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Background: The relationship between dietary factors and hernias is currently unclear. Methods: The UK Biobank was used to extract dietary factors that were used as exposures, including intake of alcohol, non-oily fish, beef, fresh fruit, oily fish, salad/raw vegetables, dried fruit, coffee, cereal, salt, tea, water, cooked vegetables, cheese, Lamb/mutton, pork, poultry, processed meat, and bread. The FinnGen biobank was used to obtain GWAS data on hernias as outcomes. The main analysis of this study was performed using the weighted median, MR-Egger, and IVW methods. Cochran's Q test was utilized to assess heterogeneity. To find potential outliers, the MR-PRESSO method was used. Leave-one-out analysis was employed to assess the IVW method's robustness. Results: Alcoholic consumption per week (OR: 0.614; p = 0.00614) reduced the risk of inguinal hernia. Alcohol intake frequency (OR: 1.309; p = 0.0477) increased the risk of ventral hernia (mainly including incisional hernia and parastomal hernia). The intake of non-oily fish (OR: 2.945; p = 0.0214) increased the risk of inguinal hernia. Salt added to food (OR: 1.841; p = 0.00267) increased the risk of umbilical hernia. Cheese intake (OR: 0.434; p = 0.000536) and dried fruit intake (OR: 0.322; p = 0.00716) decreased the risk of ventral hernia, while cooked vegetable intake (OR: 4.475; p = 0.0380) increased the risk of ventral hernia. No causal relationships were found with hernias from other dietary factors. Conclusion: Inguinal, umbilical, and ventral hernias are all related to dietary factors.
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Uncertainty exists regarding the association between diet and acute tubulointerstitial nephritis. Dietary factors served as exposures, including intake of alcohol, beef, non-oily fish, fresh fruit, oily fish, dried fruit, coffee, salad/raw vegetable, cereal, tea, water, salt, cooked vegetable, cheese, poultry, pork, Lamb/mutton, bread, and processed meat were extracted from the UK Biobank. Acute tubulointerstitial nephritis served as the outcome extracted from the FinnGen biobank. The 3 main methods of this analysis were weighted median, inverse-variance-weighted (IVW), and MR-Egger methods. The heterogeneity was measured employing Cochran Q test. The MR-PRESSO method was employed to identify possible outliers. The robustness of the IVW method was evaluated by employing the leave-one-out analysis. According to the IVW method, processed meat intake (ORâ =â 0.485; Pâ =â .00152), non-oily fish intake (ORâ =â 0.396; Pâ =â .0454), oily fish intake (ORâ =â 0.612; Pâ =â .00161), and dried fruit intake (ORâ =â 0.536; Pâ =â .00648) reduced the risk of acute tubulointerstitial nephritis. Other dietary factors were not shown to be causally related to acute tubulointerstitial nephritis. This study revealed that intake of processed meat, non-oily fish, oily fish, and dried fruit all decreased the risk of acute tubulointerstitial nephritis.
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Dieta , Nefritis Intersticial , Humanos , Nefritis Intersticial/epidemiología , Dieta/estadística & datos numéricos , Dieta/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Factores de Riesgo , Reino Unido/epidemiología , Adulto , Anciano , FrutasRESUMEN
Purpose: Conventional cephalomedullary nails (CMNs) are commonly employed for internal fixation in the treatment of reverse obliquity intertrochanteric (ROI) fractures. However, the limited effectiveness of conventional CMNs in addressing ROI fractures results in significant implant-related complications. To address challenges associated with internal fixation, a novel Proximal Femoral Bionic Nail (PFBN) has been developed. Methods: In this study, a finite element model was constructed using a normal femoral specimen, and biomechanical verification was conducted using the GOM non-contact optical strain measurement system. Four intramedullary fixation approaches-PFBN, Proximal Femoral Nail Antirotation InterTan nail (ITN), and Gamma nail (Gamma nail)-were employed to address three variations of ROI fractures (AO/OTA 31-A3). The biomechanical stability of the implant models was evaluated through the calculation of the von Mises stress contact pressure and displacement. Results: Compared to conventional CMNs, the PFBN group demonstrated a 9.36%-59.32% reduction in the maximum VMS at the implant. The A3.3 ROI fracture (75% bone density) was the most unstable type of fracture. In comparison to conventional CMNs, PFBN demonstrated more stable data, including VMS values (implant: 506.33 MPa, proximal fracture fragment: 34.41 MPa), contact pressure (13.28 MPa), and displacement (17.59 mm). Conclusion: Compared to the PFNA, ITN, and GN, the PFBN exhibits improvements in stress concentration, stress conduction, and overall model stability in ROI fractures. The double triangle structure aligns better with the tissue structure and biomechanical properties of the proximal femur. Consequently, the PFBN has significant potential as a new fixation strategy for the clinical treatment of ROI fractures.
