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Background: Cancer growth is significantly influenced by processes such as pyroptosis, apoptosis, and necroptosis that underlie PANoptosis, a proinflammatory programmed cell death. Several studies have examined the long non-coding RNAs (lncRNAs) associated with pancreatic adenocarcinoma (PAAD). However, the predictive value of lncRNAs related to PANoptosis for PAAD has not been established., Methods: The Clinical Genome Atlas database was used to obtain the transcriptome 、clinical data and the corresponding mutation data of the patients with PAAD in this study. The least absolute shrinkage and selection operator regression analysis was employed to obtain prognosis-related lncRNAs for constructing a risk signature. According to the median risk score of the signature, patients with PAAD were grouped into low- and high-risk groups to further compare the survival prognosis of different risk groups. Time-dependent receiver operating characteristic curves, c-index analysis, nomograms, principal component analysis and univariate Cox and multivariate Cox regression were performed for the internal validation of the signature. In addition, enrichment analysis of different genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Lastly, differences in tumor mutation burden (TMB), immune function, tumor immune dysfunction and rejection (TIDE), and drug response were determined for the two risk groups., Results: The signature was constructed with six PANoptosis-related lncRNAs (AC067817.2、LINC02004、AC243829.1、AC092171.5、AP005233.2、AC004687.1) that predicted the prognosis of the patients with PAAD. Survival curves showed that patients in the two risk groups had statistically significant differences in prognosis ( P  < 0.05), and multi-cox regression analysis identified risk score as an independent risk factor for PAAD prognosis, and internal validation of nomograms showed high confidence in the signature. GO and KEGG enrichment analysis showed functional and pathway differences between the high- and low-risk groups. TMB evaluation demonstrated that patients in the high-risk group had a higher frequency of mutations. The TIDE score indicated that the high-risk group had a lower risk of immunotherapy escape and better immunotherapy outcomes. Additionally, the two risk groups revealed significantly different responses to 11 anticancer drugs., Conclusion: We identified a novel risk signature for PANoptosis-related lncRNAs, which is a standalone prognostic indicator for PAAD. The PANoptosis-related lncRNA risk signature may be relevant for immunotherapy and a therapeutic target for PAAD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The incidence of early-onset colorectal cancer (EO-CRC), diagnosed in patients younger than 50 years, has increased in incidence alarmingly over the past few decades, while overall incidence and mortality of colorectal cancer are stabilizing or declining in many high-income countries. These unfavorable changes have raised significant concerns and led to extensive research, resulting in a surge in studies on EO-CRC. Our aim was to obtain a more comprehensive understanding of the current state of this field and to identify prospective research directions by performing a bibliometric analysis of EO-CRC. A total of 1952 papers on EO-CRC published from 2000 to 2022 were identified after a thorough search of the Web of Science Core Collection. The United States dominated this field, with Harvard University contributing the greatest number of papers, while the journal Familial Cancer (n = 52) published the most articles. Cooperation network analysis revealed close internal cooperation among countries, institutions and authors. Based on reference and keyword analysis, high-frequency keywords showed several popular research directions, including epidemiology (incidence, young patients, age of onset, etc.), risk factors (obesity, family history, lynch syndrome, etc.) and molecular characterization (germline mutation, genome wide association, MLH1, etc.). Overall, our research provides an overview of the current status in this field, which we hope will give researchers a comprehensive perspective on the present trends within this domain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Pre-operative accuracy of subcentimeter ground glass nodules (SGGNs) is a difficult problem in clinical practice, but there are few clinical studies on the benign and malignant prediction model of SGGNs. The aim of this study was to help identify benign and malignant lesions of SGGNs based on the imaging features of high resolution computed tomography (HRCT) and the general clinical data of patients, and to build a risk prediction model., Methods: This study retrospectively analyzed the clinical data of 483 patients with SGGNs who underwent surgical resection and were confirmed by histology from the First Affiliated Hospital of University of Science and Technology of China from August 2020 to December 2021. The patients were divided into the training set (n=338) and the validation set (n=145) according to 7:3 random assignment. According to the postoperative histology, they were divided into adenocarcinoma group and benign lesion group. The independent risk factors and models were analyzed by univariate analysis and multivariate Logistic regression. The receiver operator characteristic (ROC) curve was constructed to evaluate the model differentiation, and the calibration curve was used to evaluate the model consistency. The clinical application value of the decision curve analysis (DCA) evaluation model was drawn, and the validation set data was substituted for external verification., Results: Multivariate Logistic analysis screened out patients' age, vascular sign, lobular sign, nodule volume and mean-CT value as independent risk factors for SGGNs. Based on the results of multivariate analysis, Nomogram prediction model was constructed, and the area under ROC curve was 0.836 (95%CI: 0.794-0.879). The critical value corresponding to the maximum approximate entry index was 0.483. The sensitivity was 76.6%, and the specificity was 80.1%. The positive predictive value was 86.5%, and the negative predictive value was 68.7%. The benign and malignant risk of SGGNs predicted by the calibration curve was highly consistent with the actual occurrence risk after sampling 1,000 times using Bootstrap method. DCA showed that patients showed a positive net benefit when the predictive probability of the predicted model probability was 0.2 to 0.9., Conclusions: Based on preoperative medical history and preoperative HRCT examination indicators, the benign and malignant risk prediction model of SGGNs was established to have good predictive efficacy and clinical application value. The visualization of Nomogram can help to screen out high-risk groups of SGGNs, providing support for clinical decision-making.

