Efficacy and safety analysis of AKT inhibitor in triple-negative breast cancer: A meta-analysis and systematic review.

OBJECTIVE: To determine the clinical benefit of monotherapy with AKT inhibitors in patients diagnosed with triple-negative breast cancer (TNBC). METHODS: A systematic search was conducted in PubMed, Embase, and Cochrane Library for articles reporting treatment with AKT inhibitors in TNBC. The primary endpoint was progression-free survival and overall survival (OS). Secondary endpoints included the clinical benefit rate (CBR, included the proportion of patients with complete response, partial response, and stable disease), overall response rate (ORR, included the proportion of patients with complete response and partial response), all drug-related adverse events (AEs), and ≥3 grade drug-related grade AE. RESULTS: We included 723 patients from 5 studies and observed a pooled progression-free survival of 0.80 (95% CI: 0.62-1.02; The Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] assessment: moderate certainty) and OS of 0.7 (95% CI: 0.50-0.99; GRADE assessment: high certainty) in TNBC patients treated with AKT inhibitors. Regarding clinical benefit rate and overall response rate were 1.21 (95% CI 0.85-1.73; GRADE assessment: moderate certainty) and 1.26 (95% CI 0.91-1.73; GRADE assessment: low certainty). Only OS had a statistical difference. For the odd ratio of all grade AE and ≥3 grade AE in the therapeutic process was counted and pooled, 4.34 (95% CI 1.33-14.14; GRADE assessment: moderate certainty) and 1.76 (95% CI 1.28-2.41; GRADE assessment: moderate certainty), respectively. CONCLUSIONS: AKT inhibitors showed slightly better efficacy in the treatment of TNBC. However, further studies are needed to evaluate its long-term safety and optimal regimen, and caution should be exercised in patients with coexisting gastrointestinal disorders. The clinical characteristics of the patients and the choice of drugs should be considered on an individual basis.

Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status.

Introduction: Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

Introducción: Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC). Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricional se evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Los indicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, el grosor del pliegue cutáneo del tríceps y la circunferencia de las piernas. Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.481.222 ng/ml). Se observaron diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativas entre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales. La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml como umbral para EC. Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC.La leptina puede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.

Perception of strigolactones and the coordinated phytohormonal regulation on rice (Oryza sativa) tillering is affected by endogenous ascorbic acid.

Phytohormones play a key role in regulating tiller number. Ascorbic acid (Asc)-phytohormone interaction plays a pivotal role in the regulation of senescence. We analysed the relationship between Asc and the enzyme concentrations and gene transcript abundances related to the signal perception of strigolactones (SLs), the contents of four phytohormones (abscisic acid, ABA; jasmonic acid, JA; indole acetic acid, IAA; cytokinin, CTK), the enzyme concentrations and gene transcript abundances related to the synthesis or transportation of these four phytohormones. Our results showed that Asc deficiency leads to the upregulation of enzyme concentrations, gene transcript abundances related to the SL signal perception, ABA synthesis and IAA transport. The altered level of Asc also leads to a change in the contents of ABA, JA, IAA and CTK. These findings support the conclusion that Asc or Asc/DHA play an important role in the signal perception and transduction of SLs, and Asc may affect the coordinated regulation of SL, IAA and CTK on rice (Oryza sativa ) tillering.

Assessment of dietary nutrient intake and its relationship to the nutritional status of patients with Crohn's Disease in Guangdong Province of China.

Introduction: Background and objectives: to investigate the association between the dietary nutrient intake and nutritional status of patients with Crohn's disease (CD). Methods: sixty CD patients who had been diagnosed but had not begun treatment were enrolled. The dietary nutrient intake was recorded after three days of 24-hour recall and was calculated using NCCW2006 software. The nutrition levels were assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, handgrip strength, and the circumference of both calves. Results: eighty-five per cent of CD patients did not meet the necessary energy requirements. Of these, the protein and dietary fiber intake in 63.33 % and 100 %, respectively, were below the standard of the Chinese dietary reference. Many patients had insufficient intake of vitamins, as well as other macro- and micronutrients. An inverse association was observed between the risk of malnutrition and higher levels of energy (1,590.0-2,070.6 kcal/d, OR = 0.050, 95 % CI: 0.009-0.279) and protein (55.6-70.5 g/d, OR = 0.150, 95 % CI: 0.029-0.773). Appropriate supplementation of vitamin E, calcium, and other dietary nutrients helped to reduce the risk of malnutrition. Conclusions: significant deficiencies in dietary nutrient intake were found in CD patients, and dietary intake was associated with the nutritional status of the patient. Appropriate adjustment and supplementation of nutrient intake may reduce malnutrition risk in CD patients. The gap between actual consumption and recommendation indicates a need for improved nutritional counseling and monitoring. Early relevant advice for the dietary guidance of CD patients may be beneficial for long-term effects associated with nutritional status.

