Development and validation of a prediction model for frailty in breast cancer patients with extended survival.

BACKGROUND: Breast cancer (BC) patients with extended survival show a higher incidence of frailty. This study aimed to develop and validate a novel model combining sociodemographic factors (SF) and disease-related factors (DRF) to identify frailty in BC patients with extended survival. METHODS: This cross-sectional study examined data from 1167 patients admitted to a large urban academic medical centre. Three types of predictive models were constructed in the training set (817 patients): the SF model, the DRF model, and the SF + DRF model (combined model). The model performance and effectiveness were assessed using receiver operating characteristic (ROC) curves, calibration plots and decision curves analysis (DCA). Then the model was subsequently validated on the validation set. RESULTS: The incidence of frailty in BC patients with extended survival was 35.8%. We identified six independent risk factors including age, health status, chemotherapy, endocrine therapy, number of comorbidities and oral medications. Ultimately, we constructed an optimal model (combined model C) for frailty. The predictive model showed significantly high discriminative accuracy in the training set AUC: 0.754, (95% CI, 0.719-0.789; sensitivity: 76.8%, specificity: 62.2%) and validation set AUC: 0.805, (95% CI, 0.76-0.85), sensitivity: 60.8%, specificity: 87.1%) respectively. A prediction nomogram was constructed for the training and validation sets. Calibration and DCA were performed, which indicated that the clinical model presented satisfactory calibration and clinical utility. Ultimately, we implemented the prediction model into a mobile-friendly web application that provides an accurate and individualized prediction for BC. CONCLUSIONS: The present study demonstrated that the prevalence of frailty in BC patients with extended survival was 35.8%. We developed a novel model for screening frailty, which may provide evidence for frailty screening and prevention.

Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis.

INTRODUCTION: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. METHODS: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. RESULTS: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726-0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). CONCLUSION: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

Continuous Monitoring of Buried Free Bone Flap Microcirculation Using a Near-Infrared Spectroscopy System.

SUMMARY: Postoperative evaluation of free flaps remains a challenging task. The current accepted standard for diagnosis of vascular compromise remains clinical observation. In recent years, near-infrared spectroscopy (NIRS) has been widely used as a noninvasive objective monitoring tool for postoperative evaluation of soft-tissue flaps. However, methods for monitoring bone flaps remain inadequate. In this study, NIRS was applied for the first time to monitor free buried bone flaps that were used for mandibular reconstruction. The penetrating property of NIRS was used to measure the tissue oxygenation index (TOI) of deep tissues, which reflected the microcirculatory status of the tissues. Changes in TOI values were monitored continuously in 59 cases of free bone flaps up to 72 hours after surgery. Five cases of vascular compromise were noted by clinical observation. Two fibula flaps were total failures, one of which showed a sharp decrease in TOI value to 45% in a short period of time; the other showed a continual gradual decrease to 55%. The observed sudden (<50%) and continuous (>10%) decreases in TOI values suggest that more attention should be paid to revision surgical procedures. The authors conclude that NIRS holds promise as an objective and valid method for clinical evaluation of buried bone flaps.

A multi-center performance assessment for automated histopathological classification and grading of glioma using whole slide images.

Accurate pathological classification and grading of gliomas is crucial in clinical diagnosis and treatment. The application of deep learning techniques holds promise for automated histological pathology diagnosis. In this study, we collected 733 whole slide images from four medical centers, of which 456 were used for model training, 150 for internal validation, and 127 for multi-center testing. The study includes 5 types of common gliomas. A subtask-guided multi-instance learning image-to-label training pipeline was employed. The pipeline leveraged "patch prompting" for the model to converge with reasonable computational cost. Experiments showed that an overall accuracy of 0.79 in the internal validation dataset. The performance on the multi-center testing dataset showed an overall accuracy to 0.73. The findings suggest a minor yet acceptable performance decrease in multi-center data, demonstrating the model's strong generalizability and establishing a robust foundation for future clinical applications.

[Discovery of biomarkers related to abnormal lipid metabolism in liver and serum and intervention mechanism of ginsenoside Rb_1 in hyperlipidemia rats based on non-targeted metabolomics].

Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, ß-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.

