Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

The antigenic anatomy of SARS-CoV-2 receptor binding domain.

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 µg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19.

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Positional cloning identified HvTUBULIN8 as the candidate gene for round lateral spikelet (RLS) in barley (Hordeum vulgare L.).

KEY MESSAGE: Map-based cloning, subcellular localization, virus-induced-gene-silencing and transcriptomic analysis reveal HvTUB8 as a candidate gene with pleiotropic effects on barley spike and leaf development via ethylene and chlorophyll metabolism. Barley lateral spikelet morphology and grain shape play key roles in grain physical quality and yield. Several genes and QTLs for these traits have been cloned or fine mapped previously. Here, we report the phenotypic and genotypic analysis of a barley mutant with round lateral spikelet (rls) from cv. Edamai 934. rls had round lateral spikelet, short but round grain, shortened awn, thick glume and dark green leaves. Histocytologic and ultrastructural analysis revealed that the difference of grain shape of rls was caused by change of cell arrangement in glume, and the dark leaf color resulted from enlarged chloroplast. HvTUBULIN8 (HvTUB8) was identified as the candidate gene for rls by combination of RNA-Seq, map-based-cloning, virus-induced-gene-silencing (VIGS) and protein subcellular location. A single G-A substitution at the third exon of HvTUB8 resulted in change of Cysteine 354 to tyrosine. Furthermore, the mutant isoform Hvtub8 could be detected in both nucleus and cytoplasm, whereas the wild-type protein was only in cytoplasm and granular organelles of wheat protoplasts. Being consistent with the rare phenotype, the "A" allele of HvTUB8 was only detected in rls, but not in a worldwide barley germplasm panel with 400 accessions. VIGS confirmed that HvTUB8 was essential to maintain spike integrity. RNA-Seq results suggested that HvTUB8 may control spike morphogenesis via ethylene homeostasis and signaling, and control leaf color through chlorophyll metabolism. Collectively, our results support HvTUB8 as a candidate gene for barley spike and leaf morphology and provide insight of a novel mechanism of it in barley development.

Preoperative slow-wave sleep is associated with postoperative delirium after heart valve surgery: A prospective pilot study.

Postoperative delirium (POD) is a very common neurological complication after valve surgery. Some studies have shown that preoperative sleep disorder is associated with POD, but the correlation between preoperative slow wave sleep (SWS) and POD remains unclear. Therefore, this study aims to identify the correlation between preoperative slow wave sleep and postoperative delirium in patients with heart valve disease. This was a prospective, observational study of elective valve surgery patients admitted to the Heart Medical Center between November 2021 and July 2022. Polysomnography (PSG) was used to monitor sleep architecture from 9:30 p.m. for 1 night before surgery to 6:30 a.m. on the day of surgery. Patients were assessed for postoperative delirium from postoperative day 1 to extubation or day 5 by using the Richmond Agitation/Sedation Scale (RASS) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). A total of 60 elective valve surgery patients were enrolled in this study. Prolonged N1 (11.44%) and N2 (58.62%) sleep, decreased N3 sleep (8.75%) and REM sleep (18.24%) within normal limits were the overall sleep architecture. Compared with patients without POD, patients with POD had less slow wave sleep 1 night before surgery (5.77% vs 10.88%, p < 0.001). After adjusting for confounding factors, slow wave sleep (OR: 0.647, 95% CI 0.493-0.851, p = 0.002) was found to be a protective factor for postoperative delirium. The preoperative SWS is a predictive factor of the POD in patients undergoing valve surgery. But further studies with larger sample sizes are still needed to elucidate the relationship between preoperative slow wave sleep and postoperative delirium.

Early goal-directed mobilization in patients with acute type A aortic dissection: A randomized controlled trial.

