Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, qPCR and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2 and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2 and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A and IL-18 in AA patients were elevated, and they were correlated between each other. In OVA-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2 and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/-mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

Multi­omics approach to improve patient­tailored therapy using immune checkpoint blockade and cytokine­induced killer cell infusion in an elderly patient with lung cancer: A case report and literature review.

The 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) remains low, despite recent advances in targeted therapy and immunotherapy. Therefore, there is a need to identify alternative strategies to improve treatment outcomes. Modern diagnostics can significantly facilitate the selection of treatment plans to improve patient outcomes. In the present study, multi-form diagnostic methodologies were adopted, including next-generation sequencing-based actionable gene sequencing, programmed death ligand 1 (PD-L1) immunohistochemistry, a circulating tumor cell (CTC) assay, flow cytometric analysis of lymphocyte subsets and computed tomography, to improve disease management in an 86-year-old female patient with relapsed metastatic NSCLC. High expression of PD-L1, elevated CTC tmutations, were observed. Based on these results, the patient was initially treated with the programmed death protein 1 blocking antibody sintilimab for two cycles, resulting in the stabilization of their condition, although the patient still exhibited severe pain and other symptoms, including fatigue, malaise, a loss of appetite and poor mental state. Informed by dynamic monitoring of the patient's response to treatment, the treatment plan was subsequently adjusted to a combination therapy with sintilimab and autologous cytokine-induced killer cell infusion, which eventually led to improved outcomes in both the management of the cancer and quality of life. In conclusion, multi-omics analysis may be used to establish patient-tailored therapies to improve clinical outcomes in hard-to-treat elderly patients with metastatic NSCLC.

Dissection of Hyperspectral Reflectance to Estimate Photosynthetic Characteristics in Upland Cotton (Gossypium hirsutum L.) under Different Nitrogen Fertilizer Application Based on Machine Learning Algorithms.

Hyperspectral technology has enabled rapid and efficient nitrogen monitoring in crops. However, most approaches involve direct monitoring of nitrogen content or physiological and biochemical indicators directly related to nitrogen, which cannot reflect the overall plant nutritional status. Two important photosynthetic traits, the fraction of absorbed photosynthetically active radiation (FAPAR) and the net photosynthetic rate (Pn), were previously shown to respond positively to nitrogen changes. Here, Pn and FAPAR were used for correlation analysis with hyperspectral data to establish a relationship between nitrogen status and hyperspectral characteristics through photosynthetic traits. Using principal component and band autocorrelation analyses of the original spectral reflectance, two band positions (350-450 and 600-750 nm) sensitive to nitrogen changes were obtained. The performances of four machine learning algorithm models based on six forms of hyperspectral transformations showed that the light gradient boosting machine (LightGBM) model based on the hyperspectral first derivative could better invert the Pn of function-leaves in cotton, and the random forest (RF) model based on hyperspectral first derivative could better invert the FAPAR of the cotton canopy. These results provide advanced metrics for non-destructive tracking of cotton nitrogen status, which can be used to diagnose nitrogen nutrition and cotton growth status in large farms.

Association of Clinical Features of Colorectal Cancer with Circulating Tumor Cells and Systemic Inflammatory Markers.

Background: Circulating tumor cells (CTCs) in peripheral blood have been shown to reflect the prognosis of patients with colorectal cancer, and epithelial and mesenchymal markers further predict the likelihood of cancer dissemination. This study was conducted to identify possible association of clinical features of colorectal cancer with CTC counts, their subtypes, and systemic inflammatory markers. Methods: Blood samples of 316 colorectal cancer patients were used for CTC detection and subtyping with EpCAM, CK8/18/19, vimentin, and twist as biomarkers. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio, lymphocyte/monocyte ratio, and systemic immune-inflammation index (SII) were also measured. The relationship between clinical data and these markers or parameters was analyzed. Results: Total CTC counts were correlated with whether there was lymph node involvement but was not correlated with TNM staging. There was a difference in mesenchymal CTCs between patients with and without lymph node involvement (P < 0.05). Also, more patients with metastasis tested positive for mesenchymal CTCs (P < 0.05). Of the systemic inflammatory markers, platelet/lymphocyte ratio was positively correlated with CTC counts (P < 0.01), and lymphocyte/monocyte ratio was negatively correlated with CTC counts (P < 0.05). Conclusions: Colorectal cancer patients with the mesenchymal markers on their CTCs are more likely to have lymph node involvement or distant metastasis than those without these markers.

