Factores relacionados con la supervivencia en una cohorte de pacientes con enfermedad pulmonar obstructiva crónica grave a largo plazo: relación con la capacidad aeróbica / Related Factors for Survival in a Cohort of Patients with Severe Chronic Obstructive Pulmonary Disease in a Long-Term of Follow-Up: Relationship with Aerobic Capacity

Introducción: Sólo Oga et al. (AJRCCM 2003) relacionaron supervivencia y capacidad aeróbica en pacientes EPOC, pero en hombres y seguimiento a 5 años. Objetivos: Evaluar la supervivencia de una cohorte de pacientes EPOC grave según el consumo de oxígeno pico (VO2p) ajustado al peso. Material y Métodos: Se evaluó la supervivencia a largo plazo desde el diagnóstico de pacientes con EPOC (GOLD). Se midió el VO2p ajustado por peso en prueba cicloergo- métrica máxima (gases espirados). Se usaron técnicas estadísticas convencionales y análisis de supervivencia de LogRank (Mantel-Cox). Resultados: 70 pacientes (27% femenino); edad 68 años (RIQ 63-73); %FEV1 postBD: 39,95±2,09; VO2p: 9,25 ± 3,17 ml/kg/min. GOLD D/B/A 84,3/14,2/1,5%; GOLD II/III/IV: 15,7/61,4/22,9%. A 14 años de seguimiento, 75% había fallecido. Supervivencia: primer cuartilo de VO2p (ml/kg/min) fue 38,5 meses (RIQ 18,25-58,5) y para el cuarto cuartilo 68 meses (RIQ 48-93). A 103 meses, la diferencia en supervivencia fue: primer cuartilo vs. cuarto cuartilo de VO2p (p<0,01) y segundo vs. cuarto cuartilo (p<0,03); a 145 meses entre segundo vs. cuarto cuartilo (p=0,049). En el análisis multivariado, el VO2p alto es un factor protector sobre la mortalidad. En cambio, otras variables independientes como sexo masculino, edad >70, grado de obstrucción bronquial severo y fenotipo exacerbador frecuente se asociaron a mortalidad. Conclusión: A largo plazo, en una cohorte de pacientes hombres y mujeres EPOC grave, en análisis multivariado, el VO2p alto es factor protector sobre la mortalidad. En cambio, otras variables independientes como sexo masculino, edad >70, grado de obstrucción bronquial severo y exacerbador frecuente se asociaron a mortalidad.

Introduction: Only Oga et al. (AJRCCM 2003) related survival and aerobic capacity, but only in chronic obstructive pulmonary disease (COPD) men with 5 years of follow-up. Objective: To determine survival in a cohort of patients with severe COPD due to aerobic capacity (VO2max) adjusted by weight. Methods: Survival of COPD patients was evaluated to long-term (GOLD definition). Patients performed maximal exercise test in cicloergometry (expired gases) evaluating (VO2max). Conventional statistics and Log-Rank survival analysis (Mantel-Cox) were used. Results: We included 70 patients (27% female) followed up 60.77 months (RIQ 29- 87.85); age 68 years (RIQ 63-73); %FEV1 postBD: 39.95±2.09; VO2p: 9.25± 3.17 ml/kg/ min. GOLD D/B/A 84.3/14.2/1.5%; GOLD II/III/IV: 15.7/61.4/22.9%. After 14 years of follow-up, 75% of patients died. Survival: VO2p (ml/kg/min) first quartil was 38.5 months (RIQ 18,25-58,5); second quartil 66 months (RIQ 35-84.5); third quartil 70 months (RIQ 15-96) and fourth quartil 68 months (RIQ 48-93). After 103 months of follow-up, survival was compared: 1st vs 4rd quartil of VO2p (p<0.01) and 2nd vs. 4rd quartil (p<0.03); comparing at 145 months: 2nd vs. 4rd quartil (p=0.049). In a multivariate analysis, high VO2p is a protective factor on mortality, nevertheless other independent variables as male gender, age >70, severe airway obstruction and frequent exacerbators were associated to mortality. Conclusion: At long term of follow-up, a cohort of severe COPD patients (males and fe- males), in multivariate analysis, high VO2p is a protective factor of mortality, nevertheless other independent variables as male gender, age >70, severe airway obstruction and frequent exacerbators were associated to mortality.

