Practical prognostic tools to predict the risk of postoperative delirium in older patients undergoing cardiac surgery: visual and dynamic nomograms.

PURPOSE: Postoperative Delirium (POD) has an incidence of up to 65% in older patients undergoing cardiac surgery. We aimed to develop two dynamic nomograms to predict the risk of POD in older patients undergoing cardiac surgery. METHODS: This was a single-center retrospective cohort study, which included 531 older patients who underwent cardiac surgery from July 2021 to June 2022 at Nanjing First Hospital, China. Univariable and multivariable logistic regression were used to identify the significant predictors used when constructing the models. We evaluated the performances and accuracy, validated, and estimated the clinical utility and net benefit of the models using the receiver operating characteristic (ROC), the 10-fold cross-validation, and decision curve analysis (DCA). RESULTS: A total of 30% of the patients developed POD, the significant predictors in the preoperative model were ASA ( p < 0.001 OR = 3.220), cerebrovascular disease (p < 0.001 OR = 2.326), Alb (p < 0.037 OR = 0.946), and URE (p < 0.001 OR = 1.137), while for the postoperative model they were ASA (p = 0.044, OR = 1.737), preoperative MMSE score (p = 0.005, OR = 0.782), URE (p = 0.017 OR = 1.092), CPB duration (p < 0.001 OR = 1.010) and APACHE II (p < 0.001, OR = 1.353). The preoperative and postoperative models achieved satisfactory predictive performances, with AUC values of 0.731 and 0.799, respectively. The web calculators can be accessed at https://xxh152.shinyapps.io/Pre-POD/ and https://xxh152.shinyapps.io/Post-POD/ . CONCLUSION: We established two nomogram models based on the preoperative and postoperative time points to predict POD risk and guide the flexible implementation of possible interventions at different time points.

Atomic Defects Engineering Boosts Urea Synthesis toward Carbon Dioxide and Nitrate Coelectroreduction.

The atomic defect engineering could feasibly decorate the chemical behaviors of reaction intermediates to regulate catalytic performance. Herein, we created oxygen vacancies on the surface of In(OH)3 nanobelts for efficient urea electrosynthesis. When the oxygen vacancies were constructed on the surface of the In(OH)3 nanobelts, the faradaic efficiency for urea reached 80.1%, which is 2.9 times higher than that (20.7%) of the pristine In(OH)3 nanobelts. At -0.8 V versus reversible hydrogen electrode, In(OH)3 nanobelts with abundant oxygen vacancies exhibited partial current density for urea of -18.8 mA cm-2. Such a value represents the highest activity for urea electrosynthesis among recent reports. Density functional theory calculations suggested that the unsaturated In sites adjacent to oxygen defects helped to optimize the adsorbed configurations of key intermediates, promoting both the C-N coupling and the activation of the adsorbed CO2NH2 intermediate. In-situ spectroscopy measurements further validated the promotional effect of the oxygen vacancies on urea electrosynthesis.

Constructing machine learning models based on non-contrast CT radiomics to predict hemorrhagic transformation after stoke: a two-center study.

Purpose: Machine learning (ML) models were constructed according to non-contrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. Methods: A retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT. Results: Based on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p < 0.01) than patients without HT. The best ML algorithm for building the model was logistic regression. In the training and validation cohorts, the AUC values for the clinical, radiomics, and clinical-radiomics models for predicting HT were 0.829 and 0.876, 0.813 and 0.898, and 0.876 and 0.957, respectively. In subgroup analyses with different treatment modalities, different infarct sizes, and different stroke time windows, the assessment accuracy of the clinical-radiomics model was not statistically meaningful (all p > 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively. Conclusion: ML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment.

The ubiquitin E3 ligase RZFP1 affects drought tolerance in poplar by mediating the degradation of the protein phosphatase PP2C-9.