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PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.
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Fijación Intramedular de Fracturas , Fracturas de Cadera , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Anciano , Fracturas de Cadera/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Estudios de CohortesRESUMEN
Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.
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Citocromo P-450 CYP1A1 , Ratones Endogámicos C57BL , Ratones Noqueados , Omeprazol , Receptores de Hidrocarburo de Aril , Insuficiencia Renal Crónica , Animales , Humanos , Masculino , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Túbulos Renales/patología , Túbulos Renales/metabolismo , Túbulos Renales/efectos de los fármacos , Omeprazol/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/inducido químicamente , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND: The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated. OBJECTIVES: We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy. MATERIAL AND METHODS: We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS: In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354). CONCLUSION: According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.
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Purpose: Controversy remains regarding the optimal treatment for stage III Osteonecrosis of the femoral head (ONFH). This study presents, for the first time, the precise treatment of stage III ONFH using the "substitute the beam for a pillar" technique and performs a comparative finite element analysis with other hip-preserving procedures. Methods: A formalin-preserved femur of male cadavers was selected to obtain the CT scan data of femur. The proximal femur model was reconstructed and assembled using Mimics 20.0, Geomagic, and UG-NX 12.0 software with four different implant types: simple core decompression, fibula implantation, porous tantalum rod implantation, and partial replacement prosthesis. The finite element simulations were conducted to simulate the normal walking gait, and the stress distribution and displacement data of the femur and the implant model were obtained. Results: The peak von Mises stress of the femoral head and proximal femur in the partial replacement of the femoral head (PRFH) group were 22.8 MPa and 37.4 MPa, respectively, which were 3.1%-38.6% and 12.8%-37.4% lower than those of the other three surgical methods. Conclusion: The PRFH group exhibits better mechanical performance, reducing stress and displacement in the ONFH area, thus maintaining femoral head stability. Among the four hip-preserving approaches, from a biomechanical perspective, PRFH offers a new option for treating ONFH.
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PURPOSE: This study aimed to investigate the mid- to long-term benefits of high tibial osteotomy in advanced age patients. METHODS: This retrospective study was conducted in our hospital from January 2017 to January 2021 with data prospectively collected, 47 patients with knee osteoarthritis who over 65 years old were included, and a 1:1 propensity score (PS) of patients < 65 years were matched according to gender, body mass index, and side. Patient demographics, intraooperative and postoperative variables, and patient self-reported outcomes were compared. A generalized linear model was used to screen possible risk factors. RESULTS: A total of 94 consecutive patients were included; the average age of advanced age group was 69.47 + 4.26 years and 57.87 + 5.51 years in the younger group. There were no statistically difference in K-L grade, smoke, drink, comorbidity, ASA, blood loss, operative duration, length of stay, surgical site infection, hinge fracture, DVT, and preooperative and postoperative aFTA; significantly statistical difference of the eFI was found between two groups (P < 0.05). Two groups had comparable VAS and MOMAC scores at one year postoperatively (P > 0.05), while the younger group had lower VAS and WOMAC scores than the advanced age group at the end of follow-up (P < 0.05). Generalized linear model showed both age and eFI were associated with WOMAC scores; there was a statistically significant difference in the effect of eFI on WOMAC scores at different ages (P > 0.05). CONCLUSIONS: Compared with younger patients, advanced age patients have similar short-term benefits, but less long-term benefits. We recommend that patients proposed for HTO be discriminated by eFI, and patients with higher scores should be cautiously selected.
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Osteoartritis de la Rodilla , Osteotomía , Medición de Resultados Informados por el Paciente , Tibia , Humanos , Masculino , Femenino , Anciano , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos , Osteotomía/métodos , Osteotomía/efectos adversos , Persona de Mediana Edad , Tibia/cirugía , Autoinforme , Factores de Edad , Resultado del TratamientoRESUMEN
PURPOSE: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. METHODS: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). CONCLUSIONS: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.