Histopathological auxiliary system for brain tumour (HAS-Bt) based on weakly supervised learning using a WHO CNS5-style pipeline.

PURPOSE: Classification and grading of central nervous system (CNS) tumours play a critical role in the clinic. When WHO CNS5 simplifies the histopathology diagnosis and places greater emphasis on molecular pathology, artificial intelligence (AI) has been widely used to meet the increased need for an automatic histopathology scheme that could liberate pathologists from laborious work. This study was to explore the diagnosis scope and practicality of AI. METHODS: A one-stop Histopathology Auxiliary System for Brain tumours (HAS-Bt) is introduced based on a pipeline-structured multiple instance learning (pMIL) framework developed with 1,385,163 patches from 1038 hematoxylin and eosin (H&E) slides. The system provides a streamlined service including slide scanning, whole-slide image (WSI) analysis and information management. A logical algorithm is used when molecular profiles are available. RESULTS: The pMIL achieved an accuracy of 0.94 in a 9-type classification task on an independent dataset composed of 268 H&E slides. Three auxiliary functions are developed and a built-in decision tree with multiple molecular markers is used to automatically formed integrated diagnosis. The processing efficiency was 443.0 s per slide. CONCLUSION: HAS-Bt shows outstanding performance and provides a novel aid for the integrated neuropathological diagnostic workflow of brain tumours using CNS 5 pipeline.

The addition of iron-carbon enhances the removal of perfluoroalkyl acids (PFAAs) in constructed wetlands.

Hazardous perfluoroalkyl acids (PFAAs), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have become ubiquitous environmental persistent organic contaminants, posing serious threats to environmental health, which has led to the development of PFAA treatment methods. Wetland construction in combination with iron-carbon (CW-I), a low-maintenance and high-efficiency technology, may be capable of removing PFAAs through physico-biochemical processes. In this study, we aim to investigate the removal efficiency of PFAAs by CW-I as well as the critical functions of all components within the wetlands. Pairwise comparisons of iron-carbon and control groups revealed that iron-carbon significantly enhanced 15.9% for PFOA and 17.9% for PFOS absorption through phytouptake and substrate adsorption, with respective removal efficiencies of 71.8% ± 1.03% and 85.8% ± 1.56%. The generated iron ions stimulated plant growth and further enhanced phytouptake of PFAAs, with PFAAs accumulated primarily in root tissues with limited translocation. Observations of batch adsorption suggest that chemical and electrostatic interactions are involved in the iron-carbon adsorption process, with film and intraparticle diffusions being the rate-limiting events. Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy revealed that PFAA adsorption by substrates occurs at the molecular level, as well as the occurrence of hydrophobic force effects and ligand exchanges during the iron-carbon adsorption process. Additionally, iron-carbon significantly altered the genera, phyla, and community structure of microorganisms, and some microorganisms and their extracellular polymers may possess ability to bind PFAAs. The information provided in this study contributes to our understanding of the PFAA removal processes in CW-I and enriched the classical cases of PFAA removal by CWs.

Comparison of the profiles of patients defined by age-adapted and fixed threshold CKD criteria: a nationwide, cross-sectional study.

Background: Kidney function declines naturally with advancing age. Therefore an age-adapted estimated glomerular filtration rate (eGFR) threshold has been proposed instead of the fixed threshold for CKD definition. This study aims to describe and compare the profile of CKD patients defined by these two criteria in a Chinese population. Method: We recruited adult participants with selected biochemical tests from the Chinese Physiological Constant and Health Condition survey conducted from 2007 to 2011, with the GFR estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The age-adapted threshold of eGFR is 75, 60 and 45 ml/min/1.73 m2 for the population <40 years of age, 40-64 years and >64 years, respectively. The fixed threshold is 60 ml/min/1.73 m2 for all ages. Results: Among the recruited 23 438 participants, 480 were diagnosed with CKD by fixed threshold criteria, while 391 were diagnosed with CKD by age-adapted criteria. Patients diagnosed by fixed threshold criteria were significantly older (66.4 versus 43.4 years; P < .001) and had a higher prevalence of all CVD risk factors compared with the non-CKD population. In contrast, age-adapted criteria defined a younger patient group and were not significantly associated with diabetes or obesity. When adjusted by age and gender, fixed threshold-defined CKD was not significantly associated with the number of coexisting CVD risk factors, while age-adapted-defined CKD was significantly associated. We also found that the CKD patients defined by age-adapted criteria matched well with the 2.5th percentile of eGFR in Chinese individuals. When compared with their age- and gender-matched controls, patients included by age-adapted criteria but excluded by fixed threshold criteria had a significantly higher prevalence of hypertension (23.2% versus 7.7%; P < .001) and hyperuricaemia (25.0% versus 5.5%; P < .001), while patients included only by the fixed threshold criteria were not significantly different in the prevalence of CVD risk factors and CKD-related disturbance except for hyperuricaemia (41.2% versus 14.0%; P < .001). Conclusion: An age-adapted criterion is more closely associated with CVD risk factors and CKD-related diseases compared with fixed threshold criteria.

Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia-reperfusion acute kidney injury at an early stage by bioinformatics methods.

BACKGROUND: Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. METHODS: We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. RESULTS: A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. CONCLUSION: Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.

Augmenter of liver regeneration protects the kidney against ischemia-reperfusion injury by inhibiting necroptosis.

Necroptosis plays an important role in the pathogenesis of acute kidney injury (AKI), and necroptosis-related interventions may therefore be an important measure for the treatment of AKI. Our previous study has shown that augmenter of liver regeneration (ALR) inhibits renal tubular epithelial cell apoptosis and regulates autophagy; however, the influence of ALR on necroptosis remains unclear. In this study, we investigated the effect of ALR on necroptosis caused by ischemia-reperfusion and the underlying mechanism. In vivo experiments indicated that kidney-specific knockout of ALR aggravated the renal dysfunction and pathological damage induced by ischemia-reperfusion. Simultaneously, the expression of renal necroptosis-associated protein receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed-lineage kinase domain-like protein (MLKL) significantly increased. In vitro experiments indicated that overexpression of ALR decreased the expression of hypoxia-reoxygenation-induced kidney injury molecules, the inflammation-associated factor tumor necrosis factor-alpha (TNF-α), and monocyte chemotactic protein. Additionally, the expression of RIP1, RIP3, and MLKL, which are elevated after hypoxia and reoxygenation, was also inhibited by ALR overexpression. Both in vivo and in vitro results indicated that ALR has a protective effect against acute kidney injury caused by ischemia-reperfusion, and the RIP1/RIP3/MLKL pathway should be further verified as a probable necroptosis regulating mechanism.

Parallel functional assessment of m6A sites in human endodermal differentiation with base editor screens.

N6-methyladenosine (m6A) plays important role in lineage specifications of embryonic stem cells. However, it is still difficult to systematically dissect the specific m6A sites that are essential for early lineage differentiation. Here, we develop an adenine base editor-based strategy to systematically identify functional m6A sites that control lineage decisions of human embryonic stem cells. We design 7999 sgRNAs targeting 6048 m6A sites to screen for m6A sites that act as either boosters or barriers to definitive endoderm specification of human embryonic stem cells. We identify 78 sgRNAs enriched in the non-definitive endoderm cells and 137 sgRNAs enriched in the definitive endoderm cells. We successfully validate two definitive endoderm promoting m6A sites on SOX2 and SDHAF1 as well as a definitive endoderm inhibiting m6A site on ADM. Our study provides a functional screening of m6A sites and paves the way for functional studies of m6A at individual m6A site level.

A novel oncotherapy strategy: Direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non-small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown. EXPERIMENTAL APPROACH: Clinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r-hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r-hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined. KEY RESULTS: Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r-hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR-1-deficient NSCLC cells. r-hirudin and DTIP inhibited tumour progression through the thrombin-PAR-1-mediated RhoA and NF-κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy-induced growth and metastatic inhibition and inhibited chemotherapy-induced resistance in mice. CONCLUSIONS AND IMPLICATIONS: Thrombin makes a substantial contribution, together with PAR-1, to NSCLC malignancy. The anti-coagulants, r-hirudin and DTIP, could be used in anti-tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects.

