Updated cost-effectiveness analysis of adebrelimab plus chemotherapy for extensive-stage small cell lung cancer in China.

OBJECTIVE: The CAPSTONE-1 trial demonstrated that adebrelimab-based immunotherapy yielded a favourable survival benefit compared with chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC). This study aims to evaluate the cost-effectiveness of this immunotherapy in the treatment of ES-SCLC from a healthcare system perspective in China. DESIGN: The TreeAge Pro software was used to establish a three-state partitioned survival model. Survival data came from the CAPSTONE-1 trial (NCT03711305), and only direct medical costs were included. Utility values were obtained from the published literature. Sensitivity analysis was performed to explore the robustness of the model. The cost-effectiveness of immunotherapy was investigated through scenario and exploratory analyses in various settings. OUTCOME MEASURES: Total costs, incremental costs, life years, quality-adjusted life-years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER). RESULTS: The basic analysis revealed that the adebrelimab group achieved a total of 1.1 QALYs at a cost of US$65 385, while the placebo group attained 0.78 QALYs at a cost of US$12 741. ICER was US$163 893/QALY. Sensitivity analysis confirmed that the model was robust. Results from scenario and exploratory analyses indicated that the combination of adebrelimab and chemotherapy did not demonstrate cost-effectiveness in any scenario. CONCLUSIONS: From the perspective of the Chinese healthcare system, adebrelimab in combination with chemotherapy for the treatment of ES-SCLC was not economical compared with chemotherapy.

Vertical differences in carbon metabolic diversity and dominant flora of soil bacterial communities in farmlands.

The carbon cycle in soil is significantly influenced by soil microbes. To investigate the vertical distribution of the dominant groups in agricultural soil and the carbon metabolic diversity of soil bacteria, 45 soil samples from the 0 ~ 50 cm soil layer in Hunan tobacco-rice multiple cropping farmland were collected in November 2017, and the carbon diversity of the soil bacterial community, bacterial community composition and soil physical and chemical properties were determined. The results showed that the carbon metabolic capabilities and functional diversity of the soil bacterial community decreased with depth. The three most widely used carbon sources for soil bacteria were carbohydrates, amino acids, and polymers. The dominant bacterial groups in surface soil (such as Chloroflexi, Acidobacteriota, and Bacteroidota) were significantly positively correlated with the carbon metabolism intensity. The alkali-hydrolysable nitrogen content, soil bulk density and carbon-nitrogen ratio were the key soil factors driving the differences in carbon metabolism of the soil bacterial communities in the different soil layers.

Improving radiomic modeling for the identification of symptomatic carotid atherosclerotic plaques using deep learning-based 3D super-resolution CT angiography.

Rationale and objectives: Radiomic models based on normal-resolution (NR) computed tomography angiography (CTA) images can fail to distinguish between symptomatic and asymptomatic carotid atherosclerotic plaques. This study aimed to explore the effectiveness of a deep learning-based three-dimensional super-resolution (SR) CTA radiomic model for improved identification of symptomatic carotid atherosclerotic plaques. Materials and methods: A total of 193 patients with carotid atherosclerotic plaques were retrospectively enrolled and allocated into either a symptomatic (n = 123) or an asymptomatic (n = 70) groups. SR CTA images were derived from NR CTA images using deep learning-based three-dimensional SR technology. Handcrafted radiomic features were extracted from both the SR and NR CTA images and three risk models were developed based on manually measured quantitative CTA characteristics and NR and SR radiomic features. Model performances were assessed via receiver operating characteristic, calibration, and decision curve analyses. Results: The SR model exhibited the optimal performance (area under the curve [AUC] 0.820, accuracy 0.802, sensitivity 0.854, F1 score 0.847) in the testing cohort, outperforming the other two models. The calibration curve analyses and Hosmer-Lemeshow test demonstrated that the SR model exhibited the best goodness of fit, and decision curve analysis revealed that SR model had the highest clinical value and potential patient benefits. Conclusions: Deep learning-based three-dimensional SR technology could improve the CTA-based radiomic models in identifying symptomatic carotid plaques, potentially providing more accurate and valuable information to guide clinical decision-making to reduce the risk of ischemic stroke.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

