Recent design strategies for boosting chemodynamic therapy of bacterial infections.

The emergence of drug-resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into •OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.

Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice.

The aim of this study is to observe the changes in autophagy activities in lung tissues of mice with different degrees of pulmonary fibrosis (PF), and explore the association between PF and autophagy activity. The PF model was established by bleomycin (BLM, 25 and 35 mg/kg) atomization inhalation in C57BL/6 mice, samples were collected on the 7, 14, and 28 days after BLM administration. Hematoxylin-eosin staining was used to observe the pathological changes in lung tissues. Masson staining was utilized to assess areas of blue collagen fiber deposition in lung tissues. Quantitative real time polymerase chain reaction was used to detect the mRNA expressions of autophagy-related genes, including Atg5, Atg7, and Atg10 in lung tissues. Western blot was used to detect the protein expressions of autophagy-related genes, including p62 and LC3II/LC3I in lung tissues. Compared with control group, BLM dose-dependently decreased PaO2, mRNA expressions of Atg5, Atg7, Atg10, and LC3II/LC3I, while increased lung wet weight, lung coefficient, PF score, the blue area of collagen fibers, and p62 protein on the 7th, 14th, and 28th days. In conclusion, the more severe the PF induced by BLM, the lower the autophagy activity.

ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy.

Objective: Epilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy. Methods and results: Meta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control. Conclusion: Clinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

Influence of protective clothing and masks on facial trustworthiness in an investment game: insights from a Chinese population study.

Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants' trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people's trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.

Ocean acidification alters microeukaryotic and bacterial food web interactions in a eutrophic subtropical mesocosm.

Ocean acidification (OA) is known to influence biological and ecological processes, mainly focusing on its impacts on single species, but little has been documented on how OA may alter plankton community interactions. Here, we conducted a mesocosm experiment with ambient (∼410 ppmv) and high (1000 ppmv) CO2 concentrations in a subtropical eutrophic region of the East China Sea and examined the community dynamics of microeukaryotes, bacterioplankton and microeukaryote-attached bacteria in the enclosed coastal seawater. The OA treatment with elevated CO2 affected taxa as the phytoplankton bloom stages progressed, with a 72.89% decrease in relative abundance of the protist Cercozoa on day 10 and a 322% increase in relative abundance of Stramenopile dominated by diatoms, accompanied by a 29.54% decrease in relative abundance of attached Alphaproteobacteria on day 28. Our study revealed that protozoans with different prey preferences had differing sensitivity to high CO2, and attached bacteria were more significantly affected by high CO2 compared to bacterioplankton. Our findings indicate that high CO2 changed the co-occurrence network complexity and stability of microeukaryotes more than those of bacteria. Furthermore, high CO2 was found to alter the proportions of potential interactions between phytoplankton and their predators, as well as microeukaryotes and their attached bacteria in the networks. The changes in the relative abundances and interactions of microeukaryotes between their predators in response to high CO2 revealed in our study suggest that high CO2 may have profound impacts on marine food webs.

Unraveling the genetic and molecular landscape of sepsis and acute kidney injury: A comprehensive GWAS and machine learning approach.

OBJECTIVES: This study aimed to explore the underlying mechanisms of sepsis and acute kidney injury (AKI), including sepsis-associated AKI (SA-AKI), a frequent complication in critically ill sepsis patients. METHODS: GWAS data was analyzed for genetic association between AKI and sepsis. Then, we systematically applied three distinct machine learning algorithms (LASSO, SVM-RFE, RF) to rigorously identify and validate signature genes of SA-AKI, assessing their diagnostic and prognostic value through ROC curves and survival analysis. The study also examined the functional and immunological aspects of these genes, potential drug targets, and ceRNA networks. A mouse model of sepsis was created to test the reliability of these signature genes. RESULTS: LDSC confirmed a positive genetic correlation between AKI and sepsis, although no significant shared loci were found. Bidirectional MR analysis indicated mutual increased risks of AKI and sepsis. Then, 311 key genes common to sepsis and AKI were identified, with 42 significantly linked to sepsis prognosis. Six genes, selected through LASSO, SVM-RFE, and RF algorithms, showed excellent predictive performance for sepsis, AKI, and SA-AKI. The models demonstrated near-perfect AUCs in both training and testing datasets, and a perfect AUC in a sepsis mouse model. Significant differences in immune cells, immune-related pathways, HLA, and checkpoint genes were found between high- and low-risk groups. The study identified 62 potential drug treatments for sepsis and AKI and constructed a ceRNA network. CONCLUSIONS: The identified signature genes hold potential clinical applications, including prognostic evaluation and targeted therapeutic strategies for sepsis and AKI. However, further research is needed to confirm these findings.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Circ-USP9X accelerates deep vein thrombosis after fracture by acting as a miR-148b-3p sponge and upregulates SRC kinase signaling inhibitor 1.