Background: Hyperinflammation is a life-threatening condition associated with various clinical disorders characterized by excessive immune activation and tissue damage. Multiple cytokines promote the development of hyperinflammation; however, the contribution of IL-10 remains unclear despite emerging speculations for a pathological role. Clinical observations from hemophagocytic lymphohistiocytosis (HLH), a prototypical hyperinflammatory disease, suggest that IL-18 and IL-10 may collectively promote the onset of a hyperinflammatory state., Objective: We aimed to investigate the collaborative roles of IL-10 and IL-18 in hyperinflammation., Methods: A comprehensive plasma cytokine profile for 87 secondary HLH patients was first depicted and analyzed. We then investigated the systemic and cellular effects of coelevated IL-10 and IL-18 in a transgenic mouse model and cultured macrophages. Single-cell RNA sequencing was performed on the monocytes/macrophages isolated from secondary HLH patients to explore the clinical relevance of IL-10/IL-18-mediated cellular signatures. The therapeutic efficacy of IL-10 blockade was tested in HLH mouse models., Results: Excessive circulating IL-10 and IL-18 triggered a lethal hyperinflammatory disease recapitulating HLH-like phenotypes in mice, driving peripheral lymphopenia and a striking shift toward enhanced myelopoiesis in the bone marrow. IL-10 and IL-18 polarized cultured macrophages to a distinct proinflammatory state with pronounced expression of myeloid cell-recruiting chemokines. Transcriptional characterization suggested the IL-10/IL-18-mediated cellular features were clinically relevant with HLH, showing enhanced granzyme expression and proteasome activation in macrophages. IL-10 blockade protected against the lethal disease in HLH mouse models., Conclusion: Coelevated IL-10 and IL-18 are sufficient to drive HLH-like hyperinflammatory syndrome, and blocking IL-10 is protective in HLH models., (Copyright © 2022. Published by Elsevier Inc.)

B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation. Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59.2% (95% confidence interval [CI], 35.9% to 76.5%), and the estimated 12-month overall survival (OS) rate was 67.4% (95% CI, 43.2% to 83.1%). Only two patients had CD19-negative recurrence. In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors. Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526., Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest with respect to the research, authorship and/or publication., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The blood and immune system of coronavirus disease 2019 (COVID-19) infected patients are dysfunctional, and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms. Nevertheless, the variations of immune responses along with disease severity have not been comprehensively documented. Here, we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells (PBMCs) derived from 12 COVID-19 patients (including four moderate, four severe and four critical cases) and three healthy donors. We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage. By contrast, the quantity of natural killer (NK) cells was significantly reduced, while they exhibited enhanced immune activities. Notably, a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes, in terms of cellular composition, transcriptional discrepancy and transcription factor regulatory network. Furthermore, we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients. In addition, cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages, but weakened in critical cases. Collectively, our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity, which could provide valuable insights for the treatment of critical COVID-19 patients., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19., (© 2021. The Author(s).)

