Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

Ultra-Tough, yet Rigid and Healable Supramolecular Polymers with Variable Stiffness for Multimodal Actuators.

Variable stiffness materials have shown considerable application in soft robotics. However, previously reported materials often struggle to reconcile high stiffness, stretchability, toughness, and self-healing ability, because of the inherently conflicting requisite of these properties in molecular design. Herein, we propose a novel strategy that involves incorporating acid-base ionic pairs capable of from strong crosslinking sites into a dense and robust hydrogen-bonding network to construct rigid self-healing polymers with tunable stiffness and excellent toughness. To demonstrate these distinct features, the polymer was employed to serve as the strain-regulation layers within a fiber-reinforced pneumatic actuator (FPA). The exceptional synergy between the configuration versatility of FPA and the dynamic molecular behavior of the supramolecular polymers equips the actuator with simultaneous improvement in motion dexterity, multimodality, loading capacity, robustness, and durability. Additionally, the concept of integrating high dexterity at both macro- and micro-scale is prospective to inspire the design of intelligent yet robust devices across various domains.

Performance assessment of an artificial intelligence-based coronary artery calcium scoring algorithm in non-gated chest CT scans of different slice thickness.

Background: The coronary artery calcium score (CACS) has been shown to be an independent predictor of cardiovascular events. The traditional coronary artery calcium scoring algorithm has been optimized for electrocardiogram (ECG)-gated images, which are acquired with specific settings and timing. Therefore, if the artificial intelligence-based coronary artery calcium score (AI-CACS) could be calculated from a chest low-dose computed tomography (LDCT) examination, it could be valuable in assessing the risk of coronary artery disease (CAD) in advance, and it could potentially reduce the occurrence of cardiovascular events in patients. This study aimed to assess the performance of an AI-CACS algorithm in non-gated chest scans with three different slice thicknesses (1, 3, and 5 mm). Methods: A total of 135 patients who underwent both LDCT of the chest and ECG-gated non-contrast enhanced cardiac CT were prospectively included in this study. The Agatston scores were automatically derived from chest CT images reconstructed at slice thicknesses of 1, 3, and 5 mm using the AI-CACS software. These scores were then compared to those obtained from the ECG-gated cardiac CT data using a conventional semi-automatic method that served as the reference. The correlations between the AI-CACS and electrocardiogram-gated coronary artery calcium score (ECG-CACS) were analyzed, and Bland-Altman plots were used to assess agreement. Risk stratification was based on the calculated CACS, and the concordance rate was determined. Results: A total of 112 patients were included in the final analysis. The correlations between the AI-CACS at three different thicknesses (1, 3, and 5 mm) and the ECG-CACS were 0.973, 0.941, and 0.834 (all P<0.01), respectively. The Bland-Altman plots showed mean differences in the AI-CACS for the three thicknesses of -6.5, 15.4, and 53.1, respectively. The risk category agreement for the three AI-CACS groups was 0.868, 0.772, and 0.412 (all P<0.01), respectively. While the concordance rates were 91%, 84.8%, and 62.5%, respectively. Conclusions: The AI-based algorithm successfully calculated the CACS from LDCT scans of the chest, demonstrating its utility in risk categorization. Furthermore, the CACS derived from images with a slice thickness of 1 mm was more accurate than those obtained from images with slice thicknesses of 3 and 5 mm.

Enhancing lymph node metastasis prediction in adenocarcinoma of the esophagogastric junction: A study combining radiomic with clinical features.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported. PURPOSE: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ. METHODS: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses. RESULTS: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840). CONCLUSION: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning.

Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis.

Objective: Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models. Methods: The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots. Results: Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation. Conclusion: The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

Sivelestat improves acute lung injury by inhibiting PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL). METHODS: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway. RESULTS: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium. CONCLUSION: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway.

High-Fidelity Bioelectrodes with Bidirectional Ion-Electron Transduction Capability by Integrating Multiple Charge-Transfer Processes.

