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OBJECTIVE: To investigate the mechanism by which conbercept reverses transforming growth factor-ß2 (TGF-ß2)-induced epithelial-mesenchymal transition (EMT) in human lens epithelial cells (HLECs). METHODS: Cultured HLEC SRA01/04 cells were treated with TGF-ß2, conbercept, or both, and the changes in cell proliferation, apoptosis, and migration were observed using MTT assay, flow cytometry, scratch assay, and Transwell assay. Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers (E-Cadherin, α-SMA, and Snail), extracellular matrix components, and genes related to the TGF-ß/Smad signaling pathway. RESULTS: Conbercept significantly reduced TGF-ß2-induced EMT of SRA01/04 cells, decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA, Snail, collagen I, collagen IV, and FN1, and upregulated the protein and mRNA expressions of E-cadherin (P <0.05). Transwell assay showed significantly lower cell migration ability in TGF-ß2+conbercept group than in TGF-ß2 group (P <0.05). Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-ß2-induced EMT (P <0.01). CONCLUSION: Conbercept inhibits TGF-ß2 induced EMT by downregulating the expression of pSmad2/3 in TGF-ß/Smad signaling pathway, indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.
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Proliferación Celular , Células Epiteliales , Transición Epitelial-Mesenquimal , Cristalino , Transducción de Señal , Proteínas Smad , Factor de Crecimiento Transformador beta2 , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Factor de Crecimiento Transformador beta2/metabolismo , Cristalino/citología , Cristalino/metabolismo , Proteínas Smad/metabolismo , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Cadherinas/metabolismo , Apoptosis/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular , Proteína Smad2/metabolismoRESUMEN
Takayasu's arteritis-pulmonary artery involvement (TA-PAI) is a chronic, progressive, inflammatory disease affecting the pulmonary artery and its branches. Patients typically present with non-specific respiratory symptoms, such as fever, dyspnea, and chest pain, leading to a high rate of misdiagnosis. The diagnosis of TA-PAI is currently based on the diagnostic criteria of aortitis and imaging evidence of pulmonary artery involvement. However, pulmonary artery involvement is not typically included in the diagnostic criteria for aortitis, which may lead to a significant underestimation of the diagnostic rate of TA-PAI, particularly in cases where pulmonary artery involvement is the only manifestation. This article reports the case of a 26-year-old female patient who presented with recurrent chest pain and fever. She was initially diagnosed with pneumonia in a foreign hospital but did not show significant improvement after four months of treatment. Eventually, she was diagnosed with pulmonary artery involvement in aortitis and was stabilized with hormones, immunosuppressive drugs, and pulmonary vascular intervention. By analyzing the clinical features and diagnostic and therapeutic approaches of this case, and reviewing the relevant literature, clinicians can improve their understanding of TA-PAI.
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Neumonía , Arteria Pulmonar , Arteritis de Takayasu , Humanos , Femenino , Adulto , Arteritis de Takayasu/diagnóstico , Neumonía/diagnóstico , Arteria Pulmonar/patología , Arteria Pulmonar/diagnóstico por imagen , Dolor en el Pecho/etiologíaRESUMEN
Objective: To evaluate the efficacy and safety of internal XEN gel stent implantation or combined with phacoemusification and intraocular lens (IOL) implantation in the treatment of glaucoma. Methods: It was a retrospective case series study. Forty-five patients (28 males and 17 females; 52 eyes) who had different types of glaucoma treated at the Shenzhen Eye Hospital from December 2021 to June 2023 were included. XEN gel stent implantation (the XEN group) or XEN implantation combined with phacoemusification and IOL implantation (the combined group) were performed in these patients. The postoperative follow-up was 18 months. The observational indexes included the best corrected visual acuity (recorded as the logarithm of the minimum angle of resolution), intraocular pressure (IOP), XEN implantation quadrant, number of IOP-lowering medications, corneal endothelial cell count, operation success rate and surgical complications. The one-way repeated measures of variance, LSD-t test, and rank sum test were used for statistical analysis. Results: There were 28 patients (33 eyes) in the XEN group and 17 patients (19 eyes) in the combined group. The postoperative best corrected visual acuity had no significant