Background: The mortality of lung cancer ranks first among all malignant tumors, but there are few studies on the effect of different segmentectomy on lung function in patients with early lung adenocarcinoma. The purpose of this study was to evaluate the degree of lung function preservation and short-term results of preoperative planning combined with fluorescence thoracoscopic precision segmentectomy and traditional segmentectomy in patients with early lung adenocarcinoma., Methods: From January 1, 2020 to October 31, 2020, 60 patients underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of the First Affiliated Hospital of University of Science and Technology of China: 30 patients in precision segmentectomy group and 30 patients in traditional segmentectomy group. The clinicopathological features, perioperative data and postoperative pulmonary function of the two groups were compared., Results: The operation time of the precision group was shorter than that of the traditional group, and the difference was statistically significant (P<0.05). The preoperative pulmonary function accuracy group and the traditional group in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and carbon monoxide diffusing capacity (DLCO) were (3.65±0.63) L vs (3.54±0.64) L, (2.72±0.50) L vs (2.54±0.48) L and (20.36±3.02) mL/mmHg/min vs (19.16±3.18) mL/mmHg/min, respectively. One month after operation, the FVC, FEV1 and DLCO of pulmonary function accuracy group and traditional group were (3.35±0.63) L vs (2.89±0.57) L, (2.39±0.54) L vs (2.09±0.48) L and (17.43±3.10) mL/mmHg/min vs (15.78±2.865) mL/mmHg/min, respectively. Three months after operation, the FVC and DLCO of pulmonary function accuracy group and traditional group were (3.47±0.63) L vs (3.20±0.56) L and (19.38±3.02) mL/mmHg/min vs (17.79±3.21) mL/mmHg/min, respectively., Conclusions: Preoperative planning combined with fluorescence thoracoscopic precise segmentectomy provides advantages in intersegmental plane recognition, vascular anatomy and postoperative recovery, which significantly shortens the operation time and makes the treatment more accurate.

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) have not been well studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step RT droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48 of 52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53 of 87). One-step RT-ddPCR was tested with a 3.03% false-positive rate and lower 50% confidence interval of detection at 54.026 copies/mL plasma. There was no reduction in the blood viral load in all critical patients, whereas the general and severe patients exhibited a similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in their general and severe counterparts. Among the 52 study patients, 30 (58%) were discharged from the hospital. Among half of the 30 discharged patients, blood viral load remained positive, of which 76.9% (10 of 13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had evidence of infection. Quantitative determination of the blood viral test is of great clinical significance in the management of patients with coronavirus disease 2019., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation., Objective: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019., Methods: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019., Results: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group., Conclusions: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Metformin, as a first-line drug in the treatment of type 2 diabetes, has been proved to be safe and effective. In recent years, epidemiological studies have found that metformin can inhibit the proliferation and metastasis of lung cancer cells, and is expected to become a new anti-lung cancer drug. Lung cancer is a disease that seriously endangers human health, its morbidity and mortality have been ranked first among all malignant tumors, and the prognosis is poor. In recent years, a great deal of evidence shows that metformin can reduce the risk and mortality of tumors such as lung cancer. Its mechanisms mainly include activating adenosine monophosphate-activated protein kinase pathway, improving hyperinsulinemia and insulin resistance, promoting lung cancer cell apoptosis and inhibiting related inflammatory response. The aim of this article is to reviews the study of metformin on lung cancer.