Bioelectronics is an exciting field that bridges the gap between physiological activities and external electronic devices, striving for high resolution, high conformability, scalability, and ease of integration. One crucial component in bioelectronics is bioelectrodes, designed to convert neural activity into electronic signals or vice versa. Previously reported bioelectrodes have struggled to meet several essential requirements simultaneously: high-fidelity signal transduction, high charge injection capability, strain resistance, and multifunctionality. This work introduces a novel strategy for fabricating superior bioelectrodes by merging multiple charge-transfer processes. The resulting bioelectrodes offer accurate ion-to-electron transduction for capturing electrophysiological signals, dependable charge injection capability for neuromodulation, consistent electrode potential for artifact rejection and biomolecule sensing, and high transparency for seamless integration with optoelectronics. Furthermore, the bioelectrode can be designed to be strain-insensitive by isolating signal transduction from electron transportation. The innovative concept presented in this work holds great promise for extending to other electrode materials and paves the way for the advancement of multimodal bioelectronics.

Quantitative analysis of contrast-enhanced ultrasound and superb microvascular imaging for the evaluation of disease activity in inflammatory bowel disease.

OBJECTIVE: To evaluate the effectiveness of conventional US (ultrasound), SMI (superb microvascular imaging), and CEUS (contrast-enhanced ultrasound) features for the assessment of the activity of inflammatory bowel disease. METHODS: Conventional US, CEUS and SMI features of 76 patients were retrospectively analyzed. Patients were categorized into two groups: active group (n = 57) and inactive group (n = 19), with endoscopic results as reference standard. Results in the active group and inactive group were compared using an independent t-test, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve (ROC) analysis. Cut-off values were determined using ROC analysis, and sensitivity and specificity were calculated. US quantitative and TIC-based quantitative parameters were analyzed, and each patient was scored based on the parameters that are statistically significant and immediately available in the clinic to evaluate the diagnostic ability of conventional US, SMI, and CEUS features for active IBD patients. RESULTS: Qualitative parameters such as CEUS enhancement pattern I/II, LimbergIII/IV, and lost bowel stratification were reliable indicators of active patients. Quantitative parameters such as bowel thickness and VI of mSMI were reliable indicators of active patients. Patients scored based on these statistically significant parameters with a score ≥3, were highly suspected to be active patients. For TIC-based quantitative parameters, PE, WiAUC, WoAUC, WiWoAUC, WiR, WiPI, and WoR were statistically significant in the differentiation of active IBD from inactive IBD. CONCLUSIONS: Conventional US, SMI, and CEUS features may help in the differentiation of active IBD from inactive IBD and have potential application value in the choice of treatment options.

Distinct serum exosomal miRNA profiles detected in acute and asymptomatic dengue infections: A community-based study in Baiyun District, Guangzhou.

Background: In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to investigate the serum exosomal miRNA expression profile of dengue-infected individuals through a community survey of dengue virus (DENV) infection. Methods: A seroprevalence study of 1253 healthy persons was first conducted to ascertain the DENV infection status in Baiyun District, Guangzhou. A total of 18 serum samples, including 6 healthy controls (HC), 6 asymptomatic DENV infections (AsymptDI), and 6 confirmed dengue fever patients (AcuteDI), were collected for exosome isolation and then sRNA sequencing. Through bioinformatics analysis, we discovered distinct serum exosomal miRNA profiles among the different groups and identified differentially expressed miRNAs (DEMs). These findings were further validated by qRT-PCR. Results: The community survey of DENV infection indicated that the DENV IgG antibody positivity rate among the population was 11.97 % in the study area, with asymptomatic infected individuals accounting for 93.06 % of the anti-DENV IgG positives. The age and Guangzhou household registration were associated with DENV IgG antibody positivity by logistic regression analysis. Distinct miRNA profiles were observed between healthy individuals and DENV infections. A total of 1854 miRNAs were identified in 18 serum exosome samples from the initial analysis of the sequencing data. Comparative analysis revealed 23 DEMs comprising 5 upregulated and 18 downregulated miRNAs in the DENV-infected group (mergedDI). In comparison to AcuteDI, 18 upregulated miRNAs were identified in AsymptDI. Moreover, functional enrichment of the predicted target genes of DEMs indicated that these miRNAs were involved in biological processes and pathways related to cell adhesion, focal adhesion, endocytosis, and ECM-receptor interaction. Eight DEMs were validated by qRT-PCR. Conclusion: The Baiyun District of Guangzhou exhibits a notable proportion of asymptomatic DENV infections as suggested in other research, highlighting the need for enhanced monitoring and screening of asymptomatic persons and the elderly. Differential miRNA expression among healthy, symptomatic and asymptomatic DENV-infected individuals suggests their potential as biomarkers for distinguishing DENV infection and offers new avenues of investigating the mechanisms underlying DENV asymptomatic infections.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Comparative single-cell RNA sequencing analysis of immune response to inactivated vaccine and natural SARS-CoV-2 infection.

