Clinical Utility of Inflammatory and Nutritious Index as Therapeutic Prediction of Nivolumab plus Ipilimumab in Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Biomarkers for predicting the outcome of ipilimumab plus nivolumab (Nivo-Ipi) treatment in cancer patients have not been identified. Herein, we investigated the prognostic significance of inflammatory and nutritional markers in patients with advanced non-small cell lung cancer (NSCLC) receiving Nivo-Ipi. METHODS: Our study retrospectively analyzed 101 patients with advanced NSCLC who received Nivo-Ipi at a single institution. Inflammatory and nutritional indices were correlated with patient outcomes and included the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS). RESULTS: The NLR significantly correlated with the PLR, SII, PNI, ALI, and GPS. Regarding therapeutic efficacy, the NLR, SII, and PNI predicted a partial response, and all indices predicted progressive disease. In subgroup analyses, the SII, PNI, and ALI predicted the outcome of patients with adenocarcinoma, whereas only the PNI predicted the outcome of patients with non-adenocarcinoma. The PNI and SII were the most useful indices in patients with a programmed death ligand-1 expression level of <1% and ≥1%, respectively. CONCLUSION: The NLR, PLR, SII, PNI, ALI, and GPS were significantly associated with the outcome of Nivo-Ipi treatment in patients with NSCLC. The PNI was the most suitable marker regardless of histological type. The SII and PNI were the most promising markers for patients with and without PD-L1 expression, respectively.

Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel.

INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.

The relationship between coping self-efficacy and B cells in breast cancer patients.

BACKGROUND: Breast cancer is the most common tumor among women throughout the world. Diagnosis and treatment of breast cancer are associated with stress and depression. Self-efficacy is one of the most important personal characteristics, studied in cancer, and is correlated with depression and immunity. The aim of the study is as follows: 1. Examining the correlation between coping self-efficacy with depression, DHEA levels, and immunity 2. Examining the correlation between depression and DHEA levels 3. Studying the effect of depression and DHEA levels on immunity 4. Examining the intermediate effect of DHEA levels on the correlation between coping self-efficacy and immunity METHODS: Thirty newly diagnosed breast cancer patients recruited from the Oncology Department, Kasr EL-Aini, Cairo University (ages 51.40 + 8.24 years) responded to two questionnaires: Coping Self-Efficacy Scale (CSES) and Patient Health Questionnaire-9 (PHQ-9); blood samples were collected to measure the phenotype of patients' cellular immunity and DHEA levels by flowcytometry and ELISA technique. RESULTS: There was a significant negative correlation between CSES and PHQ-9, a significant positive correlation between PHQ-9 and B-cell count, and there is a significant negative correlation between CSES and B-cell count. The presence of DHEA has no mediatory role on correlation between CSES and B-cell count. CONCLUSION: This paper presents a new model of psychoneuroimmunology by suggesting an effect of coping self-efficacy on immunity against breast cancer patients.

The prediction of lymphocyte count and neutrophil count on the efficacy of Xuebijing adjuvant treatment for severe community-acquired pneumonia: A post hoc analysis of a randomized controlled trial.