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Glomerulonefritis por IGA , Fallo Renal Crónico , Humanos , Glomerulonefritis por IGA/complicaciones , Estudios Retrospectivos , Progresión de la Enfermedad , Riñón , Fallo Renal Crónico/complicaciones , Tasa de Filtración Glomerular , FósforoRESUMEN
BACKGROUND: Dynamic hip screws (DHS) and proximal femoral nail anti-rotation (PFNA) were recommended for basicervical femoral neck fracture (BFNF), however, with high rate of postoperative femoral neck shortening. The proximal femoral bionic nail (PFBN) was designed to decrease the postoperative complications associated with DHS and PFNA. The aim of this study is to compare the biomechanical characters of DHS, PFNA, and PFBN for fixation of BFNF. METHODS: Using finite element analysis, we created a three-dimensional model of the BFNF for this investigation. The PFBN group, the PFNA group and the DHS + DS group were our three test groups. For each fracture group, the von Mises stress and displacements of the femur and internal fixation components were measured under 2100 N axial loads. RESULTS: The PFBN group demonstrated the lowest stress on the implants, significantly lower than the PFNA and DHS + DS groups. In terms of stress on the implants, the PFBN group exhibited the best performance, with the lowest stress concentration at 112.0 MPa, followed by the PFNA group at 124.8 MPa and the DHS + DS group at 149.8 MPa. The PFBA group demonstrated the smallest displacement at the fracture interface, measuring 0.21 mm, coupled with a fracture interface pressure of 17.41 MPa, signifying excellent stability. CONCLUSIONS: Compared with DHS and PFNA, PFBN has advantages in stress distribution and biological stability. We believe the concept of triangle fixation will be helpful to reduce femoral neck shortening associated with DHS and PFNA and thus improve the prognosis of BFNF.
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Fracturas del Cuello Femoral , Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Fracturas de Cadera/cirugía , Clavos Ortopédicos , Tornillos Óseos , Biónica , Análisis de Elementos Finitos , Fracturas del Cuello Femoral/cirugía , Fémur/cirugía , Fijación Interna de Fracturas/métodos , Fijación Intramedular de Fracturas/métodosRESUMEN
There are few studies on risk factors for frozen shoulder, and even fewer Mendelian randomization (MR) studies on frozen shoulder. Therefore, we conducted a two-sample MR study to explore whether socioeconomic status (years of schooling, average total household income before tax), obesity (body mass index and waist circumference), individual behaviors (smoking initiation, alcohol intake frequency, coffee intake, nonoily fish intake, tea intake, beef intake, bread intake, cheese intake, oily fish intake, and fresh fruit intake), and diabetes (type 1 and type 2 diabetes) are associated with frozen shoulder. The exposure datasets and the outcome dataset were extracted from the MRC Integrative Epidemiology Unit at the University of Bristol Open genome-wide association studies project (https://gwas.mrcieu.ac.uk/). We conducted MR analyses using the inverse variance weighted (primary method), MR-Egger, and weighted median methods and conducted heterogeneity and pleiotropy analyses. Type 1 diabetes (OR: 1.103; 95% CI: 1.053-1.156; Pâ =â .0000410) was associated with an increased risk of frozen shoulder. Cheese intake (OR: 0.490; 95% CI: 0.267-0.899; Pâ =â .0213), non-oily fish intake (OR: 0.0993; 95% CI: 0.0220-0.448; Pâ =â .00267), years of schooling (OR: 0.453; 95% CI: 0.349-0.588; Pâ =â .00000000277), and average total household income before tax (OR: 0.434; 95% CI: 0.253-0.743; Pâ =â .00236) were discovered as protective factors. No horizontal pleiotropy was found in all analyzes we performed (Pâ >â .05). Our study indicated that type 1 diabetes was a risk factor for frozen shoulder while cheese intake, non-oily fish intake, years of schooling, and average total household income before tax were considered as protective factors for frozen shoulder.
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Bursitis , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/epidemiología , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Obesidad/epidemiología , Humanos , DietaRESUMEN
Background: No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases. Methods: BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method. Results: This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200). Conclusion: This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.