Background: Currently, there are many reports on the advantages of three portal video-assisted thoracic surgery (VATS) in the treatment of lung cancer, but there are few reports on the comparison between uniportal and three portal video-assisted thoracic surgery. In this study, we aimed to evaluate the recent curative effect of the postoperative short-term quality of life between uniportal and three portal video-assisted thoracic surgery for non-small cell lung cancer., Methods: We retrospectively evaluated 266 patients with NSCLC who underwent intended VATS lobectomy by a single surgical team in our ward between January 2016 and August 2017. The general clinical date, perioperative data and short-term life quality were individually compared and analyzed between the two groups., Results: The two groups were similar in terms of clinicopathological features, total number of dissected lymph nodes and nodal stations, postoperative complications and pulmonary complications (P>0.05). Compared with three portal VATS, the intraoperative blood loss, chest tube duration, postoperative thoracic drainage, length of stay and NRS score were significantly decreased in uniportal VATS, with significant differences (P<0.05)., Conclusions: As a more minimally invasive surgery, uniportal VATS can be safely and effectively performed for resectable lung cancer, which would achieve even better operation curative effect than three portal VATS.

Background: Previous studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has a significant impact on the prognosis of many malignant tumors such as gastric cancer, colorectal cancer and pancreatic cancer, but the study on the prognosis of patients with resectable lung adenocarcinoma is less. The aim of this study is to investigate the correlation between the NLR and the clinicopathologic features of adenocarcinoma of lung patients who underwent radical pneumonectomy. Furthermore, this study aimed to clarify the predictive and prognostic significance of NLR in patients who underwent pneumonectomy for lung adenocarcinoma., Methods: This study reviewed the medical records of 163 patients with lung adenocarcinoma who underwent pneumonectomy. The receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off value of the NLR. Survival curves were described by Kaplan-Meier method and compared by Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors., Results: When the NLR value was 2.96, the Youden index was maximal, with a sensitivity of 77.5% and a specificity of 75.9%. The 5-year survival rate in the low NLR group was higher than that in the high NLR group (P<0.05). The univariate and multivariate analyses showed that TNM staging and NLR were independent factors in predicting survival rate., Conclusions: The NLR value was a simple and useful tool to predict the prognosis of lung adenocarcinoma after radical pneumonectomy.

Objective: To investigate the value of C-reactive protein (CRP) on transplantation day in predicting early post-transplant infections and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: We retrospectively analyzed the clinical data of 78 recipients undergoing allo-HSCT. The clinical reference value of CRP on transplantation day was determined, and its sensitivity and specificity for diagnosing bacteremia was analyzed using receiver-operating characteristic curve (ROC). The incidence of transplant-related complications, overall survival, and relapse rate of the patients were analyzed with respect to the CRP level., Results: The clinical reference value of CRP for diagnosing bacteremia was 23.3 mg/L (AUC=0.735 [95% CI: 0.623-0.848], P=0.001), which had a diagnostic sensitivity and specificity of 0.793 and 0.592, respectively. Compared with the patients with low CRP levels, the patients with high CRP levels tended to have delayed neutrophil reconstitution and platelet engraftment by 0.71 days (P=0.237) and 4.09 days (P=0.048), respectively, and had a significantly higher incidence of bacteremia (17.1% vs 53.5%, P=0.001) and CMV viremia (37.1% vs 72.1%, P=0.003) within 100 days following the transplantation; the incidences of EBV viremia, pulmonary invasive fungal infection, or acute graft versus host disease (aGVHD) showed no significant difference between the two groups (41.9% vs 22.9%, P=0.094; 14.0% vs 5.7%, P=0.285; 51.2% vs 45.7, P=0.656, respectively). During the follow-up for a median of 318 (7-773) days in high-CRP group and for 299 (78-747) days in low-CRP group, the high-CRP group showed a significantly lower 2-year overall survival than the low-CRP group (42.5% vs 78.4%, P=0.022), and tended to have a higher 2-year cumulative relapse rate (52.3% vs 19.8%, P=0.235). Logistic multivariate analysis identified a high CRP level on transplantation day as the independent risk factor for post-transplant bacteremia within 100 days (OR=5.090 [95% CI: 1.115 -23.229], P=0.036)., Conclusion: A high CRP level on transplantation day can be indicative of a high risk of early post-transplant bacteremia and CMV viremia and also a poor prognosis following allo-HSCT.