BACKGROUND: Adjuvant Xuebijing therapy exhibited a protective effect on severe community-acquired pneumonia (SCAP) in previous studies. Blood inflammatory biomarkers related to the disease subtype and severity of SCAP might be associated with the effects of Xuebijing on clinical outcomes of SCAP. PURPOSE: To investigate whether neutrophils or lymphocytes are a useful biomarker of the therapeutic effect of Xuebijing on mortality and inflammation damage index. STUDY DESIGN: A post hoc analysis of a randomized, placebo-controlled and double-blinded clinical trial of Xuebijing in patients with SCAP (Clinical Trial Registration: ChiCTR-TRC-13003534). METHODS: We compared 28-day mortality (primary outcome) and four clinical scores (secondary outcome), including pneumonia severity index (PSI) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and systemic inflammatory response syndrome (SIRS) score, according to the baseline strata of neutrophil count and lymphocyte count. RESULTS: A total of 675 patients were included in the analyses, of which 334 received Xuebijing and 341 received the placebo. Xuebijing was more effective in SCAP patients with higher lymphocyte counts and lower neutrophil counts. In the lymphocyte-dominated inflammation (LDI) subgroup, defined as neutrophil count <13 × 109 cells/l and lymphocyte count ≥0.65 × 109 cells/l, Xuebijing reduced 28-day mortality by 15% while mortality of the neutrophil-dominated inflammation (NDI) subgroup decreased by 4.7% (p = 0.050). There was also greater improvement in the PSI, SOFA, APACHE II, and SIRS scores following Xuebijing treatment in the LDI subgroup compared with the NDI subgroup. CONCLUSIONS: Xuebijing treatment shows stronger protective effects in SCAP patients with higher lymphocyte and lower neutrophil counts. Our findings may facilitate the selection of the most appropriate treatments for individual patients with SCAP, including who will receive Xuebijing injections.

Prognostic value of inflammatory and nutritional indexes among advanced NSCLC patients receiving PD-1 inhibitor therapy.

Though immunotherapy has to some extent improved the prognosis of patients with advanced non-small cell lung cancer (NSCLC), only a few patients benefit. Furthermore, immunotherapy efficacy is affected by inflammatory and nutritional status of patients. To investigate whether dynamics of inflammatory and nutritional indexes were associated with prognosis, 223 patients were analysed retrospectively. The inflammatory indexes of interest were neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) while prognostic nutritional index (PNI) and the haemoglobin, albumin, lymphocyte and platelet (HALP) score were considered as nutritional indexes. Patients were divided into high and low groups or into 'increase' and 'decrease' groups based on pre-treatment cut-off values and index dynamics after 6-week follow-up respectively. High pre-treatment PLR (OR = 2.612) and increase in NLR during follow-up (OR = 2.516) were significantly associated with lower objective response rates. Using multivariable analysis, high pre-treatment PLR (HR, 2.319) and increase in SII (HR, 1.731) predicted shorter progression-free survival, while high pre-treatment NLR (HR, 1.635), increase in NLR (HR, 1.663) and PLR (HR, 1.691) and decrease in PNI (HR, 0.611) predicted worse overall survival. The nomogram's C-index in inside validation was 0.718 (95% CI: 0.670-0.766). Our results indicated both nutritional and inflammatory indexes are associated with survival outcomes. Inflammatory indexes were additionally linked to treatment response. Index dynamics are better predictors than baseline values in predicting survival in advanced NSCLC patients receiving PD-1 inhibitor combined with chemotherapy as first-line.

Development of prognostic predictive model with neutrophil-lymphocyte ratio (NLR) in patients with gastric signet ring carcinoma.

ABSTRACT: The risk factors have not been well-defined for prognosis in gastric signet ring cell carcinoma (GSRC) patients. This study is designed to prognosticate survival in GSRC patients by establishing and verifying a predictive model with neutrophil-lymphocyte ratio (NLR).A total of 147 GSRC patients from Department of Surgical Oncology, Neimenggu Baogang Hospital, Inner Mongolia Medical University were retrospectively reviewed. A predictive model was established using Cox proportional hazards. The performance of the model was evaluated by ROC curves.In present study, we found that overall survival (OS) (P < .001, Fig. 1A) and tumor recurrence rate (P = .036, Fig. 1B) in the NLR ≤ 2.8 group were significantly better than those in the NLR > 2.8 group. These results showed that NLR ≤ 2.8 was significant prognostic factor related with both OS and tumor recurrence in patients with GSRC. After adjusting for competing risk factors, NLR ≤ 2.8 (hazard ratio [HR]: 2.625, 95% confidence interval [CI]: 1.505-5.3166, P = .003), tumor size (HR: 3.024, 95% CI: 1.521-4.186, P = .005), and tumor metastasis (HR: 3.303, 95% CI: 1.25-4.525, P = .012) remained independent predictors of tumor recurrence rate and OS. Our results showed that comparing with the model without NLR (area under ROC curve: 0.798), the model with NLR (area under ROC curve: 0.826) had significant better predictive power than the model without NLR, which further confirmed the value of NLR in predicting prognosis of patients with GSRC.In conclusion, a high NLR value independently predicts poor survival in patients with GSRC after surgery. The NLR may help oncologists evaluate outcomes of patients received surgical resection and chemotherapy in order to choose alternative therapies for patients with high NLR value.

