A novel nomogram integrating body composition and inflammatory-nutritional markers for predicting postoperative complications in patients with adhesive small bowel obstruction.

Background: Postoperative complications in adhesive small bowel obstruction (ASBO) significantly escalate healthcare costs and prolong hospital stays. This study endeavors to construct a nomogram that synergizes computed tomography (CT) body composition data with inflammatory-nutritional markers to forecast postoperative complications in ASBO. Methods: The study's internal cohort consisted of 190 ASBO patients recruited from October 2017 to November 2021, subsequently partitioned into training (n = 133) and internal validation (n = 57) groups at a 7:3 ratio. An additional external cohort comprised 52 patients. Body composition assessments were conducted at the third lumbar vertebral level utilizing CT images. Baseline characteristics alongside systemic inflammatory responses were meticulously documented. Through univariable and multivariable regression analyses, risk factors pertinent to postoperative complications were identified, culminating in the creation of a predictive nomogram. The nomogram's precision was appraised using the concordance index (C-index) and the area under the receiver operating characteristic (ROC) curve. Results: Postoperative complications were observed in 65 (48.87%), 26 (45.61%), and 22 (42.31%) patients across the three cohorts, respectively. Multivariate analysis revealed that nutrition risk score (NRS), intestinal strangulation, skeletal muscle index (SMI), subcutaneous fat index (SFI), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) were independently predictive of postoperative complications. These preoperative indicators were integral to the nomogram's formulation. The model, amalgamating body composition and inflammatory-nutritional indices, demonstrated superior performance: the internal training set exhibited a 0.878 AUC (95% CI, 0.802-0.954), 0.755 accuracy, and 0.625 sensitivity; the internal validation set displayed a 0.831 AUC (95% CI, 0.675-0.986), 0.818 accuracy, and 0.812 sensitivity. In the external cohort, the model yielded an AUC of 0.886 (95% CI, 0.799-0.974), 0.808 accuracy, and 0.909 sensitivity. Calibration curves affirmed a strong concordance between predicted outcomes and actual events. Decision curve analysis substantiated that the model could confer benefits on patients with ASBO. Conclusion: A rigorously developed and validated nomogram that incorporates body composition and inflammatory-nutritional indices proves to be a valuable tool for anticipating postoperative complications in ASBO patients, thus facilitating enhanced clinical decision-making.

KLRB1 defines an activated phenotype of CD4+ T cells and shows significant upregulation in patients with primary Sjögren's syndrome.

OBJECTIVE: This study aimed to investigate the role of KLRB1 (CD161) in human CD4+ T cells and elucidate its significance in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood samples from 37 healthy controls and 44 pSS patients were collected. The publicly available single-cell RNA-Seq data from pSS patient PBMCs were utilized to analyse KLRB1 expression in T cells. KLRB1-expressing T lymphocyte subset proportions in pSS patients and healthy controls were determined by flow cytometry. CD25, Ki-67, cytokine secretion, and chemokine receptor expression in CD4+ KLRB1+ T cells were detected and compared with those in CD4+ KLRB1- T cells. Correlation analysis was conducted between KLRB1-related T-cell subsets and clinical indicators. ROC curves were generated to explore the diagnostic potential of KLRB1 for pSS. RESULTS: KLRB1 was significantly upregulated following T-cell activation, and Ki-67 and CD25 expression was significantly greater in CD4+ KLRB1+ T cells than in CD4+ KLRB1- T cells. KLRB1+ CD4+ T cells exhibited greater IL-17A, IL-21, IL-22, and IFN-γ secretion upon stimulation, and there were significantly greater proportions of CCR5+, CCR2+, CX3CR1+, CCR6+, and CXCR3+ cells among CD4+ KLRB1+ T cells than among CD4+ KLRB1- T cells. Compared with that in HCs, KLRB1 expression in CD4+ T cells was markedly elevated in pSS patients and significantly correlated with clinical disease indicators. CONCLUSION: KLRB1 is a characteristic molecule of the CD4+ T-cell activation phenotype. The increased expression of KLRB1 in the CD4+ T cells of pSS patients suggests its potential involvement in the pathogenesis of pSS and its utility as an auxiliary diagnostic marker for pSS.

Assembly dynamics of eukaryotic plankton and bacterioplankton in the Yangtze River estuary: A hybrid community perspective.

