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1.
PLoS One ; 19(7): e0306258, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39042622

RESUMEN

BACKGROUND: Surgical aortic valve replacement (SAVR) currently stands as a primary surgical intervention for addressing aortic valve disease in patients. This retrospective study focused on the role of the red blood cell distribution width (RDW) in predicting adverse outcomes among SAVR patients. METHODS: The subjects for this study were exclusively derived from the Medical Information Mart for Intensive Care database (MIMIC IV 2.0). Kaplan‒Meier (K-M) curves and Cox proportional hazards regression models were employed to assess the correlation between RDW, one-year mortality, and postoperative atrial fibrillation (POAF). The smooth-fitting curves were used to observe the relative risk (RR) of RDW in one-year mortality and POAF. Furthermore, time-dependent receiver operating characteristic (ROC) curves, the continuous-net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed for comprehensive assessment of the prognostic value of RDW. RESULTS: Analysis of RDW revealed a distinctive inverted U-shaped relationship with one-year mortality, while its association with POAF appeared nearly linear. Cox multiple regression models showed that RDW > 14.35%, along with preoperative potassium concentration and perioperative red blood cell transfusion, were significantly linked to one-year mortality (K-M curves, log-rank P < 0.01). Additionally, RDW was associated with both POAF and prolonged hospital stays (P < 0.05). There was no significant difference in length of stay in ICU. Notably, the inclusion of RDW in the predictive models substantially enhanced its performance. This was evidenced by the time-dependent ROC curve (AUC = 0.829), NRI (P< 0.05), IDI (P< 0.05), and K-M curves (log-rank P< 0.01). CONCLUSIONS: RDW serves as a robust prognostic indicator for SAVR patients, offering a novel means of anticipating adverse postoperative events.


Asunto(s)
Válvula Aórtica , Índices de Eritrocitos , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Femenino , Anciano , Pronóstico , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Estudios Retrospectivos , Persona de Mediana Edad , Válvula Aórtica/cirugía , Bases de Datos Factuales , Fibrilación Atrial/cirugía , Fibrilación Atrial/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Curva ROC , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier
2.
BMC Oral Health ; 24(1): 796, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010031

RESUMEN

BACKGROUND: The assessment of hard and soft tissue at edentulous sites is important for subsequent implant treatment design. The aim of the present study was to explore the associations between the keratinized mucosa width (KMW) and the underlying alveolar bone dimensions at partial edentulous molar sites. METHODS: In this retrospective study, a total of 110 patients with at least one missing molar were selected. The buccal KMW of the edentulous molar sites was evaluated. Cone-beam computed tomography scans were collected, and the height discrepancy between the alveolar crest and the buccal bone plate (HC-B) as well as the alveolar bone height (ABH) were measured. The KMW was compared among the HC-B and ABH groups at both maxillary and mandibular sites. Linear regression and generalized estimation equations (GEEs) were used to explore the associations between the KMW and alveolar bone dimensions at α = 0.05. RESULTS: Among the 110 patients, 158 edentulous molar sites were analyzed. The average HC-B and ABH were significantly lower at the maxillary sites (1.26 ± 1.62 mm, 11.62 ± 3.94 mm) than at the mandibular sites (3.67 ± 2.85 mm, 14.91 ± 3.01 mm, p < 0.001). The KMW was significantly lower at sites with HC-B > 2 mm than at sites with HC-B ≤ 2 mm both in the maxilla and mandible (p < 0.001). No significant differences were found between the KMW at sites with ABH < 10 mm and sites with ABH ≥ 10 mm (p > 0.05). Linear regression and GEEs analyses revealed that the HC-B was significantly associated with the KMW (B = -0.339, p < 0.001), while the association between the KMW and the ABH was not statistically significant (B = -0.046, p = 0.352). CONCLUSIONS: The buccal KMW at edentulous molar sites was significantly associated with the HC-B. Alveolar ridges presenting with a sloped configuration were more prone to possess a narrower band of keratinized mucosa. Both hard and soft tissue augmentation should be considered for implant treatment at these sites. The correlations of dynamic changes between the KMW and alveolar bone dimensions after tooth extraction should be further investigated.