Therapeutic potential of Lingjiao Gouteng decoction in acute alcohol intoxication and alcohol-induced brain injury involving the RhoA/ROCK2/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Alcohol misuse persists as a prevalent societal concern and precipitates diverse deleterious consequences, entailing significant associated health hazards including acute alcohol intoxication (AAI). Binge drinking, a commonplace pattern of alcohol consumption, may incite neurodegeneration and neuronal dysfunction. Clinicians tasked with managing AAI confront a dearth of pharmaceutical intervention alternatives. In contrast, natural products have garnered interest due to their compatibility with the human body and fewer side effects. Lingjiao Gouteng decoction (LGD), a classical traditional Chinese medicine decoction, represents a frequently employed prescription in cases of encephalopathy, although its efficacy in addressing acute alcoholism and alcohol-induced brain injury remains inadequately investigated. AIM OF THE STUDY: To investigate the conceivable therapeutic benefits of LGD in AAI and alcohol-induced brain injury, while delving into the underlying fundamental mechanisms involved. MATERIALS AND METHODS: We established an AAI mouse model through alcohol gavage, and LGD was administered to the mice twice at the 2 h preceding and 30 min subsequent to alcohol exposure. The study encompassed the utilization of the loss of righting reflex assay, histopathological analysis, enzyme-linked immunosorbent assays, and cerebral tissue biochemical assays to investigate the impact of LGD on AAI and alcohol-induced brain injury. These assessments included a comprehensive evaluation of various biomarkers associated with the inflammatory response and oxidative stress. Finally, RT-qPCR, Western blot, and immunofluorescence staining were carried out to explore the underlying mechanisms through which LGD exerts its therapeutic influence, potentially through the regulation of the RhoA/ROCK2/NF-κB signaling pathway. RESULTS: Our investigation underscores the therapeutic efficacy of LGD in ameliorating AAI, as evidenced by discernible alterations in the loss of righting reflex assay, pathological analysis, and assessment of inflammatory and oxidative stress biomarkers. Furthermore, the results of RT-qPCR, Western blot, and immunofluorescence staining manifest a noteworthy regulatory effect of LGD on the RhoA/ROCK2/NF-κB signaling pathway. CONCLUSIONS: The present study confirmed the therapeutic potential of LGD in AAI and alcohol-induced brain injury, and the protective effects of LGD against alcohol-induced brain injury may be intricately linked to the RhoA/ROCK2/NF-κB signaling pathway.

A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-containing therapy.

Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2-13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4-13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223-0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268-0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506-0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184-0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566-0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516-0.816), 0.654 (95% CI: 0.470-0.823), and 0.675 (95% CI: 0.491-0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.

Cell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition.

The binding of therapeutic antagonists to their receptors often fail to translate into adequate manipulation of downstream pathways. To fix this 'bug', here we report a strategy that stitches cell surface 'patches' to promote receptor clustering, thereby synchronizing subsequent mechano-transduction. The "patches" are sewn with two interactable nanothreads. In sequence, Nanothread-1 strings together adjacent receptors while presenting decoy receptors. Nanothread-2 then targets these decoys multivalently, intertwining with Nanothread-1 into a coiled-coil supramolecular network. This stepwise actuation clusters an extensive vicinity of receptors, integrating mechano-transduction to disrupt signal transmission. When applied to antagonize chemokine receptors CXCR4 expressed in metastatic breast cancer of female mice, this strategy elicits and consolidates multiple events, including interception of metastatic cascade, reversal of immunosuppression, and potentiation of photodynamic immunotherapy, reducing the metastatic burden. Collectively, our work provides a generalizable tool to spatially rearrange cell-surface receptors to improve therapeutic outcomes.

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification.