Introducción: Antecedentes y objetivos: investigar la asociación entre la ingesta de nutrientes y el estado nutricional de los pacientes con enfermedad de Crohn (EC). Métodos: se reclutaron 60 pacientes de EC que habían sido diagnosticados, pero no habían iniciado ningún tratamiento. La ingesta de nutrientes se registró tras 3 días de recordatorio de 24 horas y se calculó utilizando el software NCCW2006. El estado nutricional se evaluó mediante la valoración global subjetiva generada por el paciente (PG-SGA). Los indicadores incluyeron el índice de masa corporal, la circunferencia media del brazo, la circunferencia del músculo de la parte superior del brazo, el grosor del pliegue cutáneo del tríceps, la fuerza de agarre y la circunferencia de pantorrilla. Resultados: el 85 % de los pacientes de EC no cubrieron las necesidades energéticas necesarias. De estos, las ingestas de proteína y fibra dietética en el 63,33 % y el 100 %, respectivamente, era más baja que lo que recominenda la norma de referencia dietética china. Muchos pacientes tuvieron una ingesta insuficiente de vitaminas, así como de otros macronutrientes y micronutrientes. Se observó una asociación inversa entre el riesgo de desnutrición y niveles más altos de energía (1590,0-2070,6 kcal/d, OR = 0,050, IC 95 % = 0,009-0,279) y proteínas (55,6-70,5 g/d, OR = 0,150, IC 95 % = 0,029-0,773). La suplementación adecuada de vitamina E, calcio y otros nutrientes dietéticos ayudó a reducir el riesgo de desnutrición. Conclusiones: se observaron deficiencias significativas en la ingesta de nutrientes en los pacientes con EC, y la ingesta dietética se asoció con el estado nutricional del paciente. El ajuste y la suplementación adecuados de la ingesta de nutrientes pueden reducir el riesgo de malnutrición de los pacientes con EC. La diferencia entre el consumo real y la recomendación indica la necesidad de mejorar el asesoramiento y el seguimiento nutricional. El consejo temprano pertinente para la orientación dietética de los pacientes con EC puede ser beneficioso para los efectos a largo plazo asociados al estado nutricional.

Joint Detection of Serum Vitamin D, Body Mass Index, and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn's Disease.

OBJECTIVE: Vitamin D (VD) deficiency was reported to contribute to the progression of Crohn's disease (CD) and affect the prognosis of CD patients. This study investigated the role of serum VD, body mass index (BMI), and tumor necrosis factor alpha (TNF-α) in the diagnosis of Crohn's disease. METHODS: CD patients (n=76) and healthy subjects (n=76) were enrolled between May 2019 and December 2020. The serum 25-hydroxyvitamin D [25(OH)D] levels, BMI, and TNF-α levels, together with other biochemical parameters, were assessed before treatment. The diagnostic efficacy of the single and joint detection of serum 25(OH)D, BMI, and TNF-α was determined using receiver operating characteristic (ROC) curves. RESULTS: The levels of 25(OH) D, BMI, and nutritional indicators, including hemoglobin, total protein, albumin, and high-density lipoprotein cholesterol, were much lower, and the TNF-α levels were much higher in the CD patients than in the healthy subjects (P<0.05 for all). The areas under the ROC curve for the single detection of 25(OH)D, BMI, and TNF-α were 0.887, 0.896, and 0.838, respectively, with the optimal cutoff values being 20.64 ng/mL, 19.77 kg/m2, and 6.85 fmol/mL, respectively. The diagnostic efficacy of the joint detection of 25(OH)D, BMI, and TNF-α was the highest, with an area under the ROC curve of 0.988 (95%CI: 0.968-1.000). CONCLUSION: The joint detection of 25(OH)D, TNF-α, and BMI showed high sensitivity, specificity, and accuracy in CD diagnosis; thus, it would be effective for the diagnosis of CD in clinical practice.