Abscisic acid signaling has been implicated in plant responses to water deficit-induced osmotic stress. However, the underlying molecular mechanism remains unelucidated. This study identified the RING-type E3 ubiquitin ligase RING ZINC FINGER PROTEIN1 (PtrRZFP1) in poplar (Populus trichocarpa), a woody model plant. PtrRZFP1 encodes a ubiquitin E3 ligase that participates in protein ubiquitination. PtrRZFP1 mainly functions in the nucleus and endoplasmic reticulum and is activated by drought and abscisic acid. PtrRZFP1-overexpressing transgenic poplars (35S:PtrRZFP1) showed greater tolerance to drought, whereas PtrRZFP1-knockdown lines (KD-PtrRZFP1) showed greater sensitivity to drought. Under treatment with polyethylene glycol and abscisic acid, PtrRZFP1 promoted the production of NO and H2O2 in stomatal guard cells, ultimately enhancing stomatal closure and improving drought tolerance. Additionally, PtrRZFP1 physically interacted with the clade A Protein Phosphatase 2C protein PtrPP2C-9, a core regulator of abscisic acid signaling, and mediated its ubiquitination and eventual degradation through the ubiquitination-26S proteasome system, indicating that PtrRZFP1 positively regulates the abscisic acid signaling pathway. Furthermore, the PtrPP2C-9-overexpression line was insensitive to abscisic acid and more sensitive to drought than the wild-type plants, whereas the opposite phenotype was observed in 35S:PtrRZFP1 plants. In general, PtrRZFP1 negatively regulates the stability of PtrPP2C-9 to mediate poplar drought tolerance. The results of this study provide a theoretical framework for the targeted breeding of drought-tolerant traits in perennial woody plants.

MRI findings and classification of brucella spondylitis: a China multicenter study.

OBJECTIVES: To propose a magnetic resonance imaging (MRI) classification of brucellosis spondylitis (BS) to determine a standard treatment method and a standard of post-treatment MRI follow-up. METHODS: This is a multicenter retrospective cohort study. All patients diagnosed with BS at six hospitals for 12 years, were included in the study. Data were collected retrospectively from the medical records of the patients. The classification of the cases was based on MRI. We analyzed MRI features of BS was categorized them into three types. RESULTS: Six hundred fifteen patients were included in the study, 78.9% of whom were males. The mean age was 53.05 ± 11.06 years. Involvement of single vertebrae occurred in 6.2% of patients, while 72.7% involved two vertebrae and 21.1% involvement of more than two vertebrae. The most common of the lumbar spine was 64.6%. The main findings of MRI were affected vertebral endplate 2/3 above (60.7%), intervertebral space narrow (77.9%), intervertebral disc involvement (83.6%), paravertebral abscess (50.9%), disc abscess (49.6%), epidural abscess (43.3%), vertebra height change (22.1%), psoas abscess (22.0%), and abnormal vertebral accessory (10.2%). MR imaging of BS was categorized into three types. Type I: 57 (9.3%) patients; Type II: 526 (85.5%) patients, including IIa (26.5%), IIb (36.9%), and IIc (22.1%); Type IV: vertebral appendage type, 63 (10.2%) cases; Type III: 32 (5.2%) patients. CONCLUSIONS: MRI features of multicenter data can provide theoretical support for diagnosing BS. MRI classification of BS can afford better help for clinical treatment and follow-up after clinical treatment.

Revealing the impact of sample enrichment method on concentration and cytotoxicity of volatile disinfection byproducts in drinking water: A quantitative study for liquid-liquid extraction.

Liquid-liquid extraction (LLE) combined with the N2 blow-down method is a promising tool for bioanalysis of drinking water. However, detailed information on which disinfection byproduct (DBP) classes are retained in LLE extracts is currently unavailable. In this study, the recovery of seven classes of volatile DBPs and total adsorbable organic halogens (TOX) during the LLE method, combined with three common N2 blow-down methods, for bioanalysis in real tap water was analyzed at a 2-L scale, along with their corresponding cytotoxicity. The total concentration of seven classes of volatile DBPs in drinking water in Suzhou ranged from 64.6 to 83.0 µg/L, with the majority contributed by trihalomethanes (THMs: 59.9 µg/L), haloaldehydes (HALs: 5.4 µg/L), haloacetamides (HAMs: 3.4 µg/L), and haloacetonitriles (HANs: 3.2 µg/L). During the LLE - N2 blow-down process for bioanalysis, about 69-85 % of targeted volatile DBPs and 64-75 % of TOX were lost, respectively. Seven classes of volatile DBPs accounted for 52.8-64.3 % and 23.8-61.3 % of TOX in tap water and LLE - N2 blow-down samples, respectively, suggesting that targeted aliphatic DBPs are the key contributors to TOX. Furthermore, although LLE - solvent exchange had a better recovery performance than other N2 blow-down methods, the recoveries of volatile DBPs using this method were still not ideal. For example, HALs and HAMs had a slightly better recovery (>50 %), while most volatile DBPs had a poor recovery, including iodo-trihalomethanes (I-THMs, 0 %), haloketones (28 %), THMs (26 %), halonitromethanes (33 %), and HANs (38 %). During LLE - solvent exchange, 31 % and 36 % of targeted DBPs and TOX, respectively, in real tap water can be retained, which shows better performance than non-ionic macroporous copolymers (XAD). More importantly, the water volume required in this method for cytotoxicity analysis is 2 L, which greatly reduces the burden of water sample collection, transport, and pre-treatment compared to XAD (which typically requires 5 or 10 L). In general, this paper reveals the fate of volatile DBPs during LLE - N2 blow-down and indicates that LLE - solvent exchange is a good substitute for the XAD method in bioanalysis.