Cognitive impairment is a common feature among patients with diffuse glioma. The objective of the study is to investigate the relationship between preoperative cognitive function and clinical as well as molecular factors, firstly based on the new 2021 World Health Organization's updated classification of central nervous system tumors. A total of 110 diffuse glioma patients enrolled underwent preoperative cognitive assessments using the Mini-Mental State Examination and Montreal Cognitive Assessment. Clinical information was collected from medical records, and gene sequencing was performed to analyze the 18 most influenced genes. The differences in cognitive function between patients with and without glioblastoma were compared under both the 2016 and 2021 WHO classification of tumors of the central nervous system to assess their effect of differentiation on cognition. The study found that age, tumor location, and glioblastoma had significant differences in cognitive function. Several genetic alterations were significantly correlated with cognition. Especially, IDH, CIC, and ATRX are positively correlated with several cognitive domains, while most other genes are negatively correlated. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Our study suggested that, in addition to clinical characteristics such as age, histological type, and tumor location, molecular characteristics play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. This study highlights the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.

Durable Attenuation of Tumor pH-Platelet Linkage Reinstates Bioorthogonal Targeting of Residual Tumors Post-Debulking.

There are circumstances where tumors can only be partially resected. Therefore, multimodality therapy targeting post-operative residuals is important. Here, we show that bioorthogonal click chemistry enables targeted delivery to heterogeneous tumors, but its utility against tumor post-debulking is ineffective due to platelet cloaks that shield tumor cells from bioorthogonal pairing. We further discover tumor-infiltrating platelet levels respond to local pH changes. Elucidating this pH-platelet linkage, we design an injectable hydrogel for resection cavity implantation that simultaneously azido-tags tumor cells and inhibit their catalysis to acidify surrounding milieu. Unlike transient buffering, tumor acidification blockade sustains pH normalization, leading to durable platelet reduction. This reinstates bioorthogonal targeting of dibenzyl cyclooctyne-modified nanoparticles, thereby enhancing photodynamic ablation of residuals while amplifying systemic antitumor immunity. Concurrently, platelet/pH normalization interrupts metastasis cascade from invasion to circulation to colonization. Overall, attenuating tumor pH-platelet linkage unlocks bioorthogonal chemistry as a potential option for adjuvant therapy after tumor debulking.

Allogeneic "Zombie Cell" as Off-The-Shelf Vaccine for Postsurgical Cancer Immunotherapy.

Allogeneic tumor cell vaccines provide off-the-shelf convenience but lack patient specificity due to heterogeneity in tumor antigens. Here, allogeneic tumor cell corpses are converted into "zombie cells" capable of assimilating heterogeneous tumor by seizing cancer cells and spreading adjuvant infection. This causes pseudo-oncolysis of tumors, transforming them into immunogenic targets for enhanced phagocytosis. It is shown that in postoperative tumor models, localized delivery of premade "zombie cells" through stepwise gelation in resection cavity consolidates tumor surgery. Compared to analogous vaccines lacking "seizing" or "assimilating" capability, "zombie cell" platform effectively mobilizes T cell response against residual tumors, and establishes immunological memory against tumor re-challenge, showing less susceptibility to immune evasion. Despite using allogeneic sources, "zombie cell" platform functions as generalizable framework to produce long-term antitumor immunity in different tumor models, showing comparable effect to autologous vaccine. Together, with the potential of off-the-shelf availability and personalized relevance to heterogenous tumor antigens, this study suggests an alternative strategy for timely therapy after tumor surgery.

Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. AIM OF THE STUDY: This study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. MATERIALS AND METHODS: The coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. RESULTS: The administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1ß, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. CONCLUSIONS: To sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.

Genome-wide identification and characterization of the RZFP gene family and analysis of its expression pattern under stress in Populus trichocarpa.