change in the XEN group, but improved significantly (0.21±0.30 at 6 months; P<0.05) in the combined group, compared with the preoperative value. The IOP of the two groups at 18 months after surgery [(12.2±3.1) and (11.9±3.9) mmHg (1 mmHg=0.133 kPa)] was significantly lower than that before surgery [(22.1±8.5) and (19.4±10.2) mmHg; P<0.05]. The average number of IOP-lowering medications in all patients was 3 (2, 3) before surgery and 0 (0, 0) at 18 months after surgery. The difference was statistically significant (P<0.05). In the XEN group, the corneal endothelial cell count was (2 387.37±478.22) cells/mm² preoperatively and (2 193.89±311.96) cells/mm² at 12 months. The decrease showed no statistical significance. The XEN gel stent was implanted in the supranasal quadrant in 8 eyes (15.4%), in the inferonasal quadrant in 36 eyes (69.2%), and in the infratemporal quadrant in 8 eyes (15.4%). The operation success rate [complete success rate, 86.5% (45/52); conditional success rate, 9.6% (5/52)] was 96.2% (50/52). The filtering bleb scarring occurred in 9.6% (5/52) of eyes. A small amount of hyphema, postoperative shallow anterior chamber, transient hypertension, and intraoperative drain breakage were found in 7.7% (4/52) of eyes, respectively. A small amount of subconjunctival bleeding was observed in 5.8%(3/52) of eyes. Re-implantation of an XEN gel stent was performed in 5.8% (3/52) of eyes. The intraoperative conjunctival tissue rupture, hypotony macular edema, and drain exposure were observed in 1.9% (1/52) of eyes, respectively. Conclusion: The XEN gel stent implantation or combined with phacoemusification and IOL implantation was effective and safe in treating different types of glaucoma, but its long-term clinical efficacy needs further follow-up observations in multi-center, larger-scale research.
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Implantes de Drenaje de Glaucoma , Glaucoma , Implantación de Lentes Intraoculares , Facoemulsificación , Humanos , Estudios Retrospectivos , Masculino , Femenino , Implantación de Lentes Intraoculares/métodos , Glaucoma/cirugía , Facoemulsificación/métodos , Stents , Presión Intraocular , Resultado del Tratamiento , Agudeza Visual , Persona de Mediana EdadRESUMEN
Objective: To investigate the action potential firing patterns of neurons in the visual sensory layers of the superior colliculus in early postnatal mice and the electrophysiological characteristics of neurons with different firing patterns. Methods: This experimental study utilized whole-cell patch-clamp recordings performed on neurons in the visual sensory layers of the superior colliculus using brain slices from 57 healthy male C57BL/6J mice aged 14 to 20 days (weighing 5.0 to 8.9 g) using brain slices. In current-clamp mode, action potential characteristics were analyzed based on the first action potential generated by depolarizing current, and the firing patterns of neurons were recorded using step depolarizing currents. Neuronal firing patterns were analyzed using hierarchical clustering, and the active electrical properties of neurons with different firing patterns were compared. Results: A total of 135 neurons from the visual sensory layers of the superior colliculus were successfully recorded. Cluster analysis of the neuronal firing patterns identified three types of firing patterns: tonic firing (97, 72%), phasic firing (26, 19%), and single firing (12, 9%). The number of action potentials for each firing pattern was 13.30±7.38, 3.73±3.61, and 0.83±0.39, respectively, with significant differences (P<0.001). There was no significant difference in the membrane potential response to step currents among the three firing pattern types (P>0.05). The action potential amplitudes were (60.45±12.22), (53.67±13.20), and (44.04± 12.92) mV, and the afterhyperpolarization amplitudes were (13.45±13.79), (12.02±13.11), and (20.75±2.85) mV, respectively. The maximum rising slopes were (171.29±77.46), (130.14±61.83), and (78.89±37.08) V/s, and the maximum falling slopes were (-76.33±33.61), (-68.17±31.65), and (-47.97±13.92) V/s, respectively, with all differences being statistically significant (all P<0.05). There were no significant differences in the resting membrane potential, action potential threshold, half-width, and afterhyperpolarization duration among the three firing pattern types (all P>0.05). Conclusions: In the early postnatal mice, neurons in the visual sensory layers of the superior colliculus exhibit three distinct firing patterns: tonic, phasic, and single firing. These firing pattern types show significant differences in action potential amplitude, afterhyperpolarization amplitude, maximum rising slopes, and maximum falling slopes.