OBJECTIVE: To determine the safety and efficacy of early postoperative mobilization in patients who have undergone surgical repair of acute type A aortic dissection. DESIGN: Randomized controlled trial. SETTING: Heart Medical Center. SUBJECTS: Seventy-seven patients with acute type A aortic dissection were assessed. INTERVENTION: Patients were randomly allocated into: (1) the control group (usual care) (n = 38) and (2) the intervention group (early goal-directed mobilization) (n = 39). MAIN MEASURES: The primary outcome was the patient's functional status. The secondary outcomes included vital signs, serious adverse events, muscle strength, intensive care unit-acquired weakness, grip strength, duration of mechanical ventilation, length of stay, readmission rate, and health-related quality of life after 3 months. RESULTS: The vital signs of the patients were within the tolerable ranges during the entire intervention. No serious exercise-related adverse events were observed in the intervention group. The Barthel Index score (P = 0.013), Medical Research Council score (P = 0.001), grip strength (P = 0.001), and health-related quality of life (P = 0.001) were higher in the intervention group. Intensive care unit acquired weakness (P = 0.019), duration of mechanical ventilation (P = 0.002), intensive care unit stay (P = 0.002), and total length of stay (P = 0.010) were lower in the intervention group. Patients in the intervention group had a higher physical health-related quality of life (P = 0.015) at 3 months post-surgery. There was no difference in readmission rates. CONCLUSIONS: Delivery of early goal-directed mobilization in acute type A aortic dissection was safe and facilitated the recovery of daily living ability, shorter hospital stay, and improved quality of life after discharge.

The Effect of Onset Time on In-Hospital Mortality in Patients with Acute Type A Aortic Dissection of Different Gender: A Retrospective Cohort Study.

BACKGROUND: Although the research on gender in acute type A aortic dissection (AAAD) patients has increased in recent years, the results are still controversial. The effect of time of onset on in-hospital mortality in patients with AAAD of different gender is unclear. The purpose of this study was to investigate the effect of onset time on in-hospital mortality of patients with AAAD of different gender. METHODS: In this retrospective observational study, patients with AAAD were selected from June 2013 to March 2020. Patients' information was extracted from electronic medical records. Based on the onset time, the patients were categorized into four groups: group one (00:00-05:59), group two (6:00-11:59), group three (12:00-17:59), and group four (18:00-23:59). RESULTS: A total of 760 subjects were included in our study. There were 591 (77.8%) males and 169 (22.2%) females. In male patients, 79 cases died, in female patients, 19 cases died (p < 0.05). We conducted subgroup analysis according to gender, univariate Cox regression analysis of male patients showed that compared with the patients at onset time of 0:00-5:59, patients at onset time of 12:00-17:59 and 18:00-23:59 were associated with an increased risk of in-hospital mortality. Multivariate Cox regression analysis of male patients showed that the onset time of 18:00-23:59 remained as the significant risk factor of in-hospital mortality of male patients hazard ratio (HR) = 4.396 (p < 0.05). CONCLUSIONS: This analysis demonstrated that in-hospital mortality of AAAD patients was similar in different genders. In male patients, the onset time of 18:00-23:59 was significantly associated with an increased risk of in-hospital mortality.

Analysis of serum calcium change trajectories and prognostic factors in patients with acute type A aortic dissection.

OBJECTIVES: This study aimed to analyze the correlation between serum calcium changes and short-term prognosis of patients with acute type A aortic dissection. METHODS: Patients who underwent acute type A aortic dissection surgery at Fujian Heart Medical Center between June 2019 and June 2021 were retrospectively analyzed. RESULTS: A total of 383 patients were enrolled. According to the changing track of serum calcium in patients after acute type A aortic dissection, three potential category tracks were determined: high-level (n = 85), medium-level (n = 259), and continuous low-level groups (n = 39). Using the medium-level group as the control, regression analysis showed that poor prognosis risk was increased in the group with continuous low serum calcium (odds ratio = 2.454, P < 0.05) and in the group with continuous low serum calcium > 48 h (odds ratio = 3.595, P < 0.05). Age (odds ratio = 1.063, P < 0.001), body mass index (odds ratio = 1.138, P < 0.05), hypertension (odds ratio = 3.697, P < 0.05), and the highest lactic acid within 72 h after surgery(odds ratio = 1.093, P < 0.05) were independent risk factors for poor prognosis after aortic dissection. CONCLUSION: Continuous low serum calcium was an independent predictor of poor prognosis in patients with acute type A aortic dissection.

Postoperative Lactate Predicts In-Hospital Death in Patients with Acute Type A Aortic Dissection.