OBJECTIVES: This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities. METHODS: An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl2) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments. RESULTS: The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl2-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl2's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified. CONCLUSION: circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.

Understanding the influence of cytokines in intrauterine hepatitis B transmission: A cross-sectional study in China.

Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis.

Heterostructured Pt-PbS Nanobelt Achieves Remarkable Direct Formic Acid Oxidation Catalysis.

Developing efficient and CO-tolerant platinum (Pt)-based anodic catalysts is challenging for a direct formic acid fuel cell (DFAFC). Herein, we report heterostructured Pt-lead-sulfur (PtPbS)-based nanomaterials with gradual phase regulation as efficient formic acid oxidation reaction (FAOR) catalysts. The optimized Pt-PbS nanobelts (Pt-PbS NBs/C) display the mass and specific activities of 5.90 A mgPt-1 and 21.4 mA cm-2, 2.2/1.2, 1.5/1.1, and 36.9/79.3 times greater than those of PtPb-PbS NBs/C, Pt-PbSO4 NBs/C, and commercial Pt/C, respectively. Simultaneously, it exhibits a higher membrane electrode assembly (MEA) power density (183.5 mW cm-2) than commercial Pt/C (40.3 mW cm-2). This MEA stably operates at 0.4 V for 25 h, demonstrating a competitive potential of device application. The distinctive heterostructure endows the Pt-PbS NBs/C with optimized dehydrogenation steps and resisting the CO poisoning, thus presenting the remarkable FAOR performance. This work paves an effective avenue for creating high-performance anodic catalysts for fuel cells and beyond.

Retinal ganglion cell type-specific expression of synuclein family members revealed by scRNA-sequencing.

Synuclein family members (Snca, Sncb, and Scng) are expressed in the retina, but their precise locations and roles are poorly understood. We performed an extensive analysis of the single-cell transcriptome in healthy and injured retinas to investigate their expression patterns and roles. We observed the expression of all synuclein family members in retinal ganglion cells (RGCs), which remained consistent across species (human, mouse, and chicken). We unveiled differential expression of Snca across distinct clusters (highly expressed in most), while Sncb and Sncg displayed uniform expression across all clusters. Further, we observed a decreased expression in RGCs following traumatic axonal injury. However, the proportion of α-Syn-positive RGCs in all RGCs and α-Syn-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in all ipRGCs remained unaltered. Lastly, we identified changes in communication patterns preceding cell death, with particular significance in the pleiotrophin-nucleolin (Ptn-Ncl) and neural cell adhesion molecule signaling pathways, where communication differences were pronounced between cells with varying expression levels of Snca. Our study employs an innovative approach using scRNA-seq to characterize synuclein expression in health retinal cells, specifically focusing on RGC subtypes, advances our knowledge of retinal physiology and pathology.

Alginate nanogel-embedded liposomal drug carriers facilitate drug delivery efficiency in arthritis treatment.

Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.

Conversion of Phosphogypsum into Porous Calcium Silicate Hydrate for the Removal and Recycling of Pb(II) and Cd(II) from Wastewater.

The discharge of lead and cadmium wastewater, along with the pollution caused by phosphogypsum, represents a particularly urgent environmental issue. This study employed a straightforward hydrothermal method to convert phosphogypsum into porous calcium silicate hydrate (P-CSH), which was then used to remove and recover Pb(II) and Cd(II) from wastewater. The adsorption capacities of P-CSH for Pb(II) and Cd(II) were notably high at 989.3 mg/g and 290.3 mg/g, respectively. The adsorption processes adhered to the pseudo-second-order kinetics model and the Langmuir isotherm model. Due to identical adsorption sites on P-CSH for both Pb(II) and Cd(II), competitive interaction occurred when both ions were present simultaneously. Additionally, the adsorption efficacy was minimally impacted by the presence of common coexisting cations in wastewater. The dominant mechanisms for removing Pb(II) and Cd(II) via P-CSH were chemical precipitation and surface complexation. Moreover, the adsorbed heavy metals were efficiently separated and reclaimed from the wastewater through a stepwise desorption process. The primary components of the residue from stepwise desorption were quartz and amorphous SiO2. Following dissolution via pressurized alkaline leaching, this residue could be recycled for synthesizing P-CSH. This research offered a new strategy for the resourceful use of phosphogypsum and heavy metal wastewater.

