There is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and ...the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.
Based on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.
A series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.
A new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.
The immunology field has long been short of a universally applicable theoretical model that can quantitatively describe the immune response, and the theory of immune equilibrium (balance) is usually ...limited to the interpretation of the philosophical significance of immune phenomena. Therefore, it is necessary to establish a new immunological theory, namely, immunodynamic theory, to reanalyze the immune response.
By quantifying the immune dynamic equilibrium as the ratio of positive and negative immune power, the immune dynamic equilibrium equation was established. Then, the area under the curve of the positive and negative immune power was assumed to be equal in the whole process of immune response (regardless of correct or not), and through thought experiments based on this key hypothesis, a series of new concepts and expressions were derived, to establish a series of immunodynamic equations.
New concepts of immune force and immune braking force and their expression equations, namely, the theoretical equations of immunodynamics, were derived through thought experiments, and the theoretical curves of immunodynamics were obtained according to these equations.
the equivalent transformation of the theoretical equations and practical calculation of functional data, and by the methods of curve comparison and fitting, some practical equations of immunodynamics were established, and these practical equations were used to solve theoretical and practical problems that are related to the immunotherapy of infectious diseases and cancers.
The traditional theory of immune equilibrium has been mathematized and transformed from a philosophical category into a new concrete scientific theory, namely the theory of immunodynamics, which solves the dilemma that the traditional theory cannot guide individualized medical practice for a long time. This new theory may develop into one of the core theories of immunology in the future.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) in human beings, has caused a serious public health issue.
Attention ...to pancreatic injury is lacking, which may impact patients' prognosis. In this study, we explored the expression and distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in the pancreas. Combined with clinical data, we showed that pancreatic injury can occur in some COVID-19 patients.
Low detection and nonadherence are major problems in current management approaches for patients with suspected atrial fibrillation (AF). Mobile health devices may enable earlier AF detection and ...improved AF management.
This study sought to investigate the effectiveness of AF screening in a large population-based cohort using smart device–based photoplethysmography (PPG) technology, combined with a clinical care AF management pathway using a mobile health approach.
AF screening was performed with smart devices using PPG technology, which were made available for the population ≥18 years of age across China. Monitoring for at least 14 days with a wristband (Honor Band 4) or wristwatch (Huawei Watch GT, Honor Watch, Huawei Technologies Co., Ltd., Shenzhen, China) was allowed. The patients with “possible AF” episodes using the PPG algorithm were further confirmed by health providers among the MAFA (mobile AF app) Telecare center and network hospitals, with clinical evaluation, electrocardiogram, or 24-h Holter monitoring.
There were 246,541 individuals who downloaded the PPG screening app, and 187,912 individuals used smart devices to monitor their pulse rhythm between October 26, 2018, and May 20, 2019. Among those with PPG monitoring (mean age 35 years, 86.7% male), 424 (of 187,912, 0.23%) (mean age 54 years, 87.0% male) received a “suspected AF” notification. Of those effectively followed up, 227 individuals (of 262, 87.0%) were confirmed as having AF, with the positive predictive value of PPG signals being 91.6% (95% confidential interval CI: 91.5% to 91.8%). Both suspected AF and identified AF markedly increased with age (p for trend <0.001), and individuals in Northeast China had the highest proportion of detected AF of 0.28% (95% CI: 0.20% to 0.39%). Of the individuals with identified AF, 216 (of 227, 95.1%) subsequently entered a program of integrated AF management using a mobile AF application; approximately 80% of high-risk patients were successfully anticoagulated.
Based on the present study, continuous home monitoring with smart device–based PPG technology could be a feasible approach for AF screening. This would help efforts at screening and detection of AF, as well as early interventions to reduce stroke and other AF-related complications. (Mobile Health mHealth Technology for Improved Screening, Patient Involvement and Optimizing Integrated Care in Atrial Fibrillation MAFA II; ChiCTR-OOC-17014138)
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Abstract
Background
Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This ...study aimed to clarify the characteristics of patients with refractory COVID-19.
Methods
In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared.
Results
Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05).
Conclusion
In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.
In nearly 50% of patients with coronavirus disease 2019 (COVID-19), obvious clinical and radiological remission could not be attained within 10 days after hospitalization. There were obvious differences in clinical characteristics between patients with refractory versus general COVID-19.
TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of breast cancer. There is an urgent need for identification of therapeutic agents with unique ...mode of action for overcoming current challenges in TNBC treatment.
Different inhibitors were used to study the cell death manner of DMOCPTL. RNA silencing was used to evaluate the functions of GPX4 in ferroptosis and apoptosis of TNBC cells and functions of EGR1 in apoptosis. Immunohistochemical assay of tissue microarray were used for investigating correlation of GPX4 and EGR1 with TNBC. Computer-aided docking and small molecule probe were used for study the binding of DMOCPTL with GPX4.
DMOCPTL, a derivative of natural product parthenolide, exhibited about 15-fold improvement comparing to that of the parent compound PTL for TNBC cells. The cell death manner assay showed that the anti-TNBC effect of DMOCPTL mainly by inducing ferroptosis and apoptosis through ubiquitination of GPX4. The probe of DMOCPTL assay indicated that DMOCPTL induced GPX4 ubiquitination by directly binding to GPX4 protein. To the best of our knowledge, this is the first report of inducing ferroptosis through ubiquitination of GPX4. Moreover, the mechanism of GPX4 regulation of apoptosis is still obscure. Here, we firstly reveal that GPX4 regulated mitochondria-mediated apoptosis through regulation of EGR1 in TNBC cells. Compound 13, the prodrug of DMOCPTL, effectively inhibited the growth of breast tumor and prolonged the lifespan of mice in vivo, and no obvious toxicity was observed.
