Expression of CD226 in the small intestinal group 3 innate lymphoid cells (ILC3) in mice / 细胞与分子免疫学杂志

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Linfoma em cão da raça cane corso: relato de caso / Lymphoma in a cane corso dog: case report / Linfoma en un perro cane corso: relato de un caso

Os linfócitos são células de defesa do organismo que funcionam como barreira contra infecções e células cancerígenas, elas circulam pelo sistema linfático e estão presentes por todo o organismo do animal, podem se proliferar de forma maligna, caracterizando o linfoma. Acometem em sua maioria, cães de raças de grande porte, animais de meia idade e idosos. Sendo uma doença de etiologia desconhecida, vários fatores podem contribuir para sua evolução, como deficiências autoimunes, bem como hábitos alimentares ao longo da vida do animal, ou até por predisposição genética. O presente relato de caso, tem o objetivo de mostrar a evolução gradual da doença, quais sinais clínicos o animal poderá apresentar, e como os exames laboratoriais podem nos auxiliar em seu diagnóstico.(AU)

The lymphocytes are defense cells of the body that act as a barrier against infection and cancer cells, they circulate through the lymphatic system and are present throughout the animal's body, and can proliferate in a malignant way, characterizing the lymphoma. They mostly affect large breed dogs, middle-aged and elderly animals. Being a disease of unknown etiology, several factors may contribute to its evolution, such as autoimmune deficiencies, as well as food habits throughout the animal's life, or even genetic predisposition. The present case report has the objective of showing the gradual evolution of the disease, which clinical signs the animal may present, and how laboratory tests can help us in its diagnosis.(AU)

Los linfocitos son células de defensa del organismo que actúan como barrera contra infecciones y células cancerígenas, circulan por el sistema linfático y están presentes en todo el organismo del animal, pudiendo proliferar de forma maligna, caracterizando el linfoma. Afectan sobre todo a perros de razas grandes, animales de mediana edad y ancianos. Siendo una enfermedad de etiología desconocida, varios factores pueden contribuir a su evolución, como deficiencias autoinmunes, así como hábitos alimentarios a lo largo de la vida del animal, o incluso predisposición genética. El presente caso clínico tiene como objetivo mostrar la evolución gradual de la enfermedad, qué signos clínicos puede presentar el animal y cómo las pruebas de laboratorio pueden ayudarnos en su diagnóstico.(AU)

Study on the prognostic influencing factors of esophageal squamous cell carcinoma and the predictive value of inflammatory reaction indexes on its postoperative recurrence / 中华肿瘤杂志

Objective: To explore the influence factors of poor prognosis of esophageal squamous cell carcinoma (ESCC) and the predictive value of inflammatory reaction indexes including neutrophils and lymphocytes ratio (NLR), platelet and lymphocyte ratio (PLR), monocyte and lymphocyte ratio (MLR) provision and differentiation degree, infiltration depth, lymph node metastasis number on the postoperative recurrence of ESCC. Methods: A total of 130 patients with ESCC who underwent radical resection from February 2017 to February 2019 in Nanyang Central Hospital were selected and divided into good prognosis group (66 cases) and poor prognosis group (64 cases) according to the prognostic effect. The clinical data and follow-up data were collected. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor prognosis. Spearman correlation analysis was used to determine the correlation between preoperative NLR, PLR and MLR with the degree of differentiation, depth of invasion and number of lymph node metastases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of NLR, PLR and MLR in predicting poor prognosis of ESCC. Results: Univariate analysis showed that the degree of differentiation, the degree of invasion and the number of lymph node metastasis were related to the prognoses of patients with ESCC (P<0.05). Multivariate logistic regression analysis showed that the degree of differentiation, depth of invasion and number of lymph node metastases were independent influencing factors for poor prognosis of patients with ESCC, moderate differentiation (OR=2.603, 95% CI: 1.009-6.715) or low differentiation (OR=9.909, 95% CI: 3.097-31.706), infiltrating into fibrous membrane (OR=14.331, 95% CI: 1.333-154.104) or surrounding tissue (OR=23.368, 95% CI: 1.466-372.578), the number of lymph node metastases ≥ 3 (OR=9.225, 95% CI: 1.693-50.263) indicated poor prognosis. Spearman correlation analysis showed that NLR was negatively correlated with the degree of differentiation and the number of lymph node metastases (r=-0.281, P=0.001; r=-0.257, P=0.003), PLR was negatively correlated with the degree of differentiation, depth of invasion and number of lymph node metastasis (r=-0.250, P=0.004; r=0.197, P=0.025; r=-0.194, P=0.027), MLR was positively correlated with the degree of differentiation and the number of lymph node metastasis (r=0.248, P=0.004; r=0.196, P=0.025). ROC curve analysis showed that the areas under the curve of NLR, PLR and MLR in predicting poor prognosis of ESCC were 0.971, 0.925 and 0.834, respectively. The best cut-off value of NLR was 2.87. The sensitivity and specificity of NLR in predicting poor prognosis of ESCC were 90.6% and 87.9%, respectively. The optimal cut-off value of PLR was 141.75. The sensitivity and specificity for predicting poor prognosis of ESCC were 92.2% and 87.9%, respectively. The best cut-off value of MLR was 0.40. The sensitivity and specificity of MLR in predicting poor prognosis of esophageal squamous cell carcinoma were 54.7% and 100.0%, respectively. Conclusions: The degree of differentiation, the degree of invasion and the number of lymph node metastases are closely related to the poor prognosis of patients with esophageal squamous cell carcinoma. NLR, PLR and MLR can provide important information for predicting the poor prognosis of esophageal squamous cell carcinoma.