Prognostic nutritional index and its dynamics after curative treatment are independent prognostic factors on survival in non-metastatic nasopharyngeal carcinoma.

PURPOSE: We aimed to identify the prognostic and predictive values of post-treatment prognostic nutritional index (PNI) and PNI dynamics in nasopharyngeal cancer patients (NPC) in this study. METHODS: One hundred seven non-metastatic NPC patients were included. PNI was calculated by using the following formula: [10 × serum albumin value (gr/dL)] + [0.005 × total lymphocyte count (per mm3)]. ROC analysis was used for determining prognostic PNI values and univariate and multivariate statistical analyses for prognostic characterization of PNI. RESULTS: The statistically significant cut-off values for pre- and post-treatment PNI were 50.65 and 44.75, respectively. Of the pre-treatment PNI analysis, PNI ≤ 50.65 group had shorter loco-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Furthermore, for post-treatment PNI analysis, PNI ≤ 44.75 group had shorter LRRFS and OS. In univariate analysis, only pre-treatment PNI was associated with LRRFS and DMFS, while pre- and post-treatment PNI were both associated with OS. In multivariate analysis, both PNI were independent prognostic markers for OS. In the combined analysis, pre- and post-treatment PNI, differences between the groups were statistically significant, and the PNI dynamics was an independent prognostic indicator for OS. CONCLUSION: PNI is a useful, independent prognostic marker for non-metastatic NPC patients. It is used for either pre- or post-treatment patients. Furthermore, changes in pre-treatment PNI value after curative treatment is a significant indicator for OS.

Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

Prospective observational study of nutritional/immunologic indices as predictive biomarkers for the response to anti-PD-1 drugs in non-small cell lung cancer (ICI-PREDICT study).

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have markedly improved the prognosis of many patients with advanced non-small cell lung cancer (NSCLC). However, the relationship between the patient's nutritional/immunologic status and the outcomes of ICI treatment remains unclear. In previous retrospective studies, we reported that the controlling nutritional status (CONUT) score, skeletal muscle area, and neutrophil-to-lymphocyte ratio were independent predictors of the response of NSCLC patients to anti-PD-1 drugs. The aim of this prospective multi-center study is to investigate the clinical impact of pre-treatment nutritional/immunologic indices and early post-treatment changes in the indices on treatment outcomes in advanced NSCLC. The main inclusion criteria are: (1) stage IV NSCLC, or stage III NSCLC not applicable for definitive chemoradiotherapy; (2) treatment with ICIs (monotherapy or combined with chemotherapy) as first-line therapy; and (3) available data on PD-L1 expression on tumor cells. A total of 300 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2025.

2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver.

Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly alleviated CIA. Metabolomics and transcriptomics, as well as their integrative analysis, detected significant changes in the pathways of bile secretion, cholesterol and linoleic acid metabolism in the plasma, liver and spleen during the CIA process and the opposite changes following 2-DG treatment, whereas the expression of the genes regulating these metabolic pathways were changed only in the spleen. In the rat liver, levels of (S)-5-diphosphomevalonic acid in the terpenoid backbone biosynthesis pathway were significantly decreased during CIA progression and increased following 2-DG treatment, and levels of taurochenodeoxycholic acid in the pentose and glucuronate interconversions pathway showed the opposite results. In the spleen, levels of 3-methoxy-4-hydroxyphenylglycol glucuronide in bile secretion and 12(S)-leukotriene B4 in arachidonic acid metabolism were significantly decreased during CIA progression and increased following 2-DG treatment. The changes in the gene-metabolite network of bile secretion in the spleen correlated with a decreased plasma L-acetylcarnitine level in CIA rats and an increase following 2-DG treatment. Our analysis suggests the involvement of spleen and liver metabolism in CIA under the control of glycolysis.

Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer.

Background: Adipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival. Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided. Results: We found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m2) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS. Conclusions: Lower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.

Research on the application of sport dance in colleges and universities in the healthy development of sports / Pesquisa sobre a aplicação da dança esportiva nas universidades no desenvolvimento saudável dos esportes / Estudio sobre la aplicación de la danza deportiva en las universidades en el desarrollo saludable de los deportes

ABSTRACT Introduction: Immunity is closely related to health. When the body's immunity is strong, it is healthy. On the contrary, various diseases appear. Sports dance is an entertainment and fitness sports project that integrates sports, music, aesthetics, and dance, the body movement dance as the necessary content and two-person or collective exercises as the primary form of exercise. Studies have shown that long-term adherence to Tai Chi exercise can significantly increase the serum immunoglobulin IgA, IgG, and IgM levels. Objective: The paper explores the effect of physical dance exercise on serum immunoglobulin and T lymphocyte subsets of college students. Methods: The thesis randomly selected 16 male and female students in the first-grade physical dance optional course of public physical education as the experimental group. They performed physical dance exercises three times a week, 40 minutes each time, and the training intensity was controlled at a heart rate of 135-150 beats/min. Ten weeks; besides, 16 male and female students in the first grade were selected as the control group, and no physical dance exercise was performed; all the subjects were drawn from the elbow venous blood on an empty stomach at the same time before and after the experiment to measure serum immunoglobulin and T lymph Cell subpopulation content. Results: After ten weeks of sports dance training, the serum immunoglobulin IgG of both men and women in the experimental group increased significantly (P<0.01), and the CD4+% and CD4+/CD8+ ratio of T lymphocyte subgroups showed extremely significant and significant increases (P <0.01, P<0.05), serum IgM tended to increase, IgA, CD8+% tended to decrease, but there was no significant change. Conclusions: Long-term physical dance exercise can improve the body's immune function. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: la inmunidad está estrechamente relacionado con la salud. Cuando la inmunidad del cuerpo es fuerte éste está sano. En caso contrario, aparecen diversas enfermedades. La danza deportiva é um projeto de entretenimiento y fitness que integra el deporte, la música, la estética y la danza, el movimiento corporal como contenido necesario y los ejercicios de das personas ou colectivos como forma principal de ejercicio. Los estudios han demonstraram que a adesão a largo plazo al ejercicio de Tai Chi pode aumentar também os niveles séricos de imunoglobulina IgA, IgG e IgM. Objetivo: O artigo explora o efeito do exercício físico de danza em subconjuntos de imunoglobulina sérica e linfocitos T de estudiantes universitários. Métodos: Para que a tese seja selecionada aleatoriamente, 16 ex-alunos e ex-alunos do curso optativo de danza física de primer grado de educação física pública como grupo experimental. Realizaron ejercicios de danza física tres veces por semana, 40 minutes cada vez, y la intensidad del entrenamiento se controló a una frecuencia cardíaca de 135-150 latidos/min. durante as semanas; además, se selecionar 16 alumnos y alumnas de primer grado como group de control, el que no realizó ningún ejercicio físico de danza. A todos os sujetos se les extrajo sangre venosa del codo com o estómago vacío, durante, antes e depois do experimento para medir o conteúdo da subpoblación de células T y de imunoglobulina sérica. Resultados: Después de diez semanas de entrenamiento de danza deportiva, la imunoglobulina IgG sérica de hombres y mujeres en el grupo experimental aumentó complementar (P <0,01), y la proporción CD4 +% y CD4 +/CD8 + de los subgrupos de linfocitos T mostró incrementos extremadamente provados. (P <0,01,P <0,05), la IgM sérica tendió a aumentar, la IgA, CD8 +% tendió a disminuir, mas nenhum hubo cambio projetado. Conclusiones: El ejercicio de danza física a largo plazo puede mejorar la función inmunológica del cuerpo. Nivel de evidencia II; Estudios terapéuticos: investigación de los results del tratamiento.