Síndrome de Miller-Dieker: reporte de dos casos / Miller-Dieker Syndrome: Two Cases Report

Resumen Introducción: El síndrome de Miller-Dieker cuenta con un patrón de herencia autosómico dominante y pertenece al grupo de trastornos de la migración neuronal. Se caracteriza por la presencia de lisencefalia de tipo 1, retraso global del desarrollo, microcefalia, epilepsia y dismorfismos faciales dados por mutaciones en el cromosoma 17p13. El síndrome de Miller-Dieker es una enfermedad extremadamente rara con prevalencia de 1 caso por cada 100,000 recién nacidos vivos. Presentación de casos: Nosotros presentamos dos casos de síndrome de Miller-Dieker en los que datos de la exploración física y del interrogatorio fueron pistas que permitieron una fuerte sospecha diagnóstica y que a su vez el diagnóstico definitivo mediante FISH permitió brindar un adecuado manejo con la finalidad de mejorar el pronóstico a largo plazo. Conclusión: Se debe tener una alta sospecha diagnóstica mediante la exploración física dirigida a identificar alteraciones en pacientes con epilepsia de difícil control, ya que permite guiar el diagnóstico etiológico y con ello brindar un adecuado tratamiento.

Abstract Introduction: Miller-Dieker syndrome has an autosomal dominant pattern of inheritance and belongs to the group of neuronal migration disorders. It is characterized by the presence of type 1 lissencephaly, global development delay, microcephaly, epilepsy and facial dysmorphisms caused by mutations in chromosome 17p13. Miller-Dieker syndrome is an extremely rare disease with a prevalence of 1 case per 100,000 live births. Case presentation: We present two cases of Miller-Dieker syndrome in which data from the physical examination and questioning were clues that allowed a strong diagnostic suspicion and that, in turn, the definitive diagnosis by means of FISH allowed us to provide adequate management in order to improve the long-term prognosis. Conclusion: A high diagnostic suspicion must be achieved through physical examination aimed at identifying alterations in patients with difficult-to-control epilepsy, since it allows guiding the etiological diagnosis and thereby providing adequate treatment.

PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis

ABSTRACT Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelial-mesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB. (Rev Invest Clin. 2024;76(2):103-15)

Perfil molecular de cáncer de endometrio en mujeres de Bogotá DC, Colombia / Molecular profile of endometrial cancer in women from Bogota DC, Colombia

Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.

Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.

The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice / Efectos Renoprotectores Sinérgicos del Extracto de Té Verde y Gemigliptina contra la Nefrotoxicidad Inducida por Tacrolimus en Ratones

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells

The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.

Effects of echinacoside on renal injury in uremia rats and its mechanism / 中国药房

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践与服务

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Intervention effect of miR-204-3P on silica dust-induced silicosis fibrosis in rats / 环境与职业医学

Background Long-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. Objective To observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. Methods Forty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL−1) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Results The anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P<0.05), and the relative expression level of miR-204-3p in lung tissue of the miR-204-3p intervention group was increased (P＜0.05). The results of immunohistochemistry showed that compared with the control group, the expression levels of Fibronectin and Collagen I in lung tissue of the silicosis model group were increased (P＜0.05). Compared with the silicosis model group, the relative expression levels of Fibronectin and Collagen I in lung tissue of the rats in the miR-204-3p intervention group were significantly decreased (P<0.05). The results of RT-qPCR and Western blot showed that compared with the control group, the relative protein and gene expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of the silicosis model group increased (P＜0.05). Compared with the silicosis model group, the relative gene and protein expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in the miR-204-3p intervention group were decreased (P＜0.05). Conclusion Silica dust can cause lung fibrosis in rats, and overexpression of miR-204-3P in vivo can reduce silicosis fibrosis in rats caused by silica dust.