Intestinal and lung inflammatory group 2 innate lymphoid cells (iILC2s) and their related cytokines in chronic obstructive pulmonary disease / 细胞与分子免疫学杂志

Objective To investigate the relationship between intestinal inflammatory group 2 innate lymphoid cells (iILC2s) and lung ILC2s and its inflammatory response in chronic obstructive pulmonary disease (COPD). Methods Mouse COPD model was established by smoking method. The mice were randomly divided into normal group and COPD group. HE staining was used to detect the pathological changes in lung and intestine tissues of mice in normal group and COPD group, and the contents of natural ILC2s(nILC2s) and iILC2s cells were measured by flow cytometry. Wright-Giemsa staining was used to measure the number of immune cells in the bronchoalveolar lavage fluid (BALF) of mice in normal group and COPD group, and the concentration of IL-13 and IL-4 was detected by ELISA. Results In COPD mice, epithelial cells of the lung and intestinal tissues exhibited pathological hyperplasia, partial atrophy or deletion, inflammatory cell infiltration, increased pathological score and significantly increased neutrophils, monocytes, and lymphocytes in BALF. Lung iILC2s, intestinal nILC2s and iILC2s were increased significantly in the COPD group. The contents of IL-13 and IL-4 in BALF were significantly increased. Conclusion The increase of iILC2s and their related cytokines in COPD lung may be related to intestinal inflammatory ILC2s.

The role of group 3 innate lymphoid cells(ILC3) in the evolution of the immune system: An update / 细胞与分子免疫学杂志

Group 3 innate lymphoid cells (ILC3) are an ILC subset that is characterized by the expression of retinoic acid-related orphan nuclear receptor γt (RORγt) and interleukin 22 (IL-22). This review summarizes the role of ILC3 in coordinating innate immunity and adaptive immunity based on current research and elaborate the significance of ILC3 from the perspective of immune system evolution. In addition, based on immune-related functions, we propose a possible time when ILC3 appears in the evolution of the immune system. And then, the research limitations and prospects are discussed.

The role of group 2 innate lymphoid cells (ILC2) in respiratory allergic diseases: An update / 细胞与分子免疫学杂志

Group 2 innate lymphoid cells (ILC2s) are the "mirror cells" of Th2 cells. Although the total cell number of ILC2s is far less than that of CD4+ Th2 cells in the body, the activated ILC2s have a more powerful biological activity than CD4+ Th2 cells and can rapidly enhanced Th2-cell inflammatory reaction. It plays an important role in the pathogenesis of allergic respiratory diseases. The transmitters that activate ILC2s include inflammatory cytokines (IL-33, IL-25, TSLP, IL-4, IL-9), lipid transmitters (prostaglandins, leukotrienes), and other activating transmitters (ICOS, Complement C3a, neuropeptide receptor, vasoactive intestinal peptide and calcitonin gene-related peptide, etc). Activated ILC2s produce large amounts of IL-4, IL-5, IL-9, IL-13, and amphiregulin and other inflammatory mediators, and induce airway hyperresponsiveness, mucus secretion and airway remodeling and other respiratory allergic reactions. Therefore, respiratory allergic diseases, especially steroid-dependent asthma, could be treated potentially by inhibiting the activation of ILC2s. Hereby, we summarized the immunobiology of ILC2s, the initiation of ILC2s in allergic inflammation, the relationship between ILC2s and respiratory allergic diseases, and the recent advances in biological agents targeted by ILC2s.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT).@*METHODS@#This retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI).@*RESULTS@#A total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively.@*CONCLUSION@#The pretreatment inflammation-nutrition score is a practical parameter for predicting non-response to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.