RESUMEN Introducción: la inmunidad está estrechamente relacionada con la salud. Cuando la inmunidad del cuerpo es fuerte éste está sano. En caso contrario, aparecen diversas enfermedades. La danza deportiva es un proyecto de entretenimiento y fitness que integra el deporte, la música, la estética y la danza, el movimiento corporal como contenido necesario y los ejercicios de dos personas o colectivos como forma principal de ejercicio. Los estudios han demostrado que la adherencia a largo plazo al ejercicio de Tai Chi puede aumentar significativamente los niveles séricos de inmunoglobulina IgA, IgG e IgM. Objetivo: El artículo explora el efecto del ejercicio físico de danza en subconjuntos de inmunoglobulina sérica y linfocitos T de estudiantes universitarios. Métodos: Para la tesis se seleccionaron aleatoriamente a 16 alumnos y alumnas del curso optativo de danza física de primer grado de educación física pública como grupo experimental. Realizaron ejercicios de danza física tres veces por semana, 40 minutos cada vez, y la intensidad del entrenamiento se controló a una frecuencia cardíaca de 135-150 latidos/min. durante diez semanas; además, se seleccionaron 16 alumnos y alumnas de primer grado como grupo de control, el que no realizó ningún ejercicio físico de danza. A todos los sujetos se les extrajo sangre venosa del codo con el estómago vacío, durante, antes y después del experimento para medir el contenido de la subpoblación de células T y de inmunoglobulina sérica. Resultados: Después de diez semanas de entrenamiento de danza deportiva, la inmunoglobulina IgG sérica de hombres y mujeres en el grupo experimental aumentó significativamente (P <0.01), y la proporción CD4 +% y CD4 + / CD8 + de los subgrupos de linfocitos T mostró incrementos extremadamente significativos. (P <0.01, P <0.05), la IgM sérica tendió a aumentar, la IgA, CD8 +% tendió a disminuir, pero no hubo cambios significativos. Conclusiones: El ejercicio de danza física a largo plazo puede mejorar la función inmunológica del cuerpo. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

The importance of the glucose-to-lymphocyte ratio in patients with hepatocellular carcinoma treated with sorafenib.

Aim: To show the prognostic significance of the glucose-to-lymphocyte ratio (GLR) in hepatocellular carcinoma (HCC). Patients & methods: A total of 150 patients with advanced HCC who were treated with sorafenib in our center between January 2011 and December 2019 were included in the study retrospectively. Neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and GLR were analyzed to assess their prognostic value using Kaplan-Meier and Cox regression analysis before and after propensity score matching (PSM). Results: In univariate analysis before and after PSM, albumin-bilirubin grade, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, prognostic nutritional index, AFP level and GLR were found to be significantly associated with both progression-free and overall survival. In multivariate analysis before and after PSM, GLR, albumin-bilirubin grade and AFP were determined to be independent prognostic factors for progression-free and overall survival. Conclusion: The GLR prior to sorafenib treatment is a new prognostic biomarker that may predict survival in advanced HCC.

Effects of dietary supplementation with glutamine on the lymphocyte proliferation and intestinal immune gene expression in broiler chickens infected with Salmonella Enteritidis.

