Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model.

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Patient-reported physical well-being predicts good long-term survival of hematopoietic stem cell transplantation.

AIM: This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. METHODS: We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. RESULTS: Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. CONCLUSIONS: Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.

The pharmacokinetic differences between 10- and 15-µg daily vitamin D doses.

AIMS: The reference nutrient intake for vitamin D in people aged ≥4 years is 10 µg/day (400 IU/day) in the UK, but the recommended daily allowance is 15 µg/day (600 IU/day) for people aged 1-70 years in the USA. Here, we aim to compare the 25-hydroxyvitamin D (25(OH)D) serum concentration profiles between the 2 doses. METHODS: With world-wide trial data of adults aged ≥18 years, 45-93 kg, we constructed a minimal physiologically based pharmacokinetics model of serum concentrations of vitamin D and 25(OH)D using nonlinear mixed effects modelling. We used this model to forecast the mean, 2.5th and 97.5th percentiles for serum 25(OH)D concentrations in British adults aged ≥16 years. RESULTS: Our final model used bodyweight to adjust volume of each compartment and maximum clearance of 25(OH)D. No other covariate was identified. The model accurately predicted independent data from trials of a broad range of dosing regimens. We simulated British adults and showed that circulating 25(OH)D concentrations in 95% of people taking 10 µg/day for a year is predicted to reach 50 nmol/L in 32 weeks, while 97.5% of those on 15 µg/day were predicted to attain this threshold within 28 weeks. CONCLUSION: Both doses are efficacious in >95% of the British population. The daily dose of 15 µg can help 97.5% of the British adults achieve 50 nmol/L serum 25(OH)D and reach the 25 nmol/L threshold in 4 weeks.

[Effects of reductive soil disinfestation and organic fertilizer application on microbial community stability in a facility vegetable soil]. / 强还原处理和施用有机肥对设施蔬菜地土壤微生物群落稳定性的影响.

Reductive soil disinfestation (RSD) is an effective method for remediating degraded facility vegetable soils. However, the effectiveness of RSD using green manure as a carbon source in the field has not yet been clarified. We investigated the effects of RSD and organic fertilizer application on soil microbial community composition, diversity, and stability in a degraded facility vegetable soil. There were six treatments, including no fertilization (CK), no fertilization and soil flooded and mulched with plastic film (FF), soil amended with chicken manure (OM), soil amended with chicken manure and flooded and mulched with plastic film (OMR), soil amended with Sesbania cannabina (TF), and soil amended with S. cannabina and flooded and mulched with plastic film (TR). The results showed that the OMR and TR treatments significantly decreased bacterial Chao1 index, altered bacterial and fungal community structure, and increased the relative abundances of Bacillus, Rhodococcus, Clostridium, and Penicillium. The TR treatment significantly reduced the relative abundance of Fusarium. Results of redundancy analysis and Mantel test analysis suggested that soil ammonium nitrogen and dissolved organic carbon contents were the key factors influencing bacterial community composition, and soil pH was the key factor affecting fungal community composition. Results of cohesion analysis showed that the OMR and TR treatments significantly improved bacterial community stability, and that there was no difference between OMR and TR treatments. The TR treatment enhanced fungal community stability, which was significantly higher than the OMR treatment. Therefore, the RSD with green manure as carbon source could be effective remediation practice to improve soil health.

Accurate prediction of antibody function and structure using bio-inspired antibody language model.