Several studies have found that lactate correlates with surgical outcomes in patients with heart disease. However, the prognostic value of postoperative lactate in patients with acute type A aortic dissection (AAAD) remains unclear. This study aimed to investigate the relationship between postoperative lactate and in-hospital mortality in patients with AAAD. Patients who underwent AAAD surgery at Fujian Cardiac Medical Center from February 2020 to January 2022 were enrolled in this retrospective study. Correlations between in-hospital mortality and various parameters, including lactate, were investigated. A total of 357 patients were included in this study, 58 of which died. Multivariate logistic regression analysis revealed that body mass index (BMI) (odds ratio [OR] = 1.099, 95% confidence interval [CI]: 1.017-1.188, P = 0.017), cardiopulmonary bypass (CPB) time (OR = 1.005; 95% CI: 1.000-1.010, P = 0.039), and lactate (OR = 1.291, 95% CI: 1.182-1.409, P < 0.001) were independent risk factors for in-hospital mortality in AAAD patients. Receiver operating characteristic (ROC) curve analysis showed that lactate had a moderate power for in-hospital mortality (area under the curve [AUC] = 0.729, 95% CI: 0.647-0.810, P < 0.001). Furthermore, the combination of lactate, BMI, and CPB time showed better performance (AUC = 0.780; 95% CI: 0.706-0.854, P < 0.001) in predicting in-hospital mortality than in using these variables independently. Among patients undergoing AAAD surgery, postoperative lactate was significantly associated with in-hospital mortality. Lactate can be used as a potential predictor of in-hospital mortality. The combination of lactate, BMI, and CPB time showed better performance in predicting in-hospital mortality than using single one.

Clonotypic architecture of a Gag-specific CD8+ T-cell response in chronic human HIV-2 infection.

The dynamics of T-cell receptor (TCR)selection in chronic HIV-1 infection, and its association with clinical outcome, is well documented for an array of MHC-peptide complexes and disease stages. However, the factors that may contribute to the selection and expansion of CD8+ T-cells in chronic HIV-2 infection, especially at the clonal level remain unclear. To address this question, we undertook a detailed molecular characterization of the clonotypic architecture of an HLA-B*3501 restricted Gag-specific CD8+ T-cell response in donors chronically infected with HIV-2 using a combination of flow cytometry, tetramer-specific CD8+ TCR clonotyping, and in vitro assays. We show that the response to the NY9 epitope is hierarchical and narrow in terms of T-cell receptor-alpha (TCRA) and -beta (TCRB) gene usage yet clonotypically diverse. Furthermore, clonotypic dominance in shared origin CTL clones was associated with a greater magnitude of cytokine production and antigen sensitivity at limiting antigen dilution as well as enhanced cross-reactivity for known HIV-2 variants. Hence, our data suggest that effector mobilization and expansion in human chronic HIV-2 infection may be linked to the qualitative features of specific CD8+ T-cell clonotypes, which could have implications for viral control and disease outcome.

Expression and Clinical Significance of KLRG1 and 2B4 on T Cells in the Peripheral Blood and Tumour of Patients with Cervical Cancer.

BACKGROUND: Killer cell lectin-like receptor G1 (KLRG1) and 2B4 play important roles in the immune regulation and immune tolerance to tumor cells by inhibiting T cell function. However, the clinical relevance of KLRG1 and 2B4 to cervical cancer remains to be understood. METHODS: We measured the frequency of KLRG1+ or 2B4+ cells in CD4+ or CD8 + T cells derived from peripheral blood or tumour biopsies in cervical cancer patients by flow cytometry. RESULTS: Compared with healthy controls, the level of KLRG1 and 2B4 on CD8 + T cells in the blood of the patients increased significantly (P = .0056 and .0441). KLRG1 level on CD8 + T cells and 2B4 level on CD4 + T cells in peripheral blood were significantly higher than in tumor tissues (P < .0001 and P = .0003). Higher KLRG1 level on blood-derived CD8 + T cells was observed in patients older than 54 years (P = .001) or tested to be HPV-negative (P = .026). Tumor-infiltrated CD8 + T cells demonstrated elevated KLRG1 level in patients having pelvic lymph node metastasis (P = .016). Increased 2B4 level on blood-derived CD8 + T cells was also observed in patients older than 54 years (P < .001). KLRG1 expression on both CD4 + T (P = .0158) and CD8 + T (P = .0187) cells in the peripheral blood increased after radiotherapy. CONCLUSION: KLRG1 level on T cells was related to age and HPV in patients with cervical cancer, while 2B4 level on T cells was related to age, underlying their roles in the host immune response to cervical cancer. Radiotherapy can improve the immune function of patients.