An experiment was conducted to investigate the effects of glutamine (Gln) on the lymphocyte proliferation and intestinal immune relevant gene expression in broilers infected with Salmonella Enteritidis. 240 1-day-old broilers were divided randomly into four groups in a completely randomized design, each of which had 6 replicates. Birds were reared in battery cages for 21 days. The experimental groups were as follows: control group (unchallenged group, CON), basal diet; Salmonella Enteritidis challenged group (challenged with 2.0 × 104 CFU/mL of Salmonella Enteritidis, SCC), basal diet; Gln 1, basal diet plus Salmonella Enteritidis challenged plus Gln at 0.5% diet; Gln 2, basal diet plus Salmonella Enteritidis challenged plus Gln at 1.0% diet. The results showed that Salmonella Enteritidis infection led to some decrease in the relative weight of spleen and bursa (except at 21 d), lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and increased the heterophil percentage, H/L ratio, mRNA expression levels of TNF-α, NF-κB p65, IL-1ß, IL-6, and IL-8 in the jejunal and ileal mucosa compared with the measurements of these parameters in the CON group at d 4, 7, 14, and 21 (p < 0.05). On the other hand, chickens fed the Gln showed improved the relative weight of spleen and bursa, increased the lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and decreased the heterophil percentage, H/L ratio, and immune relevant gene expression in the jejunal and ileal mucosa compared with the measurements of these parameters in the SCC group (p < 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of Salmonella Enteritidis infection, and increase the intestinal immune barrier function of broilers.

Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.

20S-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits Murine Autoimmune Arthritis.

The ability to use large doses of vitamin D3 (D3) to chronically treat autoimmune diseases such as rheumatoid arthritis (RA) is prohibitive due to its calcemic effect which can damage vital organs. Cytochrome P450scc (CYP11A1) is able to convert D3 into the noncalcemic analog 20S-hydroxyvitamin D3 [20S(OH)D3]. We demonstrate that 20S(OH)D3 markedly suppresses clinical signs of arthritis and joint damage in a mouse model of RA. Furthermore, treatment with 20S(OH)D3 reduces lymphocyte subsets such as CD4+ T cells and CD19+ B cells leading to a significant reduction in inflammatory cytokines. The ratio of T reg cells (CD4+CD25+Foxp3+ T cells) to CD3+CD4+ T cells is increased while there is a decrease in critical complement-fixing anti-CII antibodies. Since pro-inflammatory cytokines and antibodies against type II collagen ordinarily lead to destruction of cartilage and bone, their decline explains why arthritis is attenuated by 20(OH) D3. These results provide a basis for further consideration of 20S(OH)D3 as a potential treatment for RA and other autoimmune disorders.

Safety and efficacy of spleen aminopeptide oral lyophilized powder for improving quality of life and immune response in patients with advanced breast cancer: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Health-related quality of life (HRQoL) is an important consideration in managing patients. Spleen aminopeptide oral lyophilized powder (SAOLP) has been used to enhance cellular immunity in a patient. This multicenter, randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the safety and efficacy of SAOLP for improving HRQoL in patients with breast cancer. Patients diagnosed with advanced breast cancer were included, and were administered SAOLP or placebo 4 mg qd for two cycles. The primary endpoint was improvement in HRQoL on day 42 measured by the EORTC QLQ-C30 and EORTC QLQ-BR23. Secondary endpoints included immunologic function, improvement in HRQoL on day 21 and 84, objective response rate, disease control rate, BMI and adverse events. On day 42, on the EORTC QLQ-C30 or EORTC QLQ-BR23, scores on the functional scales and QoL scale were significantly higher and scores on symptom scales were significantly lower in patients who received SAOLP compared to placebo (P < 0.05). On day 84, the number of CD3, CD4 and CD8 cells were significantly higher in patients who received SAOLP. There were no significant differences in objective response rate, disease control rate or BMI. SAOLP may improve HRQoL and the immune response in patients with advanced breast cancer, represents a convenient and safe adjuvant therapy.

Standardized astragalus extract for attenuation of the immunosuppression induced by strenuous physical exercise: randomized controlled trial.