Effects of arsenic and its metabolites on p53 gene expression in BEAS-2B cells / 环境与职业医学

Background Arsenic is a human carcinogen. Arsenic and its metabolites affect the expression of p53, but whether there are any changes of p53 phosphorylation and ubiquitination levels in human bronchial epithelium cells (BEAS-2B) are not clear after exposure to arsenic and its metabolites. Objective To study the effects of arsenic and its metabolites monomethylarsic acid (MMA) and dimethylarsinic acid (DMA) on the expression of tumor suppressor gene p53 in BEAS-2B cells. Methods Different concentrations of sodium arsenite (NaAsO2) were used to infect BEAS-2B cells, and the cell viability was detected with CCK-8 reagent to determine the dose and time of NaAsO2 used for the following study. Based on the results of cell viability, the cells were divided into two panels: a sodium arsenide panel and an arsenic methylation metabolite penal. The doses of sodium arsenite were 0, 2, 4, and 6 μmol·L−1 NaAsO2; the arsenic methylation metabolite panel consisted of 0 μmol·L−1 NaAsO2 group (control), 6 μmol· L−1 MMA group, 6 μmol· L−1 DMA group， and 6 μmol· L−1 NaAsO2 group. The cells were collected after 48 h treatment, and the total protein and total RNA were extracted. The relative levels of p53 mRNA expression were determined by quantitative real-time polymerase chain reaction (qRT-PCR), the relative expression levels of p53 protein, p53 Ser9 and Ser15 phosphorylated proteins were determined by Western blot, and the level of p53 ubiquitination was detected by co-immunoprecipitation (CO-IP). Results Compared with the control group, the cell viability rates in all BEAS-2B cells treated by NaAsO2 were significantly reduced (P<0.05), and the 50% cell viability was observed at 6 μmol·L−1. Compared with the control group, the relative expression level of p53 mRNA gradually decreased after NaAsO2 (2, 4, 6 μmol·L−1) treatment (P<0.05), the relative expression levels of p53 protein and Ser9 phosphorylated protein induced by NaAsO2 also decreased gradually (P<0.05), and the relative expression level of p53 Ser15 phosphorylated protein induced by NaAsO2 followed the same pattern, but it was only lower than that of the control group in the 6 μmol·L−1 NaAsO2 group (P<0.05). Compared with the control group, there were no significant effects on the relative expression levels of p53 mRNA, p53 protein, Ser9 and Ser15 phosphorylated proteins in the MMA group and the DMA group. Compared with the control group, the expression level of p53 ubiquitination was significantly decreased and the expression of K48 ubiquitination decreased significantly after NaAsO2 infection. Conclusion Arsenic causes a decrease in the expression of the p53 protein in BEAS-2B cells, largely due to inhibition of the phosphorylated pathway and a decrease in mRNA expression, and protein changes caused by a decrease in p53 ubiquitination do not play a dominant role. MMA and DMA do not affect p53 gene expression.

Protective Effect and Mechanism of Mori Folium Extract on Kidney of db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo investigate the protective effects of Mori Folium extract （MLE） on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb （db/db） mice were randomly divided into model group， metformin group， low-dose group of MLE （MLE-L）， and high-dose group of MLE （MLE-H） according to their fasting blood glucose （FBG）， with six mice in each group， and other six C57BLKS/JGpt wild littermate （m/m） mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage， and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight， bilateral kidney weight， and FBG were measured， and an oral glucose tolerance test （OGTT） was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin （HE） and periodic acid-silver （PAS） staining， and serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in serum and urinary microalbumin （U-mAlb） of mice. The expression levels of toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor-kappa B p65 （NF-κB p65） protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group， the body weight， absolute renal weight， FBG， and the area under the curve （AUC） of OGTT of mice in the model group were significantly increased （P<0.01）， and the levels of SCr， BUN， and U-mAlb， as well as TNF-α and IL-6 in serum were significantly increased （P<0.01）. The glomerular basement membrane in the kidney tissue of mice was thicker， with obvious inflammatory cell infiltration. The protein expression levels of TLR4， MyD88， and NF-κB p65 in the kidney tissue of mice were increased significantly （P<0.01）. Compared with the model group， there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced （P<0.05， P<0.01）. The FBG levels of mice in the metformin， MLE-L， and MLE-H groups started to decrease after treatment for four to eight weeks （P<0.05， P<0.01）. The AUC of mice in the MLE-H and metformin groups was significantly decreased （P<0.01）. The levels of SCr， BUN， and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）， and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased （P<0.01）. The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）. The renal tissue pathology of mice in each drug administration group was improved to varying degrees， and the protein expression levels of TLR4， MyD88， and NF-κB p65 in the MLE-H group were decreased significantly （P<0.05， P<0.01）. ConclusionMLE can improve the renal structure and function of db/db diabetic mice， and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Mechanism of Xiezhuo Jiedu Recipe in Preventing Colorectal Adenoma in Mice Through miRNA-34a-5p/PI3K/Akt Signalling Pathway / 中国实验方剂学杂志