Forest trees face many abiotic stressors during their lifetime, including drought, heavy metals, high salinity, and chills, affecting their quality and yield. The RING-type ubiquitin ligase E3 is an invaluable component of the ubiquitin-proteasome system (UPS) and participates in plant growth and environmental interactions. Interestingly, only a few studies have explored the RING ZINC FINGER PROTEIN (RZFP) gene family. This study identified eight PtrRZFPs genes in the Populus genome, and their molecular features were analyzed. Gene structure analysis revealed that all PtrRZFPs genes contained >10 introns. Evolutionarily, the RZFPs were separated into four categories, and segmental replication events facilitated their amplification. Notably, many stress-related elements have been identified in the promoters of PtrRZFPs using Cis-acting element analysis. Moreover, some PtrRZFPs were significantly induced by drought and sorbitol, revealing their potential roles in regulating stress responses. Particularly, overexpression of the PtrRZFP1 gene in poplars conferred excellent drought tolerance; however, PtrRZFP1 knockdown plants were drought-sensitive. We identified the potential upstream transcription factors of PtrRZFPs and revealed the possible biological functions of RZFP1/4/7 in resisting osmotic and salt stress, laying the foundation for subsequent biological function studies and providing genetic resources for genetic engineering breeding for drought resistance in forest trees. This study offers crucial information for the further exploration of the functions of RZFPs in poplars.

Classification of regulatory T cells and their role in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is closely related to the final infarct size in acute myocardial infarction (AMI). Therefore, reducing MIRI can effectively improve the prognosis of AMI patients. At the same time, the healing process after AMI is closely related to the local inflammatory microenvironment. Regulatory T cells (Tregs) can regulate various physiological and pathological immune inflammatory responses and play an important role in regulating the immune inflammatory response after AMI. However, different subtypes of Tregs have different effects on MIRI, and the same subtype of Tregs may also have different effects at different stages of MIRI. This article systematically reviews the classification and function of Tregs, as well as the role of various subtypes of Tregs in MIRI. A comprehensive understanding of the role of each subtype of Tregs can help design effective methods to control immune reactions, reduce MIRI, and provide new potential therapeutic options for AMI.

Online interpretable dynamic prediction models for postoperative delirium after cardiac surgery under cardiopulmonary bypass developed based on machine learning algorithms: A retrospective cohort study.

OBJECTIVE: Postoperative delirium (POD) is strongly associated with poor early and long-term prognosis in cardiac surgery patients with cardiopulmonary bypass (CPB). This study aimed to develop dynamic prediction models for POD after cardiac surgery under CPB using machine learning (ML) algorithms. METHODS: From July 2021 to June 2022, clinical data were collected from patients undergoing cardiac surgery under CPB at Nanjing First Hospital. A dataset from the same center (October 2022 to November 2022) was also used for temporal external validation. We used ML and deep learning to build models in the training set, optimized parameters in the test set, and finally validated the best model in the validation set. The SHapley Additive exPlanations (SHAP) method was introduced to explain the best models. RESULTS: Of the 885 patients enrolled, 221 (25.0%) developed POD. 22 (22.0%) of 100 validation cohort patients developed POD. The preoperative and postoperative artificial neural network (ANN) models exhibited optimal performance. The validation results demonstrated satisfactory predictive performance of the ANN model, with area under the receiver operator characteristic curve (AUROC) values of 0.776 and 0.684 for the preoperative and postoperative models, respectively. Based on the ANN algorithm, we constructed dynamic, highly accurate, and interpretable web risk calculators for POD. CONCLUSIONS: We successfully developed online interpretable dynamic ANN models as clinical decision aids to identify patients at high risk of POD before and after cardiac surgery to facilitate early intervention or care.

A risk prediction model based on machine learning for postoperative cognitive dysfunction in elderly patients with non-cardiac surgery.