These findings firstly revealed novel manner to induce ferroptosis through ubiquitination of GPX4 and provided mechanism for GPX4 inducing mitochondria-mediated apoptosis through up-regulation of EGR1 in TNBC cells. Moreover, compound 13 deserves further studies as a lead compound with novel mode of action for ultimate discovery of effective anti-TNBC drug.
Similar to heterostructures composed of different materials, possessing unique properties due to the synergistic effect between different components, the crystal‐phase heterostructures, one variety ...of hetero‐phase structures, composed of different crystal phases in monometallic nanomaterials are herein developed, in order to explore crystal‐phase‐based applications. As novel hetero‐phase structures, amorphous/crystalline heterostructures are highly desired, since they often exhibit unique properties, and hold promise in various applications, but these structures have rarely been studied in noble metals. Herein, via a one‐pot wet‐chemical method, a series of amorphous/crystalline hetero‐phase Pd nanosheets is synthesized with different crystallinities for the catalytic 4‐nitrostyrene hydrogenation. The chemoselectivity and activity can be fine‐tuned by controlling the crystallinity of the as‐synthesized Pd nanosheets. This work might pave the way to preparing various hetero‐phase nanostructures for promising applications.
Amorphous/crystalline heterophase Pd nanosheets exhibit crystallinity‐dependent chemoselectivity and catalytic activity.
Despite several clinicopathological factors being integrated as prognostic biomarkers, the individual variants and risk stratification have not been fully elucidated in lower grade glioma (LGG). With ...the prevalence of gene expression profiling in LGG, and based on the critical role of the immune microenvironment, the aim of our study was to develop an immune-related signature for risk stratification and prognosis prediction in LGG.
RNA-sequencing data from The Cancer Genome Atlas (TCGA), Genome Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) were used. Immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). Univariate, multivariate cox regression, and Lasso regression were employed to identify differentially expressed immune-related genes (DEGs) and establish the signature. A nomogram was constructed, and its performance was evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC), and calibration curves. Relationships between the risk score and tumor-infiltrating immune cell abundances were evaluated using CIBERSORTx and TIMER.
Noted, 277 immune-related DEGs were identified. Consecutively, 6 immune genes (
,
,
,
,
, and
) were identified as risk signature and Kaplan-Meier curve, ROC curve, and risk plot verified its performance in TCGA and CGGA datasets. Univariate and multivariate Cox regression indicated that the risk group was an independent predictor in primary LGG. The prognostic signature showed fair accuracy for 3- and 5-year overall survival in both internal (TCGA) and external (CGGA) validation cohorts. However, predictive performance was poor in the recurrent LGG cohort. The CIBERSORTx algorithm revealed that naïve CD4
T cells were significant higher in low-risk group. Conversely, the infiltration levels of M1-type macrophages, M2-type macrophages, and CD8
T cells were significant higher in high-risk group in both TCGA and CGGA cohorts.
The present study constructed a robust six immune-related gene signature and established a prognostic nomogram effective in risk stratification and prediction of overall survival in primary LGG.
In the case where the measurement noise involves impulsive interference, distributed estimation algorithms based on the mean-square error (MSE) criterion may suffer from severely degraded convergence ...performance or divergence. To address this problem, we modify the adapt-then-combine (ATC) diffusion LMS (DLMS) algorithm by applying the sign operation to the error signals at all agents to develop a diffusion sign-error LMS (DSE-LMS) algorithm. Furthermore, the stochastic behavior of the DSE-LMS algorithm is analyzed for Gaussian inputs and contaminated Gaussian noise based on Price's theorem. Simulation results show the robustness of the DSE-LMS algorithm against impulsive interference and validate the theoretical findings.
•The diffusion LMS algorithm may suffer from severely degraded convergence performance in impulsive interference environments.•The proposed diffusion sign-error LMS algorithm is robust against impulsive interferences.•The stochastic behavior of the diffusion sign-error LMS algorithm is analyzed based on Price's theorem.
Anthropometric measures could predict the new onset of diabetes mellitus (DM). Recently, a new anthropometric measure (a body shape index, ABSI) was developed, and ABSI could predict premature ...mortality, even better than WC and BMI. The main aims of the study were to assess the DM predictive power of ABSI based on the follow-up data over 15 years collected from a general Chinese population.
The data were collected in 1992 and then again in 2007 from the same group of 711 individuals. Because 24 of them were diagnosed with DM in 1992, our analysis was eventually based on the usable data collected from the remaining 687 individuals (male: 58.1%). ABSI was defined as WC/(BMI(2/3)height(1/2)), expressing WC and height in m. After adjusting for confounders, increasing the population ABSI by one standard deviation would result in an increased HR of 41% (95%CI: 12%-77%), compared to 73% (95%CI: 37%-118%) for BMI and 96% (95%CI: 53%-150%) for WC. WC had the best discriminatory power for DM (AROC: 0.701, 95%CI: 0.641-0.760), followed by BMI (AROC: 0.668, 95%CI: 0.601-0.734) and ABSI (AROC: 0.647, 95%CI: 0.581-0.713).
ABSI could predict the new onset of DM in the Chinese population independently. Since the confidence intervals for the HR coefficients and AROCs overlapped, the predictive ability of ABSI for DM was not better than WC and BMI. The three measures had similar predictive abilities for DM. Further studies about ethnic specificities of ABSI are needed and warranted.
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