Exploring the protective association between COVID-19 infection and laryngeal cancer: insights from a Mendelian randomization study.

Introduction: Viral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach. Methods: We utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry. We applied inverse variance weighting, MR Egger, and weighted median methods to infer causality. We performed sensitivity analysis using the "leave-one-out" method to verify robustness. Results: We found no evidence of a causal association between gene-predicted COVID-19 and laryngeal cancer [Odds ratio (OR)=0.24 (95% Confidence intervals (CI), 0.05-1.26), P=0.09]. However, we observed significant inverse associations between gene-predicted COVID-19 hospitalization [OR=0.51 (95% CI, 0.28-0.95), P=0.03] and severe patients [OR=0.62 (95% CI, 0.43-0.90), P=0.01] and laryngeal cancer. Notably, the study detected important genetic variants, such as rs13050728, that modulate the expression of interferon alpha receptor 2 (IFNAR2), indicating possible roles for immune response pathways in both COVID-19 and cancer. Discussion: This study reveals a potential interaction between COVID-19 severity, genetic factors, and laryngeal cancer, underscoring the importance of investigating the immune response mechanisms in both conditions. These findings contribute to the understanding of the complex interactions between COVID-19 and laryngeal cancer and may guide future research on the role of immune response, particularly involving IFNAR2.

A novel near-infrared fluorescent probe for real-time monitoring of leucine aminopeptidase activity and metastatic tumor progression.

This article discusses the importance of early tumor detection, particularly in liver cancer, and the role of leucine aminopeptidase (LAP) as a potential marker for liver cancer diagnosis and prognosis assessment. The article highlights the limitations of current tumor markers and the need for new markers and multi-marker approaches to improve accuracy. The authors introduce a novel near-infrared fluorescent probe, NTAP, designed for LAP detection. They describe the synthesis of the probe and evaluate its spectral properties, including the LOD was 0.0038 U/mL, and QY was 0.32 %. The kinetic properties of NTAP, such as the relationship between LAP concentration (0-0.08 U/mL), reaction time (3 min), and fluorescence excitation spectra (475 nm) and emission spectra (715 nm) are investigated. The article also discusses the stability and selectivity of the probe and its ability to detect LAP in complex samples. Cellular imaging experiments demonstrate the NATP specificity and selectivity in detecting LAP activity and its inhibition. Animal models of liver and lung metastasis are used to evaluate the probe's imaging capabilities, showing its ability to accurately locate and detect metastatic lesions. The article concludes by emphasizing the potential applications of the NTAP probe in early tumor diagnosis, treatment monitoring, and the study of tumor metastasis mechanisms.

Greenhouse gas emissions of sewage sludge land application in urban green space: A field experiment in a Bermuda grassland.

Sewage sludge land application is recognized as a strategy for recycling resource and replenishing soil nutrients. However, the subsequent greenhouse gas emissions following this practice are not yet fully understood, and the lack of quantitative research and field experiments monitoring these emissions hampers the establishment of reliable emission factors. This study investigated the greenhouse gas emission characteristics of sewage sludge land application through a field experiment that monitoring soil greenhouse gas fluxes. Seven nitrogen input treatments were implemented in a typical Bermuda grassland in China, with D and C representing the amendment of digested and composted sludge, respectively, at the nitrogen input rate of 0, 100, 200, and 300 kg N ha-1. Soil CH4, CO2, and N2O fluxes were measured throughout the entire experimental period, and soil samples from different treatments at various growth stages were analyzed. The results revealed that sewage sludge land application significantly increased soil N2O and CO2 emissions while slightly reducing soil CH4 uptake. The increased CO2 emissions were biogenic and carbon-neutral, mainly due to enhanced plant root respiration. The N2O emissions were the primary greenhouse gas emissions of sewage sludge land application, which were mainly concentrated in two 50-day periods following base and topdressing fertilization, respectively. N2O emissions following base fertilization by rotary tillage were substantially lower than those following topdressing fertilization. A logarithmic response relationship between N input rates and increased soil N2O emissions was observed, suggesting lower N2O emissions from sewage sludge land application compared to conventional N fertilizers at the same N input level. Future field experiments and meta-analysis are necessary to develop reliable greenhouse gas emission factors for sewage sludge land application.

Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Eosinophil-to-Lymphocyte Ratio (ELR) as Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

Purpose: The study comprehensively evaluated the prognostic roles of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C-reactive protein (CRP), and in-hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while elevated ELR was associated with decreased in-hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in-hospital mortality in AECOPD. The nomogram had a C-index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Contrast-enhanced Ultrasonography for Diagnosis of Small Intestinal Leiomyosarcoma with Hepatic Metastasis: A Clinical Report of One Case and Review of the Literature.

BACKGROUND: Small intestinal leiomyosarcoma is a rare malignant tumor of the gastrointestinal tract. Clinical symptoms are atypical and can be complicated by gastrointestinal bleeding and intestinal obstruction. CASE PRESENTATION: We report a case of a 73-year-old patient with small intestinal smooth muscle sarcoma with hepatic metastasis. No significant abnormalities were seen on examination of the abdomen. We performed abdominal enhancement CT, contrast-enhanced ultrasonography (CEUS), and ultrasoundguided pelvic mass puncture biopsy, and we found a heterogeneous density and echogenicity of the pelvic mass, and the enhancement was progressive with sustained hyperenhancement. The postoperative pathology was smooth muscle sarcoma of the small intestine. The typical fast-in, fast-out bull's-eye sign of metastases, characterized the liver presented with multiple hypodense and echogenic nodules and the enhancement. The clinical presentation, imaging, histologic features, and treatment are also discussed in this article. CONCLUSION: This article briefly reviews the literature on small intestinal leiomyosarcoma. The purpose of this case report is to emphasize the specificity of the case and evaluate the imaging presentation of ultrasound (US) and CEUS and the main differential diagnosis of this rare gastrointestinal tumor.

Methionine-CBS axis promotes intracellular ROS levels by reprogramming serine metabolism.

As a non-essential amino acid, cysteine could be obtained through both exogenous uptake and endogenous de novo synthesis pathways. Research has demonstrated that restricting the uptake of cystine could result in a depletion of intracellular cysteine and glutathione, ultimately leading to an increase in intracellular reactive oxygen species (ROS) levels. However, the role of methionine in regulating intracellular ROS levels is currently unclear. Here, we want to explore the role of methionine in regulating intracellular ROS levels. We found that methionine restriction could lead to a decrease in intracellular ROS levels, while supplementation with SAM can restore these levels through flow cytometry. Mechanically, we found that the methionine-SAM axis relies on CBS when regulating intracellular ROS levels. Furthermore, we speculate and prove that the methionine-SAM-CBS axis alters the metabolism of serine, thereby reducing intracellular reductive power, therefore promoting intracellular ROS levels through changing metabolite levels and genetic methods. Finally, our study revealed that high expression of CBS in tumor cells could lead to increased intracellular ROS levels, ultimately resulting in faster proliferation rates. Together, our study confirmed that methionine plays a promoting role in the regulation of intracellular ROS levels.

Tumoricidal Activity of Simvastatin in Synergy with RhoA Inactivation in Antimigration of Clear Cell Renal Cell Carcinoma Cells.

Among kidney cancers, clear cell renal cell carcinoma (ccRCC) has the highest incidence rate in adults. The survival rate of patients diagnosed as having metastatic ccRCC drastically declines even with intensive treatment. We examined the efficacy of simvastatin, a lipid-lowering drug with reduced mevalonate synthesis, in ccRCC treatment. Simvastatin was found to reduce cell viability and increase autophagy induction and apoptosis. In addition, it reduced cell metastasis and lipid accumulation, the target proteins of which can be reversed through mevalonate supplementation. Moreover, simvastatin suppressed cholesterol synthesis and protein prenylation that is essential for RhoA activation. Simvastatin might also reduce cancer metastasis by suppressing the RhoA pathway. A gene set enrichment analysis (GSEA) of the human ccRCC GSE53757 data set revealed that the RhoA and lipogenesis pathways are activated. In simvastatin-treated ccRCC cells, although RhoA was upregulated, it was mainly restrained in the cytosolic fraction and concomitantly reduced Rho-associated protein kinase activity. RhoA upregulation might be a negative feedback effect owing to the loss of RhoA activity caused by simvastatin, which can be restored by mevalonate. RhoA inactivation by simvastatin was correlated with decreased cell metastasis in the transwell assay, which was mimicked in dominantly negative RhoA-overexpressing cells. Thus, owing to the increased RhoA activation and cell metastasis in the human ccRCC dataset analysis, simvastatin-mediated Rho inactivation might serve as a therapeutic target for ccRCC patients. Altogether, simvastatin suppressed the cell viability and metastasis of ccRCC cells; thus, it is a potentially effective ccRCC adjunct therapy after clinical validation for ccRCC treatment.