Impact of a pandemic on surgical neuro-oncology-maintaining functionality in the early phase of crisis.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has extraordinarily impacted global healthcare. Neuro-oncological surgery units have peculiar features that make them highly relevant in the strategic reaction to the pandemic. In this Chinese Society of Neuro-Oncology (CSNO) initiated survey, we appraise the changes implemented in neuro-oncological surgery hospitals across different Asian countries and provide expert recommendations for responses at different stages of the pandemic. METHODS: We performed a 42-question survey of the early experience of neuro-oncological surgery practice in hospitals across different Asian countries on April 1, 2020, with responses closed on April 18, 2020. RESULTS: 144 hospitals completed the questionnaire. Most were in WHO post-peak phase of the pandemic and reported a median reduction in neuro-oncological surgery volume of 25-50%. Most (67.4%) resumed elective surgery in only COVID-19 negative patients;11.1% performed only emergency cases irrespective of COVID-19 status;2.1% suspended all surgical activity. Ninety-one (63.2%) relocated personnel from neurosurgery to other departments. Fifty-two (36.1%) hospitals suspended post-operative adjuvant therapy and 94 (65.2%) instituted different measures to administer post-operative adjuvant therapy. Majority (59.0%) of the hospitals suspended research activity. Most (70%) respondents anticipate that current neurosurgery restrictions will continue to remain for > 1 month. CONCLUSIONS: Majority of the respondents to our survey reported reduced neuro-oncological surgery activity, policy modification, personnel reallocation, and curtailment of educational/research activities in response to the COVID-19 pandemic. The persistent widespread interruption of surgical neuro-oncology in even post-peak phases of the pandemic raises serious concerns about the long-term impact of the pandemic on neuro-oncological patients and highlights the essence of timely measures for pandemic preparedness, patient triage, and workforce protection.

Artificial intelligence neuropathologist for glioma classification using deep learning on hematoxylin and eosin stained slide images and molecular markers.

BACKGROUND: Pathological diagnosis of glioma subtypes is essential for treatment planning and prognosis. Standard histological diagnosis of glioma is based on postoperative hematoxylin and eosin stained slides by neuropathologists. With advancing artificial intelligence (AI), the aim of this study was to determine whether deep learning can be applied to glioma classification. METHODS: A neuropathological diagnostic platform is designed comprising a slide scanner and deep convolutional neural networks (CNNs) to classify 5 major histological subtypes of glioma to assist pathologists. The CNNs were trained and verified on over 79 990 histological patch images from 267 patients. A logical algorithm is used when molecular profiles are available. RESULTS: A new model of the squeeze-and-excitation block DenseNet with weighted cross-entropy (named SD-Net_WCE) is developed for the glioma classification task, which learns the recognizable features of glioma histology CNN-based independent diagnostic testing on data from 56 patients with 17 262 histological patch images demonstrated patch level accuracy of 86.5% and patient level accuracy of 87.5%. Histopathological classifications could be further amplified to integrated neuropathological diagnosis by 2 molecular markers (isocitrate dehydrogenase and 1p/19q). CONCLUSION: The model is capable of solving multiple classification tasks and can satisfactorily classify glioma subtypes. The system provides a novel aid for the integrated neuropathological diagnostic workflow of glioma.

Thrombin is a therapeutic target for non-small-cell lung cancer to inhibit vasculogenic mimicry formation.

Tumor cells transform into endothelial cells by epithelial-to-mesenchymal transition, which is characterized by vasculogenic mimicry (VM). VM not only accelerates tumor progression but also increases drug-induced resistance. However, very little is currently known about the molecular determinants that enable VM. Targeting VM might bring a new breakthrough in cancer treatment. Thrombin is the key enzyme of the blood coagulation system and could contribute to tumor progression. Nevertheless, the association between thrombin and VM formation remains largely unknown. We found that VM was associated with the overall survival of non-small-cell lung cancer (NSCLC) patients, and that thrombin expression was closely related to VM formation. This research revealed that thrombin induced VM formation via PAR-1-mediated NF-κB signaling cascades. The novel thrombin inhibitors r-hirudin and DTIP inhibited VM formation and spontaneous metastases in subcutaneous tumors. Clinical pathological analysis confirmed that NSCLC patients with thrombin-positive/PAR-1-high expression had the poorest prognosis and were the most likely to form VM. The promotional activity of thrombin in VM formation and tumor metastasis was abolished in PAR-1-deficient NSCLC cells. The EGFR inhibitor gefitinib had no effect on VM and increased VEGF expression in tumors. The combination therapy of DTIP and gefitinib achieved a better therapeutic effect than either agent alone. This study is the first to illustrate that thrombin substantially contributes, together with PAR-1, to VM formation and to illustrate that VM might be a target of r-hirudin and DTIP to suppress tumor progression. The anticoagulants r-hirudin and DTIP could be employed for antitumor therapy. Combination therapy with DTIP with an EGFR inhibitor might achieve superior therapeutic effects.