Estuaries, acting as transitional habitats receiving species introductions from both freshwater and marine sources, undergo significant impacts from global climate changes. Planktonic microorganisms contribute significantly to estuarine biodiversity and ecological stability. These microorganisms primarily fall into three groups: eukaryotic plankton, particle-associated bacteria, and free-living bacteria. Understanding the structural characteristics and interactions within these subcommunities is crucial for comprehending estuarine dynamics. We collected samples from three distinct locations (< 0.1 PSU, 6.6 PSU, and 19 PSU) within the Yangtze River estuary. Samples underwent analysis for physicochemical indicators, while microbial communities were subjected to 16S/18S rRNA amplicon sequencing. Additionally, simulated mixing experiments were conducted using samples of varying salinities. Estuary samples, combined with simulated experiments, were employed to collectively examine the structural characteristics and assembly processes of estuarine microbes. Our research highlights the considerable impact of phylogenetic classification on prokaryotic behavior in these communities. We observed a transition in assembly processes from primarily stochastic for particle-associated bacteria to a predominant influence of homogeneous selection as salinity increased. Particle-associated bacterial communities exhibited a greater influence of stochastic processes compared to free-living bacteria, showcasing higher stability in diversity. The variations in composition and structure of estuarine microbial subcommunities were influenced by diverse environmental factors. Particle-associated bacteria displayed elevated network characterization values and established closer interactions with eukaryotic plankton. Structural equation modeling (SEM) analysis revealed that free-living bacteria displayed a heightened sensitivity to environmental factors and exerted a more significant influence on assembly processes and network characteristics. Simulated mixing in these environments resulted in the loss of species with similar microbial taxonomic relationships. The functioning of bacterioplankton is influenced by salinity and the processes governing their assembly, particularly in relation to different living states. These findings significantly contribute to our understanding of the intricate interplay between prokaryotic and eukaryotic plankton microorganisms in highly dynamic environments, laying a robust foundation for further exploration into the ecological mechanisms governing microbial dynamics in estuaries.

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF-κB/NLRP3 axis.

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. Nowadays, there are still no effective antiviral drugs for EV71 infection. High mobility group box 1 (HMGB1) is reported to be highly expressed in HFMD patients. However, the role and underlying mechanism of HMGB1 in EV71-associated HFMD are still unclear. HMGB1 expression was detected using RT-qPCR and western blot assays. Loss- and gain-function experiments were performed to evaluate the effects of HMGB1 on EV71-infected cells. The virus titer was examined by TCID50. CCK-8 and flow cytometry assays were applied to detect the cell viability and cell cycle. Oxidative stress was determined by relative commercial kits. HMGB1 level was elevated in the serum of EV71-infected patients with HFMD and EV71-induced RD cells. EV71 infection induced the transfer of HMGB1 from the nucleus into the cytoplasm. HMGB1 knockdown inhibited virus replication, viral protein (VP1) expression and promoted antiviral factor expression. In addition, the inhibition of HMGB1 improved cell viability, protected against S phase arrest, and inhibited EV71-induced cell injury and oxidative stress, whereas HMGB1 overexpression showed the opposite effects. In terms of mechanism, HMGB1 overexpression activated the TLR4/NF-κB/NLRP3 signaling pathway and promoted cell pyroptosis. The inhibition of TLR4 and NF-κB reversed the effects of HMGB1 overexpression on virus replication, oxidative stress, and pyroptosis. In conclusion, HMGB1 knockdown inhibits EV71 replication and attenuates pyroptosis through TLR4/NF-κB/NLRP3 axis.

Adverse events and efficacy of second-round CAR-T cell therapy in relapsed pediatric B-ALL.