Uncovering the immune response to an inactivated SARS-CoV-2 vaccine (In-Vac) and natural infection is crucial for comprehending COVID-19 immunology. Here we conducted an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In-Vac compared with those from COVID-19 patients. Our study reveals that In-Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In-Vac modestly upregulates IFN-α but downregulates NF-κB pathways, while natural infection triggers hyperactive IFN-α and NF-κB pathways. Both In-Vac and natural infection alter T/B cell receptor repertoires, but COVID-19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL-15RA/IL-15 receptor pathway after In-Vac boost, suggesting its potential role in enhancing In-Vac-induced immunity. Collectively, our study illuminates multifaceted immune responses to In-Vac and natural infection, providing insights for optimizing SARS-CoV-2 vaccine efficacy.

Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states.

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer.

Background: Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention. Methods: The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor-Immune System Interactions Database (TISIDB), and validated through western blot experiments. Results: Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B (APOB) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A (HNF4A) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells. Conclusion: Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB. Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

Ultra-Highly Stiff and Tough Shape Memory Polyurea with Unprecedented Energy Density by Precise Slight Cross-Linking.

Shape memory polymers (SMPs) have attracted significant attention and hold vast potential for diverse applications. Nevertheless, conventional SMPs suffer from notable shortcomings in terms of mechanical properties, environmental stability, and energy density, significantly constraining their practical utility. Here, inspired by the structure of muscle fibers, an innovative approach that involves the precise incorporation of subtle, permanent cross-linking within a hierarchical hydrogen bonding supramolecular network is reported. This novel strategy has culminated in the development of covalent and supramolecular shape memory polyurea, which exhibits exceptional mechanical properties, including high stiffness (1347 MPa), strength (82.4 MPa), and toughness (312.7 MJ m-3), ensuring its suitability for a wide range of applications. Furthermore, it boasts remarkable recyclability and repairability, along with excellent resistance to moisture, heat, and solvents. Moreover, the polymer demonstrates outstanding shape memory effects characterized by a high energy density (24.5 MJ m-3), facilitated by the formation of strain-induced oriented nanostructures that can store substantial amounts of entropic energy. Simultaneously, it maintains a remarkable 96% shape fixity and 99% shape recovery. This delicate interplay of covalent and supramolecular bonds opens up a promising pathway to the creation of high-performance SMPs, expanding their applicability across various domains.

Stimulation of PSTPIP1 to trigger proinflammatory responses in asymptomatic SARS-CoV-2 infections.