A bifunctional fluorescent probe based on PET & ICT for simultaneously recognizing Cys and H2S in living cells.

Most reported probes that respond to Cysteine (Cys) and Hydrogen sulfide (H2S) can only identify one analyte, or they were interfered with homocysteine (Hcy) and glutathione (GSH) when recognizing Cys and H2S. In addition, nitrobenzoxadiazole (NBD) ether, as one of thiols recognition sites, inevitably encounters the situation that Cys, GSH and H2S cannot be distinguished on the same channel at the cellular level. In this work, by introducing NBD ether and NBD amine, we constructed a bifunctional fluorescent probe NJB for dual-site response to Cys and H2S via PET & ICT processes. NJB has wonderful selectivity for identifying Cys and HS-, with limits of detection as low as 58.4 nM and 81.1 nM, respectively. Interestingly, NJB has been successfully applied to detect Cys and HS- in MCF-7 cells. Therefore, the probe that serves as a great tool for inquiring the physiological and pathological functions of Cys and H2S in living cells is promising.

The clinical significance of circulating tumor cells and T lymphocyte subtypes in pancreatic cancer patients.

Circulating tumor cells (CTCs) are sensitive and reliable biomarkers for tracing relapsed and metastatic cancer. Here, we explore the clinical significance of CTCs and T lymphocyte subtypes in patients with pancreatic cancer. A total of 106 patients with the pancreatic cancer were enrolled in this study. The enrichment and identification of CTCs were achieved before treatment by a PatrolCTC detection technique. Flow cytometry (FACS) was used to characterize CD4, CD8, natural killer (NK) cells, and Tregulatory (Treg) lymphocyte subtypes. Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-17A (IL-17A), Interleukin-10 (IL-10), and Interferon γ (IFN-γ) were measured by meso-scale discovery (MSD) assay. Among these patients, 44 (41.5%) patients with pancreatic ductal adenocarcinoma (PDAC) were female and 62 (58.5%) cases were male. Case numbers with II-IV tumor-node-metastasis (TNM) stages were 32 (30.2%), 50 (47.2%), and 24 (22.6%), respectively. The positive rate of CTCs before surgery was 37.5% (12/32), 88.0% (44/50) and 100% (24/24) in stage II, III, and IV patients, respectively. Total CTCs, mixed CTCs, and mesenchymal CTCs (MCTCs) were strongly relevant to shorter progression-free survival (PFS) of the patients. In addition, total CTCs (≥6) and positive MCTCs were also significantly correlated with recurrence and metastasis. The patients with high CTCs also had low levels of CD4, CD4/CD8 ratio, NK cells, IL-2, and IFNγ. In contrast, Treg cells had significant elevation in PDAC patients. These results indicated that CTCs number in PDAC patients was an independent indicator for worse PFS. High CTCs also had strong correlation with weak cellular immunity functions.

A bifunctional fluorescent probe based on "AND logic" for the simultaneous recognition of H2S/HNO and its bioimaging applications.

The reaction of NO and H2S to form HNO is a classical pathway in physiological conditions. The reported single recognition-type fluorescent probes are difficult to track precisely the relationships of H2S and HNO. It is necessary to develop a bifunctional fluorescence probe (NJA) for monitoring simultaneously the production of endogenous HNO and H2S. Using 7-Nitrobenzofurazan (NBD) and 2-(diphenylphosphine) benzoate as recognition sites, the obatined NJA can detect specifically HS- and HNO. The detection limit of HS- and HNO are 0.46 µM and 1.42 µM, respectively. Based on the dual recognition sites and input signals of the probe, a molecular "AND" logic gate was established to detect successfully H2S and HNO in MCF-7 cells. NJA based on "AND logic" provided a simple and robust tool for monitoring the production of endogenous HNO correlative with H2S and NO in living cells.