TG/HDL-C ratio predicts in-hospital mortality in patients with acute type A aortic dissection.

BACKGROUND: In recent years, abnormalities in serum lipids and lipoproteins have been shown to be associated with cardiovascular disease risk. However, their prognostic value for acute type A aortic dissection is unclear. This study analyzed the correlation between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and in-hospital mortality in patients with AAAD, and aimed to investigate the clinical significance of preoperative blood lipids and lipoproteins on the prognosis of acute type A aortic dissection. METHODS: A total of 361 patients who underwent type A aortic dissection surgery in Fujian Cardiac Medical Center from June 2018 to March 2020 were retrospectively collected. According to the baseline TG/HDL-C ratio, the patients were divided into 3 groups according to the tertile method, the low TG/HDL-C ratio T1 group (< 1.18) and the middle TG/HDL-C ratio T2 group (1.18-1.70). T3 group with high TG/HDL-C ratio (> 1.70). Kaplan-Meier was used for survival analysis, and Cox proportional hazards regression model was used to analyze the factors affecting the prognosis of patients. The receiver operating characteristic (ROC) curve was used for the diagnostic efficacy. RESULTS: Among the 361 patients in this study, the mean age was 52.4 ± 11.3 years, 73 (20.2%) were female, and 82 (22.7%) died in hospital. Kaplan-Meier curve showed that with the increase of TG/HDL-C ratio, the risk of in-hospital death gradually increased (P < 0.001). Multivariate Cox regression analysis showed that age (HR = 1.031), body mass index (HR = 1.052), hypertension (HR = 3.491), white blood cells (HR = 1.073), TG/HDL-C ratio (HR = 1.604), MODS (HR = 1.652) was positively correlated with in-hospital mortality (P < 0.05). After adjusting for age, sex, and other risk factors, a significant association was found between the TG/HDL-C ratio and in-hospital mortality for acute type A aortic dissection (HR = 1.472, 95% CI, 1.354-3.451, P = 0.019). CONCLUSION: Patients with type A aortic dissection have obvious abnormal blood lipid metabolism, and serum TG/HDL-C levels are positively correlated with in-hospital mortality in patients with AAAD.

Effects of chewing gum on gastrointestinal function in patients following spinal surgery: a meta-analysis and systematic review.

PURPOSE: There are conflicting opinions regarding the efficacy of chewing gum for the recovery of gastrointestinal function in patients following spinal surgery. Thus, we aimed to conduct a systematic review and meta-analysis of existing articles to evaluate the effect of gum-chewing on patients following spinal surgery. METHODS: A computer search was used to identify randomised controlled trials (RCTs) involving gum-chewing from eight databases: Cochrane Library, PubMed, Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, and WanFang Data. After evaluating the risk of bias for the included studies, we used the Revman 5.3 software to conduct a meta-analysis of the data. RESULTS: The study included seven RCTs, with a total of 706 patients. The meta-analysis reported that gum-chewing could shorten the interval between surgery and first bowel movement (mean deviation [MD] = - 23.02; 95% confidence interval [CI]: - 24.67, - 21.38; P < 0.00001), first flatus (MD = - 1.54; 95% CI - 2.48, - 0.60; P = 0.001), and first bowel sounds (MD = - 5.08; 95% CI - 6.02, - 4.15; P < 0.00001). Moreover, there was a significant reduction in postoperative analgesic dosage within 12 h (standardised mean difference [SMD] = - 0.28; 95% CI - 0.52, - 0.05; P = 0.02). However, there were no significant differences between the chewing gum and control groups (P > 0.05) regarding the postoperative nausea score, abdominal pain score, 24- and 48-h analgesic drug dosage, and length of hospital stay. CONCLUSION: To a certain extent, masticating gum can promote the recovery of gastrointestinal function and reduce the need for postoperative analgesics in patients following spinal surgery. However, this conclusion is affected by the quantity and quality of the included articles. Therefore, additional high-quality studies are needed to verify these results.