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Bronquiectasia , Carcinoma de Pulmón de Células no Pequeñas , Laringitis , Neoplasias Pulmonares , Infecciones del Sistema Respiratorio , Humanos , Análisis de la Aleatorización Mendeliana , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
Lymphatic metastasis (LM) is a significant mechanism for the spread of esophageal cancer (EC) and predicts the poor prognosis of EC patients. This research aimed to assess the survival of patients with LM from EC by developing a nomogram. In this retrospective study, EC patients with LM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were divided by year of diagnosis into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were employed to determine the prognostic factors of LM, and a nomogram was constructed. The discrimination and calibration of the nomogram were compared by the C-index, area under the curve value, and calibration plots. The survival time difference was compared using Kaplan-Meier curves. A total of 11,695 patients with EC were included in this analysis. LM occurred in 56.5% (n = 6614) of EC patients. In the post-propensity score matching (PSM) cohort, patients with LM had significantly lower median overall survival (OS) than those without LM. Multivariate Cox regression was used to identify the eleven independent prognostic factors. The C-index was 0.709 in both the training and test sets, revealing the good predictive performance of the nomogram. Based on the results of calibration plots and the receiver operating characteristic (ROC) curve, we demonstrate the great performance of the prognostic model. The survival time of EC patients with LM was remarkably lower than that of EC patients without LM. The nomogram model established in this study can precisely predict the survival of EC patients with LM.
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Neoplasias Esofágicas , Nomogramas , Humanos , Metástasis Linfática , Estudios Retrospectivos , Calibración , Programa de VERFRESUMEN
The liver is one of the most ordinary metastatic sites of gastroesophageal junction adenocarcinoma and significantly affects its prognosis. Therefore, this study tried to construct a nomogram that can be applied to predict the likelihood of liver metastases from gastroesophageal junction adenocarcinoma. 3001 eligible patients diagnosed with gastroesophageal junction adenocarcinoma between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were involved in the analysis. Patients were randomly divided into a training cohort and an internal validation cohort using R software, with an allocation ratio of 7:3. According to the consequences of univariate and multivariate logistic regression, we constructed a nomogram for predicting the risk of liver metastases. The discrimination and calibration ability of the nomogram was appraised by the C-index, ROC curve, calibration plots, and decision curve analysis (DCA). We also used Kaplan-Meier survival curves to compare differences in overall survival in patients with gastroesophageal junction adenocarcinoma with and without liver metastases. Liver metastases developed in 281 of 3001 eligible patients. The overall survival of patients with gastroesophageal junction adenocarcinoma with liver metastases before and after propensity score matching (PSM) was obviously lower than that of patients without liver metastases. Six risk factors were finally recognized by multivariate logistic regression, and a nomogram was constructed. The C-index was 0.816 in the training cohort and 0.771 in the validation cohort, demonstrating the good predictive capacity of the nomogram. The ROC curve, calibration curve, and decision curve analysis further demonstrated the good performance of the predictive model. The nomogram can accurately predict the likelihood of liver metastases in gastroesophageal junction adenocarcinoma patients.
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Adenocarcinoma , Neoplasias Hepáticas , Humanos , Nomogramas , Puntaje de Propensión , Unión EsofagogástricaRESUMEN
Introduction: IgA nephropathy (IgAN) is the most common disease leading to end-stage renal disease, and tubular fibrosis represents an important risk factor for disease progression. However, research on early molecular diagnostic indicators of tubular fibrosis and the mechanisms underlying disease progression is still lacking. Methods: The GSE93798 dataset was downloaded from the GEO database. DEGs were screened and analyzed for GO and KEGG enrichment in IgAN. The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms were applied to screen for hub secretory genes. The expression and diagnostic efficacy of hub genes were confirmed by the GSE35487 dataset. ELISA was applied to detect the expression of APOC1 in serum. The expression and localization of hub genes in IgAN were verified by the expression of IHC and IF in human kidney tissues, and the correlation of expression with clinical data was verified in the Nephroseq database. Finally, cellular experiments clarified the role of hub genes in the signaling pathway. Results: A total of 339 DEGs were identified in IgAN, of which 237 were upregulated and 102 downregulated. The KEGG signaling pathway is enriched in the ECM-receptor interaction and AGE-RAGE signaling pathway. APOC1, ALB, CCL8, CXCL2, SRPX2, and TGFBI identified six hub secretory genes using the LASSO and SVM-RFE algorithms. In vivo and in vitro experiments demonstrated that APOC1 expression was elevated in IgAN. The serum concentration of APOC1 was 1.232 ± 0.1812 µg/ml in IgAN patients, whereas it was 0.3956 ± 0.1233 µg/ml in healthy individuals. APOC1 exhibited high diagnostic efficacy for IgAN (AUC of 99.091%, specificity of 95.455%, and sensitivity of 99.141%) in the GSE93798 dataset. APOC1 expression negatively correlated with eGFR (R 2 = 0.2285, p = 0.0385) and positively correlated with serum creatinine (R 2 = 0.41, p = 0.000567) in IgAN. APOC1 exacerbated renal fibrosis, possibly in part by activating the NF-κB pathway in IgAN. Conclusion: APOC1 was identified as the core secretory gene of IgAN, which was closely associated with blood creatinine and eGFR and had significant efficacy in the diagnosis of IgAN. Mechanistic studies revealed that the knockdown of APOC1 could improve IgAN renal fibrosis by inhibiting the NF pathway, which may be a potential therapeutic target for improving renal fibrosis in IgAN.
