Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker.

BACKGROUND: Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear. METHODS: Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry. RESULTS: In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects. CONCLUSION: We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.

Higher TIGIT+ γδ TCM cells may predict poor prognosis in younger adult patients with non-acute promyelocytic AML.

Introduction: γδ T cells recognize and exert cytotoxicity against tumor cells. They are also considered potential immune cells for immunotherapy. Our previous study revealed that the altered expression of immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on γδ T cells may result in immunosuppression and is possibly associated with a poor overall survival in acute myeloid leukemia (AML). However, whether γδ T-cell memory subsets are predominantly involved and whether they have a relationship with clinical outcomes in patients with AML under the age of 65 remain unclear. Methods: In this study, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of γδ T-cell subsets, including central memory γδ T cells (TCM γδ), effector memory γδ T cells (TEM γδ), and TEM expressing CD45RA (TEMRA γδ), in peripheral blood from 30 young (≤65 years old) patients with newly diagnosed non-acute promyelocytic leukemia (also known as M3) AML (AMLy-DN), 14 young patients with AML in complete remission (AMLy-CR), and 30 healthy individuals (HIs). Results: Compared with HIs, patients with AMLy-DN exhibited a significantly higher differentiation of γδ T cells, which was characterized by decreased TCM γδ cells and increased TEMRA γδ cells. A generally higher TIGIT expression was observed in γδ T cells and relative subsets in patients with AMLy-DN, which was partially recovered in patients with AMLy-CR. Furthermore, 17 paired bone marrow from patients with AMLy-DN contained higher percentages of γδ and TIGIT+ γδ T cells and a lower percentage of TCM γδ T cells. Multivariate logistic regression analyses revealed the association of high percentage of TIGIT+ TCM γδ T cells with an increased risk of poor induction chemotherapy response. Conclusions: In this study, we investigated the distribution of γδ T cells and their memory subsets in patients with non-M3 AML and suggested TIGIT+ TCM γδ T cells as potential predictive markers of induction chemotherapy response.

The ectonucleotidases CD39 and CD73 on T cells: The new pillar of hematological malignancy.

Hematological malignancy develops and applies various mechanisms to induce immune escape, in part through an immunosuppressive microenvironment. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment (TME). Adenosine signaling through the A2A receptor expressed on immune cells, such as T cells, potently dampens immune responses. Extracellular adenosine generated by ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73) molecules is a newly recognized 'immune checkpoint mediator' and leads to the identification of immunosuppressive adenosine as an essential regulator in hematological malignancies. In this Review, we provide an overview of the detailed distribution and function of CD39 and CD73 ectoenzymes in the TME and the effects of CD39 and CD73 inhibition on preclinical hematological malignancy data, which provides insights into the potential clinical applications for immunotherapy.

Genotyping of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi from sheep and goats in China.

BACKGROUND: Few studies have molecularly characterized the potential zoonotic protozoa, Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in sheep and goats in China, therefore total 472 fecal samples were collected from eight provinces and infection rates of three protozoa were determined by PCR analysis of corresponding loci. All PCR positive samples were sequenced to identify the genotype. RESULTS: The overall infection rates for Cryptosporidium, G. duodenalis, and E. bieneusi were 1.9% (9/472), 20.6% (97/472), and 44.5% (210/472), respectively. C. xiaoi (n = 5), C. ubiquitum (n = 3), and C. anderson (n = 1) were identified in goats. 97 G. duodenalis strains were successfully detected, and assembly E (n = 96) and assembly A (n = 1) were identified. Two novel G. duodenalis multilocus genotype (MLGs) were identified, with one belonging to subgroup AI and the other to subgroup E5. Nine known genotype (BEB6, CD6, CHC8, CHG3, CHG5, Peru6, CHG1, CHG2, and COS-I) and four new genotype (CHG26, CHG27, CHG28, and CHS18) were identified in E. bieneusi, with CHG3 dominant in this group. CONCLUSIONS: The present results highlight the role of sheep and goats as reservoir hosts for this three gastrointestinal pathogens. In summary, we provided a platform for more detailed research on genotyping or subtyping intestinal pathogens to better understand their risks and modes of transmission.

Apoptosis-promoting properties of miR-3074-5p in MC3T3-E1 cells under iron overload conditions.