BACKGROUND: Early identification of elderly patients undergoing non-cardiac surgery who may be at high risk for postoperative cognitive dysfunction (POCD) can increase the chances of prevention for them, as extra attention and limited resources can be allocated more to these patients. AIM: We performed this analysis with the aim of developing a simple, clinically useful machine learning (ML) model to predict the probability of POCD at 3 months in elderly patients after non-cardiac surgery. METHODS: We collected information on patients who received surgical treatment at Nanjing First Hospital from May 2020 to May 2021. We used LASSO regression to select key features and built 5 ML models to assess the risk of POCD at 3 months in elderly patients after non-cardiac surgery. The Shapley Additive exPlanations (SHAP) and methods were introduced to interpret the best model. RESULTS: A total of 415 patients with non-cardiac surgery were included. The support vector machine (SVM) was the best-performing model of the five ML models. The model showed excellent performance compared to the other four models. The SHAP results showed that VAS score, age, intraoperative hypotension, and preoperative hemoglobin were the four most important features, indicating that the SVM model had good interpretability and reliability. The website of the web-based calculator was https://modricreagan-non-3-pocd-9w2q78.streamlit.app/ . CONCLUSION: Based on six important perioperative variables, we successfully established a series of ML models for predicting POCD occurrence at 3 months after surgery in elderly non-cardiac patients, with SVM model being the best-performing model. Our models are expected to serve as decision aids for clinicians to monitor screened high-risk patients more closely or to consider further interventions.

Effects of biochar amendment and organic fertilizer on microbial communities in the rhizosphere soil of wheat in Yellow River Delta saline-alkaline soil.

The biochar and organic fertilizer amendment have been used as an effective practice to increase soil fertility. Nevertheless, the mechanisms of microbial community response to organic fertilizer and biochar application on saline-alkali soil have not been clarified. This study investigated the effects at different concentrations of organic fertilizer and biochar on the microbial community of wheat rhizosphere soil under field experiment in the Yellow River Delta (China, YRD), using high-throughput sequencing technology. Biochar and organic fertilizer significantly influenced in most soil parameters (p < 0.05), apart from soil moisture content (M), pH, total nitrogen (TN) and soil total phosphorus (TP). Proteobacteria and Actinobacteriota were found in the rhizosphere soil as the main bacterial phyla, and the main fungal phyla were Ascomycota and Mortierellomycota. The soil bacterial and fungal communities under organic fertilizer were distinct from CK. Furthermore, redundancy analysis (RDA) directed that changes in bacterial communities were related to soil properties like pH, available phosphorus (AP), and total organic carbon (TOC), while pH, AP and TP, were crucial contributors in regulating fungal distribution. The correlation between soil parameters and bacteria or fungi varied with the application of biochar and organic fertilizers, and the interaction between the bacteria and fungi in organic fertilizer treatments formed more connections compared with biochar treatments. Our results indicated that biochar was superior to organic fertilizer under the contents set up in this study, and soil parameters increased with biochar and organic fertilizer application rate. The diversity and structure of soil bacteria and fungi differed with the application of biochar and organic fertilizer. The research provides a reference to rational application of organic fertilizer and biochar improvement in saline-alkali soil.

Application of locally responsive design of biomaterials based on microenvironmental changes in myocardial infarction.

Morbidity and mortality caused by acute myocardial infarction (AMI) are on the rise, posing a grave threat to the health of the general population. Up to now, interventional, surgical, and pharmaceutical therapies have been the main treatment methods for AMI. Effective and timely reperfusion therapy decreases mortality, but it cannot stimulate myocardial cell regeneration or reverse ventricular remodeling. Cell therapy, gene therapy, immunotherapy, anti-inflammatory therapy, and several other techniques are utilized by researchers to improve patients' prognosis. In recent years, biomaterials for AMI therapy have become a hot spot in medical care. Biomaterials furnish a microenvironment conducive to cell growth and deliver therapeutic factors that stimulate cell regeneration and differentiation. Biomaterials adapt to the complex microenvironment and respond to changes in local physical and biochemical conditions. Therefore, environmental factors and material properties must be taken into account when designing biomaterials for the treatment of AMI. This article will review the factors that need to be fully considered in the design of biological materials.