Asunto(s)
Proceso Alveolar , Tomografía Computarizada de Haz Cónico , Diente Molar , Humanos , Estudios Retrospectivos , Femenino , Masculino , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/patología , Persona de Mediana Edad , Estudios Transversales , Diente Molar/diagnóstico por imagen , Arcada Parcialmente Edéntula/diagnóstico por imagen , Arcada Parcialmente Edéntula/patología , Adulto , Anciano , Mucosa Bucal/diagnóstico por imagen , Mucosa Bucal/patología , Mandíbula/diagnóstico por imagen , Mandíbula/patología , Maxilar/diagnóstico por imagen , Maxilar/patología
3.
J Clin Periodontol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043452

RESUMEN

AIM: This study aimed to assess hard and soft tissue contour changes following micro crestal flap-alveolar ridge preservation (MCF-ARP) and natural healing (NH) in periodontally compromised molar extraction sites and to analyse the feasibility and need for bone augmentation during implant therapy. MATERIALS AND METHODS: Fifty-six patients with 70 sites were randomized into two groups at the site level (35 sites from 31 patients in the test group and 35 sites from 29 patients in the control group). Among whom, four patients contributed one tooth to the control group and one tooth to the test group. Hard tissue indicators were measured using cone beam computed tomography performed before tooth extraction and 6 months after surgery. Soft tissue contour changes were assessed using intraoral scanning performed before and immediately after surgery and also 2 weeks and 1, 3 and 6 months after surgery. RESULTS: Six months after surgery, the MCF-ARP group showed less resorption in buccal bone height (p = .032) and greater augmentation in central bone height (p = .001) and ridge width (p = .009). The mean, vertical and horizontal collapse of buccal soft tissue contour in the MCF-ARP group were 0.95 mm (p = .010), 0.61 mm (p = .019) and 0.56 mm (p = .013) less than that in the NH group, respectively. There were significantly (p = .007) fewer sites in the MCF-ARP group than in the NH group (0% vs. 26.7%) for staged bone augmentation and more sites that could be treated with simple implant procedure in the MCF-ARP group than in the NH group (71.9% vs. 56.6%). CONCLUSIONS: Compared with NH, MCF-ARP reduced bone resorption in periodontally compromised molar extraction sites and maintained the buccal soft tissue contour. MCF-ARP reduces the need for complex bone augmentation procedures in implant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on 4 February 2022, Version 1.0.

4.
PLoS One ; 19(4): e0298470, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38683794

RESUMEN

BACKGROUND: There are various therapeutic methods for treating stage IA (T1N0M0) non-small cell lung cancer (NSCLC), but no studies have systematically assessed multiple treatments to determine the most effective therapy. METHODS: Stage IA NSCLC patient data collected between 2004 and 2018 were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Treatment modalities included observation, chemotherapy alone (CA), radiation alone (RA), radiation+chemotherapy (RC), surgery alone (SA), surgery+chemotherapy (SC), surgery+radiation (SR) and surgery+radiation+chemotherapy (SRC). Comparisons were made of overall survival (OS) and lung cancer-specific survival (LCSS) among patients based on different therapeutic methods by survival analysis. RESULTS: Ultimately, 89147 patients with stage IA NSCLC between 2004 and 2018 were enrolled in this study. The order of multiple treatment modalities based on the hazard ratio (HR) for OS for the entire cohort revealed the following results: SA (HR: 0.20), SC (HR: 0.25), SR (HR: 0.42), SRC (HR: 0.46), RA (HR: 0.56), RC (HR: 0.72), CA (HR: 0.91) (P<0.001), and observation (HR: Ref). The SA group had the best OS and LCSS, and similar results were found in most subgroup analyses (all P<0.001). The order of surgical modalities based on the HR for OS for the entire cohort revealed the following results: lobectomy (HR: 0.32), segmentectomy (HR: 0.41), wedge resection (HR: 0.52) and local tumor destruction (HR: Ref). Lobectomy had the best effects on OS and LCSS, and similar results were found in all subgroup analyses (all P<0.001). CONCLUSION: SA appeared to be the optimal treatment modality for patients with stage IA NSCLC, and lobectomy was associated with the best prognosis. There may be some indication and selection bias in our study, and the results of this study should be confirmed in a prospective study.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Femenino , Masculino , Anciano , Persona de Mediana Edad , Terapia Combinada , Adulto , Anciano de 80 o más Años , Análisis de Supervivencia
5.
Front Oncol ; 14: 1294383, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444672

