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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.

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BACKGROUND: The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. OBJECTIVE AND LIMITATIONS OF THE STUDY: The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. METHODS: A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. RESULTS: Lower levels of serum GLA in rosacea patients were observed (p<0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. CONCLUSION: The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

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Abstract Background The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. Objective and limitations of the study The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. Methods A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. Results Lower levels of serum GLA in rosacea patients were observed (p < 0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. Conclusion The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

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BACKGROUND AND PURPOSE: Some kinds of antibody-drug conjugate (ADC) with high affinity to Nectin-4 have demonstrated breakthrough progress in the third-line setting for bladder cancer. However, many patients are still difficult to benefit from treatment based on the heterogeneity of tumour. As the most advanced auxiliary treatment technology, treatment visualization can most intuitively predict the effectiveness of drug treatment, and timely detect the occurrence of drug resistance. Among them, nuclear medicine molecular probes play an important role in this field. METHODS: 124/125I-EV was prepared by labelling Enfortumad Vedetin (EV), an ADC drugs widely used in clinic targeted Nectin-4, with Na124/125I using N-bromine succinimide as oxidant. The radiochemical purity was analyzed via radio-TLC and bioactivity was measured by enzyme-linked immunosorbent assay. Cell uptake assay and small-animal PET imaging were performed to verified the specificity and targeting. KEY RESULTS: 124/125I-EV was prepared with high labeling yield and radiochemical purity. ELISA assays demonstrated that 124I-EV maintained the same high bioactivity as EV with significantly higher uptake in SW780 cells (Nectin-4 positive, 4.05 ± 0.32 %IA/5 × 105 cells at 8 h) than that in T24 cells (Nectin-4 negative, 1.34 ± 0.18 %IA/5 × 105 cells, p < 0.001). In PET imaging, 124I-EV had a significantly higher accumulation in SW780 tumour than that in T24 tumour and the uptake in SW780 tumour could be specifically blocked when co-injected with cold EV. The signal-to-noise ratio at the tumour site gradually increased with time, and peaked at 72 h. CONCLUSION AND IMPLICATIONS: 124I-EV was successfully prepared with high specificity and binding affinity of Nectin-4. This radioactive probe completely simulates the internal circulation of ADC drugs and tumour uptake and retention, which will greatly improve the clinical application of ADC therapy.

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OBJECTIVES: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and -420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. METHOD: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and -420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. RESULTS: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of -420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of -420C>G polymorphism were found to be associated with an increased risk and progression of AAA. CONCLUSIONS: The -420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

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Abstract Objectives: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and −420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. Method: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and −420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. Results: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of −420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of −420C>G polymorphism were found to be associated with an increased risk and progression of AAA. Conclusions: The −420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