OBJECTIVE: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment approach for pediatric patients suffering from relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, there was a paucity of data on the challenges associated with second-round CAR-T therapy in this population. METHODS: Medical records of nine pediatric patients who received second-round CAR-T therapy in a single center from June 2019 to May 2023 were analyzed. Throughout the course of the clinical trial, we evaluated adverse events including CRS, CRES, infections, hematologic toxicity, and organ injury, as well as CAR-T responses. RESULTS: Except for one patient who chose CART therapy due to testicular relapse, the remaining patients had indications for CAR-T therapy due to relapse with bone marrow alone or combined with other site. There were no difference between the transfusion dose of CART1 and CART2. No differences of incidence and grade of CRS was found between the first-round CAR-T therapy (CART1) and second-round CAR-T therapy (CART2). Additionally, we found that the incidence of CRES was higher for CART1(3/9,33.3%) than CART2(1/9,11.1%). Our findings revealed that there were no differences of IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α between CART1 and CART2, but the peak level of IL-17A was significantly higher in patients receiving CART1 compared to those receiving CART2 (p = .011). Early and late infection rates after CART1 were higher than CART2. Based on the dynamic changes of ANC, hemoglobin and platelet, ANC, and platelet were reduced obviously post CART. It seems that the incidences of severe thrombocytopenia and severe anemia were higher in the CART1 group compared to CART2. The MRD-negative CR rates for CART1 and CART2 are 100% and 44.4%, respectively (p = .029). All patients experienced events (relapse, chemotherapy, transplantation, or death) after receiving CART2, including one died, three discharged automatically, and the remaining five patients survived. CONCLUSION: Although the remission rate of CART2 is not as high as the CART1 due to the severity of the disease, its safety regarding CRS, CRES, infections, and organ injury is still excellent. Therefore, CART2 remains a viable option for treating pediatric relapsed B-ALL.

The performance of VCS(volume, conductivity, light scatter) parameters in distinguishing latent tuberculosis and active tuberculosis by using machine learning algorithm.

BACKGROUND: Tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis (MTB) and is the ninth leading cause of death worldwide. It is still difficult to distinguish active TB from latent TB,but it is very important for individualized management and treatment to distinguish whether patients are active or latent tuberculosis infection. METHODS: A total of 220 subjects, including active TB patients (ATB, n = 97) and latent TB patients (LTB, n = 113), were recruited in this study .46 features about blood routine indicators and the VCS parameters (volume, conductivity, light scatter) of neutrophils(NE), monocytes(MO), and lymphocytes(LY) were collected and was constructed classification model by four machine learning algorithms(logistic regression(LR), random forest(RF), support vector machine(SVM) and k-nearest neighbor(KNN)). And the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) to estimate of the model's predictive performance for dentifying active and latent tuberculosis infection. RESULTS: After verification,among the four classifications, LR and RF had the best performance (AUROC = 1, AUPRC = 1), followed by SVM (AUROC = 0.967, AUPRC = 0.971), KNN (AUROC = 0.943, AUPRC = 0.959) in the training set. And LR had the best performance (AUROC = 0.977, AUPRC = 0.957), followed by SVM (AUROC = 0.962, AUPRC = 0.949), RF (AUROC = 0.903, AUPRC = 0.922),KNN(AUROC = 0.883, AUPRC = 0.901) in the testing set. CONCLUSIONS: The machine learning algorithm classifier based on leukocyte VCS parameters is of great value in identifying active and latent tuberculosis infection.

Development and validation of multiparametric models based on computed tomography enterography to determine endoscopic activity and surgical risk in patients with Crohn's disease: A multi-center study.

Objective: To develop novel multiparametric models based on computed tomography enterography (CTE) scores to identify endoscopic activity and surgical risk in patients with Crohn's disease (CD). Methods: We analyzed 171 patients from 3 hospitals. Correlations between CTE outcomes and endoscopic scores were assessed using Spearman's rank correlation analysis. Predictive models for moderate to severe CD were developed, and receiver operating characteristic (ROC) curves were constructed to determine the area under the ROC curve (AUC). A combined nomogram based on CTE scores and clinical variables was also developed for predicting moderate to severe CD and surgery. Results: CTE scores were significantly correlated with endoscopy scores at the segment level. The global CTE score was an independent predictor of severe (HR = 1.231, 95% CI: 1.048-1.446, p = 0.012) and moderate-to-severe Simplified Endoscopic Scores for Crohn's Disease (SES-CD) (HR = 1.202, 95% CI: 1.090-1.325, p < 0.001). The nomogram integrating CTE and clinical data predicted moderate to severe SES-CD and severe SES-CD scores in the validation cohort with AUCs of 0.837 and 0.807, respectively. The CTE score (HR = 1.18; 95% CI: 1.103-1.262; p = 0.001) and SES-CD score (HR = 3.125, 95% CI: 1.542-6.33; p = 0.001) were independent prognostic factors for surgery-free survival. A prognostic nomogram incorporating CTE scores, SES-CD and C-reactive protein (CRP) accurately predicted the risk of surgery in patients with CD. Conclusion: The newly developed CTE score and multiparametric models displayed high accuracy in predicting moderate to severe CD and surgical risk for CD patients.