ObjectiveKey microRNAs （miRNAs） of colorectal adenoma （CRA） were identified and analyzed by bioinformatics methods， and differentially expressed genes （DEGs） were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus （GEO） database of intestinal mucosal tissue of CRA patients， and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan， miRTarbase， and miRDB databases were used to predict the target genes of the differentially expressed miRNAs， and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software， and the TRRUST database was used to predict downstream binding transcription factors （TFs）. The mRNA intersection was enriched by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs， and the key signaling pathways were selected for animal experiments. In animal experiments， the CRA mice model was established by using sodium glycan sulfate （DSS） drinking combined with intraperitoneal injection of azomethane oxide （AOM）， and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， phosphoryl-PI3K （p-PI3K）， phosphoryl-Akt （p-Akt）， and B cell lymphoma （Bcl）-2 were detected by Western blot. The expression of Cyclin D1 （CCND1） was detected by immunohistochemistry （IHC）. In situ terminal transferase labeling （TUNEL） was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset， and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them， GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex， RNA polymerase Ⅱ transcriptional regulatory complex， enzyme-linked receptor protein signaling pathway， and DNA-binding transcriptional activator activity， cancer pathway， PI3K/Akt pathway， etc. miR-34a-5p is mainly enriched in PI3K/Akt， cell cycle， and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database， among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 （E2F1） and tumor protein P53 （TP53） were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p， down-regulate the expression of PI3K， Akt， Bcl-2， p-PI3K， and p-Akt proteins in the intestinal tissue of CRA mice， down-regulate the positive expression rate of CCND1， and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway， thus playing a role in the prevention of CRA.

Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway / 中国实验方剂学杂志

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4+ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Targeting CDT1 inhibit tumor growth and its mechanism in lung adenocarcinoma / 安徽医科大学学报

Objective To explore the clinical significance and mechanisms of chromatin licensing and DNA repli-cation factor 1(CDT1)in lung adenocarcinoma).Methods The gene expression samples of lung adenocarcinoma tissue and normal lung tissue were downloaded from the TCGA database,and perform differential analysis,GO a-nalysis,independent prognosis analysis,and correlation analysis with immunotherapy using R language.CDT1 ex-pression in lung adenocarcinoma and normal tissues was detected by PCR in clinical samples.The changes of cell proliferation and cycle in si-CDT1 knockdown group and si-NC control group were detected by flow cytometry.The invasive ability of each group was detected by Transwell.The expressions of CDT1,TPX2 and p53 in each group were detected by Western blot.Results The TCGA data analysis revealed CDT1 as a differentially expressed gene.GO analysis indicated that CDT1 was closely associated with the cell cycle.The high expression of CDT1 in lung adenocarcinoma tissues was validated in clinical samples.CDT1 could serve as an independent factor for predicting the prognosis of lung adenocarcinoma and had predictive value for immunotherapy in lung adenocarcinoma.Knock-down of CDT1 resulted in a significant decrease in cell proliferation ability compared to the control group,and cells were noticeably arrested in the G1 phase.Transwell assay results demonstrated a significant reduction in invasive capacity in the CDT1 knockdown group.Knockdown of CDT1 led to a significant decrease in TPX2 expression and a significant increase in p53 expression,while overexpression of CDT1 yielded the opposite effect.Conclusion Re-sults demonstrate the elevated expression of CDT1 in lung adenocarcinoma,its association with prognostic signifi-cance,and its impact on lung adenocarcinoma's occurrence and development by influencing TPX2 and p53.