BACKGROUND: Iron overload can promote the development of osteoporosis by inducing apoptosis in osteoblasts. However, the mechanism by which miRNAs regulate apoptosis in osteoblasts under iron overload has not been elucidated. METHOD: The miRNA expression profile in MC3T3-E1 cells under iron overload was detected by next generation sequencing. qRT-PCR was used to determine the expression of miR-3074-5p in MC3T3-E1 cells under iron overload. The proliferation of MC3T3-E1 cells was tested using CCK-8 assays, and apoptosis was measured using flow cytometry. The miRanda and TargetScan databases were used to predict the target genes of miR-3074-5p. Interaction between miR-3074-5p and the potential target gene was validated by qRT-PCR, luciferase reporter assay and western blotting. RESULTS: We found that iron overload decreased the cell viability and induced apoptosis of MC3T3-E1 cells. The results of next generation sequencing analysis showed that miR-3074-5p expression was significantly increased in MC3T3-E1 cells under iron overload conditions, which was confirmed by further experiments. The inhibition of miR-3074-5p attenuated the apoptosis of iron-overloaded MC3T3-E1 cells. Furthermore, the expression of Smad4 was decreased and was inversely correlated with miR-3074-5p expression, and overexpression of Smad4 partially reversed the viability inhibition of iron-overloaded MC3T3-E1 cells by relieving the suppression of ERK, AKT, and Stat3 phosphorylation, suggesting its regulatory role in the viability inhibition of iron-overloaded MC3T3-E1 cells. The luciferase reporter assay results showed that Smad4 was the target gene of miR-3074-5p. CONCLUSION: miR-3074-5p functions as an apoptosis promoter in iron-overloaded MC3T3-E1 cells by directly targeting Smad4.

The efficacy and safety of Chinese herbal compound or combined with western medicine for pediatric adenoidal hypertrophy: A protocol for systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) or combined with western medicine in the treatment of pediatric adenoidal hypertrophy has been widely used in clinical practice, but the overall efficacy and safety is still unclear. This paper aims to evaluate the efficacy and safety analysis of TCM or combined with western medicine for pediatric adenoidal hypertrophy. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) were searched for randomized controlled trials of TCM or combined with western medicine for pediatric adenoidal hypertrophy from the date of establishment to July 2020, and Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) were searched for unpublished grey literature. Two researchers independently applied RevMan 5.3 software for data extraction and risk assessment of bias. RESULTS: The effectiveness and safety of TCM or combined with western medicine for pediatric adenoidal hypertrophy is evaluated by means of the Adenoid (A) /(Nasopharyngeal (N) ratio, clinical efficacy, integral score of TCM syndromes, clinical single symptom score, disease specific quality of life for children with obstructive sleep apnea 18 items survey (OSA-18), Interleukin 4 (IL-4) and adverse reaction incidence. CONCLUSION: This study will provide theoretical support for the clinical application of TCM or combined with western medicine for pediatric adenoidal hypertrophy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/J76AG.

Effect of high pressure homogenization treatment on the rheological properties of citrus peel fiber/corn oil emulsion.

BACKGROUND: Citrus fiber is a main component in the peel of citrus and contains natural dietary fiber. It is often used as a functional additive to improve the texture or nutritional property of food. It is also widely used to reduce the content of absorbable fat in sausages and other meat products, and to improve food stability as an emulsifier. In this research, the dynamic rheological properties (linear and non-linear) of citrus peel fiber/corn oil (CF/CO) emulsion system under high pressure homogenization (HPH) treatment was investigated. RESULT: Rheological results illustrated HPH treatment significantly increased the apparent viscosity of the emulsion, reduced the activation energy of the emulsion and distinctly improved the viscoelasticity of the emulsion. Meanwhile, HPH treatment increased the linear viscoelastic region of the sample, and the behavior of the emulsion converted from strain thinning (without HPH treatment) to weak strain overshoot (with HPH treatment). Lissajous curves indicated the viscosity of the sample increased first and then decreased with strain increasing and the third harmonic contributed much more to the first harmonic compared with the fifth harmonic. Chebyshev stress decomposition revealed that, as strain increased, the samples with HPH treatment showed internal-cycle strain hardening behavior first, then turned to internal-cycle softening behavior. CONCLUSION: HPH treatment can significantly improve the processing performance of CF/CO emulsion as well as the stability against large periodic oscillations in food processing. © 2020 Society of Chemical Industry.