Study on Contrast-Enhanced Ultrasound Imaging and Anti-Tumor Effects of Drug-Loaded Nanodroplets with Tumor Targeting and Ultrasound Sensitivity.

BACKGROUND: Ultrasound-responsive nanodroplets (NDs) targeting tumors have shown great potential in ultrasound imaging and tumor therapy, but most of these studies are based NDs with lipid shells that cannot overcome the uptake by cells of the reticulo-endothelial system (RES). NDs with shells comprised of polyethylene glycol (PEG)-based polymers could effectively suppressed the uptake of RES, but the phase transition, contrast-enhanced imaging and drug release about these NDs have not been well illuminated. METHODS: Folate receptor targeted NDs with shells of polymers and loaded with DOX (FA-NDs/DOX) were prepared. The particle size distribution and morphology of NDs was characterized with dynamic light scattering (DLS) and microscope. Phase transition and contrast-enhanced ultrasound imaging under different mechanical indices (MIs) was studied, and the intensity of contrast enhancement were quantitatively analyzed. The targeting property of FA-NDs/DOX to MDA-MB-231 cells and cellular uptake were observed using a fluorescence microscope. The anti-tumor effects of FA-NDs/DOX combined with low-intensity focused ultrasound (LIFU) was studied through cytotoxicity tests. Flow cytometry assays were used to detect cell apoptosis. RESULTS: The average particle size of the FA-NDs/DOX was 448.0 ± 8.9 nm, and the zeta potential was 30.4 ± 0.3 mV. When exposed to ultrasound at 37 °C, ultrasound contrast enhancement of FA-NDs/DOX was observed when MI ≥0.19. A stronger acoustic signal was observed under higher MIs and concentrations. The results of quantitative analysis showed that the contrast enhancement intensity of FA-NDs/DOX (1.5 mg/mL) at MI of 0.19, 0.29 and 0.48 was 26.6 ± 0.9 dB, 97.0 ± 3.8 dB and 153.1 ± 5.7 dB, respectively. The contrast enhancement of the FA-NDs/DOX lasted for more than 30 minutes at an MI of 0.48. In targeting experiments, FA-NDs could be recognized by MDA-MB-231 cells, and significant cellular uptake was observed. The blank FA-NDs showed good biocompatibility, while the FA-NDs/DOX induced apoptosis of MDA-MB-231 and MCF-7 cells. By combining LIFU irradiation and FA-NDs/DOX treatment, the best cell-killing effect was achieved. CONCLUSIONS: The FA-NDs/DOX prepared in this study has excellent performance in contrast-enhanced ultrasound imaging, tumor targeting and enhanced chemotherapy. This FA-NDs/DOX with polymer shells provides a novel platform for ultrasound molecular imaging and tumor therapy.

Synthesis of Polyether Carboxylate and the Effect of Different Electrical Properties on Its Viscosity Reduction and Emulsification of Heavy Oil.

Heavy oil exploitation needs efficient viscosity reducers to reduce viscosity, and polyether carboxylate viscosity reducers have a significant viscosity reduction effect on heavy oil. Previous work has studied the effect of different side chain lengths on this viscosity reducer, and now a series of polyether carboxylate viscosity reducers, including APAD, APASD, APAS, APA, and AP5AD (the name of the viscosity reducer is determined by the name of the desired monomer), with different electrical properties have been synthesized to investigate the effect of their different electrical properties on viscosity reduction performance. Through the performance tests of surface tension, contact angle, emulsification, viscosity reduction, and foaming, it was found that APAD viscosity reducers had the best viscosity reduction performance, reducing the viscosity of heavy oil to 81 mPa·s with a viscosity reduction rate of 98.34%, and the worst viscosity reduction rate of other viscosity reducers also reached 97%. Additionally, APAD viscosity reducers have the highest emulsification rate, and the emulsion formed with heavy oil is also the most stable. The net charge of APAD was calculated from the molar ratio of the monomers and the total mass to minimize the net charge. While the net charge of other surfactants was higher. It shows that the amount of the surfactant's net charge affects the surfactant's viscosity reduction effect, and the smaller the net charge of the surfactant itself, the better the viscosity reduction effect.

Association of menstrual blood volume and reproductive outcomes in patients with caesarean scar pregnancy managed using uterine artery embolization and curettage.