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Background: Previous research has found a link between dietary factors and asthma. However, few studies have analyzed the relationship between dietary factors and asthma using Mendelian randomization. Methods: The IEU Open GWAS project (https://gwas.mrcieu.ac.uk/) was the source of exposure and outcome datasets. The exposure datasets included Alcoholic drinks per week, Alcohol intake frequency, Processed meat intake, Poultry intake, Beef intake, Non-oily fish intake, Oily fish intake, Pork intake, Lamb/mutton intake, Bread intake, Cheese intake, Cooked vegetable intake, Tea intake, Fresh fruit intake, Cereal intake, Salad/raw vegetable intake, Coffee intake, and Dried fruit intake. The weighted median, MR-Egger, and Inverse Variance Weighted methods were used as the main methods of Mendelian randomization analysis. Heterogeneity and pleiotropic analysis were performed to ensure the accuracy of the results. Results: Alcohol intake frequency (after removing outliers OR: 1.217; 95% CI: 1.048-1.413; p=0.00993) was related to an increased risk of Asthma. Fresh fruit intake (OR: 0.489; 95% CI: 0.320-0.748; p=0.000954) and Dried fruit intake (after removing outliers OR: 0.482; 95% CI: 0.325-0.717; p= 0.000312) were discovered as protective factors. Other dietary intakes found no causal relationship with asthma. Conclusion: This study found that dried fruit intake and fresh fruit intake were associated with a reduced risk of asthma, and alcohol intake frequency was associated with an increased risk of asthma. This study also found that other factors included in this study were not associated with asthma.
Asunto(s)
Asma , Análisis de la Aleatorización Mendeliana , Bovinos , Animales , Ovinos , Ingestión de Alimentos , Consumo de Bebidas Alcohólicas/efectos adversos , CausalidadRESUMEN
The principal treatment modalities for esophageal cancer are radiation, chemotherapy and surgery or a combination of them. In some sense, technological advances have tremendously heightened patients' survival rates. Nevertheless, the debate on the prognostic value of postoperative radiotherapy (PORT) has never ceased. On that account, this study made an effort to probe deep into the effects of PORT and surgery on the prognosis of stage III esophageal cancer. Our study included patients diagnosed with stage III esophageal cancer between 2004 and 2015 through the Surveillance, Epidemiology, and End Results (SEER) program. We performed propensity score matching (PSM) on the basis of whether surgery was carried out and whether PORT conducted. We identified the independent risk factors by multivariate Cox regression and constructed a nomogram model. In this research, we included 3940 patients, and the median follow-up is 14 months: 1932 cases without surgery; 2008 cases with surgery, and 322 cases of them underwent PORT. In the postPSM patient cohort, patients who underwent surgery had a median overall survival rate (OS) of 19.0 (95% confidence interval [CI] 17.2-20.8) and a median cancer-specific survival rate (CSS) of 23.0 (95% CI 20.6-25.3) months, which were remarkably higher than those without surgery (P < .001). The OSï¼P < .05ï¼and CSSï¼P < .05ï¼of the patients who underwent PORT were lower than those who did not. Similar results were obtained in the groups of N0 and N1. This study revealed surgery can heighten patients' survival rate, while PORT could not elevate patients' survival rate in stage III esophageal cancer patients.