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering processes. Fortunately, significant advancements in deep learning methods have facilitated the precise prediction of protein structure and function by leveraging co-evolution information from homologous proteins. Despite these advances, predicting the conformation of antibodies remains challenging due to their unique evolution and the high flexibility of their antigen-binding regions. Here, to address this challenge, we present the Bio-inspired Antibody Language Model (BALM). This model is trained on a vast dataset comprising 336 million 40% nonredundant unlabeled antibody sequences, capturing both unique and conserved properties specific to antibodies. Notably, BALM showcases exceptional performance across four antigen-binding prediction tasks. Moreover, we introduce BALMFold, an end-to-end method derived from BALM, capable of swiftly predicting full atomic antibody structures from individual sequences. Remarkably, BALMFold outperforms those well-established methods like AlphaFold2, IgFold, ESMFold and OmegaFold in the antibody benchmark, demonstrating significant potential to advance innovative engineering and streamline therapeutic antibody development by reducing the need for unnecessary trials. The BALMFold structure prediction server is freely available at https://beamlab-sh.com/models/BALMFold.

[Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Individualized nutritional intervention improves the nutritional status of liver cancer patients after transcatheter arterial chemoembolization.

Introduction: Introduction: to explore the effect of individualized nutritional intervention on the nutritional status of patients with liver cancer after transcatheter arterial chemoembolization (TACE). Methods: 56 patients who underwent TACE in our hospital from March 2022 to March 2023 were selected as the study subjects. The patients were randomly divided into a control group (28 cases) and an intervention group (28 cases). The control group received routine dietary intervention, while the intervention group received individualized nutritional intervention. We analyzed the body mass index (BMI), nutritional risk screening 2002 (NRS 2002), nutritional status, liver function status, and incidence of complications in two groups of patients before TACE, 3 days after TACE, and 1 month after TACE. Results: on the third day after TACE, the nutritional related indicators of both groups of patients showed a significantly decrease compared to those before TACE (p < 0.05), while the majority of liver function indicators significantly increased (p < 0.05). Compared with those at 3 days after TACE, the nutritional status of the intervention group patients significantly improved (p < 0.05) and liver function indicators significantly decreased (p < 0.05) 1 month after TACE. One month after TACE, all nutritional indicators in the intervention group were significantly higher than those in the control group (p < 0.05), and AST was significantly lower than that in the control group (p < 0.05). The incidence of gastrointestinal complications and electrolyte disorders in the intervention group were significantly lower than that in the control group (p < 0.05). Conclusion Individualized nutritional intervention can effectively improve nutritional status, improve liver function, and reduce the incidence of postoperative complications in liver cancer patients after TACE. It was worth promoting.

Introducción: Introducción: explorar el efecto de la intervención nutricional individualizada sobre el estado nutricional de los pacientes con cáncer de hígado después de la quimioembolización arterial (TACE). Métodos: se seleccionaron como sujetos de estudio 56 pacientes sometidos a TACE en nuestro hospital entre marzo de 2022 y marzo de 2023. Los pacientes se dividieron aleatoriamente en un grupo de control (28 casos) y un grupo de intervención (28 casos). El grupo de control recibió una intervención dietética rutinaria, mientras que el grupo de intervención recibió una intervención nutricional individualizada. Se analizó el índice de masa corporal (IMC), el cribado del riesgo nutricional 2002 (NRS 2002), el estado nutricional, el estado de la función hepática y la incidencia de complicaciones en dos grupos de pacientes antes de la TACE, 3 días después de la TACE y 1 mes después de la TACE. Resultados: al tercer día después de la TACE, los indicadores relacionados con la nutrición de ambos grupos de pacientes mostraron una disminución significativa en comparación con los de antes de la TACE (p < 0.05), mientras que la mayoría de los indicadores de la función hepática aumentaron significativamente (p < 0.05). En comparación con los 3 días después de la TACE, el estado nutricional de los pacientes del grupo de intervención mejoró significativamente (p < 0.05) y los indicadores de la función hepática disminuyeron significativamente (p < 0.05) 1 mes después de la TACE. Un mes después de la TACE, todos los indicadores nutricionales del grupo de intervención fueron significativamente superiores a los del grupo de control (p < 0.05), y la AST fue significativamente inferior a la del grupo de control (p < 0.05). La incidencia de complicaciones gastrointestinales y trastornos electrolíticos en el grupo de intervención fue significativamente inferior a la del grupo de control (p < 0.05). Conclusión: la intervención nutricional individualizada puede mejorar eficazmente el estado nutricional, mejorar la función hepática y reducir la incidencia de complicaciones postoperatorias en pacientes con cáncer de hígado tras TACE. Merece la pena promoverlo.