Background: A hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection gravely worsens the clinical progression of coronavirus disease 2019 (COVID-19). Although the undesirable effects of inflammasome activation have been correlated to the severity of COVID-19, the mechanisms of this process in the asymptomatic infection and disease progression have not yet been clearly elucidated. Methods: We performed strand-specific RNA sequencing in 39 peripheral blood mononuclear cell (PBMC) samples from asymptomatic individuals（n = 10）, symptomatic patients（n = 16） and healthy donors（n = 13）. Results: Dysregulation of pyrin inflammasomes along with the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene was identified in SARS-COV-2 infection. Notably, the PSTPIP1 expression level showed a significant negative correlation with an adjacent long-noncoding RNA (lncRNA) RP11-797A18.6 in the asymptomatic individuals compared with the healthy controls. In addition, a decline in the nuclear factor kappa B subunit 1 (NFKB1) gene expression was observed in asymptomatic infection, followed by a rise in the mild and moderate disease stages, suggesting that altered NFKB1 expression and associated proinflammatory signals may trigger a disease progression. Conclusions: Overall, our results indicate that PSTPIP1-dependent pyrin inflammasomes-mediated pyroptosis and NF-κB activation might be potential preventive targets for COVID-19 disease development and progression.

A challenging surgical technique: single-port endoscopic-assisted radical mastectomy in retrograde way and immediate reconstruction using prosthesis implantation.

Background: Endoscopic surgery for malignant breast tumors is becoming more and more popular and has been applied in the clinical setting. Single-port endoscopic-assisted radical mastectomy in retrograde way and immediate reconstruction using prosthesis implantation are rare. Therefore, this study described a new endoscopic technique for breast surgery. Methods: This is a cross-sectional study. A total of 12 patients with breast cancer diagnosed in the Department of Thyroid Breast Surgery of The Second Affiliated Hospital of Fujian Medical University from January 2019 to June 2022 were retrospectively selected and underwent axillary single-port endoscopic-assisted radical mastectomy in retrograde way and immediate reconstruction using prosthesis implantation. Results: The average operation time was 190.25±25.40 min, the average blood loss was 86.25±33.11 mL, the average drainage volume was 207.92±65.90 mL 3 days after surgery, and the average hospital stay was 9.67±2.57 days. The follow-up period ranged from 11 to 21 months, with an average of 16.75 months. Medial paresthesia was present in only one patient, which decreased or disappeared after 3 months. No complications such as wound infection or limb dysfunction occurred in the remaining patients. Postoperative follow-up showed that 10 patients were very satisfied, one patient was relatively satisfied, and one patient was not satisfied. Conclusions: Preliminary data attested the feasibility and the safety of this approach. It can improve patient satisfaction compared with traditional modified radical mastectomy for suitable candidates. However, long-term data are needed to confirm the oncological safety and the esthetic stability of the result.

Construction of a diagnostic nomogram model for predicting the risk of lymph node metastasis in clinical T1 or T2 colon cancer based on the SEER database.

Background: There are few methods related to predicting lymph node metastasis (LNM) in patients with clinically staged T1 or T2 colon cancer. In this study, we aimed to discover independent risk factors for patients with pathologic T-stage 1 (pT1) or pT2 colon cancer with LNM and to develop a nomogram for predicting the probability of LNM for patients with clinically staged T1 or T2 colon cancer. Methods: All data were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors for LNM were identified using univariate and multivariate logistic regression analyses, and these factors were used to construct a nomogram. The discriminatory power, accuracy, and clinical utility of the model were evaluated using receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA), respectively. Results: According to the inclusion and exclusion criteria, 32,803 patients with stage pT1 or pT2 colon cancer who had undergone surgery were selected from the SEER database. The data showed that the incidence of LNM in patients with pT1 and pT2 colon cancer was 17.11%. The age, histological grade, histological type, T classification, M classification, and tumour location were independent risk factors identified through univariate and multivariate analyses, and these factors were used to construct a nomogram. The ROC curve analysis showed that the area under the curve (AUC) of the ROC of the predictive nomogram for LNM risk was 0.6714 [95% confidence interval (CI): 0.6621-0.6806] in the training set and 0.6567 (95% CI: 0.6422-0.6712) in the validation set, indicative of good discriminatory power of the model. Calibration curve analysis demonstrated good agreement between the nomogram prediction and actual observation. DCA showed excellent clinical utility of the prediction model. Conclusions: The incidence of LNM was high in patients with pT1 and pT2 colon cancer. The nomogram established in this study can accurately predict the risk of LNM in patients with clinically staged T1 or T2 colon cancer before further clinical intervention, which allows clinicians to develop optimal treatment.

