Preoperative ultrasound combined with routine blood tests in predicting the malignant risk of pancreatic cystic neoplasms

Objective:Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms (PCN) may help clinicians make better intervention choices and will be essential for individualized treatment.Methods:Preoperative ultrasound and laboratory examination findings, and demographic characteristics were collected from patients. Multiple logistic regression was used to identify independent risk factors associated with malignant PCN, which were then included in the nomogram and validated with an external cohort. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model.Results:Malignant PCN were found in 83 (40.7%) and 33 (38.7%) of the model and validation cohorts, respectively. Multivariate analysis identified age, tumor location, imaging of tumor boundary, blood type, mean hemoglobin concentration, neutrophil-to-lymphocyte ratio, carbohydrate antigen 19-9, and carcinoembryonic antigen as independent risk factors for malignant PCN. The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations. A nomogram score cutoff of 192.5 classified patients as having low vs. high risk of malignant PCN. The model achieved good C-statistics of 0.929 (95% CI 0.890–0.968, P < 0.05) and 0.951 (95% CI 0.903–0.998, P < 0.05) in predicting malignancy in the development and validation cohorts, respectively. NRI = 0.268; IDI = 0.271 (P < 0.001 for improvement). The DCA curve indicated that our model yielded greater clinical benefits than the comparator model.Conclusions:The nomogram showed excellent performance in predicting malignant PCN and may help surgeons select patients for detailed examination and surgery. The nomogram is freely available at https://wangjunjinnomogram.shinyapps.io/DynNomapp/.     

Hedgehogs as Amplifying Hosts of Severe Fever with Thrombocytopenia Syndrome Virus,China

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9–11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China.     

Role of Inflammatory Factors in Mediating the Effect of Lipids on Nonalcoholic Fatty Liver Disease: A Two-Step,Multivariable Mendelian Randomization Study

Aims/hypothesis: 20–80% of Nonalcoholic Fatty Liver Disease (NAFLD) have been observed to have dyslipidemia. Nevertheless, the probable mechanism of dyslipidemia’s effect on NAFLD remains unclear. Mendelian randomization (MR) was utilized to investigate the relationship between lipids, inflammatory factors, and NAFLD; and also, to determine the proportion mediated by interleukin-17(IL-17) and interleukin-1β(IL-1β) for the effect between lipids and NAFLD. Methods: Summary statistics of traits were obtained from the latest and largest genome-wide association study (GWAS). The UK Biobank provided a summary of lipid statistics, which comprised up to 500,000 participants of European descent. And NAFLD GWAS summary statistics were obtained from the FinnGen Biobank which included a total sample size of 218,792 participants of European ancestry. In order to gain an overall picture of how lipids affect NAFLD, MR with two samples was carried out. Multivariable MR determined lipids direct effects on NAFLD after adjusting for inflammatory factors, namely IL-1β, interleukin-6(IL-6), interleukin-16(IL-16), IL-17, and interleukin-18(IL-18); those lipids comprise HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TGs), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). For the purpose of determining the MR impact, an inverse variance weighted (IVW) meta-analysis of each Wald Ratio was carried out, while other methods were also performed for sensitivity analysis. Results: We discovered a positive association between genetically predicted TGs levels and a 45.5% elevated risk of NAFLD, while genetically predicted IL-1β [(IVW: OR 1.315 (1.060–1.630), p = 0.012) and IL-17 [(IVW: OR 1.468 (1.035–2.082), p = 0.032] were positively associated with 31.5% and 46.8% increased risk of NAFLD, respectively. Moreover, TG was positively associated with 10.5% increased risk of IL-1β and 17.3% increased risk of IL-17. The proportion mediated by IL-17 and IL-1β respectively and both was 2.6%, 3.1%, 14.1%. Conclusion: Genetically predicted TGs, IL-1β, and IL-17 were positively associated with increased risk of NAFLD, with evidence that IL-1β and IL-17 mediated TGs effect upon NAFLD risk. It indicated that early diet management, weight management, lipid-lowering and anti-inflammatory treatment should be carried out for patients with hyperlipidemia to prevent the NAFLD.     

Mushroom Polysaccharides as Potential Candidates for Alleviating Neurodegenerative Diseases

Neurodegenerative diseases (NDs) are a widespread and serious global public health burden, particularly among the older population. At present, effective therapies do not exist, despite the increasing understanding of the different mechanisms of NDs. In recent years, some drugs, such as galantamine, entacapone, riluzole, and edaravone, have been proposed for the treatment of different NDs; however, they mainly concentrate on symptom management and confer undesirable side effects and adverse reactions. Therefore, there is an urgent need to find novel drugs with fewer disadvantages and higher efficacy for the treatment of NDs. Mushroom polysaccharides are macromolecular complexes with multi-targeting bioactivities, low toxicity, and high safety. Some have been demonstrated to exhibit neuroprotective effects via their antioxidant, anti-amyloidogenic, anti-neuroinflammatory, anticholinesterase, anti-apoptotic, and anti-neurotoxicity activities, which have potential in the treatment of NDs. This review focuses on the different processes involved in ND development and progression, highlighting the neuroprotective activities and potential role of mushroom polysaccharides and summarizing the limitations and future perspectives of mushroom polysaccharides in the prevention and treatment of NDs.     

Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer

Background Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1⁺CD8⁺ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1⁺CD8⁺ T cells in the tumour microenvironment and its clinical significance in GC.Designs This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.Results Here, we demonstrated that PD-1⁺CD8⁺ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1⁺CD8⁺ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1⁺CD8⁺ T cell high infiltration indicated an exhausted phenotype of global CD8⁺ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1⁺CD8⁺ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways.Conclusions Our study highlighted that PD-1⁺CD8⁺ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.Subject terms: Gastric cancer, Cancer microenvironment, Tumour immunology     

Value of subcarinal lymph node dissection in esophageal cancer surgery: A case-control study

We investigated the value of subcarinal lymph node dissection in esophageal cancer surgery. Altogether, 240 patients with esophageal cancer admitted to our department between June 2012 and January 2016 were prospectively assigned to an experimental group (subcarinal lymph node dissection group, n = 120 cases) and a control group (uncleaned group, n = 120 cases). The number of subcarinal lymph nodes and the rate of subcarinal lymph node metastasis were determined, and the factors influencing subcarinal lymph node metastasis were analyzed using logistic regression in the experimental group. The operation time, postoperative complications, intraoperative blood loss, postoperative hospital stay, total postoperative hospital cost, and 5-year survival rate were compared between the 2 groups. In the experimental group, an average of 6.03 subcarinal lymph nodes were dissected, and the lymph node metastasis rate was 18.33%. The subcarinal lymph node metastasis rate in the experimental group was related to the size of the subcarinal lymph nodes, depth of tumor invasion, and tumor location. The 5-year survival rate was higher in the experimental group than in the control group (44.2% vs 30.0%, χ² = 6.407, P = .04). The subcarinal lymph node metastasis rate in patients with esophageal cancer is high. Patients with mid-thoracic esophageal cancers that infiltrate beyond the esophageal muscle layer with subcarinal lymph node size > 1.0 cm should undergo lymph node resection, despite increased operation time, incidence of postoperative pulmonary infection, hospitalization time, and total postoperative cost; lymph node resection may improve the 5-year survival rate.     

Vitamin B12 as a novel risk biomarker of spinal fractures

Spinal fractures are common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and a high risk of spinal fractures. However, the underlying factors for spinal fractures in patients with osteoporosis are unclear. A total of 105 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And vitamin B12, vitamin B2, vitamin A, and vitamin B9 in the blood were tested. Pearson’s chi-squared and spearman tests were performed to analyze the correlation between spinal fractures and relative parameters. Univariate and multivariate logistic regression, univariate and multivariate Cox proportional hazards regression analysis. There exists strong relation between the expression level of vitamin B12 and spinal fractures. Pearson’s chi-square and Spearman correlation test showed a strong association between vitamin B12 and vitamin B9 and a spinal fracture. Univariate logistic regression analysis showed that vitamin B12 and vitamin B9 were significantly associated with a spinal fracture. Multivariate logistic regression analysis showed that vitamin B12 was associated considerably with a spinal fracture. In addition, Cox regression analysis showed that vitamin B12 expression was significantly associated with maintenance time from recovery to recurrence (MTRR) of spinal fractures in patients with osteoporosis. Enhanced vitamin B12 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of a spinal fracture. The higher the vitamin B12, the higher the risk of spinal fracture and the shorter the time to spinal fracture recurrence.     

Molecular typing and prognostic model of lung adenocarcinoma based on cuprotosis-related lncRNAs

BackgroundPrevious research has shown the heterogeneity of lung adenocarcinoma (LUAD) accounts for the different effects and prognoses of the same treatment. Cuprotosis is a newly discovered form of programmed cell death involved in the development of tumors. Therefore, it is important to study the long non-coding RNAs (lncRNAs) that regulate cuprotosis to identify molecular subtypes and predict survival of LUAD.MethodsThe expression profile, clinical, and mutation data of LUAD were downloaded from The Cancer Genome Atlas (TCGA), and the “ConsensusClusterPlus” package was used to cluster LUADs based on cuprotosis-related lncRNAs (CR-lncRNAs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were used to construct a prognostic model. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were used for assessing immune cells infiltration and immune function. The tumor microenvironment (TME) score was calculated by ESTIMATE, and the tumor mutational burden (TMB) and Tumor Immune Dysfunction and Exclusion (TIDE) were used to evaluate the efficacy of immunotherapy.ResultsFirstly, 501 CR-lncRNAs were identified based on the co-expression relationship of 19 cuprotosis genes. And univariate Cox further obtained 34 prognosis-related CR-lncRNAs. The unsupervised consensus clustering divided LUAD samples into cluster A and cluster B, and showed cluster A had better prognosis, more immune cells infiltration, stronger immune function, and a higher TME score. Subsequently, we used Lasso Cox regression to construct a prognostic model, and univariate and multivariate Cox analyses showed the risk score could be an independent prognostic indicator. Immune cells infiltration, immune function, and TME score were increased markedly in the low-risk group, while TMB and TIDE suggested the efficacy of immunotherapy might be increased in high-risk group.ConclusionsOur research identified two new molecular subtypes and constructed a novel prognostic model of LUAD which could provide new direction for its diagnosis, treatment, and prognosis.