Effect of LINC00894 gene on proliferation and metastasis of gastric cancer cells via miR-205-5p/ZEB1 axis / 安徽医科大学学报

Objective To investigate the effects of long non-coding RNA 00894(LINC00894)gene on prolifera-tion and metastasis of human gastric cancer cells,and to verify the regulatory relationship of LINC00894,miR-205-5p and ZEB1 in gastric cancer.Methods The expression level of LINC00894 in gastric cancer cell lines,normal gastric lines,clinical gastric cancer and normal gastric tissue samples were determined by RT-qPCR.Through fol-low-up,the relationship between the expression level of LINC00894 and the prognosis of gastric cancer patients was explored.LINC00894 knockdown cell lines and overexpression cell lines were constructed,and the knockdown and overexpression efficiency was detected by RT-qPCR.Cell proliferation and metastatic capacity were determined by CCK 8,clone formation and Transwell assays.Dual-luciferase reporter assays,RT-qPCR assays and Western blot assays were used to examine the targeted regulatory relationships of LINC00894,miR-205-5p and ZEB1.Results The expression of LINC00894 gene in gastric cancer tissues or cells was significantly higher than that in normal gas-tric tissues or cells,moreover,gastric cancer patients with high LINC00894 gene expression had a worse prognosis.The knockdown of LINC00894 inhibited the viability,clonogenesis,migration and invasion ability of gastric cancer cells,and conversely,the overexpression of LINC00894 obtained the opposite results.LINC00894 promoted ZEB1 expression by targeted downregulation of miR-205-5p expression.LINC00894 promoted the expression of ZEB1 by targeting miR-205-5p and down-regulating its expression.Conclusion LINC00894 serves as an oncogene in gastric cancer and may promote proliferation and metastasis of gastric cancer cells via regulating miR-205-5p/ZEB1 axis.

Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer disease / 北京大学学报(医学版)

Objective:To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1(LncRNA NEAT1)and miR-27a-3p in serum and cerebro-spinal fluid of patients with Alzheimer disease(AD).Methods:Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered,according to the clinical dementia rating scale score,they were grouped into mild group(≤ 1 point,n=41)and moderate-to-severe group(＞1 point,n=25).Another 66 cases of serum and cerebrospinal fluid sam-ples from outpatient physical examination personnel were regarded as the control group.The general infor-mation on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1(BACE1),β-amyloid(Aβ)40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scores;Pearson method was per-formed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio(SUVR)and cerebrospinal fluid miR-27a-3p,NEAT1,BACE1,Aβ42 and Aβ40 levels.Results:The MMSE score[21(17,25),9(7,11)vs.27(21,34)],MoCA score[17(12,21),10(7,13)vs.27(21,31)],serum miR-27a-3p level(0.55±0.13,0.46±0.06 vs.0.97± 0.22),cerebrospinal fluid miR-27a-3p(0.48±0.10,0.35±0.10 vs.1.03±0.31),Aβ42 levels[(303.55±36.77)ng/L,(231.45±34.14)ng/L vs.(499.99±53.63)ng/L]and Aβ42/Aβ40 ra-tio(0.030±0.008,0.022±0.007 vs.0.048±0.010)of AD patients in mild group and moderate-to-severe group were all lower than those in the control group,and the moderate-to-severe group were lower than the mild group(all P＜0.05);the serum NEAT1 level(2.31±0.64,3.13±0.76 vs.1.05± 0.20),SUVR(1.50±0.29,1.76±0.52 vs.0.74±0.15),and cerebrospinal fluid NEAT1(3.51± 1.24,4.30±1.65 vs.1.01±0.23)and B ACE 1 levels[(55.78±5.98)μg/L,(72.32±16.08)μg/L vs.(21.39±3.73)μg/L]were higher than those in the control group,and the moderate-to-se-vere group were higher than the mild group(all P＜0.05).Serum NEAT1 level in AD patients was posi-tively correlated with SUVR,cerebrospinal fluid NEAT1 and BACE1(r=0.350,0.606,0.341,P＜0.05),and negatively correlated with MMSE score and MoCA score(r=-0.473,-0.482,all P＜0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level,MMSE score and MoCA score(r=0.695,0.424,0.412,all P＜0.05),and negatively correlated with SUVR and cerebrospinal fluid BACE1 level(r=-0.521,-0.447,all P＜0.05).Conclusion:The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are con-sistent,the level of NEAT1 is increased,and the level of miR-27a-3p is decreased.The levels of the two are negatively correlated,which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