Integrated ATAC-seq and RNA-seq Analysis of In Vitro Cultured Skeletal Muscle Satellite Cells to Understand Changes in Cell Proliferation.

Skeletal muscle satellite cells, the resident stem cells in pig skeletal muscle, undergo proliferation and differentiation to enable muscle tissue repair. The proliferative and differentiative abilities of these cells gradually decrease during in vitro cultivation as the cell passage number increases. Despite extensive research, the precise molecular mechanisms that regulate this process are not fully understood. To bridge this knowledge gap, we conducted transcriptomic analysis of skeletal muscle satellite cells during in vitro cultivation to quantify passage number-dependent changes in the expression of genes associated with proliferation. Additionally, we explored the relationships between gene transcriptional activity and chromatin accessibility using transposase-accessible chromatin sequencing. This revealed the closure of numerous open chromatin regions, which were primarily located in intergenic regions, as the cell passage number increased. Integrated analysis of the transcriptomic and epigenomic data demonstrated a weak correlation between gene transcriptional activity and chromatin openness in expressed genic regions; although some genes (e.g., GNB4 and FGD5) showed consistent relationships between gene expression and chromatin openness, a substantial number of differentially expressed genes had no clear association with chromatin openness in expressed genic regions. The p53-p21-RB signaling pathway may play a critical regulatory role in cell proliferation processes. The combined transcriptomic and epigenomic approach taken here provided key insights into changes in gene expression and chromatin openness during in vitro cultivation of skeletal muscle satellite cells. These findings enhance our understanding of the intricate mechanisms underlying the decline in cellular proliferation capacity in cultured cells.

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment.

Background: The systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment. Methods: We conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test. Results: A total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001). Conclusion: Preoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.

LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM.

Applying LASSO logistic regression for the prediction of biliary complications after ex vivo liver resection and autotransplantation in patients with end-stage hepatic alveolar echinococcosis.

BACKGROUND: The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model. METHODS: This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method. RESULTS: The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417-0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit. CONCLUSIONS: A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.

Optimization of tracheoesophageal fistula model established with T-shaped magnet system based on magnetic compression technique.

BACKGROUND: The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula (TEF), but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control. We designed a T-shaped magnet system to overcome these problems and verified its effectiveness via animal experiments. AIM: To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs. METHODS: Twelve beagles were randomly assigned to groups in which magnets of the T-shaped scheme (study group, n = 6) or normal magnets (control group, n = 6) were implanted into the trachea and esophagus separately under gastroscopy. Operation time, operation success rate, and accidental injury were recorded. After operation, the presence and timing of cough and the time of magnet shedding were observed. Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing, and gross specimens of TEFs were obtained. Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery, and gross specimens were obtained. Fistula size was measured in all animals, and then harvested fistula specimens were examined by hematoxylin and eosin (HE) and Masson trichrome staining. RESULTS: The operation success rate was 100% for both groups. Operation time did not differ between the study group (5.25 min ± 1.29 min) and the control group (4.75 min ± 1.70 min; P = 0.331). No bleeding, perforation, or unplanned magnet attraction occurred in any animal during the operation. In the early postoperative period, all dogs ate freely and were generally in good condition. Dogs in the control group had severe cough after drinking water at 6-9 d after surgery. X-ray indicated that the magnets had entered the stomach, and gastroscopy showed TEF formation. Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm ± 1.29 mm (range, 3.52-6.56 mm). HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas. Dogs in the study group did not exhibit obvious coughing after surgery. X-ray examination 2 wk after surgery indicated fixed magnet positioning, and gastroscopy showed no change in magnet positioning. The magnets were removed using a snare under endoscopy, and TEF was observed. Gross specimens showed well-formed fistulas with a diameter of 6.11 mm ± 0.16 mm (range, 5.92-6.36 mm), which exceeded that in the control group (P < 0.001). Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining, and the structure was more regular than that in the control group. CONCLUSION: Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets. Most importantly, this model offers better controllability, which improves the flexibility of follow-up studies.