Study on the predictive significance of PLR, SII and RPR in ovarian endometriotic cyst / 中华妇产科杂志

Objective: To investigate the predictive value of platelet-to-lymphocyte ratio (PLR), red blood cell distribution width to platelet count ratio (RPR) and systemic immune inflammation index (SII) in the staging and postoperative recurrence of ovarian endometrial cysts. Methods: Retrospective analysis was made on the clinical data of patients who underwent laparoscopic surgery for ovarian cysts in the Affiliated Hospital of Qingdao University from January 2018 to January 2020. The patients with ovarian endometriosis cyst confirmed by pathology after surgery were the observation group (n=350), and the patients with other benign ovarian cyst were the control group (n=150). The preoperative platelet count, platelet distribution width, absolute number of neutrophils, lymphocyte absolute number, absolute number of monocytes, red blood cell distribution width, and serum cancer antigen 125 (CA125) of the patients in two groups were recorded, and PLR, neutrophil-to-lymphocyte ratio (NLR), RPR, SII, and systemic inflammation response index (SIRI) were calculated and analyzed. The general data of all patients and the follow-up data within 2 years after the operation of the observation group were statistically recorded to evaluate the diagnostic value of PLR, RPR and SII for ovarian endometrial cyst, and the predictive value of staging and recurrence within 2 years after the operation. Results: PLR, NLR, SII (median: 147.53, 1.86, and 488.70 respectively) and CA125 (median: 59.41 kU/L) in the observation group were significantly higher than those in the control group, while RPR (median: 0.16) was lower than that in the control group, with significant differences (all P<0.01). There was no significant difference in SIRI between the two groups (P>0.05). The PLR and SII (median: 122.73, 345.00) of the observation group at stage Ⅲ and Ⅳ were higher than those of patients at stage Ⅰ and Ⅱ, and the RPR was lower than that of patients with stage Ⅰ and Ⅱ, with significant differences (all P<0.001). The PLR, NLR, SII, SIRI (median: 179.63, 2.75, 762.96, and 1.06 respectively) and CA125 (median: 108.83 kU/L) in patients with recurrence were significantly higher than those in patients without recurrence 2 years after the operation, and the differences were statistically significant (all P<0.001). The area under curve (AUC) of CA125 in the diagnosis of ovarian endometriosis cyst was 0.951, the sensitivity was 85.7%, and the specificity was 93.0%, which were higher than those of PLR and SII; the AUC of PLR+SII+CA125 in the diagnosis of ovarian endometriosis cyst was 0.952. The AUC of RPR predicting the stage of ovarian endometriosis cyst was 0.713, higher than PLR and SII, lower than CA125; the AUC of RPR+SII+CA125 in predicting the stage of ovarian endometriotic cyst was 0.825, with sensitivity of 68.7% and specificity of 85.7%. The AUC predicted by SII for recurrence of ovarian endometriotic cyst within 2 years after the operation was 0.803, higher than NLR, PLR, SIRI and CA125; the AUC of PLR+SII+CA125, sensitivity, specificity was 0.813, 81.5% and 73.0%, higher than SII. Conclusion: PLR, RPR and SII are related to the staging of ovarian endometriotic cyst, and SII has a certain predictive value for the recurrence of ovarian endometriotic cyst after surgery.

Analysis of high-risk factors for failure of autologous arteriovenous fistula in hemodialysis patients / 中华危重病急救医学