Bioinformatic Analysis and In Vitro and In Vivo Experiments Reveal That Fibrillarin Participates in the Promotion of Lung Metastasis in Hepatocellular Carcinoma.

Lung metastasis, the most frequent metastatic pattern in hepatocellular carcinoma, is an important contributor to poor prognosis. However, the mechanisms responsible for lung metastasis in hepatocellular carcinoma remain unknown. Aiming to explore these mechanisms, weighted gene coexpression network analysis (WGCNA) was firstly used to find hub genes related to lung metastasis. Then, we obtained 67 genes related to lung metastasis in hepatocellular carcinoma which were mainly related to ribosomal pathways and functions, and a protein interaction network analysis identified that fibrillarin (FBL) might be an important hub gene. Furthermore, we found that FBL is highly expressed in hepatocellular carcinoma and that its high expression increases the rate of lung metastasis and indicates a poor prognosis. Knockdown of FBL could significantly reduce proliferation and stemness as well as inhibiting the migration and invasion of hepatocellular carcinoma cells. Moreover, we found that FBL might be involved in the regulation of MYC and E2F pathways in hepatocellular carcinoma. Finally, we demonstrated that the knockdown of FBL could suppress hepatocellular carcinoma cell growth in vivo. In conclusion, ribosome-biogenesis-related proteins, especially Fibrillarin, play important roles in lung metastasis from hepatocellular carcinoma.

Hepatitis B Virus Promotes Hepatocellular Carcinoma Progression Synergistically With Hepatic Stellate Cells via Facilitating the Expression and Secretion of ENPP2.

Background: Hepatitis B virus (HBV) infection is a major risk factor causing hepatocellular carcinoma (HCC) development, but the molecular mechanisms are not fully elucidated. It has been reported that virus infection induces ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) expression, the latter participates in tumor progression. Therefore, the aim of the present study was to investigate whether HBV induced HCC malignancy via ENPP2. Methods: HCC patient clinical data were collected and prognosis was analyzed. Transient transfection and stable ectopic expression of the HBV genome were established in hepatoma cell lines. Immunohistochemical staining, RT-qPCR, western blot, and ELISA assays were used to detect the expression and secretion of ENPP2. Finally, CCK-8, colony formation, and migration assays as well as a subcutaneous xenograft mouse model were used to investigate the influence of HBV infection, ENPP2 expression, and activated hepatic stellate cells (aHSCs) on HCC progression in vitro and in vivo. Results: The data from cancer databases indicated that the level of ENPP2 was significant higher in HCC compared within normal liver tissues. Clinical relevance analysis using 158 HCC patients displayed that ENPP2 expression was positively correlated with poor overall survival and disease-free survival. Statistical analysis revealed that compared to HBV-negative HCC tissues, HBV-positive tissues expressed a higher level of ENPP2. In vitro, HBV upregulated ENPP2 expression and secretion in hepatoma cells and promoted hepatoma cell proliferation, colony formation, and migration via enhancement of ENPP2; downregulation of ENPP2 expression or inhibition of its function suppressed HCC progression. In addition, aHSCs strengthened hepatoma cell proliferation, migration in vitro, and promoted tumorigenesis synergistically with HBV in vivo; a loss-function assay further verified that ENPP2 is essential for HBV/aHSC-induced HCC progression. Conclusion: HBV enhanced the expression and secretion of ENPP2 in hepatoma cells, combined with aHSCs to promote HCC progression via ENPP2.

EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c.

EZH2, a histone methyltransferase, has been shown to involve in cancer development and progression via epigenetic regulation of tumor suppressor microRNAs, whereas BMI1, a driver of hepatocellular carcinoma (HCC), is a downstream target of these microRNAs. However, it remains unclear whether EZH2 can epigenetically regulate microRNA expression to modulate BMI1-dependent hepatocarcinogenesis. Here, we established that high EZH2 expression correlated with enhanced tumor size, elevated metastasis, increased relapse, and poor prognosis in HCC patients. Further clinical studies revealed that EZH2 overexpression was positively correlated to its gene copy number gain/amplification in HCC. Mechanistically, EZH2 epigenetically suppressed miR-200c expression both in vitro and in vivo, and more importantly, miR-200c post-transcriptionally regulated BMI1 expression by binding to the 3'-UTR region of its mRNA. Furthermore, miR-200c overexpression inhibits the growth of HCC cells in vivo. Silencing miR-200c rescued the tumorigenicity of EZH2-depleted HCC cells, whereas knocking down BMI1 reduced the promoting effect of miR-200c depletion on HCC cell migration. Finally, combination treatment of EZH2 and BMI1 inhibitors further inhibited the viability of HCC cells compared with the cells treated with EZH2 or BMI1 inhibitor alone. Our findings demonstrated that alteration of EZH2 gene copy number status induced BMI1-mediated hepatocarcinogenesis via epigenetically silencing miR-200c, providing novel therapeutic targets for HCC treatment.