The Application of Sesamoid Position in Diagnosing Thumb Metacarpophalangeal Joint Dorsal Dislocation: A Retrospective Study.

OBJECTIVES: The position of sesamoid of thumb metacarpophalangeal (MCP) joint changed clearly when the joint was dislocated dorsally. However, the significance of sesamoid location in diagnosing joint dislocation was unclear. The present study aimed to explore the positional relationship between sesamoid bone and thumb metacarpophalangeal joint in normal and dorsal dislocation joints. METHODS: Between January 2018 and August 2023, we collected 60 isometric plain films from sixty outpatients and reviewed 56 anisometric plain films from twenty-eight emergency patients with dorsal dislocation of thumb MCP joint at Tianjin Hospital, then took measurements on the hand X-ray images. The sesamoid length on its longitudinal axis was defined as DP, the distance between the distal edge of sesamoid and thumb MCP joint was defined as DJ, and the ratio of DJ and DP was R. An independent-samples t-test and paired-samples t-test was utilized to analyze difference among data groups. RESULTS: The 60 isometric images were from 30 male and 30 female outpatients with normal bone structure in their hands, and the 56 anisometric images of the 28 emergency patients included both preoperative and postoperative materials. Among the outpatients, the actual distance between the distal edge of sesamoid and thumb MCP joint space (DJ) was 2.09 mm and 1.40 mm in males and females, respectively. The authentic average length of sesamoid (DP) was 4.46 mm in males and 4.22 mm in females. The average value of R (the ratio of DJ and DP) in males and females was 0.49 and 0.34, respectively. There were gender-related statistical differences in DJ (p < 0.01) and R (p=0.01), but no statistical difference in DP (p > 0.05). For the 28 emergency patients, the mean value of R was -0.47 before joint reduction and 0.58 after joint reduction, with statistical difference between them (p < 0.01). CONCLUSIONS: There was significant difference in the relative position between sesamoid and thumb MCP joint when joint dislocation and joint reduction. The distal edge of sesamoid beyond thumb MCP joint could be an evidence in diagnosing joint dorsal dislocation. The distal edge of sesamoid below thumb MCP joint could be an evidence of joint reduction.

A nomogram for predicting lymph nodes metastasis at the inferior mesenteric artery in rectal cancer: a retrospective case-control study.

According to past and current literature, metastasis of the lymph nodes at the inferior mesenteric artery (IMA-LN), also known as 253LN of colorectal cancer has been seldom investigated. To date, there are still controversies on whether the 253LN need to be routinely cleaned. Using specific criteria, 347 patients who underwent radical resection for rectal cancer between April 2019 and July 2022 were selected for the study. Logistic regression was used to determine the likelihood that a patient may suffer 253LN metastasis, and a nomogram for 253LN metastasis subsequently developed. The c-index and calibration curve were used to evaluate precision and discrimination in the nomogram, and the appropriateness of the final nomogram for the clinical setting determined using decision curve analysis (DCA). 253LN metastases appeared in the pathological specimens of 29 (8.4%) of the selected patients. Logistic regression showed that preoperative parameters including serum carcinoembryonic antigen (CEA) value ( > 5 ng / ml, OR = 2.894, P = 0.023), distance from anal margin (> 9 cm, OR = 2.406, P = 0.045) and degree of differentiation (poor, OR = 9.712, P < 0.001) were significantly associated with 253LN metastasis. A nomogram to predict 253LN metastasis in rectal cancer was developed and showed considerable discrimination and good precision (c-index = 0.750). Furthermore, DCA confirmed that the nomogram has some feasibility for the clinical environment. Clinicopathological and radiological patient data can be pivotal for making surgical decisions relating to 253LN metastasis. A nomogram was developed using this data, providing an objective method that can significantly improve prognoses in colorectal cancer.