OBJECTIVE@#To investigate the high risk factors of failure of autologous arteriovenous fistula (AVF) in hemodialysis patients.@*METHODS@#A retrospective study was conducted, patients with maintenance hemodialysis (MHD) undergoing AVF admitted to General Hospital of Western Theater Command from January 2021 to December 2022 were enrolled, including 107 patients with normal AVF and 168 patients with AVF dysfanction. According to the causes of AVF failure, the patients were divided into AVF stenosis group (n = 103) and AVF thrombosis group (n = 65). Age, gender, body mass index (BMI) and comorbidities (hypertension, diabetes, coronary heart disease) and other clinical data of all patients were collected. Hemoglobin, hematocrit, white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein (CRP), high density lipoprotein, low density lipoprotein, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) within 1 month of AVF use in normal dialysis patients and 1 week before AVF failure. Multivariate Logistic regression was used to analyze the independent risk factors of AVF dysfuction in MHD patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on AVF dysfuction in MHD patients.@*RESULTS@#(1) There were significant differences in age, BMI, hypertension, hemoglobin, hematocrit, PLR and CRP [age (years): 56.94±14.32, 58.83±14.05, 51.57±13.19; BMI (kg/m2): 22.83±3.10, 21.27±4.98, 23.35±2.72; hypertension: 93.20%, 64.62%, 86.92%; hemoglobin (g/L): 110.82±22.16, 88.70±24.00, 87.95±23.45; hematocrit: 0.350±0.069, 0.282±0.076, 0.275±0.071; PLR: 197.35±113.59, 192.55±138.25, 162.12±73.25; CRP (mg/L): 10.01±4.02, 8.18±5.42, 3.17±1.30, all P < 0.05], among AVF stenosis group, AVF thrombosis group and AVF normal group, there were statistically significant differences no statistically significant difference was found in other indexes among three groups. (2) Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.849, 95% confidence interval (95%CI) was 1.278-18.397, P = 0.020], elevated CRP levels (OR = 2.104, 95%CI was 1.533-2.888, P = 0.000) were associated with AVF stenosis. Elevated CRP levels (OR = 1.984, 95%CI was 1.442-2.730, P = 0.000) was an independent risk factor for AVF thrombosis. Analysis of ROC curve showed that the area under the curve (AUC) of AVF dysfunction predicted by CRP was 0.712, 95%CI was 0.637-0.786, P = 0.000; CRP cut-off value was 1.8 mg/L, the sensitivity was 67.0%, the specificity was 83.7%.@*CONCLUSIONS@#Elevated CRP is an independent risk factor for AVF failure in hemodialysis patients, which can be used to predict the occurrence of AVF failure.

Predictive value of PASS score combined with NLR and CRP for infected pancreatic necrosis in patients with severe acute pancreatitis / 中华危重病急救医学

OBJECTIVE@#To investigate the predictive value of pancreatitis activity scoring system (PASS) combined with Neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) for infected pancreatic necrosis (IPN) in patients with severe acute pancreatitis (SAP).@*METHODS@#Clinical data of SAP patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected, including basic information, vital signs at admission, first laboratory indexes within 48 hours of admission. The PASS scores at admission and 24, 48 and 72 hours after admission were calculated. According to the diagnostic criteria of IPN, the patients were divided into the non-IPN group and the IPN group, and the independent risk factors of SAP complicating IPN were determined by using univariate analysis and multifactorial Logistic regression. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of NLR, CRP, and PASS score, alone and in combination for IPN in patients with SAP.@*RESULTS@#A total of 149 SAP patients were enrolled, including 102 in the non-IPN group and 47 in the IPN group. The differences in PASS score at each time point, NLR, CRP, procalcitonin (PCT), blood urea nitrogen, blood chloride, and days of hospitalization between the two groups were statistically significant. Multifactorial Logistic regression analysis showed that 72 hours admission PASS score [odds ratio (OR) = 1.034, 95% confidence interval (95%CI) was 1.005-1.065, P = 0.022], NLR (OR = 1.284, 95%CI was 1.139-1.447, P = 0.000), and CRP (OR = 1.015, 95%CI was 1.006-1.023, P = 0.001) were independent risk factors for IPN in patients with SAP. ROC curve analysis showed that the area under the ROC curve (AUC) of the PASS score at 72 hours of admission, NLR, and CRP alone in predicting IPN in SAP patients were 0.828, 0.771, and 0.701, respectively. The AUC of NLR combined with CRP, PASS combined with NLR, and PASS combined with CRP were 0.818, 0.895, and 0.874, respectively. The combination of PASS score at 72 hours after admission, NLR, and CRP had a better predictive ability for IPN in patients with SAP (AUC = 0.922, 95%CI was 0.877-0.967), and the sensitivity was 72.3% when the cut-off value was 0.539.@*CONCLUSIONS@#The predictive value of the PASS score at 72 hours after admission, NLR and CRP in combination for IPN in SAP patients is better than that of the combination of each two and individual detection and has better test efficacy.