RESUMEN

Background: As lung squamous cell carcinoma (LUSC) patients are at increased risk of developing a second primary cancer, this complicates the patient's condition and thus makes prognostic assessment more difficult, posing a significant prognostic challenge for clinicians. Our goal was to assess the prognosis of LUSC patients with a second primary tumor, and provide insights into appropriate therapy and monitoring strategies. Methods: Data was obtained for LUSC patients from the Surveillance, Epidemiology, and End Results (SEER) database. The LUSC patients were divided into three groups (LS-SPM, OT-LUSC and LUSC-only). Univariate and stratified analyses were performed for the baseline and clinical characteristics of the participants. Multiple regression and Kaplan-Meier survival analyses were also performed, followed by a final life table analysis. Results: In our sample of 101,626 patients, the HR for OS in the LS-SPM group was 0.40 in univariate analysis. Kaplan-Meier survival curves showed that LS-SPM patients had considerably longer lifespans compared to the other groups. The LS-SPM patients had median and mean survival times of 64 months and 89.11 months. Unadjusted and adjusted multiple regression analyses showed that LS-SPM patients had a superior survival compared to LUSC-only and OT-LUSC groups. Conclusion: LS-SPM patients have a good prognosis with aggressive therapy and immune monitoring. The present study offers novel insights into the pathophysiological causes and treatments for LS-SPM.

6.
Angiology ; : 33197241227275, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212979

RESUMEN

There are numerous causes of abdominal aortic calcification (AAC), among which the relationship between serum uric acid and AAC still needs to be investigated further. The aim of this research was to ascertain whether serum uric acid is correlated with AAC. Our study included 3007 participants. We described the study population characteristics and utilized univariate analysis, stratified analysis, multiple equation regression analysis, smoothed curve fitting, and threshold effects analysis. AAC Total 24 score is used to reflect the range of aortic calcification at each vertebral level. As serum uric acid increased, the AAC Total 24 score first decreased and then increased. The fold point is located when serum uric is at 3.5 mg/dL. After adjusting for 16 covariates, the beta values for the groups with moderate and high serum uric acid levels were 0.34 and 0.53, respectively, compared with the low serum uric acid tertile group (P < .05). Our research indicates a negative correlation between serum acid level and AAC when serum uric acid <3.5 mg/dl, but it is positively correlated with the formation of AAC when serum uric acid >3.5 mg/dl.

7.
Clin Oral Implants Res ; 35(1): 131-139, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37962104

RESUMEN

OBJECTIVE: This study aimed to compare hard- and soft-tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. MATERIALS AND METHODS: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. RESULTS: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3 , whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3 . Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. CONCLUSIONS: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR-ONN-16009433).


Asunto(s)
Aumento de la Cresta Alveolar , Diente Molar , Aumento de la Cresta Alveolar/métodos , Colágeno/uso terapéutico , Diente Molar/cirugía , Extracción Dental , Alveolo Dental/cirugía , Humanos
8.
Environ Sci Pollut Res Int ; 31(4): 6527-6542, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38151562

RESUMEN

Microplastics (MPs) are known to cause liver toxicity as they can spread through the food chain. Most researches on their toxicity have focused on individual organs, neglecting the crucial "gut-liver axis"-a bidirectional communication pathway between the gut and liver. Probiotics have shown promise in modulating the effects of environmental pollutants. In this study, we exposed mice to Lactobacillus rhamnosus GG (LGG, 100 mg/kg b.w./d) and/or polystyrene microplastics (PS-MPs, 5 mg/kg b.w./d) for 28 d via gavage to investigate how probiotics influence live toxicity through the gut-liver axis. Our results demonstrated that PS-MPs induced liver inflammation (increased IL-6 and TNF-α) and disrupted lipid metabolism. However, when combined with LGG, these effects were alleviated. LGG also improved colon health, rectifying ciliary defects and abnormal mucus secretion caused by PS-MPs. Furthermore, LGG improved gut microbiota dysbiosis induced by PS-MPs. Metabolomics and gene expression analysis (Cyp7a1 and Cyp7b1) indicated that LGG modulated bile acid metabolism. In summary, LGG appears to protect the liver by maintaining gut homeostasis, enhancing gut barrier integrity, and reducing the liver inflammation. These findings confirm the potential of LGG to modulate liver toxicity caused by PS-MPs through the gut-liver axis, offering insights into probiotics' application for environmental pollutant detoxification.