Identification of Critical Pathways and Potential Key Genes in Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: The poorly differentiated pancreatic adenocarcinoma (PDAC) is an extremely lethal neoplasm without effective biomarkers for early detection and prognosis prediction, which is characteristically unresponsive to chemotherapeutic regimens. This study aims at searching for key genes which could be applied as novel prognostic biomarkers and therapeutic targets in PDAC. METHODS: Clinical samples were collected and a comprehensive differential analysis of seven PDAC samples by integrating RNA-seq data of tumor tissues and matched normal tissues from both our cohort and gene expression profiling interactive analysis (GEPIA) were performed to discover potential prognostic genes in PDAC. Pathway enrichment analysis was carried out to determine the biological function of PDAC differentially expressed genes (DEGs), and protein-protein interaction (PPI) network was constructed for functional modules analysis. Real-time PCR was performed to validate expression of hub genes. RESULTS: A total of 126 PDAC-specific expressed genes identified from seven PDAC samples were predominantly enriched in cell adhesion, integral component of membrane, signal transduction and chemical carcinogenesis, IL-17 signaling pathway, indicating that obtained genes might play a unique role in PDAC tumorigenesis. Furthermore, survival analysis revealed that five genes (CEACAM5, KRT6A, KRT6B, KRT7, KRT17) which exhibited high expression levels in tumor tissues were obviously correlated with the prognosis of PDAC patients and KRT7 was positively correlated with KRT6A, KRT6B, KRT17 expression. In addition, real-time PCR demonstrated that the expression level of the hub genes was consistent with RNA-seq analysis. DISCUSSION: The current study suggested that CEACAM5, KRT6A, KRT6B, KRT7, and KRT17 may represent novel prognostic biomarkers as well as novel therapeutic targets for poorly differentiated PDAC.

Precursor B-cell lymphoblastic leukemia with surface immunoglobulin light chain expression in 2 chinese patients.

BACKGROUND: Precursor B-cell acute lymphocytic leukemia (ALL) with surface immunoglobulin light chain expression is a rare disease entity. The differential diagnosis is difficult but critical for disease management. AIMS: We report 2 cases (1 adult and 1 infant) of precursor B-cell ALL who presented at diagnosis with surface immunoglobulin light chain expression revealed by flow cytometric immunophenotyping and discuss its clinical significance. CASE REPORT: The 2 patients presented with nonspecific symptoms such as fever, pallor, fatigue or lymphadenopathy. Flow cytometric immunophenotyping showed that both patients expressed CD34/CD19/CD10/CD22/CD9/HLA-DR/CD38/CD123/CD13 (partial) and had unexpected single λ light chain expression. Cytogenetic analysis revealed t(9;22)(q34;q11) in the adult patient and normal karyotype in the infant. Both cases were diagnosed and managed as precursor B-ALL, and the patients showed good response to treatment regimens. CONCLUSION: We describe 2 cases of precursor B-ALL with unexpected surface light chain expression. The exceedingly rare immunophenotypes have diagnostic implication for immunophenotyping of this malignancy. Treatment regimens for precursor B-cell ALL are suitable for such cases.

[Clinical features and therapeutic response of aplastic anemia patients with or without cytogenetic abnormalities].