BACKGROUND: This paper aimed to verify how a supplementation of rower's diet with Astragalus Membranaceus Root (AMR) modulated their immune system response to maximal physical exertion. METHODS: The double-blind study included 18 members of the Polish Rowing Team assigned to the supplemented group (n = 10), and the placebo group (n = 8). The participants performed a 2000 m test on a rowing ergometer at the beginning and at the end of the six-week of intensive training camp during which the supplemented group received 500 mg of AMR. Blood samples were obtained prior to, 1 min after completing, and 24 h after the exertion test. The levels of interleukin 2 (IL2), interleukin 4 (IL4), interleukin 10 (IL10), interferon ɤ (IFN-É£), and lactic acid were determined. Subpopulations of T regulatory lymphocytes [CD4+/CD25+/CD127-] (Treg), cytotoxic lymphocytes [CD8+/TCRαß+] (CTL), natural killer cells [CD3-/CD16+/CD56+] (NK), and TCRδγ-positive cells (Tδγ) were determined with flow cytometry. RESULTS: After the camp, the initial NK and Treg levels sustained at the baseline, while Tδγ counts increased relative to the levels in the placebo group. In the supplemented subgroup, a decrease in IL2 level in reaction to maximal exertion clearly deepened while the change in IL-2/IL-10 level induced by the recovery after this exertion clearly increased, relative to the changes in the placebo group. CONCLUSIONS: AMR restored the immunological balance in strenuously trained athlets through a stabilization of NK and Treg cells with a positive trend in Tδγ towards Th1 response during restitution by cytokine IL2 modulation.

Probiotic fermentation of Ganoderma lucidum fruiting body extracts promoted its immunostimulatory activity in mice with dexamethasone-induced immunosuppression.

Ganoderma lucidum is a legendary traditional Chinese medicine with various bioactivities. This study was conducted (a) to explore the in vitro fermentation of the water extracts of G. lucidum fruiting body with Lactobacillus acidophilus and Bifidobacterium breve and (b) to investigate the effect of fermentation broth (GLFB) on dexamethasone (DEX)-induced immunosuppressed mice. Our results demonstrated that probiotic fermentation of G. lucidum fruiting body extracts underwent structural changing of major ganoderic acid components, such as ganoderic acid A (GA) into GC2, and this fermentation process involves changing of several metabolic pathways in the probiotic strains. GLFB could significantly improve the immunity, intestinal integrity, and gut microbiota dysbiosis in DEX-treated mice, and the immunostimulatory activity of GLFB was found closely related to its direct regulation on the expansion of CD4+ T cells in Peyer's patches of mice. These data implied that probiotic fermentation of G. lucidum fruiting body extracts promoted its immunostimulatory activity via biotransformation of components such as GA. This research provides a theoretical support for the development and application of G. lucidum fermentation by probiotics.

Predictive Value of a Prognostic Model Based on Lymphocyte-to-Monocyte Ratio Before Radioiodine Therapy for Recurrence of Papillary Thyroid Carcinoma.

BACKGROUND: The aim of this study was to investigate the predictive value of a prognostic model based on the lymphocyte-to-monocyte ratio (LMR) before radioiodine treatment for the recurrence of papillary thyroid carcinoma (PTC). METHODS: Clinicopathological data of 441 patients with papillary thyroid cancer were collected retrospectively. The Receiver operating characteristic (ROC) was used to determine the optimal cut-off value for predicting PTC recurrence by LMR before radioiodine treatment. Recurrence was the endpoint of the study, and survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Univariate and multifactorial analyses were performed using Cox proportional-hazards models to identify risk factors associated with PTC recurrence. RESULTS: The ROC curve showed that the best cut-off value of LMR before radioiodine treatment to predict recurrence in patients with PTC was 6.61, with a sensitivity of 54.1%, a specificity of 73%, and an area under the curve of 0.628. The recurrence rate was significantly higher in the low LMR group (16%) than in the high LMR group (5%) (P = 0.001, χ2 = 12.005). Multifactorial analysis showed that LMR < 6.61 (P = 0.006; HR = 2.508) and risk stratification (high risk) (P = 0.000; HR = 5.076) before radioiodine treatment were independent risk factors predicting recurrence in patients with PTC. Patients with preoperative LMR < 6.61 and high risk stratification had the lowest recurrence-free survival rate and the shortest recurrence-free survival time. CONCLUSIONS: The LMR-based prognostic model before radioactive iodine treatment is valuable for early prediction of PTC recurrence and it can be used in clinical practice as a supplement to risk stratification and applied in combination to help screen out patients with poorer prognosis early.