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Potenciales de Acción , Ratones Endogámicos C57BL , Neuronas , Técnicas de Placa-Clamp , Colículos Superiores , Animales , Ratones , Masculino , Colículos Superiores/fisiología , Potenciales de Acción/fisiología , Neuronas/fisiología , Fenómenos ElectrofisiológicosRESUMEN
The regulation of blood flow in the human eye, aqueous humor production, and the outflow channels of aqueous humor are all controlled by the autonomic nervous system (ANS), encompassing both sympathetic and parasympathetic nerves. Patients with primary glaucoma often exhibit autonomic nervous system dysfunctions, which may exacerbate visual impairment. The homeostasis of the autonomic nervous system is influenced by circadian rhythms, physical exercise, emotional states, medications, and other factors. Previous studies have indicated that activities such as aerobic exercise, yoga breathing, and meditation can promote the restoration of autonomic nervous system balance, thereby reducing intraocular pressure. However, further evidence is required to substantiate the efficacy of ANS activity regulation as an effective adjunct therapy for primary glaucoma. This review examines the role and mechanisms of autonomic nervous system regulation in the context of primary glaucoma.
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Sistema Nervioso Autónomo , Glaucoma , Humanos , Sistema Nervioso Autónomo/fisiopatología , Glaucoma/fisiopatología , Glaucoma/terapia , Humor Acuoso/fisiología , Presión Intraocular/fisiologíaRESUMEN
Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.
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Fibras Nerviosas Mielínicas , Secuenciación Completa del Genoma , Humanos , Femenino , Adulto Joven , Fibras Nerviosas Mielínicas/patología , Retina/patología , Predisposición Genética a la EnfermedadAsunto(s)
Carcinoma Neuroendocrino , Inmunohistoquímica , Proteínas Represoras , Humanos , Proteínas Represoras/metabolismo , Carcinoma Neuroendocrino/metabolismo , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/diagnóstico , Sensibilidad y Especificidad , Coloración y Etiquetado/métodos , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismoRESUMEN
The application of tyrosine kinase inhibitors and targeted immunotherapy has revolutionized the therapeutic strategies and clinical outcome for BCR::ABL1-positive B-cell acute lymphoblastic leukemia (BCR::ABL1(+) B-ALL). The classification was updated successively by the World Health Organization and the International Consensus Classification in 2022. The risk stratification of this entity, for the first time, was modified by the National Comprehensive Cancer Network in 2023, both minimal residual disease assessment and IKZF1(plus) genotyping recognized as critical prognostic factors. These important updates would have significant implications for clinical management. Therefore, this review focused on the latest advances in the classification and prognostic evaluation of BCR::ABL1(+) B-ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Pronóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Proteínas de Fusión bcr-abl/genética , Neoplasia Residual/diagnósticoRESUMEN
AIM: The purpose of this study was to identify robust radiological features from intratumoral and peritumoral regions, evaluate MRI protocols, and machine learning methods for overall survival stratification of glioma patients, and explore the relationship between radiological features and the tumour microenvironment. MATERIAL AND METHODS: A retrospective analysis was conducted on 163 glioma patients, divided into a training set (n=113) and a testing set (n=50). For each patient, 2135 features were extracted from clinical MRI. Feature selection was performed using the Minimum Redundancy Maximum Relevance method and the Random Forest (RF) algorithm. Prognostic factors were assessed using the Cox proportional hazards model. Four machine learning models (RF, Logistic Regression, Support Vector Machine, and XGBoost) were trained on clinical and radiological features from tumour and peritumoral regions. Model evaluations on the testing set used receiver operating characteristic curves. RESULTS: Among the 163 patients, 96 had an overall survival (OS) of less than three years postsurgery, while 67 had an OS of more than three years. Univariate Cox regression in the validation set indicated that age (p=0.003) and tumour grade (p<0.001) were positively associated with the risk of death within three years postsurgery. The final predictive model incorporated 13 radiological and 7 clinical features. The RF model, combining intratumor and peritumor radiomics, achieved the best predictive performance (AUC = 0.91; ACC = 0.86), outperforming single-region models. CONCLUSION: Combined intratumoral and peritumoral radiomics can improve survival prediction and have potential as a practical imaging biomarker to guide clinical decision-making.
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Objective: To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation. Methods: This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children's Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized. Results: Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy. Conclusions: BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.
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Ácidos y Sales Biliares , Familia 7 del Citocromo P450 , Mutación , Humanos , Familia 7 del Citocromo P450/genética , Masculino , Femenino , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/sangre , Lactante , Estudios Retrospectivos , Recién Nacido , Hígado/metabolismo , Esteroide HidroxilasasRESUMEN
Objective: To exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes. Methods: This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1â¶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital's medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups. Results: After propensity score matching (1â¶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group (t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group (χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group (t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups (t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group (χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group (χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group (χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle (χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions: PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.