A convenient nucleic acid test on the basis of the capillary convective PCR for the on-site detection of enterovirus 71.

The recent and continuing epidemic of enterovirus 71 in China has affected millions of children and resulted in thousands of deaths. Timely diagnosis and management is essential for disease control. Current enterovirus 71 molecular tests require resources that are unavailable for on-site testing. We have developed a simple-to-operate nucleic acid test, the convenient and integrated nucleic acid test, for local medical institutions. It uses a convective PCR for rapid amplification, a dipstick for visual detection of PCR products, and a simple commercial kit for nucleic acid extraction. By using a specially designed reagent and reaction tube containing a dipstick, the amplification and detection processes are well integrated and simplified. Moreover, cross contamination that may be caused by an open-tube detection system can be avoided. On the basis of the convenient and integrated nucleic acid test, an enterovirus 71 assay for on-site testing was developed. After evaluating known hand, foot, and mouth disease virus stocks of 17 strains of 11 different serotypes, this assay showed a favorable detection spectrum and no cross-reactivity. Its clinical performance was established by testing 141 clinical samples and comparing the results with a nested RT-PCR method. The assay showed a clinical sensitivity and specificity of 98.5% and 100%, respectively. Our results suggest that this convenient and integrated nucleic acid test enterovirus 71 assay may serve as an on-site diagnosis tool.

[Finite element study of maxillary Le Fort-I osteotomy with rigid internal fixation].

OBJECTIVE: To study the biomechanical characteristic of maxillary Le fort- I osteotomy with rigid internal fixation (RIF) , so as to choose best fixation method. METHODS: The 3-dimensional finite element models of maxillary Le Fort-I osteotomy with 9 kinds of RIF methods were established. Then the models were divided into three groups to calculate the stress distribution of the maxilla and the displacement of bone segment under 3 kinds of occlusion condition. The fixation stability of the different RIF methods was evaluated. RESULTS: Under the incisor occlusion condition, the stress of the cranio maxillary complex transmits mainly along the nasal-maxillary buttress. Under the premolar and molar occlusion condition, the stress transmits along the alveolar process first, then turns to the nasal-maxillary and zygomatic-maxillary buttress. The focused stress position of the internal fixation system is at the connection between the screws and the plate and at the plate near the osteotomy line. Under the premolar occlusion condition, the displacement of bone segment with different RIF methods was (in a decreasing order) 0.396509 mm (with bio-absorbable plate), 0.148393 mm (with micro-plate ), 0.078436 mm (with mini-plate) in group 1; 0.188791 mm (fixing at the nasal-maxillary buttress), 0.121718 mm (fixing at the zygomatic-maxillary buttress), 0.078436 mm (fixing at the both buttress) in group 2; 0.091023 mm (with straight plate), 0.078436 mm (with L shape plate), 0.072450 mm (with Y shape plate), 0.065617 mm (with T shape plate) in group 3. CONCLUSIONS: The fixation stability of using the bio-absorbable plate in Le Fort-I osteotomy is less stable than using the titanium plate. Fixing at the zygomatic-maxillary buttress is more stable than at the naso-maxillary buttress. The fixation stability is different by using different shapes of plates.

[Establishment and primary analysis of the three-dimensional finite element model of mandibular bilateral sagittal split ramus osteotomy with rigid internal fixation].

OBJECTIVE: Establish the three-dimensional finite element models of mandibular bilateral sagittal split ramus osteotomy (BSSRO) with rigid internal fixation (RIF), for further study of BSSRO. METHODS: CT scanned technology and the finite element software (ANSYS) were used to establish the original three-dimensional model of mandible, modify the model to animate the BSSRO, then establish the model of RIF, last mesh the model to establish the finite element model of BSSRO with RIF. Apply 100 N occlusion force at the central incisor; calculate the stress distribution of the mandible and the RIF. RESULTS: Three-dimensional finite element models of BSSRO with RIF were established, such as miniplate model, bicortical fixation screw model. When biting with the incisor and fixed with upper plate, the stress of the medial screw position of the distal and medial segment of mandible is high. When fixed with bicortical fixation screw, the highest stress position located at the internal surface of the medial screw' s position of the distal segment of mandible. CONCLUSIONS: The mentioned methods proved feasible in establishing the finite element models of BSSRO with RIF . The models can be applied to the study of BSSRO with RIF.