Circulating leptin levels in the assessment of Crohn’s disease activity and its relation to nutritional status / Los niveles circulantes de leptina en la evaluación de la actividad de la enfermedad de Crohn y su relación con el estado nutricional

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn’s disease (CD).Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessedusing the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included bodymass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs.Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,48 ± 1,222 ng/ml). Significant differences were seenin NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGAscores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showedassociation between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD.Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional toolfor evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improvenutritional status.(AU)

Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC).Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricionalse evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Losindicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, elgrosor del pliegue cutáneo del tríceps y la circunferencia de las piernas.Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.48 ± 1.222 ng/ml). Se obser-varon diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativasentre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales.La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml comoumbral para EC.Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC. La leptinapuede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.(AU)

Assessment of dietary nutrient intake and its relationship to the nutritional status of patients with Crohn’s Disease in Guangdong Province of China / Evaluación de la ingesta de nutrientes y su relación con el estado nutricional de los pacientes con enfermedad de Crohn en la provincia de Guangdong de China

Background and objectives: to investigate the association between the dietary nutrient intake and nutritional status of patients with Crohn’s disease (CD). Methods: sixty CD patients who had been diagnosed but had not begun treatment were enrolled. The dietary nutrient intake was recorded after three days of 24-hour recall and was calculated using NCCW2006 software. The nutrition levels were assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, handgrip strength, and the circumference of both calves. Results: eighty-five per cent of CD patients did not meet the necessary energy requirements. Of these, the protein and dietary fiber intake in 63.33 % and 100 %, respectively, were below the standard of the Chinese dietary reference. Many patients had insufficient intake of vitamins, as well as other macro- and micronutrients. An inverse association was observed between the risk of malnutrition and higher levels of energy (1,590.0-2,070.6 kcal/d, OR = 0.050, 95 % CI: 0.009-0.279) and protein (55.6-70.5 g/d, OR = 0.150, 95 % CI: 0.029-0.773). Appropriate supplementation of vitamin E, calcium, and other dietary nutrients helped to reduce the risk of malnutrition. (AU)

Antecedentes y objetivos: investigar la asociación entre la ingesta de nutrientes y el estado nutricional de los pacientes con enfermedad de Crohn (EC). Métodos: se reclutaron 60 pacientes de EC que habían sido diagnosticados, pero no habían iniciado ningún tratamiento. La ingesta de nutrientes se registró tras 3 días de recordatorio de 24 horas y se calculó utilizando el software NCCW2006. El estado nutricional se evaluó mediante la valoración global subjetiva generada por el paciente (PG-SGA). Los indicadores incluyeron el índice de masa corporal, la circunferencia media del brazo, la circunferencia del músculo de la parte superior del brazo, el grosor del pliegue cutáneo del tríceps, la fuerza de agarre y la circunferencia de la pantorrilla. Resultados: el 85 % de los pacientes de EC no cubrieron las necesidades energéticas necesarias. De estos, las ingestas de proteína y fibra dietética en el 63,33 % y el 100 %, respectivamente, era más baja que lo que recominenda la norma de referencia dietética china. Muchos pacientes tuvieron una ingesta insuficiente de vitaminas, así como de otros macronutrientes y micronutrientes. Se observó una asociación inversa entre el riesgo de desnutrición y niveles más altos de energía (1590,0-2070,6 kcal/d, OR = 0,050, IC 95 % = 0,009-0,279) y proteínas (55,6-70,5 g/d, OR = 0,150, IC 95 % = 0,029-0,773). La suplementación adecuada de vitamina E, calcio y otros nutrientes dietéticos ayudó a reducir el riesgo de desnutrición. (AU)