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Transferencia de Embrión , Fertilización In Vitro , Síndrome del Ovario Poliquístico , Índice de Embarazo , Adulto , Femenino , Humanos , Embarazo , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Hormona Folículo Estimulante/sangre , Infertilidad Femenina/terapia , Infertilidad Femenina/etiología , Hormona Luteinizante/sangre , Síndrome de Hiperestimulación Ovárica/etiología , Síndrome de Hiperestimulación Ovárica/epidemiología , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/terapia , Resultado del Embarazo , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The microbial communities residing in the mosquito midgut play a key role in determining the outcome of mosquito pathogen infection. Elizabethkingia anophelis, originally isolated from the midgut of Anopheles gambiae possess a broad-spectrum antiviral phenotype, yet a gap in knowledge regarding the mechanistic basis of its interaction with viruses exists. The current study aims to identify pathways and genetic factors linked to E. anophelis antiviral activity. The understanding of E. anophelis antiviral mechanism could lead to novel transmission barrier tools to prevent arboviral outbreaks. We utilized a non-targeted multi-omics approach, analyzing extracellular lipids, proteins, metabolites of culture supernatants coinfected with ZIKV and E. anophelis. We observed a significant decrease in arginine and phenylalanine levels, metabolites that are essential for viral replication and progression of viral infection. This study provides insights into the molecular basis of E. anophelis antiviral phenotype. The findings lay a foundation for in-depth mechanistic studies.
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Flavobacteriaceae , Virus Zika , Virus Zika/fisiología , Animales , Flavobacteriaceae/metabolismo , Flavobacteriaceae/genética , Anopheles/virología , Anopheles/microbiología , Infección por el Virus Zika/virología , Antivirales/farmacología , Antivirales/metabolismo , Replicación Viral , Fenilalanina/metabolismo , Arginina/metabolismo , MultiómicaRESUMEN
Cutaneous squamous cell carcinoma (cSCC) comprises 20% of cases of nonmelanoma skin cancers in the United States. In total, 3% to 5% of squamous cell carcinoma (SCC) are metastatic at the time of presentation, associated with significant mortality due to a lack of standardized treatment options. In total, 95% of these tumors are amenable to the initial standard of treatment, which is surgical resection. However, a small percentage of them require systemic therapy as they are either locally advanced to regional lymph nodes or have distant metastasis. The common sites of presentation of cSCC are the scalp and the face with predictable spread to the intra-parotid, upper jugular, and perifacial lymph nodes. In our case report, however, our patient had a large lump lesion on the upper back, an unusual site of presentation of cSCC, with locally advanced metastasis to the left axillary lymph nodes. Subsequently, the tumor marker study revealed a positive SMARCA4 variant (the essential ATPase subunit of the Switch (SWI)/Sucrose Nonfermenting (SNF) chromatin-remodeling complex) that is even rarer in the context of cSCC. Furthermore, abnormalities in SWI/SNF chromatin-remodeling complex subunits have shown promising results as a target therapy for immune checkpoint inhibitor (ICI) therapy. We present an atypical presentation site of locally advanced rare variant SMARCA4-positive cSCC in a patient who received treatment with chemoradiation and systemic therapy with ICI after primary surgical resection. To date, only 2 cases of SMARCA4-positive cSCC were found in the literature with no details of the treatment received. Our case is unique in its atypical site of presentation as well as showing partial response to radiotherapy (RT) and systemic therapy with ICI.