Life cycle assessment of greenhouse gas emissions of typical sewage sludge incineration treatment route based on two case studies in China.

The rapidly increasing amount of municipal sewage sludge generated in China necessitates a thorough examination and evaluation of available treatment options. In recent years, thermal-drying and incineration technology has gained popularity, however, it may lead to significant greenhouse gas (GHG) emissions. Nevertheless, the differences in boundary conditions and technological characteristic across various cases may affect emission levels significantly. Therefore, this study utilizes a life cycle assessment to estimate the GHG emissions associated with two typical sludge incineration routes in China: direct thermal-drying combined with coal co-incineration incinerator in Case 1 and indirect thermal-drying and self-sustain combustion in Case 2. The entire treatment processes, containing different functional units, were comprehensively investigated. The results demonstrate that Case 1 and Case 2 produce 1133.33 and 350.89 kg CO2-eq/tDS (sludge dry solid) of GHG emissions, respectively. In Case 1, coal co-incineration produces 828.63 kg CO2-eq/tDS of GHG emissions, accounting for 73.1% of the total GHG emissions. Moreover, the exhaust gas treatment is a significant GHG emission source, accounting for 9.2% and 16.9% of the total GHG emissions in Case 1 and Case 2, respectively. Additionally, the sludge thickening and dewatering unit in Case 2 produces 213.75 kg CO2-eq/tDS of GHG emissions, accounting for 60.9% of the total GHG emissions. Analysis of energy flow and heat balance characteristics indicate that the indirect heat transfer method used in thermal-drying leads to significant heat loss, which limits heat recovery potential and hinders GHG emission reduction. This study proposed a scenario case based on Case 2, addressing the issues with the improvement of heat transfer process and reduction of electricity consumption, potentially reducing GHG emissions by 8.8%. Additionally, applying an exhaust gas heat recovery system could further offset up to 22.8% of the total GHG emission.

An integrated strategy combining network toxicology and feature-based molecular networking for exploring hepatotoxic constituents and mechanism of Epimedii Folium-induced hepatotoxicity in vitro.

Epimedii Folium (EF), a commonly used herbal medicine to treat osteoporosis, has caused serious concern due to potential hepatotoxicity. Until now, its intrinsic hepatotoxic mechanism and hepatotoxic ingredients remain unclear. Here, a novel high-throughput approach was designed to investigate the intrinsic hepatotoxic of EF. High-content screen imaging (HCS) and biochemical tests were first performed to obtain the cytotoxicity parameter matrix of 17 batch EF samples. EF-treated alpha mouse liver 12 (AML12) cells showed increased reactive oxygen species (ROS), reduced glutathione (GSH) and mitochondrial membrane potential (MMP), and apoptosis and cholestasis were further observed. Network toxicology predicted that EF-triggered hepatotoxiciy was involved in transcription factor (TF) activity. The FXR expression, screened by a TF PCR array, exhibited down-regulation following EF extract administration. Moreover, EF inhibited bile acid (BA) metabolism pathway in an FXR-dependent manner. Pearson correlation between the cytotoxicity parameter matrix and quantification feature table obtained from UHPLC-QTOF data of EF suggested 7 prenylated flavonoids possessed potent hepatotoxicities and their cytotoxicity order was further summarized. The transcriptional repression effects of them on FXR were also verified. Collectively, our findings indicate that FXR is probably responsible for EF-induced hepatotoxicity and prenylated flavonoids may be a major class of hepatotoxic constituents in EF.

Endoscopic ultrasound diagnosis system based on deep learning in images capture and segmentation training of solid pancreatic masses.