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ABSTRACT Introduction Sports injury is a common injury among professional tennis players compared to other sports. Updated rehabilitation methods can accelerate players' recovery and ensure a return to sporting activity. However, contemporary rehabilitation monitoring practices want updated reporting. Objective Monitoring tennis players' function and recovery methods during rehabilitation training after injury. Methods The tennis player underwent arthroscopic capsulotomy of the left ankle joint, free body removal, and synovectomy. The athlete's body composition, blood routine, biochemistry, nutritional indices, and physiological indicators were monitored. Data were collected before, during, and at the end of the four months (6-10 months) of rehabilitation after the operation. Results 1 month after the operation, weight and lean mass decreased significantly; body fat percentage increased; static heart rate increased significantly (P<0.05). Three months after surgery, the athlete's lean mass increased significantly to 43.7 kg; body fat percentage decreased to 24.5% (P<0.05); hemoglobin, serum iron, total protein, and albumin improved; in rehabilitation during October, blood routine and biochemical blood indices were regular; Resting, maintained-load and recovery heart rate decreased significantly (P<0.05). Conclusion Tennis players should begin function monitoring, rehabilitation training, and nutritional recovery as soon as possible after ankle joint surgery. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução A lesão esportiva é uma lesão comum entre os tenistas profissionais, em comparação com outros esportes. Métodos atualizados de reabilitação podem acelerar a recuperação dos jogadores e garantir um retorno à atividade esportiva. Porém o monitoramento das práticas de reabilitação contemporâneas carece de relatórios atualizados. Objetivo Explorar o monitoramento da função e métodos de recuperação dos jogadores de tênis durante o treinamento de reabilitação após uma lesão. Métodos O tenista foi submetido a capsulotomia artroscópica da articulação do tornozelo esquerdo, remoção de corpo livre e sinovectomia. Foram monitorados a composição corporal do atleta, rotina sanguínea, bioquímica sanguínea, indicadores nutricionais e indicadores fisiológicos. Esses dados foram coletados antes, durante e ao final dos 4 meses (6-10 meses) de reabilitação após a operação. Resultados 1 mês após a operação, o peso e a massa magra diminuíram significativamente, aumentando a porcentagem de gordura corporal; o ritmo cardíaco estático aumentou significativamente (P<0,05). 3 meses após a cirurgia, a massa magra do atleta aumentou significativamente para 43,7 kg, a porcentagem de gordura corporal caiu para 24,5% (P<0,05); a hemoglobina, o ferro sérico, a proteína total e a albumina melhoraram. Na reabilitação durante o mês de outubro, a rotina sanguínea e os índices bioquímicos do sangue foram normais; a frequência cardíaca em repouso, com carga mantida e de recuperação diminuiu significativamente (P<0,05). Conclusão Os tenistas devem começar o monitoramento das funções, treinamento de reabilitação e recuperação nutricional o mais rápido possível após uma cirurgia na articulação do tornozelo. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción La lesión deportiva es una lesión común entre los tenistas profesionales en comparación con otros deportes. Los métodos de rehabilitación actualizados pueden acelerar la recuperación de los jugadores y garantizar la vuelta a la actividad deportiva. Sin embargo, el seguimiento de las prácticas contemporáneas de rehabilitación carece de informes actualizados. Objetivo Explorar el seguimiento de la función y los métodos de recuperación de los tenistas durante el entrenamiento de rehabilitación después de una lesión. Métodos El tenista fue sometido a una capsulotomía artroscópica de la articulación del tobillo izquierdo, a la extracción del cuerpo libre y a la sinovectomía. Se controló la composición corporal del atleta, la rutina sanguínea, la bioquímica sanguínea, los indicadores nutricionales y los indicadores fisiológicos. Estos datos se recogieron antes, durante y al final de los 4 meses (6-10 meses) de rehabilitación tras la operación. Resultados 1 mes después de la operación, el peso y la masa magra disminuyeron significativamente, aumentando el porcentaje de grasa corporal; la frecuencia cardíaca estática aumentó significativamente (P<0,05). 3 meses después de la operación, la masa magra de la atleta aumentó significativamente hasta 43,7 kg, el porcentaje de grasa corporal disminuyó hasta el 24,5% (P<0,05); la hemoglobina, el hierro sérico, la proteína total y la albúmina mejoraron. En el periodo de entrenamiento de rehabilitación en el mes de octubre, la rutina sanguínea y los índices bioquímicos sanguíneos fueron normales; la frecuencia cardíaca en reposo, con carga mantenida y en recuperación disminuyó significativamente (P<0,05). Conclusión Los jugadores de tenis deben comenzar el control de la función, el entrenamiento de rehabilitación y la recuperación nutricional lo antes posible después de la cirugía de la articulación del tobillo. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