Efficacy and Safety of Oral Hydration 1 Hour After Extubation of Patients Undergoing Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND: Thirst is one of the most common and uncomfortable symptoms in patients after cardiac surgery. The postextubation time for early oral hydration (EOH) remains unclear, and there is a lack of studies on its safety and effectiveness. OBJECTIVE: The aim of this study was to investigate the effects of oral hydration 1 hour after extubation on thirst, salivary pH, salivary flow, oral mucosa, halitosis, gastrointestinal adverse reactions, aspiration pneumonia, and satisfaction in patients undergoing cardiac surgery. METHODS: Eighty-four patients who underwent cardiac surgery were randomly assigned into 2 groups, for either conventional oral hydration (COH) or EOH. The EOH group drank 30 mL of warm water 1 hour post extubation and thereafter 50 mL hourly for 4 hours. The COH group had nil per os for 4 hours after extubation. If no dysphagia was evident after 4 hours, the patients were instructed to slowly drink water. Thirst intensity was evaluated every hour before the intervention. Nausea and vomiting were recorded after drinking water. The salivary pH, unstimulated salivary flow rate, oral odor, and oral mucosal moisture were evaluated at 1 hour post extubation, immediately before the intervention, and at 4 hour post intervention. Aspiration pneumonia data were collected within 72 hours post intervention. Satisfaction was assessed before leaving the intensive care unit. RESULTS: The scores for thirst (3.38 ± 1.04; F = 306.21, P < .001), oral mucosa (2.03 ± 0.74; P < .001), and halitosis (2.77 ± 0.63; P < .001) in the EOH group were significantly lower than those in the COH group. The EOH group had significantly higher salivary pH (6.44 ± 1.06; P < .001), unstimulated salivary flow rates (0.18 ± 0.08; P < .001), and patient satisfaction (4.28 ± 0.45; P < .001) than the COH group. Nausea and vomiting did not differ significantly between groups (P = .60). Aspiration pneumonia was not observed in either group. CONCLUSIONS: Oral hydration 1 hour after extubation significantly alleviated thirst and stabilized the oral environment without gastrointestinal adverse reactions or aspiration pneumonia, and with increased patient satisfaction.

Admission Hyperglycemia in Acute Type A Aortic Dissection Predicts for a Prolonged Duration of Mechanical Ventilation.

Previous studies have demonstrated that admission hyperglycemia is a predictor of mortality and poor prognosis in patients with cardiovascular diseases, such as acute myocardial infarction. However, the prognostic value of admission hyperglycemia in patients with acute type A aortic dissection (AAAD) has never been explored. To clarify the association between hyperglycemia and in-hospital outcomes, we retrospectively analyzed 734 patients with AAAD. The interest endpoints were in-hospital mortality rate, the duration of intensive care unit and hospital stays, the occurrence of prolonged mechanical ventilation (PMV), and other complications. All patients were divided into the normal blood glucose group (≤ 140 mg/dL) and hyperglycemia group (> 140 mg/dL), to compare the in-hospital outcomes rate in the two groups. There were 531 (72.3%) patients with normal blood glucose levels and 203 (27.7%) patients with hyperglycemia. The in-hospital mortality rate was 21.1%, and no statistically significant differences were found between the two groups (20.3% versus 23.2%, P = 0.403). PMV is the most frequent postoperative complication, the incidence of which was significantly higher in the hyperglycemia group than in the normal blood glucose group (59.6% versus 50.8%, P = 0.040). The logistic regression analysis revealed that hyperglycemia (odds ratio (OR): 1.492; 95% CI: 1.014 to 2.197; P = 0.042) was an independent risk factor for PMV after adjusting for confounding factors. Age (OR: 1.021; 95% CI: 1.006-1.037; P = 0.007) and body mass index (OR: 1.101; 95% CI: 1.051-1.153; P < 0.001) were also associated with PMV. In conclusion, our study showed for the first time that a strong correlation between admission hyperglycemia and increased postoperative PMV in patients with AAAD, but not with in-hospital mortality rate.

Distinct tumour antigen-specific T-cell immune response profiles at different hepatocellular carcinoma stages.