BACKGROUND: Early detection of solid pancreatic masses through contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) is important. But CH-EUS is difficult to learn. PURPOSE: To design a deep learning-based CH-EUS diagnosis system (CH-EUS MASTER) for real-time capture and segmentation of solid pancreatic masses and to verify its value in the training of pancreatic mass identification under endoscopic ultrasound (EUS). METHODS: We designed a real-time capture and segmentation model for solid pancreatic masses and then collected 4530 EUS images of pancreatic masses retrospectively, used for training and testing of this model at a ratio of 8:2. The model is loaded into the EUS host computer to establish the CH-EUS MASTER system. A crossover trial was then conducted to evaluate the model's value in EUS trainee training by successfully conducting two groups of EUS trainees in model learning and trainer-guided training. The intersection over union (IoU) and the time to find the lesion were used to evaluate the model performance metrics, and the Mann-Whitney test was used to compare the IoU and the time to find the lesion in different groups of subjects. Paired t-test was used to compare the effects before and after training. When α ≤ 0.05, it is considered to have a significant statistical difference. RESULTS: The model test showed that the model successfully captured and segmented the pancreatic solid mass region in 906 EUS images. The real-time capture and segmentation model had a Dice coefficient of 0.763, a recall rate of 0.941, a precision rate of 0.642, and an accuracy of 0.842 (when the threshold is set to 0.5), and the median IoU of all cases was 0.731. For the AI training effect, the average IoU of eight trainees improved from 0.80 to 0.87 (95% CI, 0.032-0.096; p = 0.002). The average time for identifying lesions in the pancreatic body and tail improved from 22.75 to 17.98 s (95% CI, 3.664-5.886; p < 0.01). The average time for identifying lesions in the pancreatic head and uncinate process improved from 34.21 to 25.92 s (95% CI, 7.661-8.913; p < 0.01). CONCLUSION: CH-EUS MASTER can provide an effect equivalent to trainer guidance in training pancreatic solid mass identification and segmentation under EUS.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy.

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center (Shanghai, China) were reviewed. The following body composition parameters were calculated using computed tomography: skeletal muscle index (SMI), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI). Pretreatment serum adipocytokine levels, including interleukin 6, insulin, leptin, monocyte chemoattractant protein-1, adiponectin, and resistin, were measured using the multiplex bead-based immunoassays. Cox regression and Kaplan-Meier methods were used for survival analyses. Of the 453 mCRPC patients initially identified, 105 were included in the analysis. High VATI group patients had longer PFS (median, 10 months vs 7 months, P = 0.008) and OS (median, 24 months vs 15 months, P = 0.017), compared with low VATI group patients. SMI and SATI were not significantly associated with PFS or OS. Of the six detected adipocytokines, only leptin was associated with mCRPC prognosis. High leptin group patients had shorter PFS (median, 7 months vs 12 months, P = 0.0018) and OS (median, 17 months vs 22 months, P = 0.042), compared with low leptin group patients. Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS, while a high leptin level was an independent risk factor for PFS and OS. Therefore, VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

HMOX1 promotes lung adenocarcinoma metastasis by affecting macrophages and mitochondrion complexes.

Background: Metastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis. Methods: Pan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network. Results: HMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin. Conclusions: Our analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.

Iron(II)-Catalyzed Nitrene Transfer Reaction of Sulfoxides with N-Acyloxyamides.

An iron(II)-catalyzed nitrene transfer reaction of sulfoxides with N-acyloxyamides has been developed, leading to the efficient construction of N-acyl sulfoximines with high functional-group compatibility. The current catalytic transformation was carried out under an air atmosphere at ambient temperature and could be scaled up to gram scale with a catalyst loading of 1 mol %. Application of the methodology was demonstrated by facile C-H acetoxylation and olefination using the N-acyl sulfoximine as the directing group.

Combination of Androgen Deprivation Therapy with Radical Local Therapy Versus Androgen Deprivation Therapy Alone for Newly Diagnosed Oligometastatic Prostate Cancer: A Phase II Randomized Controlled Trial.