[Effect of Intrauterine Perfusion of Granulocyte Colony-Stimulating Factor on Endometrium and Blood Flow Parameters in Patients With Thin Endometrium: A Prospective Controlled Clinical Trial]. / å®«è ”çŒæ³¨ç²’ç»†èƒžé›†è½åˆºæ¿€å› å­æ”¹å–„è–„åž‹å­å®«å† è†œæ‚£è€ å† è†œåŠè¡€æµå‚æ•°çš„å‰çž»æ€§ä¸´åºŠå¯¹ç §è¯•éªŒ.

Objective: To investigate the effects of intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF) on the endometrial thickness, volume, and blood flow parameters of patients with thin endometrium and their clinical outcomes. Methods: We designed a prospective non-randomized synchronous controlled trial and recruited patients with thin endometrium who underwent frozen-thawed embryo transfer (FET) at Mianyang Central Hospital between September 1, 2021 and September 1, 2023. They were divided into two groups, an experimental group of patients who received the experimental treatment of intrauterine perfusion with G-CSF and a control group of patients who did not receive the experimental treatment. The general data and the clinical outcomes of the two groups were analyzed and compared. The endometrial thickness, volume and blood flow parameters of patients in the experimental group before and after intrauterine perfusion with G-CSF were analyzed. Results: The clinical data of 83 patients were included in the study. The experimental group included 51 cases, while the control group included 31 cases. There were no significant differences in the baseline data between the two groups. The clinical pregnancy rate of the experimental group (56.86%) was higher than that of the control group (50.00%) and the rate of spontaneous abortion in the experimental group (27.59%) was lower than that in the control group (37.50%), but the differences were not statistically significant (P>0.05). In the experimental group, the postperfusion endometrial thickness ([0.67±0.1] cm) was greater than the preperfusion endometrial thickness ([0.59±0.09] cm), the postperfusion ([1.84±0.81] cm3) was greater than the preperfusion endometrial volume ([1.54±0.69] cm3), and the postperfusion vascularization flow index (VFI) (1.97±2.82) was greater than the preperfusion VFI (0.99±1.04), with all the differences being statistically significant (P<0.05). Conclusion: Intrauterine perfusion with G-CSF can enhance the endometrial thickness, volume, and some blood flow parameters in patients with thin endometrium.

Fusion Genes Landscape of Lung Cancer Patients From Inner Mongolia, China.

Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.

Programmed cell death disrupts inflammatory tumor microenvironment (TME) and promotes glioblastoma evolution.

Glioblastoma (GBM) is the most common malignant brain tumor and has a dismal prognosis even under the current first-line treatment, with a 5-year survival rate less than 7%. Therefore, it is important to understand the mechanism of treatment resistance and develop new anti-tumor strategies. Induction of programmed cell death (PCD) has become a promising anti-tumor strategy, but its effectiveness in treating GBM remains controversial. On the one hand, PCD triggers tumor cell death and then release mediators to draw in immune cells, creating a pro-inflammatory tumor microenvironment (TME). One the other hand, mounting evidence suggests that PCD and inflammatory TME will force tumor cells to evolve under survival stress, leading to tumor recurrence. The purpose of this review is to summarize the role of PCD and inflammatory TME in the tumor evolution of GBM and promising methods to overcome tumor evolution.

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Achieving High Operating-Temperature Self-powered X-Ray Detection in Multilayered Hybrid Perovskites through Arylamine Intercalation.