Gypenoside Inhibits Endothelial Cell Apoptosis in Atherosclerosis by Modulating Mitochondria through PI3K/Akt/Bad Pathway.

Atherosclerosis remains the most common cause of deaths worldwide. Endothelial cell apoptosis is an important process in the progress of atherosclerosis, as it can cause the endothelium to lose their capability in regulating the lipid homeostasis, inflammation, and immunity. Endothelial cell injury can disrupt the integrity and barrier function of an endothelium and facilitate lipid deposition, leading to atherogenesis. Chinese medicine techniques for preventing and treating atherosclerosis are gaining attention, especially natural products. In this study, we demonstrated that gypenoside could decrease the levels of serum lipid, alleviate the formation of atherosclerotic plaque, and lessen aortic intima thickening. Gypenoside potentially activates the PI3K/Akt/Bad signal pathway to modulate the apoptosis-related protein expression in the aorta. Moreover, gypenoside downregulated mitochondrial fission and fusion proteins, mitochondrial energy-related proteins in the mouse aorta. In conclusion, this study demonstrated a new function of gypenoside in endothelial apoptosis and suggested a therapeutic potential of gypenoside in atherosclerosis associated with apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway.

Fungal pneumonia manifesting as cavitary lesions in a critically ill elderly patient.

Elderly patients with fungal pneumonia experience higher mortality and are more likely to be misdiagnosed. The diagnosis and treatment of fungal pneumonia in elderly patients is challenging. We herein present a clinical case of pulmonary fungal infection (PFI) manifesting as cavitary lesions in an 85-year-old male with multiple organ failure. Broad-spectrum antibiotics showed unsatisfactory result in this case. Computed tomography (CT) of the chest showed multiple pulmonary cavities with gas-fluid levels in the right upper and middle lobe, and patchy blurred shadows in the lower lobe. The diagnosis of fungal pneumonia was made after ruling out other causes of fever. The patient showed good response to anti-fungal treatment. Physicians must consider the possibility of fungal pneumonia in elderly patients who do not respond to antibiotic treatment after exclusion of immune response, tumor, tuberculosis, and other systemic infections.

Significance of tumor-associated autoantibodies in the early diagnosis of lung cancer.

OBJECTIVES: Autoantibodies tumor-associated antigens (TAAs) could be a valuable tool for the diagnosis or early detection of cancer due to their relatively high specificity and stability. The purpose of this study is to detect the level of tumor-associated autoantibodies in lung cancer and assess the diagnostic potential of autoantibodies in screening strategy for early stage lung cancer. MATERIALS AND METHODS: Levels of tumor-associated autoantibodies (AAbs) were measured against a panel of seven TAAs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE and MAGEA1) in 397 patients with pulmonary lesions (305 with newly diagnosis of NSCLC, 47 with SCLC and 45 with benign nodule) and 74 control persons without any nodules in the lung after chest MDCT scan. The sensitivity, specificity for patients and control persons, positive rate of the panel in different pathology, stage, size of lesion, age and gender were compared and analyzed. RESULTS: The AAbs panel could distinguish malignant lesions from benign lesions and control people, with sensitivity of 56.53% and specificity of 91.60%. The specificity could be further increased to 95.80%, when combined with CT. The AAbs also showed high diagnostic value of malignant nodule, and it would be a new method for judgment of malignant nodules that are less than 8 mm in diameter. No significant differences were seen based on pathology, NSCLC stages, tumor size, age or gender. CONCLUSION: This assay confirms the value of AAbs panel as a diagnostic tool combined with CT scan.