Asunto(s)
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Probióticos , Ratones , Animales , Poliestirenos , Microplásticos , Plásticos , Hígado , Inflamación
9.
J Clin Periodontol ; 51(3): 354-364, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38111083

RESUMEN

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.


Asunto(s)
Pérdida de Hueso Alveolar , Resorción Ósea , Implantes Dentales , Periimplantitis , Animales , Humanos , Ratones , Pérdida de Hueso Alveolar/tratamiento farmacológico , Citocinas , Inflamación , Osteoclastos , Periimplantitis/tratamiento farmacológico , Receptores CCR2
10.
Medicine (Baltimore) ; 102(50): e36449, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38115354

RESUMEN

Pulmonary function, one of the main indicators of respiratory system assessment, is difficult to measure in specific cases. The study investigated the association between serum iron levels and pulmonary function. The cross-sectional study was conducted using data from 5319 participants from the 2010-2012 National Health and Nutrition Examination Survey. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow from 25% to 75% of FVC were used as indicators of pulmonary function to analyze the relationship of serum iron and pulmonary function. Univariate and stratified analyses, multiple equation regression analysis, smoothed curve fitting analysis, and threshold effect analysis were performed to explore the relationship between pulmonary function and serum iron concentrations. Threshold effect analysis revealed a nonlinear relationship between serum iron levels and FVC, as well as FEV1, with inflection points observed at 8.1 (µmol/L) and 8.4 (µmol/L), respectively. When serum iron concentrations fell below the inflection point, there was no statistically significant relationship between serum iron and FVC (P = .065) or FEV1 (P = .095) (P > .005). However, when serum iron concentrations exceeded the inflection point, both FVC (ß = 6.87; 95% confidence interval [CI] = 3.95, 9.79; P < .0001) and FEV1 (ß = 7.09; 95% CI = 4.54, 9.64; P < .0001) exhibited a positive correlation with increasing serum iron levels. Additionally, forced expiratory flow from 25% to 75% of FVC (mL/s) demonstrated a positive association with serum iron (ß = 6.72; 95% CI = 2.30, 11.13; P = .0029). Serum iron level was positively correlated with pulmonary function within a certain range of serum iron concentration. Serum iron level may be a protective factor for pulmonary function.


Asunto(s)
Hierro , Pulmón , Humanos , Estudios Transversales , Encuestas Nutricionales , Volumen Espiratorio Forzado , Capacidad Vital
11.
Sci Rep ; 13(1): 19151, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932413

RESUMEN

Immunogenic cell death (ICD) has been demonstrated to activate T cells to kill tumor cells, which is closely related to tumor development, and long noncoding RNAs (lncRNAs) are also involved. However, it is not known whether ICD-related lncRNAs are associated with the development of lung adenocarcinoma (LUAD). We downloaded ICD-related genes from GeneCards and the transcriptome statistics of LUAD patients from The Cancer Genome Atlas (TCGA) and subsequently developed and verified a predictive model. A successful model was used together with other clinical features to construct a nomogram for predicting patient survival. To further study the mechanism of tumor action and to guide therapy, we performed enrichment analysis, tumor microenvironment analysis, somatic mutation analysis, drug sensitivity analysis and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Nine ICD-related lncRNAs with significant prognostic relevance were selected for model construction. Survival analysis demonstrated that overall survival was substantially shorter in the high-risk group than in the low-risk group (P < 0.001). This model was predictive of prognosis across all clinical subgroups. Cox regression analysis further supported the independent prediction ability of the model. Ultimately, a nomogram depending on stage and risk score was created and showed a better predictive performance than the nomogram without the risk score. Through enrichment analysis, the enriched pathways in the high-risk group were found to be primarily associated with metabolism and DNA replication. Tumor microenvironment analysis suggested that the immune cell concentration was lower in the high-risk group. Somatic mutation analysis revealed that the high-risk group contained more tumor mutations (P = 0.00018). Tumor immune dysfunction and exclusion scores exhibited greater sensitivity to immunotherapy in the high-risk group (P < 0.001). Drug sensitivity analysis suggested that the predictive model can also be applied to the choice of chemotherapy drugs. RT-qPCR analysis also validated the accuracy of the constructed model based on nine ICD-related lncRNAs. The prognostic model constructed based on the nine ICD-related lncRNAs showed good application value in assessing prognosis and guiding clinical therapy.


Asunto(s)
Adenocarcinoma , ARN Largo no Codificante , Humanos , Pronóstico , Muerte Celular Inmunogénica , Pulmón , Microambiente Tumoral
12.
Medicine (Baltimore) ; 102(40): e35341, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37800757

RESUMEN

A growing number of studies have found that the lymph node ratio (LNR) is an important indicator of prognosis in non-small-cell lung cancer (NSCLC). Impact analysis for LNR was performed for survival in patients undergoing surgery for stage III NSCLC compared to the surveillance, epidemiology and end results databank. Clinicopathological variables, such as cancer-specific survival (CSS), were taken from the surveillance epidemiology and end result databank of stage III NSCLC patients who underwent surgery, and the LNR threshold stratification of NSCLC patients was computed by X-tile. CSS was assessed by the Kaplan-Meier method with CSS-independent risk factors calculated by multivariate Cox regression analysis. In total, 7011 lung cancer patients were included. Multifactorial analysis showed that LNR and positive node category had predictive value for stage III NSCLC. In patients with stage IIIA NSCLC, Kaplan-Meier analysis demonstrated that patients with T1-2N2 stage had clearly superior CSS than those with T3-4N1 stage (P < .001), which conflicted with the results from the assessment of primary tumor, lymph nodes, and metastasis/N stage. The cutoff values for LNR were 0.31 and 0.59. Kaplan-Meier analysis demonstrated that the CSS was substantially better in patients with LNR-low than in those with LNR-medium or LNR-high (P < .001), which was also proven by multivariate competing risk regression. Subgroup analysis suggested that the survival advantage of a lower LNR was achieved in all subgroups (sex, race, etc). In stage III NSCLC, the LNR is a valuable factor for assessing prognosis, in which a higher LNR indicates a worse prognosis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Pronóstico , Neoplasias Pulmonares/patología , Índice Ganglionar , Estudios Retrospectivos , Estadificación de Neoplasias , Metástasis Linfática/patología , Ganglios Linfáticos/patología
13.
Medicine (Baltimore) ; 102(34): e34545, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37653755

RESUMEN

RATIONALE: With the advancement of targeted therapies, epidermal growth factor receptor tyrosine kinase inhibitors have become the preferred initial treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is effective against exon 19 and 21 mutations as well as the T790M mutation. It has been approved by both the food and drug administration and European Medicines Agency for the treatment of non-small cell lung cancer patients with locally advanced or metastatic EGFR-mutated tumors, including those who have acquired T790M mutations. PATIENT CONCERNS: To evaluate the effectiveness of osimertinib in treating patients with EGFR-mutated advanced lung adenocarcinoma and bone metastases, we present the treatment outcomes of 3 patients with EGFR 19 deletion-mutated advanced lung adenocarcinoma and bone metastases who received osimertinib treatment in recent years. All 3 cases involved elderly female patients, aged 62, 62, and 54, respectively. DIAGNOSES: All 3 cases exhibited a diagnosis of pulmonary adenocarcinoma accompanied by osseous metastases, with genetic testing revealing the presence of an EGFR 19del mutation. INTERVENTIONS: In the first case, following 17 months of gefitinib therapy, disease progression prompted a switch to osimertinib treatment. In the second case, bone metastases were detected after 20 months of pemetrexed-carboplatin chemotherapy, leading to a transition to osimertinib therapy. In the third case, after 11 months of erlotinib treatment, bone metastases were identified. Subsequent interventions, including radiation therapy, pemetrexed-carboplatin chemotherapy, pemetrexed-bevacizumab maintenance therapy, and docetaxel chemotherapy, failed to arrest the progression of bone metastases. As a result, a combination of osimertinib and anlotinib targeted therapy was administered. OUTCOMES: All 3 patients experienced relatively good and favorable survival outcomes, with a progression-free survival of 22.7 months, 12 months, and 17.7 months, respectively. LESSONS: These cases suggest that osimertinib is a promising treatment option for patients with EGFR 19 deletion-mutated lung adenocarcinoma and bone metastases, although further clinical studies are needed to confirm its efficacy.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Óseas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Femenino , Humanos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Carboplatino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Pemetrexed , Inhibidores de Proteínas Quinasas/uso terapéutico , Estados Unidos , /uso terapéutico
14.
J Clin Periodontol ; 50(12): 1644-1657, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37697486