Body composition parameters correlate with the endoscopic severity in Crohn's disease patients treated with infliximab.

Background: The disease activity status and behavior of Crohn's disease (CD) can reflect the severity of the disease, and changes in body composition are common in CD patients. Aims: The aim of this study was to investigate the relationship between body composition parameters and disease severity in CD patients treated with infliximab (IFX). Methods: Patients with CD assessed with the simple endoscopic score (SES-CD) and were treated with IFX were retrospectively collected, and body composition parameters at the level of the 3rd lumbar vertebrae were calculated from computed tomography (CT) scans of the patients. The correlation of patients' body composition parameters with disease activity status and disease behavior was analyzed, and the diagnostic value of the relevant parameters was assessed using receiver operating characteristic (ROC) curves. Results: A total of 106 patients were included in this study. There were significant differences in the subcutaneous adiposity index (SAI) (p = 0.010), the visceral adiposity index (VAI) (p < 0.001), the skeletal muscle mass index (SMI) (p < 0.001), and decreased skeletal muscle mass (p < 0.001) among patients with different activity status. After Spearman and multivariate regression analysis, SAI (p = 0.006 and p = 0.001), VAI (p < 0.001 and p < 0.001), and SMI (p < 0.001and p = 0.007) were identified as independent correlates of disease activity status (both disease activity and moderate-to-severe activity), with disease activity status independently positively correlated with SAI and SMI and independently negatively correlated with VAI. In determining the disease activity and moderate-to-severe activity status, SMI performed best relative to SAI and VAI, with areas under the ROC curve of 0.865 and 0.801, respectively. SAI (p = 0.015), SMI (p = 0.011) and decreased skeletal muscle mass (p = 0.027) were significantly different between different disease behavior groups (inflammatory disease behavior group, complex disease behavior group) but were not independent correlates (p > 0.05). Conclusion: Body composition parameters of CD patients treated with IFX correlate with the endoscopic disease severity, and SMI can be used as a reliable indicator of disease activity status.

Novel insight into histological and molecular astrocytoma, IDH-mutant, Grade 4 by the updated WHO classification of central nervous system tumors.

BACKGROUND: The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH-mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH-mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes. METHODS: Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH-mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. RESULTS: Altogether 33 patients with astrocytoma, IDH-mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral-necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas. CONCLUSIONS: Our study scrutinized IDH-mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.

Transcriptome profiling reveals multiple regulatory pathways of Tamarix chinensis in response to salt stress.

KEY MESSAGE: Multiple regulatory pathways of T. chinensis to salt stress were identified through transcriptome data analysis. Tamarix chinensis (Tamarix chinensis Lour.) is a typical halophyte capable of completing its life cycle in soils with medium to high salinity. However, the mechanisms underlying its resistance to high salt stress are still largely unclear. In this study, transcriptome profiling analyses in different organs of T. chinensis plants in response to salt stress were carried out. A total number of 2280, 689, and 489 differentially expressed genes (DEGs) were, respectively, identified in roots, stems, and leaves, with more DEGs detected in roots than in stems and leaves. Gene Ontology (GO) term analysis revealed that they were significantly enriched in "biological processes" and "molecular functions". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that "Beta-alanine metabolism" was the most differentially enriched pathway in roots, stems, and leaves. In pair-to-pair comparison of the most differentially enriched pathways, a total of 14 pathways, including 5 pathways in roots and leaves, 6 pathways in roots and stems, and 3 pathways in leaves and stems, were identified. Furthermore, genes encoding transcription factor, such as bHLH, bZIP, HD-Zip, MYB, NAC, WRKY, and genes associated with oxidative stress, starch and sucrose metabolism, and ion homeostasis, were differentially expressed with distinct organ specificity in roots, stems, and leaves. Our findings in this research provide a novel approach for exploring the salt tolerance mechanism of halophytes and identifying new gene targets for the genetic breeding of new plant cultivars with improved resistance to salt stress.