BACKGROUND: Cancer-testis antigens (CTAs) and tumour-associated antigens (TAAs) are frequently expressed in hepatocellular carcinoma (HCC); however, the role of tumour-antigen-specific T cell immunity in HCC progression is poorly defined. We characterized CTA- and TAA-specific T cell responses in different HCC stages and investigated their alterations during HCC progression. METHODS: Fifty-eight HCC patients, 15 liver cirrhosis patients, 15 chronic hepatitis B patients and 10 heathy controls were enrolled in total. IFN-γ ELSPOT using CTAs, including MAGE-A1, MAGE-A3, NY-ESO-1, and SSX2, and two TAAs, SALL4 and AFP, was performed to characterize the T-cell immune response in the enrolled individuals. The functional phenotype of T cells and the responsive T cell populations were analyzed using short-term T-cell culture. RESULTS: T cell responses against CTAs and TAAs were specific to HCC. In early-stage HCC patients, the SALL4-specific response was the strongest, followed by MAGE-A3, NY-ESO-1, MAGE-A1 and SSX2. One-year recurrence-free survival after transcatheter arterial chemoembolization plus radiofrequency ablation treatment suggested the protective role of CTA-specific responses. The four CTA- and SALL4-specific T cell responses decreased with the progression of HCC, while the AFP-specific T cell response increased. A higher proportion of CD4+ T cells specific to CTA/SALL4 was observed than AFP-specific T cell responses. CONCLUSIONS: The IFN-γ ELISPOT assay characterized distinct profiles of tumour-antigen-specific T cell responses in HCC patients. CTA- and SALL4-specific T cell responses may be important for controlling HCC in the early stage, whereas AFP-specific T cell responses might be a signature of malignant tumour status in the advanced stage. The application of immunotherapy at an early stage of HCC development should be considered.

Feeding intolerance and risk of poor outcome in patients undergoing cardiopulmonary bypass surgery.

We conducted a prospective, observational study to determine the incidence of feeding intolerance (FI) within 7 d of initiating enteral nutrition (EN) in patients undergoing cardiopulmonary bypass (CPB) and to evaluate the association between FI and a poor prognosis. Patients who underwent CPB surgery at Fujian Medical University Union Hospital between March 2020 and June 2020 were enrolled. According to the presence or absence of FI within 7 d after EN, patients were divided into FI and non-FI groups. According to the occurrence of a poor prognosis (death, gastrointestinal haemorrhage, acute kidney injury, liver insufficiency, neurological events (cerebral infarction, cerebral haemorrhage and epilepsy) and prolonged mechanical ventilation (> 48 h)), patients were divided into poor prognosis and good prognosis groups. The mean age of the 237 CPB patients, including 139 men and ninety-eight women, was 53·80 (sd 12·25) years. The incidence of FI was 64·14 %. Multivariate logistic regression analysis showed factors independently associated with poor prognosis after CPB included FI (OR 2·138; 95 % CI 1·058, 4·320), age (OR 1·033; 95 % CI 1·004, 1·063), New York Heart Association (NYHA) class III/IV cardiac function (OR 2·410; 95 % CI 1·079, 5·383), macrovascular surgery (OR 5·434; 95 % CI 1·704, 17·333) and initial sequential organ failure assessment score (OR 1·243; 95 % CI 1·010, 1·530). Thus, the incidence of FI within 7 d of EN after CPB was high, which was associated with a poor prognosis.

New insights into the evolution of wheat avenin-like proteins in wild emmer wheat (Triticum dicoccoides).

Fifteen full-length wheat grain avenin-like protein coding genes (TaALP) were identified on chromosome arms 7AS, 4AL, and 7DS of bread wheat with each containing five genes. Besides the a- and b-type ALPs, a c type was identified in the current paper. Both a and b types have two subunits, named x and y types. The five genes on each of the three chromosome arms consisted of two x-type genes, two y-type genes, and one c-type gene. The a-type genes were typically of 520 bp in length, whereas the b types were of 850 bp in length, and the c type was of 470 bp in length. The ALP gene transcript levels were significantly up-regulated in Blumeria graminis f. sp. tritici (Bgt)-infected wheat grain caryopsis at early grain filling. Wild emmer wheat [(WEW), Triticum dicoccoides] populations were focused on in our paper to identify allelic variations of ALP genes and to study the influence of natural selection on certain alleles. Consequently, 25 alleles were identified for TdALP-bx-7AS, 13 alleles were identified for TdALP-ax-7AS, 7 alleles were identified for TdALP-ay-7AS, and 4 alleles were identified for TdALP-ax-4AL Correlation studies on TdALP gene diversity and ecological stresses suggested that environmental factors contribute to the ALP polymorphism formation in WEW. Many allelic variants of ALPs in the endosperm of WEW are not present in bread wheat and therefore could be utilized in breeding bread wheat varieties for better quality and elite plant defense characteristics.