F-53B mediated ROS affects uterine development in rats during puberty by inducing apoptosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Nomogram Predicting Grade ≥2 Acute Radiation Enteritis in Patients With Cervical Cancer Receiving Concurrent Chemoradiotherapy.

OBJECTIVE: To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy. METHODS: A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared. RESULTS: Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram ( P <0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group ( P <0.05). CONCLUSION: The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.

Role of jianxin granules in heart failure: evidence from network pharmacology, molecular docking and experimental verification.

BACKGROUND: Jianxin (JX) granules is a traditional Chinese medicine widely used in the treatment of heart failure (HF), but the mechanism is unclear. This study aimed to investigate the mechanism of JX granules in the treatment of HF based on network pharmacology analysis and in-vivo experiments. METHODS: A series of network pharmacology methods was employed to ascertain potential targets and critical pathways implicated in the therapeutic action of JX granules against HF. Subsequently, molecular docking was utilized to investigate the binding affinity of key active constituents within JX granules to these targets. In-vivo experiments, echocardiography, hematoxylin and eosin, Masson's trichrome assay, and western blot analysis were conducted to validate the efficacy and mechanism of JX granules in treating rats with HF. RESULTS: A total of 122 active components, 896 drug targets, 1216 HF-related targets, and 136 targets pertinent to drug-disease interactions were identified. 151 key targets and 725 core clusters were detected through protein-protein interaction network analysis. Among these, interleukin 6 (IL-6), vascular endothelial growth factor a (VEGFA), and serine/threonine kinase 1 (AKT1) were core hub genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed the critical pathways, including epidermal growth factor receptor (EGFR), advanced glycation end products (AGEs) and their receptors (RAGE) pathway, along with hypoxia-inducible factor 1 (HIF-1) signaling pathway. Molecular docking studies demonstrated high binding affinities between key targets and the pivotal active ingredients of Danshenol A, salvianolic acid B, and arachidonic acid. Furthermore, animal studies corroborated that JX granules improve cardiac function and reduce myocardial fibrosis, potentially by modulating the expression of IL-6, VEGFA, and p-AKT1. CONCLUSIONS: The bioactive components within JX granules, such as Danshenol A, salvianolic acid B, and arachidonic acid may exert therapeutic effects on HF through modulation of IL-6, VEGFA, and AKT1 gene expression. This study provides a scientific basis for subsequent clinical application of JX granules and an in-depth investigation of their mechanisms of action.

A novel approach to wound healing: Green synthetic nano-zinc oxide embedded with sodium alginate and polyvinyl alcohol hydrogels for dressings.

Wound healing constitutes a formidable challenge within the healthcare system, attributable to infection risks and protracted recovery periods. The pressing need for innovative wound healing methods has spurred the urgency to develop novel approaches. This study sought to advance wound healing by introducing a novel approach employing a composite sponge dressing. The composite sponge dressing, derived from LFL-ZnO (synthesized through the green methodology utilizing Lactobacillus plantarum ZDY2013 fermentation liquid), polyvinyl alcohol (PVA), and sodium alginate (SA) via a freeze-thaw cycle and freeze-drying molding process, demonstrated notable properties. The findings elucidate the commendable swelling, moisturizing, and mechanical attributes of the SA/LFL-ZnO/PVA composite sponge dressing, characterized by a porous structure. Remarkably, the dressing incorporating LFL-ZnO exhibited substantial inhibition against both methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus). Hemolysis and cytotoxicity tests corroborated the excellent biocompatibility of the sponge dressing. In vivo evaluation of the therapeutic efficacy of the 1 mg/mL LFL-ZnO composite dressing on scald wounds and S. aureus-infected wounds revealed its capacity to accelerate wound healing and exert pronounced antibacterial effects. Consequently, the composite sponge dressings synthesized in this study hold significant potential for application in wound treatment.