This study aimed to assess the association of menstrual blood volumes (MBV) and reproductive outcomes in patients after uterine artery embolization (UAE) combined with curettage for caesarean scar pregnancy (CSP). This retrospective observational study enrolled women who underwent UAE plus curettage for CSP at the Interventional Department of Henan Provincial People's Hospital between December 2012 and December 2017. The primary outcome was pregnancy rate and the secondary outcomes were live birth rate (LBR) and interpregnancy interval. This study finally included 37 women (16 women with normal MBV and 21 women with decreased MBV) with pregnancy intention after UAE plus curettage for CSP. The pregnancy rate in women with normal MBV was higher than those with decreased MBV (81.3% vs. 47.6%; P = 0.048). There were no differences between the two groups regarding the interpregnancy interval (18.4 ± 8.7 vs. 22.2 ± 10.0 months, P = 0.233), and LBR (63% vs. 38%, P = 0.191). In conclusion, Women with normal MBV after UAE combined with curettage for CSP management might have a higher pregnancy rate compared with patients with decreased MBV, but there were no differences in LBR between the two groups.

GSDME-dependent pyroptosis signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear. In this study, we established a rat DN model by intraperitoneal injection of streptozotocin (STZ) successfully. Structural and functional disorders in the kidney were exhibited on the 12th week after STZ injection; the expressions of caspase-3 and GSDME at protein level in renal cortex were significantly up-regulated. At the 20th week, GSDME-N increased significantly, accompanied by the upregulation of caspase-1 in renal cortex and the release of mature IL-1ß (mIL-1ß) in serum. Furthermore, we found the protein levels of GSDME, caspase-3, caspase-1 and IL-1ß were all increased in HK2 and HBZY-1 cells under high-glucose conditions. We also found that the expression of GSDME-N significantly decreased when caspase-3 was knockdown. In contrast, knockdown of GSDME has no effect on caspase-3. Interestingly, either caspase-3, caspase-1 or GSDME knockdown reduced the release of mIL-1ß. Finally, injection of adeno-associated virus (AAV) 9-shGSDME into the rat kidney reduced kidney damage and renal cell pyroptosis in comparison with wild-type diabetic rats. These results indicated that the activation of caspase-1 induced IL-1ß maturation, and the activation of caspase-3 mediated cleavage of GSDME responsible for the formation of plasma membrane pore, followed by cytoplasmic release of mIL-1ß. Overall, we identified a pro-pyroptosis role for GSDME in DN, which does provide an important basis for clinical therapeutic studies.

New scoring system combining computed tomography body composition analysis and inflammatory-nutritional indicators to predict postoperative complications in stage II-III colon cancer.

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.

ALK-JNK signaling promotes NLRP3 inflammasome activation and pyroptosis via NEK7 during Streptococcus pneumoniae infection.

Streptococcus pneumoniae (S. pneumoniae), a clinically important pathogen worldwide, causes serious invasive diseases, such as pneumonia, otitis media, and meningitis. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, an important component of the innate immune system, plays a key role in defense against pathogen infection; however the specific activation mechanism induced by S. pneumoniae infection is not fully understood. Here, primary mouse macrophages were selected as the in vitro cell model, and the effect of kinases on S. pneumoniae infection-induced NLRP3 inflammasome activation was investigated in vivo and in vitro using the western blot/RT-PCR/Co-IP/immunofluorescence staining/ELISA with or without kinase inhibitor or siRNA pretreatment. In this study, we found that the formation of the NEK7-NLRP3 complex significantly increased during S. pneumoniae infection and that anaplastic lymphoma kinase (ALK) and Jun N-terminal kinase (JNK) were phosphorylated rapidly. ALK and JNK inhibitors significantly reduced the ability of bacterial killing, the gene expression of NLRP3 inflammasome, the formation of apoptosis-associated speck-like protein containing caspase-recruitment domain (ASC) specks and the NEK7-NLRP3 complex, which in turn decreased the activation level of NLRP3 inflammasome-associated molecules and the maturation of interleukin-1ß (IL-1ß). In addition, ALK regulated the phosphorylation of JNK. Interestingly, the ALK/JNK/NEK7-NLRP3 signaling pathway is also involved in regulating pyroptosis and IL-1ß secretion triggered by S. pneumoniae infection. In conclusion, our data suggest, for the first time, that the ALK/JNK/NEK7-NLRP3 signaling pathway may play an important role in NLRP3 inflammasome activation and pyroptosis and consequently regulate the host immune response upon S. pneumoniae infection.