Polar metal halide hybrid perovskites (PHPs) that exhibit outstanding bulk photovoltaic effect (BPVE), excellent semiconductor features, and strong radiation absorption ability, have shown prominent advantages in highly sensitive direct X-ray detection. However, it is still a challenge to explore PHPs with high BPVE temperature ranges, answering the demand of developing thermally stable passive X-ray detection. Herein, by intercalating arylamine into lead tribromide and inducing order-disorder phase transition, a 2D multilayered PHPs (BZA)2(MA)Pb2Br7 (BZPB, BZA = benzylamine, MA = methylamine) is synthesized. BZPB crystallizes in a polar space group Aea2 at a low-temperature phase and demonstrates a significant open-circuit of 0.3 V deriving from BPVE under X-ray irradiation. Meanwhile, the strong X-ray absorption coefficient and outstanding carrier transport capability of the bilayered lead halide framework associated with the polar BPVE give BZPB excellent X-ray detection abilities. At 0 V bias, the impressive sensitivity of BZPB is 98 µC Gy-1 cm-2. Importantly, the introduction of the rigid BZA ring increases the energy barrier of phase transition and thus dramatically enhances the X-ray detection operating temperature of BZPB up to 409 K without significant performance degradation. This work strongly reveals the great potential of rational design of metal halide hybrid perovskites for X-ray detection applications.

Establishing a machine learning model based on dual-energy CT enterography to evaluate Crohn's disease activity.

OBJECTIVES: The simplified endoscopic score of Crohn's disease (SES-CD) is the gold standard for quantitatively evaluating Crohn's disease (CD) activity but is invasive. This study aimed to develop and validate a machine learning (ML) model based on dual-energy CT enterography (DECTE) to noninvasively evaluate CD activity. METHODS: We evaluated the activity in 202 bowel segments of 46 CD patients according to the SES-CD score and divided the segments randomly into training set and testing set at a ratio of 7:3. Least absolute shrinkage and selection operator (LASSO) was used for feature selection, and three models based on significant parameters were established based on logistic regression. Model performance was evaluated using receiver operating characteristic (ROC), calibration, and clinical decision curves. RESULTS: There were 110 active and 92 inactive bowel segments. In univariate analysis, the slope of spectral curve in the venous phases (λHU-V) has the best diagnostic performance, with an area under the ROC curve (AUC) of 0.81 and an optimal threshold of 1.975. In the testing set, the AUC of the three models established by the 7 variables to differentiate CD activity was 0.81-0.87 (DeLong test p value was 0.071-0.766, p > 0.05), and the combined model had the highest AUC of 0.87 (95% confidence interval (CI): 0.779-0.959). CONCLUSIONS: The ML model based the DECTE can feasibly evaluate CD activity, and DECTE parameters provide a quantitative analysis basis for evaluating specific bowel activities in CD patients. CRITICAL RELEVANCE STATEMENT: The machine learning model based on dual-energy computed tomography enterography can be used for evaluating Crohn's disease activity noninvasively and quantitatively. KEY POINTS: Dual-energy CT parameters are related to Crohn's disease activity. Three machine learning models effectively evaluated Crohn's disease activity. Combined models based on conventional and dual-energy CT have the best performance.

Hyaluronidase inhibits TGF-ß-mediated rat periodontal ligament fibroblast expression of collagen and myofibroblast markers: An in vitro exploration of periodontal tissue remodeling.

OBJECTIVE: To determine the effect of hyaluronic acid (HA) degradation by hyaluronidase (HYAL) in inhibiting collagen fiber production by rat periodontal ligament cells (rPDLCs). DESIGN: Primary rPDLCs were isolated from the euthanized rats and used for in vitro experiments. The appropriate HYAL concentration was determined through CCK-8 testing for cytotoxicity detection and Alizarin red staining for mineralization detection. RT-qPCR and western blot assays were conducted to assess the effect of HYAL, with or without TGF-ß, on generation of collagen fiber constituents and expression of actin alpha 2, smooth muscle (ACTA2) of rPDLCs. RESULTS: Neither cell proliferation nor mineralization were significantly affected by treatment with 4 U/mL HYAL. HYAL (4 U/mL) alone downregulated type I collagen fiber (Col1a1 and Col1a2) and Acta2 mRNA expression; however, ACTA2 and COL1 protein levels were only downregulated by HYAL treatment after TGF-ß induction. CONCLUSIONS: Treatment of rPDLCs with HYAL can inhibit TGF-ß-induced collagen matrix formation and myofibroblast transformation.

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.

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.

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.

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.

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.

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.