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy.

The induction of cuproptosis, a recently identified form of copper-dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis-inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis-mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor-infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death-1 (PD-1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis-mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.

Application of three-dimensional printing in cardiovascular diseases: a bibliometric analysis.

AIM: This paper aimed to explore the application of three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend. METHODS: The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information. RESULTS: A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles ( n =8) was also from there. The Frontiers in Cardiovascular Medicine published most papers ( n =25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations ( n =520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure. CONCLUSIONS: The authors summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.

Association between NOS3 gene polymorphisms and genetic susceptibility to congenital heart Disease: A systematic review and meta-analysis.

BACKGROUND: Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for angiogenesis. However, the relationship between NOS3 gene polymorphisms and genetic susceptibility to congenital heart disease (CHD) was still unclear. METHODS: We searched five databases including Pubmed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang, to find all studies on NOS3 gene polymorphisms and CHD. Rstudio was used to merge the data included in the study to obtain OR, 95%CI, and forest plots. RESULTS: Five relevant literatures were included, including three sites of NOS3 gene, rs1799983 (G894T), rs2070744 (T-786C), and rs7830 (G10T). Several models including the homozygous model of rs1799983 (G894T) gene polymorphism (TT VS GG: OR = 1.602, 95%CI: 1.098 âˆ¼ 2.337, P = 0.027), rs7830 (G10T) gene polymorphism allele model (A VS C: OR = 1.171, 95%CI: 1.029 âˆ¼ 1.333, P = 0.017), homozygous model (AA VS CC: OR = 1.474, 95%CI: 1.122 âˆ¼ 1.936, P = 0.005) and implicit model (AA VS CC + AC: OR = 1.451, 95%CI: 1.133 âˆ¼ 1.859, P = 0.003) indicated that there was a correlation. The results of the combined analysis of each gene model of rs2070744 (T-786C) gene polymorphism sites were not statistically significant, and their P values were all>0.05. CONCLUSION: rs1799983 (G894T) and rs7830 (G10T) polymorphic sites might play a role in the susceptibility of sporadic congenital heart disease and increase the risk of CHD. Yet, it is still necessary to expand the sample size and conduct more prospective/retrospective studies to confirm whether the rs2070744 (T-786C) polymorphism tended to increase the incidence of CHD.

Lactiplantibacillus plantarum P101 Attenuated Cyclophosphamide-Induced Liver Injury in Mice by Regulating the Nrf2/ARE Signaling Pathway.

Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, Lactiplantibacillus plantarum P101 or Lactobacillus rhamnosus GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, Lactiplantibacillus plantarum P101 exhibited more pronounced effects than Lactobacillus rhamnosus GG. Furthermore, Lactiplantibacillus plantarum P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of Lactiplantibacillus plantarum P101 to alleviate cyclophosphamide-induced hepatotoxicity.

Ultrasound-based radiomics model for predicting molecular biomarkers in breast cancer.