RESUMEN

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.


Asunto(s)
Quimiocina CCL2 , Periodontitis , Animales , Humanos , Ratones , Quimiocina CCL2/metabolismo , Quimiocinas , Ligandos , Ratones Endogámicos C57BL , Periodontitis/prevención & control , Microtomografía por Rayos X
15.
Clin Respir J ; 17(11): 1145-1157, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37723579

RESUMEN

BACKGROUND: Lymph node (LN) metastasis is crucial in non-small cell lung cancer (NSCLC) prognosis and treatment, but the TNM system lacks LN quantity consideration. Our goal is to investigate the role of positive LNs (nPLN) and positive LN rate (LNR) in overall survival (OS) and assess whether they offer higher value in prognostic assessment of NSCLC than N-stage. METHODS: Patients were stratified into four subgroups using X-Tile software. Statistical analysis was conducted using the Kaplan-Meier method, univariate analysis, and multivariate Cox regression analysis. Model performance was evaluated using the Harrell consistency index (C-index), Akaike information criterion (AIC), and Bayesian information criterion (BIC). The prognostic performance of the nodal classification was validated using overall survival as the endpoint. RESULTS: The survival curves demonstrate distinct disparities between each nPLN and LNR category. A pronounced trend toward deteriorating overall survival from N-PLN 1 to N-PLN 2+ was observed across all tumor size categories. However, the differences between each LNR category were only significant for tumors ≤3 cm and 5-7 cm. Notably, both nPLN and LNR classifications displayed a higher C-index, lower AIC, and lower BIC compared with the N staging. Furthermore, the LNR classification provided superior prognostic stratification when compared with the nPLN classification. CONCLUSIONS: Our results demonstrate that nPLN and LNR classifications may offer improved prognostic performance compared with the current N classification for LN-positive NSCLC patients. Nonetheless, more studies are needed to assess the feasibility of incorporating these classifications into the next TNM staging system.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Ganglios Linfáticos/patología , Neoplasias Pulmonares/patología , Teorema de Bayes , Escisión del Ganglio Linfático , Pronóstico , Estadificación de Neoplasias , Metástasis Linfática/patología , Estudios Retrospectivos
18.
Sci China Life Sci ; 66(12): 2711-2754, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37480469

RESUMEN

Transgenic models are useful tools for studying the pathogenesis of and drug development for Alzheimer's Disease (AD). AD models are constructed usually using overexpression or knock-in of multiple pathogenic gene mutations from familial AD. Each transgenic model has its unique behavioral and pathological features. This review summarizes the research progress of transgenic mouse models, and their progress in the unique mechanism of amyloid-ß oligomers, including the first transgenic mouse model built in China based on a single gene mutation (PSEN1 V97L) found in Chinese familial AD. We further summarized the preclinical findings of drugs using the models, and their future application in exploring the upstream mechanisms and multitarget drug development in AD.


Asunto(s)
Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Ratones Transgénicos , Precursor de Proteína beta-Amiloide/genética , Modelos Animales de Enfermedad , Pensamiento , Péptidos beta-Amiloides/genética
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