Neutrophil-lymphocyte and platelet-lymphocyte ratios for assessing disease activity in patients with rheumatoid arthritis receiving tofacitinib treatment / 南方医科大学学报

OBJECTIVE@#To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib.@*METHODS@#This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity.@*RESULTS@#PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients.@*CONCLUSION@#NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia / 中国当代儿科杂志

OBJECTIVES@#To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth.@*RESULTS@#The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05).@*CONCLUSIONS@#Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura / 中国实验血液学杂志

OBJECTIVE@#To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP).@*METHODS@#One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed.@*RESULTS@#In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%.@*CONCLUSION@#Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.

Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.@*RESULTS@#The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.@*CONCLUSION@#Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Can NLR be a biomarker for mucositis and gvhd in patients undergoing allogeneic HSCT?

Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment for many diseases; however, it can induce complications such as Oral Mucositis (OM) and Graft-versus- Host Disease (GVHD). The neutrophil-lymphocyte ratio (NLR) is a peripheral biomarker of systemic inflammation and an independent prognostic factor for several inflammatory diseases. Aim: This study aimed to evaluate the association of NLR with OM and GVHD in patients undergoing allogeneic HSCT. Methods: Patients who underwent allogeneic HSCT at the Bone Marrow Transplant Service of the Hospital de Clínicas Complex of the Federal University of Paraná were included in the study. Socio-demographic data and blood counts were collected from patients' medical records. The NLR was calculated and associated with OM and GVHD. Results: 45 patients were included in the study. Although NLR was higher in patients with OM and oral GVHD, no statistical difference was observed, and no relationship between OM and GVHD with NLR could be stated. Conclusion: Although both OM and GVHD are associated with an inflammatory response as well as the immune system, it was not associated with NLR. Further investigation considering other variables related to HSCT might find possible associations, as it could favor patient management and prevention

Le taux de lymphocytes T CD4 au diagnostic de la séropositivité au virus de l'immunodéficience humaine à Libreville, 2022 / CD4 T lymphocyte count at diagnosis of human immunodeficiency virus seropositivity in Libreville, 2022

Introduction. L'efficacité du traitement antirétroviral dans la restauration immunitaire dépend fortement du stade de l'infection et du taux de lymphocyte TCD4 au moment de l'introduction du traitement. Nous avons évalué le taux de lymphocytes TCD4 à la découverte de la séropositivité au VIH pour caractériser le niveau d'infection de chaque patient. Matériel et méthodes. C'est une étude transversale et descriptive qui s'est déroulée dans le laboratoire de virologie de la faculté de médecine de Libreville. Nous avons analysé les données de la cohorte DERIRADO. Résultats. Nous avons inclus 133 patients. L'âge médian était de 45 ans (Q1-Q3 :37 ; 52). La médiane de LTCD4 était de 388 cellules/mm3 (Q1-Q3 : 250 ; 556). Le diagnostic était avancé chez 112 (84%) patients. Conclusion. La découverte de la séropositivité au Virus de l'Immunodéficience Humaine est faite à un stade d'immunodépression avancé chez la majorité des patients. Ce constat relève la nécessité de mettre en route les politiques de sensibilisation pour cibler les populations clés et amener le plus grand nombre au dépistage de l'infection par le Virus de l'Immunodéficience Humaine si l'on veut diminuer la courbe de transmission.

Introduction. The effectiveness of antiretroviral therapy in immune restoration largely depends on the stage of infection and the TCD4 lymphocyte count at the time of treatment initiation. We evaluated the rate of TCD4 lymphocytes at the discovery of HIV seropositivity to characterize the level of infection of each patient. Methods. This was a cross sectional descriptive and analytic study whose setting was the laboratory of virology of the faculty of medicine of Libreville. Our data source was DERIRADO cohort. Results. We included 133 patients. The median age was 45 (Q1- Q3:37;52). The median LTCD4 was 388 cells/mm3 (Q1-Q3: 250; 556). The diagnosis was advanced in 112 (84%) patients. Conclusion. The diagnosis of seropositivity to the Human Immunodeficiency Virus is made at a stage of immunosuppression in the majority of patients. This highlights the need to implement sensitization policies to target key populations and bring as many people as possible to screening in order to reduce the transmission curve

Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca / Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters

Resumo Fundamento A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). Objetivos Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. Métodos Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. Resultados Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. Conclusão A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos

Abstract Background Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. Objectives This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. Methods Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. Results Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. Conclusion Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.