Conjuntivo/complicaciones , Síndrome de Sjögren/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Esclerodermia Sistémica/complicaciones , Silicosis/complicacionesRESUMEN
Neutrophil extracellular traps (NETs) are novel inflammatory cell death in neutrophils. Emerging studies demonstrated NETs contributed to cancer progression and metastases in multiple ways. This study intends to provide a prognostic NETs signature and therapeutic target for lung adenocarcinoma (LUAD) patients. Consensus cluster analysis performed by 38 reported NET-related genes in TCGA-LUAD cohorts. Then, WGCNA network was conducted to investigate characteristics genes in clusters. Seven machine learning algorithms were assessed for training of the model, the optimal model was picked by C-index and 1-, 3-, 5-year ROC value. Then, we constructed a NETs signature to predict the overall survival of LUAD patients. Moreover, multi-omics validation was performed based on NETs signature. Finally, we constructed stable knockdown critical gene LUAD cell lines to verify biological functions of Phospholipid Scramblase 1 (PLSCR1) in vitro and in vivo. Two NETs-related clusters were identified in LUAD patients. Among them, C2 cluster was provided as "hot" tumor phenotype and exhibited a better prognosis. Then, WGCNA network identified 643 characteristic genes in C2 cluster. Then, Coxboost algorithm proved its optimal performance and provided a prognostic NETs signature. Multi-omics revealed that NETs signature was involved in an immunosuppressive microenvironment and predicted immunotherapy efficacy. In vitro and in vivo experiments demonstrated that knockdown of PLSCR1 inhibited tumor growth and EMT ability. Besides, cocultural assay indicated that the knockdown of PLSCR1 impaired the ability of neutrophils to generate NETs. Finally, tissue microarray (TMA) for LUAD patients verified the prognostic value of PLSCR1 expression. In this study, we focus on emerging hot topic NETs in LUAD. We provide a prognostic NETs signature and identify PLSCR1 with multiple roles in LUAD. This work can contribute to risk stratification and screen novel therapeutic targets for LUAD patients.
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Adenocarcinoma del Pulmón , Trampas Extracelulares , Inmunoterapia , Neoplasias Pulmonares , Aprendizaje Automático , Humanos , Trampas Extracelulares/metabolismo , Trampas Extracelulares/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Animales , Ratones , Pronóstico , Neutrófilos/inmunología , Neutrófilos/metabolismo , Proteínas de Transferencia de Fosfolípidos/genética , Proteínas de Transferencia de Fosfolípidos/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral/inmunologíaRESUMEN
Congenital infiltrating lipomatosis of the face (CILF) is a rare congenital disease of the head and neck region. In this study, the cases of 20 patients diagnosed with CILF were reviewed retrospectively to analyse the characteristics of the disease. The symptoms, signs, and clinical progression were investigated. Radiological changes were analysed according to the distribution of the trigeminal nerve. The pathological features of the fatty facial lesions, jaw hyperplasia, and lingual lesions were further identified. All 20 patients demonstrated hemifacial hypertrophy at birth. None had a family history of the disease. Significant radiological features of CILF (prevalence ≥90%) included thickened buccal subcutaneous fat, palatal submucosal fat, and temporal subcutaneous fat, maxillary tuberosity heteroplasia, and fatty infiltration of the masseteric intermuscular space. With regard to the trigeminal nerve, the frontal branch region (CNV1) was rarely affected, while the maxillary (CNV2) and mandibular (CNV3) branch regions showed considerable changes. Pathologically, CILF was observed to be characterized by the infiltration of mature adipose tissue into the adjacent buccal soft tissue, osteal remodelling surrounded by sheets of mature lipocytes and supporting fibrovascular stroma, and lingual hamartoma. In summary, CILF exhibits distinct characteristics that are related to the regions controlled by the maxillary and mandibular branches of the trigeminal nerve, suggesting that CILF may be associated with early neural development.
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Lipomatosis , Humanos , Femenino , Masculino , Estudios Retrospectivos , Lipomatosis/diagnóstico por imagen , Lipomatosis/patología , Lipomatosis/congénito , Niño , Adolescente , Cara/patología , Cara/anomalías , Cara/diagnóstico por imagen , Preescolar , Tomografía Computarizada por Rayos X , Adulto , LactanteRESUMEN
Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage â , 259 patients (64.6%) with stage â ¡, and 68 patients (17.0%) with stage â ¢. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage â , 95 patients (23.7%) in stage â ¡, 206 patients (51.4%) in stage â ¢, and 50 patients (12.5%) in stage â £. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage â ; 62.0 months for stage â ¡, 39.2 months for stage â ¢, and 30.3 months for stage â £; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages â ¢ and â £ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Pronóstico , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
OBJECTIVE: The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). PATIENTS AND METHODS: One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. RESULTS: Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-ß-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). CONCLUSIONS: The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.
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Insuficiencia Cardíaca , Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Hiperuricemia/complicaciones , Ácido Úrico , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Insuficiencia Cardíaca/complicaciones , Tasa de Filtración Glomerular , Albúminas , HemoglobinasRESUMEN
OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.