Background: Breast cancer (BC) is the most common cancer in women and is highly heterogeneous. BC can be classified into four molecular subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker protein Ki-67. However, they can only be obtained by biopsy or surgery, which is invasive. Radiomics can noninvasively predict molecular expression via extracting the image features. Nevertheless, there is a scarcity of data available regarding the prediction of molecular biomarker expression using ultrasound (US) images in BC. Objectives: To investigate the prediction performance of US radiomics for the assessment of molecular profiling in BC. Methods: A total of 342 patients with BC who underwent preoperative US examination between January 2013 and December 2021 were retrospectively included. They were confirmed by pathology and molecular subtype analysis of ER, PR, HER2 and Ki-67. The radiomics features were extracted and four molecular models were constructed through support vector machine (SVM). Pearson correlation coefficient heatmaps are employed to analyze the relationship between selected features and their predictive power on molecular expression. The receiver operating characteristic curve was used for the prediction performance of US radiomics in the assessment of molecular profiling. Results: 359 lesions with 129 ER- and 230 ER+, 163 PR- and 196 PR+, 265 HER2- and 94 HER2+, 114 Ki-67- and 245 Ki-67+ expression were included. 1314 features were extracted from each ultrasound image. And there was a significant difference of some specific radiomics features between the molecule positive and negative groups. Multiple features demonstrated significant association with molecular biomarkers. The area under curves (AUCs) were 0.917, 0.835, 0.771, and 0.896 in the training set, while 0.868, 0.811, 0.722, and 0.706 in the validation set to predict ER, PR, HER2, and Ki-67 expression respectively. Conclusion: Ultrasound-based radiomics provides a promising method for predicting molecular biomarker expression of ER, PR, HER2, and Ki-67 in BC.

Dynamic changes in lactate levels within the first 24 hours in septic patients as a prognostic indicator: A retrospective cohort study utilizing latent class growth analysis.

Elevated lactate levels are common in sepsis patients. This study aimed to assess the effect of dynamic changes in lactate levels within the first 24 hours following admission on patient prognosis. We extracted data from the Medical Information Mart for Intensive Care (MIMIC)-IV database and classified patients using latent class growth analysis (LCGA). This analysis classified sepsis patients into different groups based on dynamic changes in lactate levels during the initial 24 hours post-admission, dividing this time frame into four periods (0-3 h, 3-6 h, 6-12 h, and 12-24 h). The highest lactate level recorded in each period was then used for patient classification. We subsequently compared the baseline characteristics and outcomes between these different groups. Our study encompassed 7,830 patients, whom LCGA successfully divided into two classes: class 1 (steady lactate class) and class 2 (increasing lactate class). Class 2 demonstrated a worse clinical status at baseline, as indicated by vital signs, disease severity scores, and laboratory results. Importantly, class 2 also had a significantly higher 28-day mortality rate than class 1 (55.6% vs 13.5%, P < 0.001). In conclusion, LCGA effectively categorized sepsis patients into two distinct groups based on their dynamic changes in lactate levels during the first 24 hours post-admission. This methodology has potential utility in clinical practice for managing sepsis patients.

The effect of metabolic syndrome on postoperative complications and long-term survival of patients with colorectal cancer.

Background: Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC. Methods: We included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS. Results: We included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS. Conclusions: MetS affects the long-term survival of patients with CRC without affecting postoperative complications.

Emerging Memtransistors for Neuromorphic System Applications: A Review.

The von Neumann architecture with separate memory and processing presents a serious challenge in terms of device integration, power consumption, and real-time information processing. Inspired by the human brain that has highly parallel computing and adaptive learning capabilities, memtransistors are proposed to be developed in order to meet the requirement of artificial intelligence, which can continuously sense the objects, store and process the complex signal, and demonstrate an "all-in-one" low power array. The channel materials of memtransistors include a range of materials, such as two-dimensional (2D) materials, graphene, black phosphorus (BP), carbon nanotubes (CNT), and indium gallium zinc oxide (IGZO). Ferroelectric materials such as P(VDF-TrFE), chalcogenide (PZT), HfxZr1-xO2(HZO), In2Se3, and the electrolyte ion are used as the gate dielectric to mediate artificial synapses. In this review, emergent technology using memtransistors with different materials, diverse device fabrications to improve the integrated storage, and the calculation performance are demonstrated. The different neuromorphic behaviors and the corresponding mechanisms in various materials including organic materials and semiconductor materials are analyzed. Finally, the current challenges and future perspectives for the development of memtransistors in neuromorphic system applications are presented.