OBJECTIVE: To compare clinical features and therapeutic response of patients with aplastic anemia with and without cytogenetic abnormalities. METHODS: Clinical features of 133 patients with successful chromosomal analysis were retrospectively studied, and therapeutic response between patients with and without cytogenetic abnormalities was compared. RESULTS: Cytogenetic abnormalities were found in 9 patients, which included trisomy 8 (4 cases), monosomy 7 (2 cases) and Xq- (1 case), 1q- (1 case) and 7q- (1 case). No significant difference was detected between patients with or without cytogenetic abnormalities in terms of age (50 vs. 58, P=0.337), sex ratio (male 55.56% vs. 62.10%, female 44.44% vs. 37.90%, P=0.762), or episode of acute aplastic anemia (44.44% vs. 37.10%, P=0.728). Patients with cytogenetic abnormalities had a tendency towards poorer rate of therapeutic response, which was however not significantly different from those without (55.56% vs. 79.03%, P=0.116). All of the 4 patients with +8 responded to treatment, whilst none of those with -7 or 7q- did. CONCLUSION: No significant difference was found between aplastic anemia patients with or without cytogenetic abnormalities in terms of clinical features and therapeutic response. Patients with trisomy 8 seem to have a favorable response towards treatment.

Biphenotypic hematologic malignancy: a case report of the 8p11 myeloproliferative syndrome in a child.

SUMMARY: The 8p11 myeloproliferative syndrome, also known as stem cell leukemia/lymphoma, is a rare, atypical, myeloproliferative disorder and lymphoid malignancy associated with chromosomal abnormalities involving the 8p11 chromosomal band. Translocations associated with this syndrome result in the fusion of the fibroblast growth factor receptor 1 (FGFR 1) gene with various partners, resulting in ligand-independent FGFR activity. To date, 8 partner genes have been identified in association with FGFR1 rearrangements. The most frequent FGFR1 translocation partner is the zinc finger gene ZNF198 located at 13q11. Disease phenotypes associated with this translocation include poor prognosis and transformation to acute leukemia and non-Hodgkin lymphoma. In common with a T-cell phenotype, obtaining and maintaining remission is difficult by conventional chemotherapy. This study describes an illustrative case of 8p11 myeloproliferative syndrome/stem cell leukemia/lymphoma outlining its chief features and historical developments.

[Effect of Arsenic Trioxide on Myelomonocytic Progenitor Cells in Patients with Myelodysplastic Syndrome in Vitro]

The Effect of arsenic trioxide (As(2)O(3)) on myelomonocytic progenitor cells of patients with myelodysplastic syndrome was studied. Bone marrow CFU-GM was assayed in the agar semi-solid culture, and the bone marrow cells were incubated in liquid culture and the expressions of CD33, CD15 and bcl-2 on the marrow cells were detected by APAAP method in 24 patients. The suppressive effects of As(2)O(3) to CFU-GM were increased with the rise of As(2)O(3) concentrations. The suppression of As(2)O(3) (0.388 micro mol/L) to cluster formation was stronger than to colony formation, the suppressive rates were 70.78% vs 34.05% in low-risk group, and 86.76% vs 65.86% in high-risk group (P < 0.01), respectively. 0.194 micro mol/L of As(2)O(3) decreased clusters and increased colonies in low-risk group, but decreased clusters and did not change colonies in high-risk group. High concentration (1.94 micro mol/L) of As(2)O(3) downregulated the expression rate of CD33 and CD15 in both groups, and low concentration (0.194 micro mol/L) downregulated the expression rate of CD33 and upregulated the expression rate of CD15 in low-risk group, but decreased expression of CD33 and did not alter CD15 in high-risk group. At the same time, the high concentration of As(2)O(3) downregulated expression of bcl-2 and resulted in karyopyknosis and cytoplasm condensation; low concentration generated similar effect on expression of bcl-2 and cell morphology in high-risk group, but did not affect in low-risk. It is concluded that As(2)O(3) suppressed myelopoiesis and impelled myelomonocytic cells to apoptosis, low concentration of As(2)O(3) induced the proliferation and differentiation of myelomonocytic cells in low-risk group, however, suppressed the growth of myelomonocytic cells and accelerated the cells apoptosis in high-risk group.