Diagnostic value of plasma SPINK4 expression in colorectal adenocarcinoma and progressive adenoma / 重庆医学

Objective To investigate the clinical diagnostic value of plasma serine protease inhibitor Ka-zal-type 4(SPINK4)expression in colorectal adenocarcinoma(CRC)and progressive adenoma(AA).Methods A total of 62 patients with CRC(CRC group)and 15 patients with AA(AA group)diagnosed by colonoscopy and pathological examination in this hospital from June 2020 to December 2021 were selected,and 22 healthy people undergoing physical examination during the same period were selected as the HC group.The expression of SPINK4 in plasma was detected by ELISA,and the expression of CEA in plasma was detected by electrochemiluminescence,and the correlation was analyzed.The diagnostic efficiency was analyzed by re-ceiver operating characteristic(ROC)curve,and the expression of p53 in CRC tissues was detected by immu-nohistochemistry.Results The expression of plasma SPINK4 in the CRC group and AA group was lower than that in the HC group(Z=3.72,-0.41,P＜0.05),and the expression of CEA in the CRC group was higher than that in the HC group(Z=-3.63,P＜0.05).The area under the curve(AUC),accuracy,sensi-tivity and specificity of SPINK4 combined with CEA in the diagnosis of CRC and AA were higher than those of SPINK4 and CEA alone.The positive rate of mutant type p53 in SPINK4 low expression group and CEA high ex-pression group was significantly increased in CRC patients(72.55％,75.00％,P＜0.05).Conclusion The expression of plasma SPINK4 is decreased in CRC and AA,and the combined detection of SPINK4 and CEA has a good di-agnostic efficiency in CRC and AA.

Expression and clinical significance of phosphorylated FGFR1Y654 in esophageal squamous cell carcinoma / 陆军军医大学学报

Objective To explore the relationship between p-FGFR1Y654 expression and clinical pathological characteristics of esophageal squamous cell carcinoma patients and its prognostic value.Methods Tumor tissue samples from 103 cases of esophageal squamous cell carcinoma and 58 normal esophageal tissues were surgically collected in the General Hospital of Western Theater between January 2017 and July 2020.The expression of p-FGFR1Y654 in the tissues was detected using immunohistochemical assay,and its correlation with relevant clinicopathological parameters and prognosis was analyzed.Results The expression of p-FGFR1Y654 in esophageal squamous cell carcinoma tissues was significantly higher than that in normal tissue(P＜0.01).Its expression level was closely related to overall survival(OS,P＜0.05),but not related to age,gender,tumor stage or tumor size.Multivariate COX regression analysis showed that N-stage was identified as an independent prognostic factor for recurrence free survival(RFS)in esophageal squamous cell carcinoma patients.Survival analysis indicated that patients with low expression of p-FGFR1Y654 had significantly higher RFS and OS than those with high expression(P=0.032,95％CI:1.08～4.65;P=0.004,95％CI:2.14-11.51).Conclusion p-FGFR1Y654 is highly expressed in esophageal squamous cell carcinoma tissue,and is associated with poor prognosis in these patients.p-FGFR1Y654 may be a potential therapeutic target for esophageal squamous cell carcinoma.