The Predictive Value of a New Inflammatory-Nutritional Score for Quality of Life after Laparoscopic Distal Gastrectomy for Gastric Cancer.

We explored the predictive value of various inflammatory-nutritional indicators for postoperative quality of life (QoL) in gastric cancer (GC) patients undergoing laparoscopic distal gastrectomy (LDG) and developed a novel inflammatory-nutritional score (INS). In this study, 156 GC patients who underwent LDG were included. We used multiple linear regression to analyze the correlation between postoperative QoL and inflammatory-nutritional indicators. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct INS. Hemoglobin was positively correlated with physical functioning (ß =8.5; p = 0.003) and cognitive functioning (ß = 3.5; p = 0.038) 3 mo, after surgery. Prognostic nutritional index (PNI) was positively associated with global health status (ß =5.8; p = 0.043). Albumin-alkaline phosphatase ratio (AAPR) was negatively correlated with emotional functioning 12 mo, after surgery (ß = -5.7; p = 0.024). Neutrophil-lymphocyte ratio (NLR), Lymphocyte- monocyte ratio (LMR), AAPR, hemoglobin and PNI were selected using LASSO regression analysis to construct INS. The C-index values of the model in the training group and the validation group were 0.806 (95% CI, 0.719-0.893) and 0.758 (95% CI: 0.591-0.925), respectively. INS had particular predictive value for postoperative QoL in patients undergoing LDG and provided a reference for risk stratification and clinical practice.

CT-based radiomics for the identification of colorectal cancer liver metastases sensitive to first-line irinotecan-based chemotherapy.

BACKGROUND: Chemosensitivity prediction in colorectal cancer patients with liver metastases has remained a research hotspot. Radiomics can extract features from patient imaging, and deep learning or machine learning can be used to build models to predict patient outcomes prior to chemotherapy. PURPOSE: In this study, the radiomics features and clinical data of colorectal cancer patients with liver metastases were used to predict their sensitivity to irinotecan-based chemotherapy. METHODS: A total of 116 patients with unresectable colorectal cancer liver metastases who received first-line irinotecan-based chemotherapy from January 2015 to January 2020 in our institution were retrospectively collected. Overall, 116 liver metastases were randomly divided into training (n = 81) and validation (n = 35) cohorts in a 7:3 ratio. The effect of chemotherapy was determined based on Response Evaluation Criteria in Solid Tumors. The lesions were divided into response and nonresponse groups. Regions of interest (ROIs) were manually segmented, and sample sizes of 1×1×1, 3×3×3, 5×5×5 mm3 were used to extract radiomics features. The relevant features were identified through Pearson correlation analysis and the MRMR algorithm, and the clinical data were merged into the artificial neural network. Finally, the p-model was obtained after repeated learning and testing. RESULTS: The p-model could distinguish responders in the training (area under the curve [AUC] 0.754, 95% CI 0.650-0.858) and validation cohorts (AUC 0.752 95% CI 0.581-0.904). AUC values of the pure image group model are 0.720 (95% CI 0.609-0.827) and 0.684 (95% CI 0.529-0.890) for the training and validation cohorts respectively. As for the clinical data model, AUC values of the training and validation cohorts are 0.638 (95% CI 0.500-0.757) and 0.545 (95% CI 0.360-0.785), respectively. The performances of the latter two are less than that of the former. CONCLUSION: The p-model has the potential to discriminate colorectal cancer patients sensitive to chemotherapy. This model holds promise as a noninvasive tool to predict the response of colorectal liver metastases to chemotherapy, allowing for personalized treatment planning.

Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation.

Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis. Recent studies reported that reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of heart diseases. Therefore, we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury. Herein, we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles (MMPP) improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway. In LPS-induced murine sepsis model, after a single dose intravenously injection of MMPP treatment, MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis. In vitro, MMPP inhibited cardiomyocyte death by attenuating oxidative stress, inflammation and maintaining mitochondrial homeostasis. Collectively, our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation, which might be a novel therapeutic approach in future.

A self-healing polymerized-ionic-liquid-based polymer electrolyte enables a long lifespan and dendrite-free solid-state Li metal batteries at room temperature.