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Carcinoma de Células Escamosas , ADN Helicasas , Proteínas Nucleares , Neoplasias Cutáneas , Factores de Transcripción , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , ADN Helicasas/genética , Factores de Transcripción/genética , Proteínas Nucleares/genética , Masculino , Metástasis Linfática , AncianoRESUMEN
BACKGROUND: Early screening using low-dose computed tomography (LDCT) can reduce mortality caused by non-small-cell lung cancer. However, â¼25% of the 'suspicious' pulmonary nodules identified by LDCT are later confirmed benign through resection surgery, adding to patients' discomfort and the burden on the healthcare system. In this study, we aim to develop a noninvasive liquid biopsy assay for distinguishing pulmonary malignancy from benign yet 'suspicious' lung nodules using cell-free DNA (cfDNA) fragmentomics profiling. METHODS: An independent training cohort consisting of 193 patients with malignant nodules and 44 patients with benign nodules was used to construct a machine learning model. Base models using four different fragmentomics profiles were optimized using an automated machine learning approach before being stacked into the final predictive model. An independent validation cohort, including 96 malignant nodules and 22 benign nodules, and an external test cohort, including 58 malignant nodules and 41 benign nodules, were used to assess the performance of the stacked ensemble model. RESULTS: Our machine learning models demonstrated excellent performance in detecting patients with malignant nodules. The area under the curves reached 0.857 and 0.860 in the independent validation cohort and the external test cohort, respectively. The validation cohort achieved an excellent specificity (68.2%) at the targeted 90% sensitivity (89.6%). An equivalently good performance was observed while applying the cut-off to the external cohort, which reached a specificity of 63.4% at 89.7% sensitivity. A subgroup analysis for the independent validation cohort showed that the sensitivities for detecting various subgroups of nodule size (<1 cm: 91.7%; 1-3 cm: 88.1%; >3 cm: 100%; unknown: 100%) and smoking history (yes: 88.2%; no: 89.9%) all remained high among the lung cancer group. CONCLUSIONS: Our cfDNA fragmentomics assay can provide a noninvasive approach to distinguishing malignant nodules from radiographically suspicious but pathologically benign ones, amending LDCT false positives.
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Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Aprendizaje Automático , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Biopsia Líquida/métodos , Detección Precoz del Cáncer/métodos , Tomografía Computarizada por Rayos X/métodos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/diagnósticoRESUMEN
BACKGROUND: Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, it is increasingly recognized that multi-omic molecular approaches are a powerful avenue through which to understand complex and heterogeneous disease biology. We hypothesize that merging these two promising frontiers of cancer research will improve the discriminatory capacity of current models and allow for improved clinical utility. METHODS: We have compiled a cohort of patients with glioblastoma, brain metastasis, and primary central nervous system lymphoma. Cell-free methylated DNA immunoprecipitation (cfMeDIP) and shotgun proteomic profiling was obtained from the cerebrospinal fluid (CSF) of each patient and used to build tumour-specific classifiers. RESULTS: We show that the DNA methylation and protein profiles of cerebrospinal fluid can be integrated to fully discriminate lymphoma from its diagnostic counterparts with perfect AUC of 1 (95% confidence interval 1-1) and 100% specificity, significantly outperforming single-platform classifiers. CONCLUSIONS: We present the most specific and accurate CNS lymphoma classifier to date and demonstrates the synergistic capability of multi-platform liquid biopsies. This has far-reaching translational utility for patients with newly diagnosed intra-axial brain tumours.
Asunto(s)
Biomarcadores de Tumor , Neoplasias del Sistema Nervioso Central , Metilación de ADN , Proteoma , Humanos , Biopsia Líquida/métodos , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Biomarcadores de Tumor/líquido cefalorraquídeo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Persona de Mediana Edad , Masculino , Anciano , Adulto , Linfoma/líquido cefalorraquídeo , Linfoma/diagnóstico , Linfoma/genética , Linfoma/patología , Epigenoma , Proteómica/métodos , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/diagnóstico , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismoRESUMEN
OBJECTIVE: A metabolism score for visceral fat (METS-VF) is an innovative method to access abdominal fat and visceral fat. So far, the relationship between the METS-VF index and chronic obstructive pulmonary disease (COPD) has remained unclear. We investigated the relationship between the METS-VF index and COPD prevalence utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. PATIENTS AND METHODS: A binary logistic regression analysis was performed using NHANES 2007-2018 data to assess the relationship between the METS-VF index and COPD prevalence. The relationship was verified by fitted smooth curves, generalized additive models, threshold effect analyses, subgroup analyses, and sensitivity analyses. RESULTS: In total, 7,680 subjects were recruited for the study, including 772 self-reported having COPD. The METS-VF index was positively related to COPD prevalence when adjusted for all covariates. The METS-VF index was classified by quartiles, and participants who scored highest on METS-VF were at a greater risk of COPD than those who scored lowest. According to a threshold effect analysis, the METS-VF index was negatively correlated with COPD prevalence with a METS-VF index <7.00, without statistical significance. Once the METS-VF index exceeded 7.00, there was a robust positive correlation between the METS-VF index and COPD prevalence. In the analysis of subgroups, the METS-VF index was positively correlated with COPD prevalence among subjects who were male, aged 40-59, and without asthma or hypertension. The results were robust in sensitivity analyses. METS-VF showed a significantly better diagnostic value for COPD than Body Mass Index (BMI). CONCLUSIONS: The METS-VF index has a non-linear and positive correlation with COPD prevalence in the middle-aged and elderly American population.