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ABSTRACT Sarcopenia, a concept reflecting the loss of skeletal muscle mass, was reported to be associated with the prognosis of several tumors. However, the prognostic value of sarcopenia in patients with renal cancer remains unclear. We carried out this metaanalysis and systematic review to evaluate the prognostic value of sarcopenia in patients with renal cell carcinomas. We comprehensively searched PubMed, Embase, and Cochrane Library from inception to December 2018. Hazard ratio (HR) and 95% confidence interval (CI) were pooled together. A total of 5 studies consisting of 771 patients were enrolled in this quantitative analysis, 347 (45.0%) of which had sarcopenia. Patients with sarcopenia had a worse OS compared with those without sarcopenia (HR=1.76; 95%CI, 1.35-2.31; P <0.001). In the subgroup of patients with localized and advanced/metastatic diseases, sarcopenia was also associated with poor OS (HR=1.48, P=0.039; HR=2.14, P <0.001; respectively). With a limited sample size, we did not observe difference of PFS between two groups (HR=1.56, 95% CI, 0.69-3.50, P=0.282). In the present meta-analysis, we observed that patients with sarcopenia had a worse OS compared with those without sarcopenia in RCC. Larger, preferably prospective studies, are needed to confirm and update our findings.

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Non-invasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in the early diagnosis of tumors, especially in gastric cancer. Here, we designed and evaluated a novel 111In-DOTA-F56 peptide as a radioactive analogue of F56 (peptide WHSDMEWWYLLG) to bind VEGFR1. It was obtained by radiolabeling DOTA-F56 with 111InCl3 with 98% radiochemical purity and 1.4 ± 0.4 GBq/µmol specific activity. 111In-DOTA-F56 was obtained by the reaction of DOTA-F56 (10 µg) with 111InCl3 in pH 4.0 sodium acetate buffer at 85 °C for 20 min. 111In-DOTA-F56 shows good stability in 0.01 M Phosphate Buffered Saline (PBS) and 5% Human Serum Albumin (HSA). 111In-DOTA-F56 has a high binding affinity for human gastric cancer BGC-823 cells. Bio-distribution studies of 111In-DOTA-F56 were performed in nude mice xenografted with human gastric cancer BGC-823 cells and the results revealed tumor uptake accumulation. A blocking dose of DOTA-F56 significantly reduced the tumor uptake of 111In-DOTA-F56. Tumors were observed with Micro-SPECT images, and the uptake in the tumor increased with time from 4 h to 24 h. The MIP of the Micro-SPECT also showed that the excess DOTA-F56 can specifically block 111In-DOTA-F56 in a mouse tumor model. We successfully synthesized the 111In-DOTA-F56 VEGFR1-targeted peptide as a non-invasive molecule with fine radiochemical properties. Micro-SPECT indicates tumor uptake, which can be further blocked by excess of the F56 peptide, indicating that 111In-DOTA-F56 peptide has potential for early detection of VEGFR1 positive gastric cancer and is worthy of further clinical investigations.

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Sarcopenia, a concept reflecting the loss of skeletal muscle mass, was reported to be associated with the prognosis of several tumors. However, the prognostic value of sarcopenia in patients with renal cancer remains unclear. We carried out this meta-analysis and systematic review to evaluate the prognostic value of sarcopenia in patients with renal cell carcinomas. We comprehensively searched PubMed, Embase, and Cochrane Library from inception to December 2018. Hazard ratio (HR) and 95% confidence interval (CI) were pooled together. A total of 5 studies consisting of 771 patients were enrolled in this quantitative analysis, 347 (45.0%) of which had sarcopenia. Patients with sarcopenia had a worse OS compared with those without sarcopenia (HR=1.76; 95%CI, 1.35-2.31; P<0.001). In the subgroup of patients with localized and advanced/metastatic diseases, sarcopenia was also associated with poor OS (HR=1.48, P=0.039; HR=2.14, P<0.001; respectively). With a limited sample size, we did not observe difference of PFS between two groups (HR=1.56, 95% CI, 0.69-3.50, P=0.282). In the present meta-analysis, we observed that patients with sarcopenia had a worse OS compared with those without sarcopenia in RCC. Larger, preferably prospective studies, are needed to confirm and update our findings.

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