The implementation of high-safety Li metal batteries (LMBs) needs more stable and safer electrolytes. The solid-state electrolytes (SSEs) with their advantageous properties stand out for this purpose. However, low Li/electrolyte interfacial instability and uncontrolled Li dendrites growth trigger unceasing breakage of the solid electrolyte interphase (SEI), leading to fast capacity degradation. In response to these shortcomings, a new type of polymer electrolyte with self-healing capacity is introduced by grafting ionic liquid chain units into the backbones of polymers, which inherits the chemical inertness against the Li anode, allowing high Li+ transport, wide electrochemical window, and self-healing traits. Benefiting from the strong external H-bonding interactions, the obtained polymer electrolyte can spontaneously reconstruct dendrite-induced defects and fatigue crack growth at the Li/electrolyte interface, and, in turn, help tailor Li deposition. Owing to the resilient Li/electrolyte interface and dendrite-free Li plating, the equipped Li|LFP batteries display a high initial specific capacity of 134.7 mA h g-1, rendering a capacity retention of 91.2% after 206 cycles at room temperature. The new polymer electrolyte will undoubtedly bring inspiration for developing practical LMBs with highly improved safety and interfacial stability.

Quantitative Radiological Features and Deep Learning for the Non-Invasive Evaluation of Programmed Death Ligand 1 Expression Levels in Gastric Cancer Patients: A Digital Biopsy Study.

RATIONALE AND OBJECTIVES: Programmed Death-Ligand 1 (PD-L1) is an important biomarker for patient selection of immunotherapy in gastric cancer (GC). This study aimed to construct and validate a non-invasive virtual biopsy system based on radiological features and clinical factors to predict the PD-L1 expression level in GC. MATERIALS AND METHODS: 217 patients who received gastrectomy for GC were consecutively enrolled in this study, with 157 patients from center 1 as the training cohort and 60 patients from center 2 as the external validation cohort. 1205 quantitative radiomics features were extracted from preprocessed pre-operative contrast-enhanced CT images of enrolled patients. A radiological signature was computed using a regression random forest model and was integrated with clinical factors in a multilayer perceptron. The performance of the digital biopsy system was evaluated by the receiver operating characteristic (ROC) curve and calibration curve in both the training and validation cohort. RESULTS: 15 features were selected for the construction of radiological signature, which was significantly associated with expression levels of PD-L1 in both the training cohort (p<0.0001) and the external validation cohort (p<0.01). The hybrid deep learning model integrating the radiological signature and clinical factor could accurately distinguish GCs with high PD-L1 expression levels in both the training cohort (AUC = 0.806, 95%CI: 0.736-0.875) and the validation cohort (AUC = 0.784, 95%CI: 0.668-0.901). CONCLUSIONS: Our results indicate that the combination of deep learning and quantitative radiological features are potential approaches for the non-invasive evaluation of PD-L1 expression levels in GC. The digital biopsy system could provide valuable suggestive information for clinical decision-making of immunotherapy in GC.

Noninvasive Prediction of Ki-67 Expression in Hepatocellular Carcinoma Using Machine Learning-Based Ultrasomics: A Multicenter Study.

OBJECTIVES: To investigate the ability of ultrasomics to predict Ki-67 expression in hepatocellular carcinoma (HCC). METHODS: A total of 244 patients from three hospitals were retrospectively recruited (training dataset, n = 168; test dataset, n = 43; and validation dataset, n = 33). Lesion segmentation of the ultrasound images was performed manually by two radiologists. In total, 1409 ultrasomics features were extracted. Feature selection was conducted using the intra-class correlation coefficient, variance threshold, mutual information, and recursive feature elimination plus eXtreme Gradient Boosting. The support vector machine was combined with the learning curve and grid search parameter tuning to construct the clinical, ultrasomics, and combined models. The predictive performance of the models was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy. RESULTS: The ultrasomics model performed well on the training, test, and validation datasets. The AUC (95% confidence interval [CI]) for these datasets were 0.955 (0.912-0.981), 0.861 (0.721-0.947), and 0.665 (0.480-0.819), respectively. The combination of ultrasomics and clinical features significantly improved model performance on all three datasets. The AUC (95% CI), sensitivity, specificity, and accuracy were 0.986 (0.955-0.998), 0.973, 0.840, and 0.869 on the training dataset; 0.871 (0.734-0.954), 0.750, 0.829, and 0.814 on the test dataset; and 0.742 (0.560-0.878), 0.714, 0.808, and 0.788 on the validation dataset, respectively. CONCLUSIONS: Ultrasomics was proved to be a potential noninvasive method to predict Ki-67 expression in HCC.