Development and validation of an MRI-Based nomogram to predict the effectiveness of immunotherapy for brain metastasis in patients with non-small cell lung cancer.

Introduction: The variability and unpredictability of immune checkpoint inhibitors (ICIs) in treating brain metastases (BMs) in patients with advanced non-small cell lung cancer (NSCLC) is the main concern. We assessed the utility of novel imaging biomarkers (radiomics) for discerning patients with NSCLC and BMs who would derive advantages from ICIs treatment. Methods: Data clinical outcomes and pretreatment magnetic resonance images (MRI) were collected on patients with NSCLC with BMs treated with ICIs between June 2019 and June 2022 and divided into training and test sets. Metastatic brain lesions were contoured using ITK-SNAP software, and 3748 radiomic features capturing both intra- and peritumoral texture patterns were extracted. A clinical radiomic nomogram (CRN) was built to evaluate intracranial progression-free survival, progression-free survival, and overall survival. The prognostic value of the CRN was assessed by Kaplan-Meier survival analysis and log-rank tests. Results: In the study, a total of 174 patients were included, and 122 and 52 were allocated to the training and validation sets correspondingly. The intratumoral radiomic signature, peritumoral radiomic signature, clinical signature, and CRN predicted intracranial objective response rate. Kaplan-Meier analyses showed a significantly longer intracranial progression-free survival in the low-CRN group than in the high-CRN group (p < 0.001). The CRN was also significantly associated with progression-free survival (p < 0.001) but not overall survival. Discussion: Radiomics biomarkers from pretreatment MRI images were predictive of intracranial response. Pretreatment radiomics may allow the early prediction of benefits.

Using MRI radiomics to predict the efficacy of immunotherapy for brain metastasis in patients with small cell lung cancer.

BACKGROUND: Brain metastases (BMs) are common in small cell lung cancer (SCLC), and the efficacy of immune checkpoint inhibitors (ICIs) in these patients is uncertain. In this study we aimed to develop and validate a radiomics nomogram based on magnetic resonance imaging (MRI) for intracranial efficacy prediction of ICIs in patients with BMs from SCLC. METHODS: The training and validation cohorts consisted of 101 patients from two centers. The interclass correlation coefficient (ICC), logistic univariate regression analysis, and random forest were applied to select the radiomic features, generating the radiomics score (Rad-score) through the formula. Using multivariable logistic regression analysis, a nomogram was created by the combined model. The discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. Kaplan-Meier curves were plotted based on the nomogram scores. RESULTS: Ten radiomic features were selected for calculating the Rad-score as they could differentiate the intracranial efficacy in the training (area under the curve [AUC], 0.759) and the validation cohort (AUC, 0.667). A nomogram was created by combining Rad-score, treatment lines, and neutrophil-to-lymphocyte ratio (NLR). The training cohort obtained an AUC of 0.878 for the combined model, verified in the validation cohort (AUC = 0.875). Kaplan-Meier analyses showed the nomogram was associated with progression-free survival (PFS) (p = 0.0152) and intracranial progression-free survival (iPFS) (p = 0.0052) but not overall survival (OS) (p = 0.4894). CONCLUSION: A radiomics nomogram model for predicting the intracranial efficacy of ICIs in SCLC patients with BMs can provide suggestions for exploring individual-based treatments for patients.

Noninvasive radiomic biomarkers for predicting pseudoprogression and hyperprogression in patients with non-small cell lung cancer treated with immune checkpoint inhibition.

This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. We retrospectively analyzed 105 patients with NSCLC, from three institutions, treated with immune checkpoint inhibitors (ICIs) and categorized them into training and independent testing set. Subsequently, we processed CT scans with a series of image-preprocessing techniques, and 6008 radiomic features capturing intra- and peritumoral texture patterns were extracted. We used the least absolute shrinkage and selection operator logistic regression model to select radiomic features and construct machine learning models. To further differentiate between progressive disease (PD) and hyperprogressive disease (HPD), we developed a new radiomics model. The logistic regression (LR) model showed optimal performance in distinguishing PP from HPD, with areas under the receiver operating characteristic curve (AUC) of 0.95 (95% confidence interval [CI]: 0.91-0.99) and 0.88 (95% CI: 0.66-1) in the training and testing sets, respectively. Additionally, the support vector machine model showed optimal performance in distinguishing PD from HPD, with AUC of 0.97 (95% CI: 0.93-1) and 0.87 (95% CI: 0.72-1) in the training and testing sets, respectively. Kaplan‒Meier survival curves showed clear stratification between PP predicted by the radiomics model and true progression (HPD and PD) (hazard ratio = 0.337, 95% CI: 0.200-0.568, p < 0.01) in overall survival. Our study demonstrates that radiomic features extracted from baseline CT scans are effective in predicting PP and HPD in patients with NSCLC treated with ICIs.

Strategies for Preventing Esophageal Stenosis After Endoscopic Submucosal Dissection and Progress in Stem Cell-Based Therapies.

Endoscopic submucosal dissection (ESD) has been widely used in the early neoplasia of the esophagus. However, postoperative esophageal stenosis is a big problem, particularly when a large circumferential proportion of esophageal mucosa is resected. Currently, there are several methods available to prevent esophageal stenosis after ESD, including steroid administration, esophageal stent implantation, and endoscopic balloon dilation (EBD). However, the therapeutic effects of these are not yet satisfactory. Stem cell-based therapies has shown promising potential in reconstructing tissue structure and restoring tissue function. In this study, we discussed the current strategies for preventing esophageal stenosis after ESD and perspectives of stem cell-based therapies for the prevention of esophageal stenosis.

A retrospective pilot study of transarterial chemoembolisation using camrelizumab-eluting Callisphere beads for unresectable hepatocellular carcinoma.

BACKGROUND: Our objective was to assess the efficacy and safety of initial hepatic arterial infusion of chemotherapy combined with transarterial chemoembolisation using camrelizumab-eluting Callisphere beads (camrelizumab-DEB-TACE) for treating unresectable hepatocellular carcinoma (HCC). METHODS: Enrolment included patients with unresectable HCC who underwent camrelizumab-DEB-TACE treatment from September 2021 to February 2023. The assessment included the examination of tumour response, overall survival (OS), progression-free survival (PFS), and the monitoring of adverse events (AEs). RESULTS: Twenty-one patients were included in the study. The objective response rates (ORR) and disease control rates (DCR) were 55.0% and 90.0% at 1 month and 57.9% and 78.9% at 3 months, respectively. The median PFS and OS were 7.4 and 15.5 months months, respectively. Among the 21 patients, 4 underwent more than 2 procedures of camrelizumab-DEB-TACE, with a mean of 1.9 ± 1.1 procedures (range: 1-4) per patient. No severe complications or treatment-related mortalities were observed. In addition, no patient developed severe AEs related to camrelizumab, such as reactive cutaneous capillary endothelial proliferation, immune-related pneumonia, or immune-related myocarditis. Nineteen patients experienced at least one type of AEs related to DEB-TACE, with abdominal pain (n = 16, 76.2%) being the most prevalent AE. CONCLUSION: Camrelizumab-DEB-TACE demonstrated effectiveness and safety as a treatment for unresectable HCC, with no occurrence of severe camrelizumab-related AEs.

A century-long record of polycyclic aromatic hydrocarbon deposition in the Old Yellow River Estuary, China.

Polycyclic aromatic hydrocarbons (PAHs) are potential geochemical indicators for assessing the impact of human activities and can be used to reconstruct historical human activities. This study collected a 108 cm sediment core from the 5th lobe of the Yellow River Delta for the first time and analyzed the historical distribution characteristics of PAHs in this area. The results showed that the sedimentation history of the core was from 1908 to 2014. The average value of PAHs was 28.93 ng/g. Biomass and coal combustion sources were the main sources of PAHs in the low-value areas, while oil spill sources were the main sources in the significantly higher PAHs areas in the 1960s, mid-1980s, late 1990s, and late 2010s, which was consistent with the development history of Shengli Oilfield. Compared with global estuaries, the historical industrial activity intensity in this area was weaker.

Niche differentiation and influencing factors of nitrite oxidation bacteria Nitrospira in sediments of the Luan River estuary in China.

In the estuarine sediment, the nitrite oxidation process mediated by bacteria significantly influences nitrification. Nitrospira is the most widely distributed nitrite-oxidizing bacteria (NOB) and can adapt to various environments. In this study, the Nitrospira-specific primer nxrB 169F-638R was used to analyze the microbial communities in the sediments of low-, middle-, and high-level zones in the Luan River estuary. The structure of the microbial community and its response to environmental factors were also assessed. The abundance and diversity of Nitrospira were the highest in the low-level zone and lowest in the high-level zone. Lineage II and lineage IV were the dominant Nitrospira at 43.58% and 32.09%, respectively. The distribution pattern of Nitrospira was also affected by complex environmental factors, such as the concentration of NH4+, Fe, and Cu cations. This study provides novel insights into the niche differentiation and adaptation strategies of Nitrospira in an estuarine sediment environment and will help to facilitate single-step nitrification.

Local injection of adipose-derived mesenchymal stem cells in silk fibroin solution on the regeneration of lower esophageal sphincter in an animal model of GERD.

Presently, various tissue engineering methods using adult stem cells and biomaterials are being confirmed to regenerate vessels, cardiac muscle, bladder, and intestines. However, there are few studies about the repair of the lower esophageal sphincter (LES) may help alleviate the symptoms of gastroesophageal reflux disease (GERD). This study aims to determine whether Adipose-Derived Stem Cells (ADSCs) combined with regenerated silk fibroin (RSF) solution could regenerate the LES. In vitro, the ADSCs were isolated, identified, and then cultured with an established smooth muscular induction system. In vivo, in the experimental groups, CM-Dil labeled ADSCs or induced ADSCs mixed with RSF solution were injected into the LES of rats after the development of the animal model of GERD respectively. The results showed that ADSCs could be induced into smooth muscular-like cells with the expression of h-caldesmon, calponin, α-smooth muscle actin, and a smooth muscle-myosin heavy chain in vitro. In vivo, the thickness of LES in the experiment rats was much thicker than those in the controlled groups. This result indicated that ADSCs mixed with RSF solution might contribute to the regeneration of the LES, thus reducing the occurrence of GERD.

Cuproptosis-Related LncRNA Signature for Predicting Prognosis of Hepatocellular Carcinoma: A Comprehensive Analysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has a poor prognosis. Cuproptosis is a novel mode of cell death that has only recently been discovered. Considering the critical role of lncRNAs in liver cancer development, the aim of this study was to construct a prognostic signature based on cuproptosis-related lncRNAs (CRlncRNAs). We downloaded RNA-sequencing data and corresponding clinical information of patients with HCC from The Cancer Genome Atlas (TCGA) database. To verify the robustness of the model, we added an external validation set obtained from the Gene Expression Omnibus (GEO): GSE40144. In addition, we identified the cuproptosis-related genes (CRGs) based on previous reports. Pearson correlation analysis, univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were utilized to screen for genes associated with prognosis. On this basis, multivariate Cox regression and stepAIC were used to further construct and optimize the prognostic model. The simplified signature with the lowest Akaike information criterion (AIC) value was considered the prognostic signature. Seven different algorithms were used to perform immune infiltration analysis. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was utilized to find the difference in immune function between the high- and low-risk groups. Finally, in vitro experiments were performed by quantitative real-time PCR (qRT-PCR) analysis using HCC cell lines to validate the expression of prognostic genes. We identified 3 lncRNAs (CYTOR, LINC00205, and LINC01184) as independent risk factors for HCC. The receiver operating characteristic (ROC) curves calculated that the AUC at 1, 3, and 5 years reached 0.717, 0.633, and 0.607, respectively. The expression levels of 41 immune checkpoints differed significantly between the high- and low-risk groups, and there were significant differences in sensitivity to immunotherapy between the high- and low-risk groups. The risk model could also serve as a promising predictor of immunotherapeutic response, which has been verified by the TIDE algorithm (p < 0.001). Overall, we propose a signature related to CRlncRNAs that can be used to predict the prognosis of HCC patients, which was validated in external cohort and in vitro experiments.

Sila-spirocyclization involving unstrained C(sp3)-Si bond cleavage.

C - Si Bond cleavage is one of the key elemental steps for a wide variety of silicon-based transformations. However, the cleavage of unstrained Si-C(sp3) bonds catalyzed by transition metal are still in their infancy. They generally involve the insertion of a M - C(sp2) species into the C - Si bond and consequent intramolecular C(sp2)‒Si coupling to exclusively produce siloles. Here we report the Pd-catalyzed sila-spirocyclization, in which the Si-C(sp3) bond is activated by the insertion of a M - C(sp3) species and followed by the formation of a new C(sp3)‒Si bond, allowing the construction of diverse spirosilacycles. This reactivity mode, which is strongly supported by DFT calculations may open an avenue for the Si-C(sp3) bond cleavage and silacycle synthesis.

Drug-Eluting Embolics Chemoembolization for the Management of Recurrent or Advanced Head and Neck Cancer.

PURPOSE: To characterize the safety, tolerability, and efficacy of chemoembolization using drug-eluting embolic (DEE) microspheres in patients with recurrent and advanced head and neck cancer. MATERIALS AND METHODS: In this retrospective study, 32 patients (mean age, 57.2 years ± 2.8; 17 women) with recurrent (n = 16) and advanced (n = 16) head and neck cancer were treated with chemoembolization using DEE microspheres loaded with doxorubicin. Treatment response, overall survival, local progression-free survival, and adverse events were evaluated. RESULTS: At 6 months after the procedure, the objective response and disease control rates were 25% and 69%, respectively. The median overall survival and local progression-free survival were 14.5 and 13.6 months, respectively. Seven (22%) patients experienced adverse events after the chemoembolization procedure. All the adverse events were related to postembolization syndrome, including vomiting and nausea (n = 1), pyrexia (n = 2), and localized pain (n = 7). No severe adverse events or procedure-related deaths were observed. CONCLUSIONS: Chemoembolization using DEE microspheres was safe and tolerable in patients with recurrent and advanced head and neck cancer.

Transarterial chemoembolization of unresectable renal cell carcinoma with doxorubicin-loaded CalliSpheres drug-eluting beads.

The safety and efficacy of drug-eluting beads transarterial chemoembolization (DEB-TACE) for unresectable renal cell carcinoma (RCC) still unknown. We aimed to assess the feasibility, safety and clinical efficacy of DEB-TACE with doxorubicin-loaded CalliSpheres beads (CB) in patients with unresectable RCC. Between 2016 and 2020, thirty-five patients with unresectable RCC underwent DEB-TACE with doxorubicin-loaded CB. The objective response rate (ORR) was the primary endpoint, and overall survival (OS) and progression-free survival (PFS) were the secondary endpoints. Fifteen-seven times of DEB-TACE were performed in 35 patients using doxorubicin-loaded (median 60 mg) CB. Fifteen patients underwent an additional session of DEB-TACE, with intervals of 1 to 1.5 months. Twenty-one patients underwent transarterial infusion with cisplatin or oxaliplatin before DEB-TACE. The median follow-up time was 9.0 months (Range 1.8-43.6 months). ORR and DCR were 47.1% and 94.1%, 29.0% and 87.1%, 23.1% and 84.6% respectively at 1-, 3-, and 6- months after DEB-TACE. The median PFS was 21.4 months, and the 3-, 6- and 12- month PFS rates were 84.7%, 73.7% and 62.3%, respectively. The median OS was 24.6 months, and the 3-, 6- and 12- month OS rates were 93.9%, 87.6% and 65.2%, respectively. There were no treatment-related deaths or severe adverse events of grade 3 or more. In conclusion, DEB-TACE with doxorubicin-loaded CB is a safe, feasible and effective palliative treatment option for patients with unresectable RCC.

Arsenic Release from Soil Induced by Microorganisms and Environmental Factors.

In rhizospheric soil, arsenic can be activated by both biological and abiotic reactions with plant exudates or phosphates, but little is known about the relative contributions of these two pathways. The effects of microorganisms, low-molecular-weight organic acid salts (LMWOASs), and phosphates on the migration of As in unrestored and nano zero-valent iron (nZVI)-restored soil were studied in batch experiments. The results show that As released by microbial action accounted for 17.73%, 7.04%, 92.40%, 92.55%, and 96.68% of the total As released in unrestored soil with citrate, phytate, malate, lactate, and acetate, respectively. It was only suppressed in unrestored soil with oxalate. In restored soil, As was still released in the presence of oxalate, citrate, and phytate, but the magnitude of As release was inhibited by microorganisms. The application of excess nZVI can completely inhibited As release processes induced by phosphate in the presence of microorganisms. Microbial iron reduction is a possible mechanism of arsenic release induced by microorganisms. Microorganisms and most environmental factors promoted As release in unrestored soil, but the phenomenon was suppressed in restored soil. This study helps to provide an effective strategy for reducing the secondary release of As from soils due to replanting after restoration.

A Hemolysis Image Detection Method Based on GAN-CNN-ELM.

Since manual hemolysis test methods are given priority with practical experience and its cost is high, the characteristics of hemolysis images are studied. A hemolysis image detection method based on generative adversarial networks (GANs) and convolutional neural networks (CNNs) with extreme learning machine (ELM) is proposed. First, the image enhancement and data enhancement are performed on a sample set, and GAN is used to expand the sample data volume. Second, CNN is used to extract the feature vectors of the processed images and label eigenvectors with one-hot encoding. Third, the feature matrix is input to the map in the ELM network to minimize the error and obtain the optimal weight by training. Finally, the image to be detected is input to the trained model, and the image with the greatest probability is selected as the final category. Through model comparison experiments, the results show that the hemolysis image detection method based on the GAN-CNN-ELM model is better than GAN-CNN, GAN-ELM, GAN-ELM-L1, GAN-SVM, GAN-CNN-SVM, and CNN-ELM in accuracy and speed, and the accuracy rate is 98.91%.

Pirarubicin-loaded CalliSpheres® drug-eluting beads for the treatment of patients with stage III-IV lung cancer.

BACKGROUND: CalliSpheres® beads (CB) have been used recently for patients with hepatocellular carcinoma. However, the safety and effect of drug-eluting bead transarterial chemoembolization (DEB-TACE) in patients with stage III-IV lung cancer are still unknown. PURPOSE: To evaluate the safety and efficacy of DEB-TACE with pirarubicin-loaded CB for the treatment of stage III-IV lung cancer. MATERIAL AND METHODS: From July 2016 to April 2020, 29 patients with stage III-IV primary lung cancer underwent DEB-TACE with pirarubicin-loaded CB. The objective response rate (ORR) was the primary endpoint; the secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-nine patients received DEB-TACE with pirarubicin-loaded (median 60 mg) CB, with no severe adverse events or treatment-related deaths. After DEB-TACE, hemoptysis disappeared within 1-3 days in all patients, and the symptoms of cough or expectoration were significantly improved in 12 patients. ORR and disease control rate at one, three, and six months after DEB-TACE were 39.3% and 96.4%, 26.1% and 69.6%, and 29.4% and 58.8%, respectively. The median PFS was 6.3 months (range 1.1-30.1 months), and the three-, six-, and 12-month PFS rates were 70.2%, 50.1%, and 27.1%, respectively. The median OS was 10.2 months (range 1.1-44.6 months), and the three-, six, and 12-month OS rates were 87.9%, 68.6%, and 39.8%, respectively. CONCLUSION: DEB-TACE with pirarubicin-loaded CB is safe, feasible, and well-tolerated for patients with stage III-IV lung cancer, and symptom control was a potential benefit of treatment.

Spatial Distribution Pattern Evolution of the Population and Economy in Russia since the 21st Century.

Under the background of "the Belt and Road" and "China, Mongolia and Russia economic corridor" initiatives, this paper studied the spatial distribution pattern evolution of population and economy in Russia since the 21st century, which could provide implications for the regional development planning, economic optimization layout, energy resource development, transportation infrastructure construction between China and Russia. Combined with the panel data of population, GDP, land area, etc., we used the gravity center analysis, geographic concentration degree, and inconsistency index to study Russia's population pattern evolution trend, economic pattern evolution trend, spatial inconsistency types of population distribution and economic development. The results and conclusions are as follows. Russia's population and economic gravity centers have migrated towards the northwest direction. Russia's population and economic distribution pattern presents the unbalanced development trend, which could be characterized by the differentiation pattern of "High West, Low East" and "High South, Low North" divided by the Ural Federal District. In the southwest areas of Russia, the population concentration degree is higher than the economic concentration degree in most federal subjects. In the northeast areas of Russia, the economic concentration degree is higher than the population concentration degree in most federal subjects.

Clinical outcomes of uterine arterial chemoembolization with drug-eluting beads for advanced-stage or recurrent cervical cancer.

PURPOSE: To study the clinical efficacy and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) among women with advanced-stage or recurrent cervical cancer. METHODS: This retrospective cohort study enrolled women with cervical cancer who were treated by DEB-TACE between April 3, 2017 and July 12, 2021. Inclusion criteria were pathologic diagnosis of cervical cancer, II-IVa period, being aged 18 to 80 years, patient's inclination of treatment with DEB-TACE, and complete clinicopathologic data. Direct medical cost, hospital stay, resection frequency, treatment responses, adverse events, overall survival, and progression-free survival were investigated. RESULTS: A total of 16 women with cervical cancer were treated by DEB-TACE. DEB-TACE was successfully performed in all patients, with no major complications or adverse events. A total of 10 minor complications were observed in 9 women (56.3%) after the procedure. Seven (43.8%) women experienced mild to moderate post-embolization pain. The tumors decreased 3 and 6 months after the treatment. The frequency of complete response, partial response, stable disease, and progressive disease was 1 (40%), 3 (40%), 12 (15%), and 0 (0%), respectively, resulting in an objective response rate of 25.0% and a disease control rate of 100.0% after 1 month. The median hospital stay was 9.5 days, and the direct medical cost was 5.9 × 104 ¥. The median follow-up time was 4.1 months (interquartile range 2.6-23.7 months). The median overall survival was 19.1 months, and the 1- and 3-year survival rate was 64.9% and 46.4%, respectively. CONCLUSION: DEB-TACE with diamminedichloroplatinum-preloaded beads may be an effective and safe treatment for women with advanced-stage or recurrent cervical cancer.