BACKGROUND: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor. OBJECTIVE: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa). DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases. INTERVENTION: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival. RESULTS AND LIMITATIONS: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008). CONCLUSIONS: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone. PATIENT SUMMARY: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Can visceral adipose tissue and skeletal muscle predict recurrence of newly diagnosed Crohn's disease in different treatments.

BACKGROUND AND AIMS: It is crucial to manage the recurrence of Crohn's disease (CD). This study is aimed to explore whether visceral adipose tissue (VAT) and skeletal muscle (SM) are associated with the recurrence of CD upon different treatments. METHODS: All patients with a definite diagnosis of CD were retrospectively divided into three groups according to distinct treatment regimens: 5-amino salicylic acid group (Group A), steroids + azathioprine (Group B) and biologics (Group C). The pretreatment computerized tomography (CT) images and clinical data were collected. The VAT area, mesenteric fat index (MFI), the ratio of VAT area to fat mass (VAT area/FM) were assessed. The primary end point was the recurrence of CD within 1 year of follow-up. RESULTS: A total of 171 CD patients were enrolled, including 57 (33.33%) patients in Group A, 70 (40.94%) patients in Group B and 44 (25.73%) patients in Group C. Patients with 1-year recurrence had higher MFI (P = 0.011) and VAT area/FM (P = 0.000). ROC curve demonstrated that patients with the ratio of VAT area/FM and MFI higher than 0.578 and 1.394 tended to have recurrence with the AUC of 0.707 and 0.709. Similar results could be observed in Group A & B but not in Group C. CONCLUSIONS: High VAT area/FM and MFI are related to recurrence within 1 year for newly diagnosed CD patients treated by 5-amino salicylic or azathioprine + steroids rather than biologics. We could not observe any radiological data associated with the recurrence of CD patients under biological treatment.

A rare case of right upper lung cancer with azygos lobe and partial anomalous pulmonary venous return.

BACKGROUND: The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer. CASE PRESENTATION: We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVR, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein. CONCLUSIONS: AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction is more conducive to the correct performing of this type of surgery.

Bacteroides fragilis prevents aging-related atrial fibrillation in rats via regulatory T cells-mediated regulation of inflammation.

BACKGROUND: Aging plays a critical role in the genesis of atrial fibrillation (AF) and also changes the gut microbes. Whether the aging-associated gut dysbiosis contributes to the development of aging-related AF and whether the gut microbes can be a target to prevent aging-related AF remains unknown. METHODS AND RESULTS: 16S rRNA gene sequencing was performed to reveal the changes of gut microbes in elderly patients with AF, and the result showed that the intestinal abundance of B. fragilis was significantly decreased in elderly patients with AF. Subsequently, we examined the impact of B. fragilis supplementation on AF promotion, atrial structural remodeling and inflammation response in D-galactose induced aging rats. We found that oral administration of B. fragilis prevented AF inducibility and duration, which was associated with attenuation of atrial senescence, apoptosis and fibrosis. Furthermore, B. fragilis significantly diminished the systemic and atrial inflammation, which is accompanied by an increase in the number of Treg cells in the spleen and blood. More importantly, we found that the circulation level of polysaccharide A (PSA), the metabolite synthesized by B. fragilis, was reduced in elderly patients with AF and could predict the occurrence of AF, and B. fragilis increased the circulation concentration of PSA in D-galactose induced aging rats. CONCLUSIONS: The abundance of B. fragilis was lower in elderly patients with AF. Oral administration of B. fragilis significantly attenuated inflammatory response by increasing Treg cells, thereby preventing atrial structural remodeling and inhibiting AF promotion in D-galactose induced aging rats. This study provides experimental evidence for the effectiveness of targeting gut microbes in the prevention of aging-related AF.

Identification of prognostic biomarkers in papillary renal cell carcinoma and PTTG1 may serve as a biomarker for predicting immunotherapy response.

OBJECTIVE: This study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC). METHODS: Two microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort. RESULTS: Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with patients' prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p < .001; HR = 2.673, p = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort (χ2=3.99, p < .05). CONCLUSIONS: Eight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.Key messages:Eight genes, including BUB1B, CCNB1, CCNB2, MAD2L1, TTK, CDC20, PTTG1, and MCM were found to be negatively associated with pRCC patients' prognosis.Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort.